Standard Oficial Mexican NOM-164-SSA1-2015, Drug good manufacturing practices.

Outside a seal with the coat of arms, which says: United States Mexicans-Ministry of health.
MIKEL ANDONI ARRIOLA PEALOSA , Commissioner Federal for the protection against risks Health and
President of the Committee consultative national of standardization of regulation and promotion health, with
Foundation in them articles 39, of the law organic of the Administration public Federal; 4, of the law Federal of
procedure administrative; 3o., fractions XXII and XXIV,13, paragraph to, fraction I, 17 Bis, fraction III, 194, 194
Bis, 195, first paragraph, 197, 201, 205 , 210, 212, 221, 222, 225, 226, 227 and 231, of the law General of health;
3., fraction XI, 38, fraction II, 40, fractions I and XIII, 41, 43, 47, fraction IV and 51, of itlaw Federal on metrology
and standardization; 8, 9, 10, 11, 15, fraction V, 18, 100, 109, 110 and 112, of the Regulation of inputs for
health; 28 and 33 of the regulations of the Federal law on metrology and Standardization, 2, paragraph C,
fraction X, 36 and 37, of the regulation inside of the Secretariat of health, and 3, fractions I, literal b and l and II,
10, fractions IV and VIII, of theregulation of the Commission Federal for protection against risks health, and
WHEREAS
That pursuant to the provisions of article 46, section I, of the Federal law on metrology and Normalization,
June 30, 2015, andNational Advisory Committee for the standardization of regulation l and Health
promotion, approved the first draft of this standard;
Dated 9 September 2015, in compliance with the agreement of the National Advisory Committee
of Standardization of regulation and health promotion and the provisions of article 47, section I, of the law Federal
metrology and standardization, was published in the official journal of the Federation, the project of the this
standard to that effect within the following sixty calendar days subsequent to such publication, interested parties
submit reviews to the aforementioned Committee;
It was published in the official journal of the Federation, the response to comments previous, dated received
by the Committee, in accordance with article 47, subparagraph III, of the Federal envelope law metrology and
standardization, and
That in view of the above considerations, with the approval of the Advisory Committee National
standardization of regulation and health promotion, have seen fit to issue and order the publication in the official
journal of the Federation of the
Standard Oficial Mexican NOM-164-SSA1-2015, Good practices Manufacturing of
DRUGS
PREFACE
Participated in the elaboration of this standard the following administrative units and Institutions:
SECRETARY OF HEALTH.
Commission for protection against health risks Federal.
Permanent of the pharmacopoeia of the United States Mexican Commission.
GENERAL HEALTH COUNCIL.
Commission interinstitutional of the basic picture of inputs from the Health Sector.
MEXICAN INSTITUTE OF SOCIAL SECURITY.
Institutional Division of basic tables of health supplies.
INSTITUTE OF SECURITY AND SOCIAL SERVICES FOR WORKERS IN THE STATE.
Address of administration.
UNIVERSIDAD NACIONAL AUTNOMA DE MXICO.
Faculty of chemistry.
INSTITUTO POLITCNICO NACIONAL.
National School of biological sciences.
NATIONAL CHAMBER OF THE TRANSFORMATION INDUSTRY.
Section 89.
Sector medical.
NATIONAL CHAMBER OF THE PHARMACEUTICAL INDUSTRY.
NATIONAL ACADEMY OF SCIENCES PHARMACEUTICAL, A.C.
ASSOCIATION FARMACEUTICA MEXICANA, A.C.
NATIONAL COLLEGE OF PHARMACEUTICAL CHEMICAL BIOLOGISTS MEXICO, A.C.
PRODUCTION CHEMICAL PHARMACEUTICAL, BC
ASOCIACIN MEXICANA DE LABORATORIOS FARMACEUTICOS, BC
MEXICAN ASSOCIATION OF INDUSTRIES OF PHARMACEUTICAL, BC RESEARCH
NATIONAL ASSOCIATION OF MANUFACTURERS OF MEDICINES, BC
INDEX
0. introduction.
1. objective and field of application.
2. references.
3. definitions.
4. symbols and abbreviations.
5. system of management of quality.
6. quality risk management.
7. staff.
8. facilities and equipment.
9. qualification and validation.
10. systems of production.
11. laboratorio de Control de Calidad.
12. removal product aftermarket.
13. subcontracted activities.
14. destruction and final disposal of waste.
15. distributors.
16. manufacture of drugs for use in clinical trials.
17. concordance with international and Mexican regulations.
18. bibliography.
19. enforcement.
20. Vigency
20.1 Appendix A normative. Classification of manufacturing areas.
20.2 Appendix B normative. Annual product review.
 0. introduction
Health is a cornerstone for development and welfare, in this context, the drugs are one of the most important
elements in the manufacture of medicines, which are essential for the care health. The manufacturing of drugs
includes the operations that are performed from the reception of the inputs, production, packaging, labelling,
quality control, release, storage and distribution andgood manufacturing practices compliance is essential to
ensure the quality and purity of drugs.

1. objective and field of application

1.1 Objective.
This standard establishes the minimum requirements for the process of manufacturing of the drugs or active
ingredients sold in the country or for drugs in development for use in clinical research.
1.2 Field of application.
This norm is compliance compulsory for all establishments engaged in the manufacture of drugs or active
ingredients sold in the country, or drugs in development for use in research clinic and distribution of drugs or
active principles stores.
2. references
For the correct application of this standard, it is suggested to consult the following Mexican official
standards in force or that the substitute:
2.1 Standard Oficial Mexican NOM-002-SCFI-2011, Productos preenvasados-Contenido NET-tolerances
and verification methods.
2.2 Standard officer Mexican NOM-052-SEMARNAT-2005, laying down the characteristics, the procedure
for the identification, classification and hazardous waste listings.
2.3 Standard Official Mexican NOM-001-SEMARNAT-1996, that sets those limits maximum permissible of
pollutants in the downloads of water waste in waters and property national.
2.4 Modification to the Norma Oficial Mexicana NOM-127-SSA1-1994, environmental Salud. Water for use
and human consumption. Limits permissible of quality and treatments that must submit is the water
for your purification.
2.5 Standard Oficial Mexican NOM-059-SSA1-2013, Buenas drug manufacturing practices.
2.6 Standard Official Mexican NOM-073-SSA1-2005, stability of drugs and drugs
2.7 Standard Oficial Mexican NOM-062-ZOO-1999, Especificaciones techniques for the production, care
and use of laboratory animals.
2.8 Standard Oficial Mexican NOM-253-SSA1-2012, for the disposal of human blood and its components for
therapeutic purposes.
2.9 Standard Oficial Mexican NOM-026-STPS-2008, colours and signals of safety and hygiene,
and identification of risks by fluids driven in piping.
3. definitions
For purposes of this rule means:
3.1 corrective action , to the activities that are planned and executed, with the aim of eliminating a deviation
or non compliance.
3.2 preventive action activities that are planned and implemented, to eliminate the cause of a deviation or
non conformity or another potentially undesirable situation.
3.3 Waters mothers, liquid obtained from separations performed to obtain of intermediates and finished
products, which contain reusable and/or recoverable amounts of raw, intermediate and/or finished product.
3.4 technical agreement , the document in which are formalized and detailed the conditions that will
be carried out activities or services between the parties and in which clearly describes the duties and
responsibilities of each of them, especially in relation to aspects of quality and GMP.
3.5 Store, the area where raw materials, materials, intermediates and drugs, are saved in controlled
conditions of order and cleanliness.
 3.6 restraint , to the set of physical and operational conditions that prevent the release of particles of high
risk abroad, which includes physical barriers, collectors and air systems independent and dedicated, as well as
the treatment of effluents, air extraction and waste materials before disposal.
3.7 good practices of , the set of guidelines and activities related, manufacturing aimed at ensuring that
manufactured drugs have and maintain the characteristics of purity and quality required for use.

3.8 Calibration, the set of operations that determine, under specific conditions the relationship between the
values indicated by an instrument, measuring, system represented by a material measure and values known to
a pattern of reference.
3.9 Rating, to the realization of them tests specific based in knowledge scientific, for demonstrate that them
equipment, facilities, personal and suppliers comply with them requirements previously established, which must
be completed before validate them processes.
3.10 Quality, to compliance with specifications established to ensure the fitness of use.
3.11 production campaign, to the manufacture of a series of batches of the same product in a period set of
time followed by activities of cleaning and/or sanitizing, before making another product. Different products are
not producidos at the same time butusing the same equipment.
3.12 training , to activities designed to generate or develop staff skills.
3.13 certificate of analysis , a summary of the results of the determinations made at samples of raw
materials, materials or other inputs, intermediate product and finished product, the references of analysis or test
methods and determination of compliance to specifications previously established, supported by the authorized
person.
3.14 good manufacturing practices certificate the document issued by the health authority of a country,
following a visit carried out health check to a settlement, to confirm your State of compliance with good
manufacturing practices in accordance with the regulatory framework health applicable.
3.15 Component, all substances involved in the different stages of manufacture of the drug.
3.16 pollution, to the presence of undesirable physical, chemical or biological entities.
3.17 Cross-contamination, the presence of undesirable physical, chemical or biological entities, from other
manufacturing processes.
3.18 Control of process, to the verification that is takes to out in those processes to ensure that is happening
it specified in them documents of manufacturing.
3.19 Post harvest, recovered from the mother liquor product.
3.20 Deviation or non-conformity, non-compliance with a previously established requirement.
3.21 Document master, to the document authorized that contains the information to perform and control the
operations of them processes and activities related with the manufacture of a product.
3.22 Specification, to the description of a material, substance or product, that includes them parameters
of quality, their limits of acceptance and the reference of the methods to use for its determination.
3.23 Stage criticism, the stage of production that must be specially controlled to ensure that
the intermediate product or finished product meets their specifications.
3.24 Manufacturing, the operations involved in the production of a drug from the reception of supplies until
their release as a finished product.
3.25 Drug, to all natural, synthetic or biotechnological substance having activity drug, and which is identified
by its physical properties, chemical or biological action, which not is presented in pharmaceutical form and who
fulfils the conditions to be used as a drug or ingredient in a drug.
3.26 Date, which indicates the end of the period of useful life of the drug.
3.27 Date of reanalysis, to the date limit for use a drug or intermediate; to continue using it must be again
sampled and analyzed with the purpose of confirm that continues serving them specifications of quality
established.
3.28 management of risks of quality, to the process systematic for the assessment, control, communication
and review of the quality of the drugs risks.
3.29 Working instructions, detailed, sequential, and specific description of a task.
 3.30 Inputs, to all of those raw materials, primary packaging, packaging material and product in any of its
stages that are received in a plant.

3.31 Release of lot, with the opinion that indicates the layout of the product from a review systematic to
ensure quality from all aspects, particularly those of the good practice manufacturing.
3.32 cleaning , the process for non-viable particles to levels decrease.
3.33 cell line the type of cell population caused by consecutive population subcultures cell phone that can
be stored.
3.34 lot, to the specific quantity of any raw material or input, intermediate, or drug, that has was developed
in a cycle of production, under equivalent conditions of operation and during a period determined.
3.35 subject premium , to the substance of any origin natural or synthetic that is use for the elaboration of
drugs.
3.36 Print, to any label, instructive or material conditioning present in the finished product.
3.37 Shows, to the amount of material whose composition is representative of the batch that will to
be considered.
3.38 lot number , to the alphanumeric combination that specifically identifies a batch.
3.39 Production order, a copy of the master production order, which is assigned a lot number and is used
as a guide and registration of operations for each production lot.
3.40 Master production order, the document indicating the specifications and quantities of each one of the
components used, as well as the conditions to be followed for the manufacture of the product.
3.41 Period of expiration, to the time during which a drug content in your container of marketing and
preserved in the conditions indicated in its label, remains within them specifications established.
3.42 Period of reanalysis, to the time during which a drug or intermediate that is preserved in
them conditions indicated by the manufacturer, remains within the specifications of quality established for his
use.
3.43 Policy, to the set of general criteria that establish the framework for the performance activities in the
field of the present standard and must be authorized by the highest hierarchical level of the Organization.
3.44 Standard operation (standard operating procedure) procedure, the document containing the
instructions necessary to carry out reproducible way an operation.
3.45 Manufacturing process, to carry out the operations necessary to carry out the transformation from raw
materials to finished or intermediate products.
3.46 departure (sublots), a part of a product or amount of an intermediate product or drug that is produced
in a single manufacturing operation and which is identified by a key.
3.47 Production, the operations involved in the processing of inputs to transform them in an intermediate
product or drug.
3.48 Intermediate product, partially processed material which will be submitted to later stages of production,
before becoming finished product.
3.49 Finished product, the drug or ingredient which has met all its stages of manufacturing.
3.50 Protocol, to the plan of work written that sets the objectives, procedures, methods and criteria of
acceptance, to perform a study.
3.51 Recovery, to the treatment of materials by a process to make them suitable for your use.
3.52 Records, evidence of actions undertaken to demonstrate compliance of the instructions.
3.53 Remnant, to the amount of product that is in a team of process or in a container as consequence of its
handling during the process of production or packaging.

3.54 Report, to document the accomplishment of operations, projects or specific enquiries, which includes
results, conclusions and recommendations.
3.55 Reprocessing, to submit a batch total or in part, to one or more defined stages of the validated process
ofmanufacturing due to non-compliance with specifications.
 3.56 temporary retention or quarantine the State of the inputs and outputs that prevent your disposal for
a later stage or release, and which can be seen through physical separation or other media.
3.57 rework, to submit a batch total or partial to one or more undefined the validated process stages
of manufacturing due to non-compliance with specifications.
3.58 Annual review of the quality of the product, or product review to the historical analysis of the quality
of a product, which takes as a reference all applicable regulatory documents, criteria international recognized
generally, as well as internal guidelines of each company.
3.59 Sanitizing, to the action of eliminating or reducing the levels of viable particles by means of
agents physical or chemical, after the cleaning activity.
3.60 Critical systems, to hereandscrews which have direct impact on processes and products.
3.61 Quality management system, the way cormo organization directed and controlled its
activities associated with quality.
3.62 transfer of technology , systematic procedure that is followed for the knowledge and experience during
the development and/or commercialization to another responsible unit and authorized. Technology transfer
includes the transfer of documents and the ability to showed the unit receiving effective critical technology
elements performance transferred to the satisfaction of all parties and compliance with regulations.
3.63 traceability, to the capacity of rebuild the history, location of an element or of a activity, through records
of identification.
3.64 validation , documentary evidence generated through scientific collection and evaluation of data
obtained in the qualification and the PRUspecific ebas, along throughout the life cycle of a product, whose
purpose is to demonstrate the functionality, consistency and robustness of a given process as soon as to its
ability to deliver a quality product.
4 symbols and abbreviations
When this standard refers to the following symbols and abbreviations mean:
4.1 BPD Good documentation practices.
4.2 BPF Good manufacturing practices.
4.3 BPL Good laboratory practices.
4.4 C Degrees Celsius.
4.5 LAYER Corrective actions, preventive actions (for its acronym in English, Corrective Action
and Preventive Action).
4.6 COFEPRIS Commission for protection against health risks Federal.
4.7 EMSF Master record of the place of manufacture.
4.8 FEUM Pharmacopoeia of the United States of Mexico.
4.9 HEPA High efficiency air filters (for its acronym in English, High Efficiency Particulate Air).

4.10 HR Relative humidity.

4.11 HVAC Air conditioning and heating system (for its acronym in English, Heating,Ventilation
and Air Conditioning).
4.12 More less.
4.13 > Greater than.
4.14 > Greater than or equal to.
4.15 < Less than or equal to.
4.16 m3 Cubic meter.
4.17 m Micrometer.
 4.18 mm Mm.
4.19 n.a. Does not apply.
4.20 PA Pascal.
4.21 PIC/S Pharmaceutical Inspection co-operation Scheme.
4.22 PMV Validation master plan.
4.23 % Percentage.
4.24 RAP Annual product review.
4.25 Secretariat Secretary of health.
4.26 UFC Colony forming units.

5. quality management system

5.1 Generalities.
5.1.1 The system of management of quality, must take into account the set of measures adopted in a
way planned and systematic, in order to ensure that the drugs are of the required quality for the use to which
they are intended. Quality management must therefore incorporate standards of GMP, BPD, BPL and the
principles of risk management, including the use of proper tools.
5.1.2 The management of quality, should be applied to all stages of the product lifecycle, from
the manufacture of the drug in phase of research, technology transfer, trade, manufacturing until the
discontinuation of the drug. The management of quality must extend is to the period of
development farmoquimico, must encourage it innovation and it improves continuous, and strengthen the union
between the development farmoquimico and them activities of manufacturing.
5.1.3 Is responsibility of the address General or high address ensure that it implements and
keep management system of quality, identifying and providing appropriate resources (human, financial, facilities
and appropriate equipment) to continually improve its effectiveness.
5.1.4 Of quality management must ensure that:
5.1.4.1 The manufacture of drugs is leads to out following a system of management of quality supported by
a quality policy and a system of documentation that has been designed, planned, implemented, maintained and
subjected to continuous improvement that allows that the products may be marketed only or supplied once they
have been released by the quality unit with the attributes of quality appropriate.
5.1.4.2 Knowledge of the product and the process is managed throughout the life cycle of the product.
5.1.4.3 Drugs are designed and developed taking GMP requirements into account.
5.1.4.4 Production and quality control operations are described clearly and adopt the BPF and BPL.
5.1.4.5 The responsibilities of the management of the system should be clearly specified.
5.1.4.6 Are taken the appropriate measures to ensure that the manufacture, supply, use of raw
materials, packaging materials, the selection and monitoring of providers are correct and which are Verify that
each delivery comes from approved supply chain.
5.1.4.7 There are procedures or technical agreements quality to ensure the management of the
activities subcontracted.
5.1.4.8 It establishes and maintains a State of execution of the process and the product quality
control measures of monitoring and the results of these measures are taken into account for the release of
the lot, for the investigation of deviations, and to carry out preventive actions that allow to eliminate recurrence.
5.1.4.9 All the necessary controls on intermediate products, are conducted as well as the process controls
and validations.

5.1.4.10 Will facilitates the improvement continuous.

 5.1.4.11 There are measures implemented for the prospective evaluation of changes planned as well as
your approval prior to the implementation, whereas the notification and approval by the authorities regulatory,
where appropriate.
5.1.4.12 Upon implementation of any planned change, an evaluation is being conducted for confirm that the
quality objectives are achieved.
5.1.4.13 During the investigation of deviations, suspect defective products or another type of problems, an
analysis of the cause must be root. This analysis can be determined based on the principles of risk
management. In cases where the root cause (s) cannot be determined, must be considered the cause or causes,
and address these. Must identify is and adopt is actionscorrective and/or preventive appropriate (layer) in
response to the research carried out. The effectiveness these actions should be monitored and assessed, in line
with the principles of risk management of the quality.
5.1.4.14 No drug sold or supplied without previously a qualified person has certificate that each production
batch has been produced and controlled according to requirements of release. In the case of antibiotics must
adhere to applicable legal provisions.
5.1.4.15 Is adopt measures that ensure that the drugs are stored and are distributed of such mode that the
quality is maintained full during the period of force.
5.1.4.16 There is a procedure for self-inspection and/or quality audits to assess regularly the effectiveness
and implementation of the quality management system.
5.1.4.17 Them items minimum that will contain the system of management of quality are:
5.1.4.17.1 Quality manual.
5.1.4.17.2 System of audits.
5.1.4.17.3 Complaints management.
5.1.4.17.4 Management of product out of specification or not as.
5.1.4.17.5 Deviations and system layer management.
5.1.4.17.6 Removal of product.
5.1.4.17.7 Control of changes.
5.1.4.17.8 PMV.
5.1.4.17.9 RAP.
5.1.4.17.10 Technology transfer.
5.1.4.17.11 Risk management.
5.1.4.17.12 Document control.
5.1.4.17.13 Returns.
5.2 Documentation.
5.2.1 The documentation generation.
5.2.1.1 Documents should set and adhere to established. The requirements apply equal way to all forms of
media documentation. Generation electronic systems of documents need to be understood, be well documented,
validated and have adequate controls.
5.2.1.2 The documents of the system must be written in language Spanish. When the documents are in two
languages or more, always include the version in Spanish. Some documents may be in hybrid form, for example,
in electronic format and others on paper.
5.2.1.3 Documents containing instructions must be drafted in an orderly manner and be easy to check. The
style and language of the documents must match your intended use.
5.2.2 Documentation control.
5.2.2.1 Relations and measures of control for master documents, official copies, the records and data
management have to be set both for hybrid systems as for the homogeneous.

5.2.2.2 Must of implement is controls appropriate for documents electronic such as templates, forms and
master documents.You must have adequate controls to ensure the integrity of records throughout the retention
period.
 5.2.2.3 Documents designed, prepared, inspected and distributed pursuant to in the quality management
system.
Must comply with the applicable sections of the product specifications. The reproduction of documents of
work starting from documents original not should allow the introduction of any error in the process of
reproduction.
5.2.3 Shelter of documents.
5.2.3.1 The place of receipt of all related documents must be clearly defined to the manufacture of
drugs. Must implement is measures of control that ensure the integrity of the documents during all the period of
shelter and evaluate such measures.
5.2.3.2 Must be to safeguard the manufacture of each batch manufactured at least record one year after its
expiration date or for the case in which assigned date of reanalysis, at least three years after it was distributed
in its entirety.
5.2.3.3 For other types of documents, the conservation period will depend on the activity that
the documentation support. The documentation that supports critical processes including raw data, such as
those relating to validation or stability, to support the period of revocation or reparse should retained while the
drug is to be marketed. It can be deemed acceptable remove certaindocumentation (for example, primary data
to support a report of validation or stability) when data has been replaced by a new complete package of data.
5.2.3.4 Should document a justification for this and be taken into account the requirements of
conservation batch documentation; for example, in the case of data validation, the primary data
processes companions must be retained for a period at least as extensive as the records of all the batch whose
release is based on this validation exercise.
5.2.3.5 Any different at the mentioned time guard must be based on the legal provisions applicable.
5.2.4 BPD.
5.2.4.1 Documents containing instructions must be approved, signed and dated. All the types of documents
should be defined and adhere to the quality management system. The requirements apply of equal way to all
the forms of media's documentation.
5.2.4.2 Documents of the quality management system should be periodically checked and keep updated.
5.2.4.3 The documents must not be handwritten; however, when documents require the introduction of data,
enough space should be left to allow the realization of such tickets.
Handwritten documents, records must be clear, legible and indelible form.
The activity log must be done at the time of the activity according to the chronological order.
5.2.4.4 Any correction to the recording of an activity or a document must be signed and dated and allow the
reading of the original information.
5.2.4.5 When required an explanation of the reason for the correction should be documented; these records
must contain the date and identify who performed the activity.
5.2.4.6 There must be a mechanism for identifying signatures and headings of the staff that
runs the operation.
5.2.5 Types of documents.
The documents that make up the system of documentation include but are not limited to:
5.2.5.1 Quality manual.
Must have a Manual of quality or document that contains the description of the system of Quality
management, including the responsibilities of the Directorate.
The Manual must ensure the periodic review of the quality management system.

5.2.5.2 EMSF.
5.2.5.2.1 Must be with an EMSF, describing the activities related to compliance with GMP, which must be
delivered to COFEPRIS.
5.2.5.2.1.1 The updates of the EMSF is make of knowledge of the COFEPRIS through writing free.
5.2.5.2.1.2 Effect of providing the content of the EMSF plus as described in point 5.2.5.2, the recipients of
this standard will be available for the preparation of the EMSF website
http://www.cofepris.gob.mx/AS/Documents/anexositemasterfile.pdf., which includes explanatory notes for
pharmaceutical manufacturers on the preparation of the EMSF, established by the PIC/S.
5.2.5.2.2 Maintenance of the EMSF.
Any technical changes to the content of the EMSF must be evaluated by the Control system of Changes,
trying to be of a change greater is must update the EMSF and notify to it COFEPRIS through the update of the
document.
5.2.5.2.2.1 Are considered changes over which is described to contin business, but not limited to mas not
limited:
5.2.5.2.2.1.1 Change of the responsible health, the head of the production unit and/or responsible for the
unit's quality.
5.2.5.2.2.1.2 Changes in critical systems.
5.2.5.2.2.1.3 Modifications in plants that impact the quality of drugs.
5.2.5.2.2.1.4 Inclusion of new drugs that need new validation of cleaning.
5.2.5.2.2.2 If there are minor changes, the EMSF must update at least every two years and notified to the
COFEPRIS.
5.2.5.3 Specifications.
5.2.5.3.1 Should there be specifications for them materials raw, materials of container and
packaging, intermediate and finished product.
5.2.5.3.2 Specifications of materials raw, materials of packaging and materials of packaging.
These specifications must include at least the following:
5.2.5.3.3 Description of materials: name, internal code, reference (pharmacopoeias or manufacturer
specifications).
5.2.5.3.4 Approved for raw materials manufacturer.
5.2.5.3.5 Manufacturer approved of the container parent.
5.2.5.3.6 Provider approved of the other inputs.
5.2.5.3.7 A sample of printed materials.
5.2.5.3.8 Instructions for the sampling and testing to perform.
5.2.5.3.9 The limits of acceptance for qualitative determinations and quantitative.
5.2.5.3.10 Storage conditions.
5.2.5.3.11 Period of reanalysis and number of reanalysis.
5.2.5.3.12 Precautions for the handling of material.
5.2.5.4 Intermediate product specifications.
5.2.5.4.1 There should be intermediate, including the time and conditions product specifications storage.
5.2.5.5 Specifications of product finished must include at least the following:
5.2.5.5.1 Generic name of the product and internal code assigned.
5.2.5.5.2 Chemical formula of the product.
5.2.5.5.3 Physical form in which it is marketed and container primary.
5.2.5.5.4 Instructions for sampling.

5.2.5.6 Method of analysis.

5.2.5.6.1 Limits of acceptance for qualitative determinations and quantitative.
5.2.5.6.2 Storage conditions.
5.2.5.6.3 Period of revocation or the product reanalysis.
5.2.5.6.4 Precautions for the handling of the product.
5.2.5.7 Master production order.
 5.2.5.7.1 Must exist in writing an order and master production for each product instructions and size lot to
manufacture, these master documents will serve to generate working documents.
5.2.5.7.2 The production order must include at least:
5.2.5.7.2.1 Generic denomination of the product and an internal code assigned.
5.2.5.7.2.2 Form physical.
5.2.5.7.2.3 Concentration or presentation.
5.2.5.7.2.4 Lot size.
5.2.5.7.2.5 List of raw materials, materials, code and quantities, including those that do not appear in the
finished product.
5.2.5.7.2.6 Performance expected with the limits of acceptance for each stage of the process.
5.2.5.7.3 Production instructions should include at least:
5.2.5.7.3.1 The area in which each stage of the process is done.
5.2.5.7.3.2 The equipment you use.
5.2.5.7.3.3 Methods or the cross-references for the preparation of the critical process equipment production
as they are the operations of Assembly, calibration, cleaning, sterilization, among others.
5.2.5.7.3.4 Clearance of the area to use that will ensure that it is free of previous products, equipment
and materials not required.
5.2.5.7.3.5 Check that the area is in clean condition to start production of the product.
5.2.5.7.3.6 Detailed instructions for how to perform each step of the process, the critical parameters of
the process such as time, temperature, specific conditions.
5.2.5.7.3.7 Controls in process to be carried out, the frequency and acceptance limits.
5.2.5.7.3.8 Specific conditions necessary for handling and storage, according to the nature of the product.
5.2.5.8 Packaging and labelling order.
5.2.5.8.1 There should be an order and master instructions for packaging and labelling for each product and
for each batch size, these master documents will serve to generate documents of work.
5.2.5.8.2 The order of packaging should include at least it next:
5.2.5.8.2.1 Generic denomination of the product internal code assigned.
5.2.5.8.2.2 The product batch.
5.2.5.8.2.3 Form physical.
5.2.5.8.2.4 Final presentation.
5.2.5.8.2.5 Description and primary container size.
5.2.5.8.2.6 Complete list of all the necessary materials for the packaging of the product and its packing,
including codes, quantities and if applicable the cross-reference to your specifications.
5.2.5.8.2.7 Performance expected with the limits of acceptance for each stage of the process.
5.2.5.8.3 The packaging instructions must include at least the following:
5.2.5.8.3.1 Graphic representation of the product packaging or the cross-reference for consultation.

5.2.5.8.3.2 Clear the work area that will ensure that it is free from previous or material products not required.
5.2.5.8.3.3 Check that the area is in clean condition to start packaging of the product.
5.2.5.8.3.4 Detailed instructions on how to perform each step of the process, including the parameters critics
of the process and equipment used.
5.2.5.8.3.5 Controls in process to be done, instructions for sampling, frequency and limits acceptance.
5.2.5.8.3.6 Instructions for the reconciliation of printed materials.
5.2.5.8.3.7 Specific conditions necessary for handling and storage, according to the nature of the product.
5.2.5.9 Record of lots and of games.
 5.2.5.9.1 Must be a production record for each batch of product, and contain the order and instructions of
production with the record of activities carried out for the preparation of the product.
5.2.5.9.2 This file should contain at least the following:
5.2.5.9.2.1 Order and instructions of production.
5.2.5.9.2.2 When the batch is in different headings, must point out is to what corresponds the number
total games.
5.2.5.9.2.3 Lot number of the product.
5.2.5.9.2.4 Numbers of lots and assorted amounts of all materials included in the formula.
5.2.5.9.2.5 Dates and times of beginning and end of the most important stages of production.
5.2.5.9.2.6 Identification of who carried out the operation with the initial of the name and surname,
this information must be traceable to a register of operators and supervisors of production areas.
5.2.5.9.2.7 Records of the monitoring.
5.2.5.9.2.8 Registration process with the results obtained and the people who controls the carried out (name
and first name initial).
5.2.5.9.2.9 Yields obtained during the various stages of production.
5.2.5.9.2.10 Any deviation to the instructions of production should be recorded, investigated, rated and
evaluated. The research should be completed for the release of the batch.
5.2.5.9.2.11 Each record production must be signed in accordance by the responsible Health or qualified
person certifying that the product was produced according the GMP.
5.2.5.9.3 Record of packaging and labelling.
5.2.5.9.3.1 There should be a record of packaging and labelling for each lot and starting from product
and contain instructions and activities for packaging register.
5.2.5.9.3.2 The batch packaging record should contain at least the following:
5.2.5.9.3.2.1 Order and packaging instructions.
5.2.5.9.3.2.2 Number of the lot and starting from the product.
5.2.5.9.3.2.3 Quantity of the product.
5.2.5.9.3.2.4 Lot numbers and quantities of the primary and secondary packaging materials.
5.2.5.9.3.2.5 The reconciliation of materials of container and packaging for determine the amount used,
the sent to destruction and the materials returned.
5.2.5.9.3.2.6 Date and start time, and end of the stages of packaging.
5.2.5.9.3.2.7 Identification of who executed the operation, this information must be traceable to a list of
signatures of operators and supervisors of the areas of conditioning.
5.2.5.9.3.2.8 Records of the monitoring.
5.2.5.9.3.2.9 Registration of controls in process with the results obtained and the people to the carried out.

5.2.5.9.3.2.10 Yields obtained during the various stages of conditioning.

5.2.5.9.3.2.11 Any deviations to the packaging instructions should be recorded, investigated
and evaluated. The research should be completed for the release of the batch.
5.2.5.9.3.2.12 Yields obtained during the various stages of packaging.
5.2.5.9.3.2.13 Each record packaging must be signed in accordance by the responsible Health or an
authorized person that the product was packaged compliance GMP.
5.2.5.10 Analytical and test methods.
5.2.5.10.1 Should exist procedures written that describe the methods, equipment and instruments used for
the analysis or evaluation of the inputs and product in the different stages of manufacture.
5.2.5.10.2 Registration of analyses and evaluations must be retained.
5.2.5.11 Sampling.
 5.2.5.11.1 There should be written procedures for the sampling of the inputs used in the manufacture of
drugs, these should include the methodology of sampling equipment, utensils, amounts to sample and
instructions for the handling of material that will prevent contamination of the input sampling or alter the quality
of the same.
5.2.5.12 Other documents related to the fulfilment of BPF.
5.2.5.12.1 Documents related to the fulfilment of BPF to all those who are considered related to the
manufacturing of a drug, from the acquisition of them inputs for its manufacture until its distribution as product
finished.
5.2.5.12.2 Must be available written documentation related to GMP compliance for the personnel responsible
for the activities described in these, this documentation should correspond to the level assigned in the quality
management system and can be in the form of policies, procedures, protocols, work instructions, reports, among
others.
5.2.5.12.3 There should be documented evidence of the use of these documents or the realization
of activities describing them.
5.2.5.12.4 Should there be documentation written for them following activities or processes, this list no
is limited and may there be more documents related:
5.2.5.12.5 Cleaning and sanitization of areas, equipment and systems critical.
5.2.5.12.6 Operation and maintenance of equipment and instruments.
5.2.5.12.7 Qualification and validation of equipment, processes and critical and computational systems.
5.2.5.12.8 Training, qualification and verification of the effectiveness of the training of the BPF, hygiene,
clothing and technical issues related to its business.
5.2.5.12.9 List of signatures of the staff involved in the manufacture of drugs in all its stages.
5.2.5.12.10 Technology transfer.
5.2.5.12.11 Environmental monitoring.
5.2.5.12.12 Pest control.
5.2.5.12.13 Investigation of deviations or non conformities.
5.2.5.12.14 Report of complaints.
5.2.5.12.15 Report of change control.
5.2.5.12.16 Refund of products.
5.2.5.12.17 Removal of product from the market.
5.2.5.12.18 Self-inspection.
5.2.5.12.19 Audits to suppliers.
5.2.5.12.20 Purchase of inputs.
5.2.5.12.21 Reception and inspection of supplies.
5.2.5.12.22 Storage.

5.2.5.12.23 Distribution.
5.2.5.12.24 Review of the quality of the product.
5.2.5.13 Is must count with the evidence documentary of the use chronological of areas, equipment,
instruments, methods, calibration, maintenance, cleaning and any activity that impacts the quality of the product
and that requires a log; these records must contain the date and to identify who carried out the activity.
5.2.5.13.1 Each establishment must have the following legal documents:
5.2.5.13.2 License health or notice of performance.
5.2.5.13.3 Notice of health responsible.
5.2.5.13.4 Certificate of current BPF.
5.2.5.13.5 A current copy of the FEUM and their corresponding supplements.
 5.2.5.13.6 Record of each drug containing at least:
5.2.5.13.7 Specifications, analytical methods, production, master order master orders of packaging and
labelling.
5.2.5.13.8 Must exist a relationship of all the documents that operate within the system of
management quality.
5.3 Audits.
5.3.1 There must be procedures that establish the process of execution of an audit that contain at least:
5.3.1.1 The scope of each type of audit.
5.3.1.2 The qualification of the auditor group including:
5.3.1.2.1 Experience, training, skills, availability and independence.
5.3.1.2.2 Implementation process: planning, responsibilities, requirements, records and reporting.
5.3.1.2.3 The frequency of audits and the establishment of a permanent program of audits.
5.3.2 For effects of this standard the audits are classified in: audits internal (autoinspecciones), audits to
suppliers and audits of regulatory institutions.
5.3.2.1 Internal audits (self-inspection):
There should be a system of self-inspection for the evaluation of the management system of quality and
level compliance in BPF.
5.3.2.1.1 Self-inspection audits should be conducted by staff i ndependiente to the area audited. Estas can
also be performed by external staff.
5.3.2.1.2 The following aspects should be evaluated according to a preset to verify program its conformity
with the principles of the system of management of quality.
5.3.2.1.3 All the self-inspection must be registered. The reports shall include all the observations made
during the inspections and, where appropriate, proposals for corrective measures and/or preventive must
register in the system layer of the establishment.
5.3.2.1.4 The results of the self-inspection must be communicated to the staff involved.
5.3.2.2 Audits to suppliers.
5.3.2.2.1 The settlements should be determined based on an assessment of those risks input suppliers that
have an impact on the quality, safety and efficacy of the drug.
5.3.2.2.2 There should be a procedure for the implementation of audits for suppliers of inputs, analysis
services providers, providers of services to critical systems and equipment and manufacturers of manufacturing
processes.
5.3.2.2.3 Should there be a regular, audit program as well as, have documentary evidence to demonstrate
compliance with the same.
The periodicity of audits for suppliers should be established based on the level of risk in the process, the
impact and the previous qualification reports.

5.3.2.2.4 Reports of audits for suppliers should be part of the qualification record of the provider, and must
include the classification of findings, non-conformities or deviations found, so as the commitment to correct
dates. In case of detecting critical deviations, such deviations should be investigated and generate immediate
action based on the level of risk.
5.3.2.2.5 The approval of the provider must include an assessment that provide evidence adequate (for
example, quality history) that manufacturer can consistently provide input to meet established specifications.
5.3.2.2.6 Rating and audit information providers must be available for review by the Secretariat.
5.3.2.3 Audits of regulatory institutions.
5.3.2.3.1 There should be a procedure for audits of entities that regulatory attention includes and not limited
a:
5.3.2.3.1.1 Receipt of the audit by the responsible health or a person designated by him, of pursuant to 7.1.6,
of this standard (representative of the quality unit).
 5.3.2.3.1.2 Preparation of information to be submitted.
5.3.2.3.1.3 Registration, evaluation and closure of non-conformities during an audit of the entities regulatory.
5.3.2.3.2 The results of audits by regulatory bodies should be communicated to staff involved in the
implementation of the actions as well as the Directorate-General or senior management.
5.4 Complaints management.
5.4.1 There should be a person in charge of the management of complaints.
5.4.2 Should be investigated in accordance with a procedure all complaints concerning the quality of
the drug, reported orally or written.
5.4.3 When it is required should be extensive research lots manufactured prior to or subsequent.
5.4.4 Is must carry a record of complaints that contains at least:
5.4.4.1 Name, address, telephone or any contact details of who reported the complaint.
5.4.4.2 Description of the complaint.
5.4.4.3 Date of the complaint.
5.4.4.4 Corrective and preventive actions carried out and who carried out them.
5.4.4.5 Response sent to who reported the complaint.
5.4.4.6 Conclusions of the investigation and final destination of lot or batch of the drug.
5.4.4.7 An analysis of the trends, frequency and reasons of complaints must be of quality reported.
5.4.4.8 Must be implemented corrective and preventive measures resulting from this analysis.
5.5 Handling of product outside specifications and/or not conforming.
5.5.1 Drugs in any of its stages which do not comply with stated specifications or are manufactured outside
the established procedures should be identified and placed on hold temporary or quarantined.
5.5.2 A report of diversion or non-conformity must be issued to define the level and the extension of the
no conformity, as well as to establish the actions corrective such as if can be reconditioned, recovered,
reprocessed, reworked or rejected.
5.5.3 The process of recovery, reproceso or rework should be authorized by the responsible Health or by the
person who this desine in terms of point 7.1.6, of this standard.
5.5.4 There should be a procedure that describes:
5.5.4.1 Identification of the nonconforming product.
5.5.4.2 Control of non-conforming product including segregation and the prevention of inadvertent
use product or facility where it was processed.

5.5.4.3 The actions to take in case of reconditioned, recovered, reproceso or rework batches.
5.5.4.4 The responsible sanitary or authorized person must set the final disposal of the product.
5.5.5 The recovered batches should be subjected to quality analysis and documentation must
demonstrate the quality of the recovered batch is equivalent to the original process.
5.5.6 Retrabajados lots should be subjected to quality analysis and studies of stability of agreement with the
corresponding Norma Oficial Mexicana and the documentation must demonstrate that it complies with original
product specifications.
5.5.7 Reprocessed lots should be subjected to quality and accordance with appraisal analysis of risk may or
not to undergo stability studies in accordance with the official Mexican standard NOM -073-SSA1-2005 stability
of drugs and medicines, to demonstrate that it complies with the original product specifications.
5.5.8 The products rejected must be identified and segregated to s or disposal or final destination. Esta must
be carried out according to the procedure established for this purpose.
5.5.9 An order and rework, recovery or specific reprocessing instructions must be issued to each batch.
5.5.10 In the case of reprocesses a lot different to the original lot number, must be assigned which must be
authorized by the responsible health.
5.6 Layer.
 5.6.1 There must be a system for the implementation of the resulting from the non-conformities,
layer complaints, returns, out of specifications, audits, trends, and which define the own system.
5.6.2 Should be a methodology for the m Aejo of deviations that evaluate the event according to the risk
associated, class event, promptly determine actions to remove it and check the effectiveness of actions
taken. Criticisms deviations and older should be investigated using Tools to determine the root cause. The
research and its conclusions must be documented.
5.6.3 Monitoring and effectiveness of the layer set.
5.7 Change control.
5.7.1 There should be a documented control system changes that include risk management for
the evaluation and impact of the proposed suppliers, processes, systems, critical systems change computer,
areas, facilities, equipment, analytical methods, specifications, documentation, regulatory and product quality
provisions.
5.7.2 The changes not planned should consider is as deviations or non conformities.
5.7.3 Must settle for a Committee or technical group comprising representatives from the areas involved and
by the head of the quality unit, who will review, evaluate and approve the proposed change.
5.7.4 The proposal of change in the specifications internal of quality of the intermediate or substance
active must be evaluated.
5.7.5 There should be a procedure for the classification of the type of return, according to the valuation of
the risk, to determine the level of testing, validation, and documentation required to justify changes in a validated
process.
5.7.6 Them changes can classify is as less or more depending on the nature and the scope of them changes,
and the effects that these can cause in the process.
5.7.7 After the change is implemented, there must be an evaluation of the first batches produced or tested
under change.
5.7.8 If the change affects the period of expiration or reparse period should be evaluated, samples of drug
or intermediate produced by the modified process can be placed in a program of accelerated stability or can be
added to the stability monitoring program.
5.7.9 Must follow-up on the implementation of the approved changes and ensure its seal of according to the
previously established.

5.8 Returns.
5.8.1 Is should establish a procedure for the handling of the products intermediate or drugs returned and
determine the destination end of these.
5.8.2 Intermediate products or returned drugs should not be incorporated into containers with intermediates
or approved drugs.
5.8.3 When there is doubt of the quality of those products intermediate or drugs returned, these
must reprocessed, reshaped or destroyed.
5.8.4 The reprocessing or rework of returns may not be performed by dealers.
5.8.5 Records of the intermediate products or returned drugs deemed should be to the less data from the
client that performed the return, name of the intermediate product, or return, drug number of batch, starting,
returned quantity and reason for the return.
5.8.6 Assessment to prove that the product meets the specifications, standards of integrity, security, identity,
quality and purity should include: analysis of the route of distribution and return, storage conditions of the
returned product, the labelling, and the decision conditions and final destination of the product.
5.8.7 Not is permitted the recovery of product returned if during the assessment the conditions of
the container, cases or boxes, or labelling texts generate doubts about the integrity, security, identity,
concentration, quality or purity of the product.
5.8.8 Recovery of expired, returned product is not permitted or whose period of reanalysis is not covered
with long-term stability studies.
5.9 Annual review of product.
 5.9.1 There should be a systematic annual review of the quality of each drug. Responsible for health you
must ensure the implementation of the RAP system and appoint the person responsible for its
execution and diffusion.
5.9.1.1 The objectives of the RAP are those of the verification of the performance of the product, the
consistency of themanufacturing process and the determination of the need for revalidation of the manufacturing
processes.
The RAP determines the need to carry out changes in the manufacturing process, in the controls in process
and the specifications. E include the identification of improvements to the product and to the manufacturing
process, based on the analysis of trends, and risk assessment.
5.9.1.2 Not be allows the grouping of products regardless of that during its production is employ similar
equipment and processes.
5.9.2 There should be a procedure to carry out the RAP containing the objectives to determine and justify
the selected areas in the review, as well as the possible extension of the review.
Them results of the RAP should summarize is in the format that is specified in the Appendix regulatory
B attached to this standard.
5.9.2.1 The results of the RAP should be evaluated and determine if any action should be
conducted corrective and/or a revalidation. The reasons for performing these corrective measures must
be documented. Measures to be determined must be completed in a timely and effective manner.
5.10 Technology transfer.
5.10.1 The technology transfer should be a planned and documented, that approach is consider trained
personnel, qualification and validation requirements, manufacturing and control systems of quality, and should
be formalized through a technical agreement or Protocol as applicable.
5.10.2 Lots of technology transfer may not be marketed.
6. quality risk management.
6.1 The establishment must have a management system of quality to ensure risks of form scientific and
systematic them actions to identify, mitigate and control them potential failures in them systems, operations and
processes that affect the quality of the products.
6.2 The methodology for the analysis of risk systems, operations and processes must be be supported in
proven analytical tools that ensure effective and logical management of the priorities and strategies for the
management of risks of quality.

6.3 There should be a set of procedures that evidence the implementation, training and qualification of the
personal Manager of the system of management of risks of quality and its application.
6.4 Carried out risk assessments must be documented so that they are the basis for of the PMV, as well as
the evidence for deviations and changes of critical systems, technical operations and processes and be the
support evaluation of preventive and corrective actions.
6.5 There must be an efficient method of communication to ensure that the analysis and actions documented
in the methodology of risk is of the knowledge of the Organization as part of the system of management of
quality.
6.6 Continuous verification of the result of the risk management process should be set in Quality which
guarantee its validity and robustness of the quality management system.
6.7 The implementation of the quality risk management may refer to the following
address electronichttp://www.cofepris.gob.mx/AS/Paginas/Establecimientos%20y%20productos%20biologicos/
CertificadoBuenasPracticasFabricacion.aspx, donde are available in Spanish language for viewing the Of
medications of the PIC/s GMP Guide of annex 20
7. personal.
7.1 General information
7.1.1 Is the responsibility of the manufacturer have the sufficient number of qualified personnel to carry to out
all activities required for the manufacture of drugs. The personal should receive induction in BPF from its
recruitment, be trained in them activities that goes to perform and continuously trained.
7.1.2 Staff involved in any aspect of manufacturing with impact on the quality of the product must have the
required profile and be continuously trained and qualified.
 7.1.2.1 In addition to the basic training in the theory and practice in the system of quality management and the
BPF, recently recruited staff should receive appropriate training prior to the execution of tasks that are assigned.
7.1.2.2 Staff working in areas with risk of contamination, as the areas clean or areas where very active, toxic,
infectious or sensitising, substances are handled should receive training specific.
7.1.3 There should be a flow chart, approved and updated, in which clearly established the levels of authority
and the interrelations of those different departments or areas. Liabilities must be clearly indicated in the job
description.
7.1.4 There must be a responsible for health in accordance with the legal provisions applicable, the which
should occupy the highest hierarchical level of quality unit and report to the highest authority of the Organization.
7.1.5 The responsible health is responsible for the quality of the product, together with the highest authority
of the Organization has the responsibility to ensure that you there is a system of quality
management. Responsible for public health should have the academic training, knowledge and
experience sufficient for decision making in aspects of BPF.
7.1.6 Delegation of functions.
7.1.6.1 The responsible health may designate in writing to the (s) person (s) who will attend (n) different tasks
including the signature of operational documents when he is absent or under circumstances special to that
warrant, for example concurrent projects, workload.
7.1.6.2 It (s) people designated will have that comply with the requirements established in the legal provisions
for health managers.
7.1.6.3 The equivalent is responsible for public health in plants installed outside the country the
person Authorized, Technical Director, or representative of the unit of quality.
7.1.7 The responsible health must authorize the master documents ensuring compliance with of BPF and
them documents basic of the system of management of quality, the documents generated from these may be
signed according to it declared in its system of documentation.
7.1.8 The owner of the establishment will be responsible for solidarity with health responsible for
the compliance with this standard and the other applicable legal provisions.
7.1.9 Manufacturing and quality unit unit must be completely independent in of the organizational structure,
not depending or reporting one another.

7.2 Resource management.

7.2.1 General information
Personnel must know and clearly understand their responsibilities and functions, as well as the principles of
GMP regulations that apply to you.
7.2.2 Profile, description and responsibilities of each position and be should establish written congruent to
those operations and to the application of the BPF.
7.2.3 There should be a system of selection, training, assessment and qualification, to ensure that the staff
has academic training, knowledge and experience necessary to play duties and responsibilities according to
provisions of the profile.
7.2.4 Must exist a program annual of training that includes themes of BPF, operations specific to the put,
hygiene and safety, is must keep evidence of your application. The training should include specific topics for
personnel working in areas where there is a risk of contamination or manipulation of materials or products that
are highly active, toxic, or sensitive.
7.2.5. the effectiveness of the training should be assessed periodically, through tests of competition
demonstrating the skill or expertise of the staff in the assigned tasks.
7.2.6 Staff pursuing positions of responsibility must have sufficient authority to meet with their responsibilities,
so must possess the training and technical and scientific knowledge and experience practice in the manufacture,
control and quality assurance of drugs enabling you to have a professional judgement based on the application
of science in problem-solving principles, independent practical that might occur in the manufacture and control
of drugs.
7.2.7 Responsible for the production and quality units must be professionals in the field pharmaceutical,
chemical and/or biological, authorized to exercise in terms of the provisions legal applicable. Responsible for
quality unit must comply with the provisions applicable to the health managers.
 7.3 Responsible for the fabrication unit must:
7.3.1 Ensure that the products are manufactured according to the instructions written in order of obtain the
preset quality.
7.3.2 Approve the instructions related to the operations of manufacturing and ensure its compliance.
7.3.3 Ensure that the manufacture of each batch of product record includes all records related to the
manufacturing and testing of the product.
7.3.4 Check that has been carried out the maintenance of areas, equipment and services related to
the manufacturing including instruments calibration.
7.3.5 Ensure that grades and validations scheduled systems, held processes, equipment and services.
7.3.6 Ensure that staff receive induction training and regular training required for the execution of their
functions.
7.4 The quality unit responsible for should be:
7.4.1 Approve or reject inputs, intermediate products, bulk products and finished products.
7.4.2 Ensure that is carried to out all the determinations and testing established.
7.4.3 Ensure the evaluation of the manufacture of each batch of product records before your release.
7.4.4 Approve specifications, sampling instructions, testing methods and analytical determinations.
7.4.5 Ensure that the analysis carried out by contract are reliable.
7.4.6 Verify that the maintenance of the facilities, equipment and instruments carry out of the analytical areas.
7.4.7 Ensure that they are carried out: the validation of analytical methods non-compendial, studies
of applicability of compendial methods, equipment qualification and calibration of analytical instruments.
7.4.8 Ensure that staff receive induction training and regular training required for the execution of their
functions.

7.5 Consultores.
Consultants who advise on the manufacturing and control must have a proven level of your training
academic, knowledge and experience that les allow advise on the topic specific to the that were contracted
Should keep are records in which figure the name, the address, the ratings, and the type of service provided
by these consultants.
7.6 Health and safety.
7.6.1 Should establish are programs of training in practices of hygiene, safety and clothing of the personal
that enters to the areas of production and control of quality.
7.6.2 Staff must undergo medical examination at the time of its incorporation. It is manufacturer responsibility
make sure that you put in knowledge of staff, States of health that may have an impact on the quality of the
products. After the first medical examination, must be be others, whenever it is necessary for the work and health
of personnel. Personnel who carry out Visual inspections should undergo periodic studies of visual acuity.
7.6.3 The staff are suffering from an infectious disease or having injuries exposed skin, and be be determined
by a medical examination or observation, suspended its activities until this condition is corrected or qualified
medical personnel determine that the person does not endanger your own safety and the quality of the
products. The staff should be instructed to report this condition.
7.6.4 Staff must wear clean and adequate clothing for the activity that will run, with the features required for
the protection of personnel and product.
7.6.5 The requirements of clothing for every area of manufacturing, storage and quality control should be be
defined in writing.
7.6.6 There must be written instructions from the washing of clothing, including that used in the manufacture
of products of high risk areas, which is indicated in your treatment and/or disposal.
7.6.7 In the case of using disposable clothing should be a procedure for your disposal.
7.6.8 Staff not must smoke, eat, drink, Chew and storing food and medicine in the areas of manufacturing,
warehouse and laboratory of quality control.
 7.6.9 The personal not must use jewelry or cosmetics in the areas of manufacturing, including the
laboratories and the vivarium.
7.6.10 It must instruct the staff to wash their hands before entering and leaving the areas of production.
7.6.11 The personal should avoid the contact direct with them products intermediate and/or drugs.
7.6.12 The entry of visitors to the areas of manufacturing and quality control must be controlled and
not compromising the quality of the product. Visitors should follow hygiene instructions and personal security,
including the use of clothing, these provisions also apply to employees temporary, contractors, auditors or
anyone else previously authorized to enter the areas. Thevisitors must be accompanied at all times by personnel
of the company.
8 facilities and equipment.
8.1 Generalities.
8.1.1 Areas and equipment must be located, designed, constructed, installed and maintained in conditions
that enable its proper operation and cleaning.
8.1.2 Areas, manufacturing equipment and critical systems that impact directly on the quality of the product
must be qualified and validated.
8.1.3 Is must count with systems alternate of supply of energy, to maintain the conditions of the critical
operations of the manufacturing process.
8.1.4 The areas of production, sampling, weighing, packaging primary and all those where is are exposed
components and their inherent services (particularly systems of air) of penicillin, cephalosporin, cytotoxic,
hormonal steroidal products of groupsandrogens, estrogens and progestogens, must be completely independent
and self-contained.

8.1.4.1 Products immunosuppressants that demonstrate that they have high drug or high activity toxicity,
may be made in areas common, prior authorization of the Secretariat, which is based in the assessment of the
risk of them products, implementation of precautions specific for the management common of products,
manufacturing by campaign and the validation of cleaning corresponding.
8.1.5 The manufacturing areas be classified and comply with the criteria set out in Appendix To regulatory,
of this standard.
8.1.6 Should set is e implement is controls adequate to prevent the pollution cross personnel and materials.
8.1.7 If the drug, materials or intermediate product microbiological specifications, the facilities must be
designed in such a way to limit exposure to contaminants microbiological.
8.2 Installations.
8.2.1 Considerations.
8.2.1.1 The design and construction of the areas of manufacturing, laboratory and other rooms that
are involved in the manufacturing (including them areas intended for the handling of animals) must be
of materials appropriate to the use and that allow its cleaning, keep them free of dust, insects, pest and facilitate
its maintenance, in order minimize risk of pollution.
8.2.1.2 Maintenance activities in facilities and buildings under a program are to be made to ensure that repair
and maintenance operations do not pose a risk to the quality of the product.
8.2.1.3 All facilities and buildings must be subject to instructions for cleaning and When you apply your
sanitizing.
8.2.1.4 The lighting, temperature, humidity and ventilation of the areas must be appropriate to the activities
carried out in each one of them and should not affect directly or indirectly the product, equipment and staff.
8.2.1.5 Entry of personnel to facilities or areas must be checked according to the activities that they are
carried out. The areas of production and packaging should not be used as a passage-way for the staff and
supplies.
8.2.2 Production areas.
8.2.2.1 Areas of production of final stages such as discharge of purification, mixing, drying or packaging of
the drug must be sanitary finish; all services such as: lamps and pipes, points of ventilation and extraction, energy
supply, must be designed and installed to prevent accumulation of dust and make cleaning easier.
 8.2.2.2 The design and location of areas must be such that the flow of personnel, supplies and product
in process, finished products and wastes is carried out in a logical and sequential order according to the process
of manufacturing; avoiding cross flows, minimizing the risk of mixtures, confusions, omissions of
stages, contamination to the product and considering the appropriate levels of cleanliness.
8.2.2.3 It must demonstrate that the size and number of areas is consistent with the capability of
manufacturing, equipment, diversity of products and type of activities carried out in each one of them avoiding
mixtures, confusions, omissions of stages and pollution.
8.2.2.4 The design of the areas of manufacture of stages end must contemplate quarters for the access
of personal, change of clothing according to the classification of the appendix to policy of this standard.
8.2.2.5 The piping must be identified, according to the code of the NOM-026-STPS-2008, colors and signals
of safety and hygiene, and identification of risks by fluids in pipes. And in the cases in that apply the flow direction.
8.2.2.6 The pipes that transfer raw materials, intermediate or bulk products should be must be identified and
be clean inert material.
8.2.2.7 Production areas drains must have traps or some device that prevent backflow or contamination. In
the areas class a/b, used for aseptic production are banned drains.
8.2.2.8 Must have areas for the storage of accessories assortment or sampling of materials raw and
accessories of the equipment of manufacture. Areas should be kept such accessories in giving the same
conditions according to the area in which they are used.

8.2.2.9 They need areas or cabinets specific to save own area, tools substances or materials required for the
maintenance of manufacturing equipments. These areas or cabinets must meet the same conditions of cleaning
of the area which are theequipment.
8.2.2.9.1 For the case of tools or materials that are used for maintenance or repair of the equipment, that do
not are own of the area, must exist a procedure of cleaning for his introduction to the area.
8.2.2.10 In facilities multiproduct should of have is with areas separated for each one of them processes of
manufacture simultaneous; in case of processes in which is carried out over one operation unitary of way
continuous must make is the assessment of risk and justify with this the design of them areas.
8.2.2.11 Areas where sampling is done and/or heavy raw materials should be defined and avoid mixtures,
confusion or cross-contamination, as well as to preserve the same specifications.
8.2.2.12 Must have a specific area for assorted orders that ensures the quality of the input.
8.2.2.13 Areas, manufacturing equipment and processes must have the required critical systems by the type
of process, such as: HVAC, compressed air, water for pharmaceutical use, clean steam, between other.
8.2.2.14 Should be avoided that the installation and the maintenance access to the HVAC, water and systems
of support is a source of pollution for the product.
8.2.2.15 Production areas must have outlets identified critical systems and services employees.
8.2.2.16 The system HVAC must be designed and made according to the considerations
minimum established in the FEUMso you allow comply with the classification of the area required according to
the Appendix to normative of this standard.
8.2.2.17 Must have a system of monitoring of critical variables in compliance with the established in the
normative appendix A of this standard and the FEUM.
8.2.2.18 Production areas where dusts are generated (sampling, heavy, mixed or other process) must have
systems of extraction and collection of powders which by design avoid Cross and environmental pollution.
8.2.2.19 The production of any products that are not considered drugs or intermediate for the production of
a drug such as herbicides and pesticides, it should not be performed in licensed for the production of
pharmaceuticals facilities.
8.2.2.20 Be classified production areas requiring controlled environmental conditions with base in the
appendix to policy of this standard.
8.2.2.21 By the characteristics or nature of the product or process is required a condition of temperature
and/or HR different from those established in the normative appendix A of this standard, must be justified in the
associated technical documentation.
8.2.2.22 Make sure equipment and instruments used to perform controls on process will not be affected
directly or indirectly by the process and vice versa.
 8.2.2.23 Packaging operations should be performed in a specific area, designed and located in so that the
flow of personnel, supplies and product in process to avoid contamination, confusion and mixing of products and
inputs.
8.2.3 Storage areas.
8.2.3.1 Storage areas should be n be designed and constructed to ensure them good practical storage, they
must comply with conditions of cleanliness, temperature and relative humidity required by the type of inputs or
products, and to carry out its monitoring and verification.
8.2.3.2 Reception of inputs and outputs must be designed and constructed in such a way that the protect the
exterior environment, allowing inspection and cleaning.
8.2.3.3 Must have an area of shipment that ensures the conservation of the properties of the drugs and
intermediates.
8.2.3.4 They must have delimited areas for storage of inputs and outputs, recovered or returned. Rejected
products should be in segregated and identified areas.

8.2.3.5 The inputs and products classified as narcotic drugs and psychotropic substances (controlled)
must have a segregated, safe area and access controlled and restricted.
8.2.4 Areas of quality control.
8.2.4.1 The quality control laboratory must be separated physically from production areas and stores.
8.2.4.1.1 Must have system of injection and extraction of air in order to count with positive pressure respect
to the environment external.
8.2.4.2 Design and construction of the laboratory of quality control should have facilities and space enough
for the tests and analysis carried out in them, to avoid mixtures and pollution.
8.2.4.2.1 In the case of high-risk, products must have facilities for handling sure signs that prevent personnel
exposure and pollution to the environment.
8.2.4.3 Areas designated for biological, microbiological tests and instruments must be physically separated
between them.
8.2.4.4 If the instrumental area has instruments sensitive to vibration, interference electrical, moisture or
requiring special conditions, keep them in separate quarters or ensure the conditions recommended by the
manufacturer for your protection.
8.2.4.5 You must have a specific area for signs of retention of inputs and outputs, to comply with the
conditions of preservation of their properties.
8.2.4.6 Must have a specific and separate area for the management of samples for analysis of drugs,
considered as high risk product in process and finished product.
8.2.4.7 Are considered drugs or intermediates of high risk to the penicillin, cephalosporins and hormonal
steroidal groups of androgens, estrogens and progestogens; as well as those drugs high pharmacological activity
or high toxicity.
8.2.5 Auxiliary areas.
8.2.5.1 The areas devoted to the health service and dining rooms should be separated from areas
of manufacturing.
8.2.5.2 Areas destined for ropera, dressing, washing, showers and toilets must be in places of easy access
and its size must be in correspondence with the number of workers.
8.2.5.3 Health services must communicate directly, not located in pass routes with the manufacturing areas.
8.2.5.4 Areas of maintenance must be separate and outside areas of manufacturing. If is requires an area of
maintenance within production areas, it must comply with the sanitary conditions of the area where is.
8.2.5.5 Facilities for the handling of laboratory animals must be isolated from the areas of manufacturing and
comply with the applicable legal provisions.
8.2.5.6 There must be areas for the hygiene of the staff, these must be separated from areas of production,
they must have toilets and showers, the showers must have hot and cold water.
8.2.5.7 Must have a programme for the prevention, control and eradication of harmful fauna.
 8.2.5.8 Should exist procedures written for the use of rodenticides, insecticides, fungicides and
agents fumigants, of cleaning and disinfection to prevent the contamination of equipment, materials raw, material
of packaging / labeling, intermediate and drugs.
8.3 Team.
8.3.1 The equipment of manufacture must be designed and located to comply with the use proposed and
avoid risk of pollution, should allow its disassembly / Assembly, cleaning, maintenance and
sterilization If applied.
8.3.2 You must set an identification system that allows to visualize the State of cleanliness and the content
team.
8.3.3 Production equipment should only be used within its qualified operating range.
8.3.4 You must set a system of identification of critical instruments and equipment that allows know and verify
your qualification or current calibration status.

8.3.5 The location of manufacturing equipments must not hamper the movements of personnel, or ventilation
system vents, these should facilitate the flow of materials, ensure the order of the processes to control the risk
of confusion or mixture of any stage of the process.
8.3.5.1 When the team requires be installed in a space open, this should provide the protection suitable to
the production process, this mainly applies to closed systems or containment.
8.3.6 Control systems must be in visible places and be consistent with the kind of area in which will be
operated.
8.3.7 Materials that are considered for the design and construction of manufacturing equipments and
the Accessories that are in direct contact with the drug must not alter the features and quality of this or their
intermediates.
8.3.8 Lubricants, coolants or other substances required for the operation of the equipment of manufacturing,
not must be in direct contact with the product or packaging. In the case of lubricants or other substances required
for the operation of the manufacturing equipment that could be in contact with the product must be at least food
grade, purchased under a specification and set its management.
8.3.9 Closed or restraint equipment should be used whenever possible, when required use computers open
or process needs a closed team must be open should be followed the necessary measures that will prevent the
risk of contamination.
8.3.10 The equipment of manufacturing obsolete should be removed from the areas of production.
8.3.11 The equipment damaged and in hopes of maintenance should be identified and do not represent a
risk for staff and operation.
8.3.12 The washing, cleaning and maintenance of manufacturing equipments must not put at risk the quality
of the products, the safety of them operators, nor be source of pollution.
8.3.13 Manufacturing equipments, accessories, utensils and all pipes should be cleaned and maintained in
accordance with written procedures described activities to make this effective and reproducible.
8.3.14 You must set the duration of the cleaning equipment or utensil based on studies of validation.
8.3.15 When you manufacture in campaigns, equipment cleaning intervals should be established
and production utensils that prevent pollution or polluting development.
8.3.16 Those teams not dedicated must clean is between the manufacture of different products.
8.3.17 Must be defined through validation studies the levels of acceptance of traces of product or cleaning
agents, their intermediates.
8.3.18 Cleaning procedures must include:
8.3.18.1 To rea and since of the responsible of the cleaning of the equipment.
8.3.18.2 Period of cleaning and/or sanitizing.
8.3.18.3 A complete description of methods and materials, including the dissolution of the agents of cleaning
used to clean the equipment.
8.3.18.4 Instructions for the Assembly and disassembly of each item of equipment to ensure an adequate
cleaning.
 8.3.18.5 Instructions for the removal or destruction of the previous batch identification.
8.3.18.6 Instructions to avoid contamination of the clean equipment before use.
8.3.18.7 Verification of the cleaning of the equipment of manufacture prior to use.
8.3.18.8 Set the maximum time that can elapse between the final of the process and cleaning of the team.
8.4 Critical systems.
8.4.1 The system of purification and distribution of water for the manufacturing of drugs, when you
apply, must be designed, constructed and maintained to ensure the required quality of water, in accordance
with the FEUM.

8.4.1.1 Drinking water, must comply with the stipulations in the FEUM and the current NOM-127-SSA1.
8.4.2 The systems of air must be designed, built and maintained in accordance with the FEUM, for ensure
the classification required in the appendix to policy of this standard.
8.4.2.1 To class A, B and C must have minimum with filters HEPA terminal of 99.97% of 0.3 m. In the case
of class D must have as minimum with filters of efficiency of 95% and for ISO-class 9 must have as minimum
with filters of efficiency of 85%.
9. qualification and validation
9.1 Generalities.
Essential for the fulfillment of the BPF is the qualification and validation, allowing demonstrate that the
manufacture of drugs meets the basic functionality, features consistency and robustness to ensure the quality of
drugs.
The validation of processes is not a point in time event but it involves an approach related to the life cycle of
the product, which should be considered that the variability is a feature intrinsic to production processes; see
this variability, control and analyze the impact on the quality of drugs should lead to continuous improvement
processes.
9.2 Impact of validation.
The manufacturer must determine the impact of the elements of the manufacturing quality of the
product, using the management of risks as the tool to determine the scope of the qualification and validation.
9.3 Qualification and validation.
An essential requirement for validation is the qualification of all the elements involved in the process, system
or method to validate.
9.4 PMV.
9.4.1 There should be a plan written for the development of qualification and validation activities, which must
be authorized by the higher level hierarchical organization and responsible for healthcare, in which should be
established the scope, responsibilities and priorities of the qualification and validation.
9.4.2 The PMV must contain:
9.4.2.1 Validation policy.
9.4.2.2 Organizational structure for the validation activities.
9.4.2.3 Responsibilities.
9.4.2.4 Committee of validation or equivalent.
9.4.2.5 List of the facilities, equipment, systems, methods and processes to qualify or validate.
9.4.2.6 Formats to use is for those protocols and reports.
9.4.2.7 Array of training and qualification of staff.
9.4.2.8 Control of changes.
9.4.2.9 Reference to applicable documents.
9.4.2.10 Analytical methods.
9.4.2.11 Computer systems that impact the quality of the product.
9.4.2.12 Critical systems.
 9.4.2.13 manufacturing equipment.
9.4.2.14 Procedure or cleaning methods.
9.4.2.15 Procedure or methods of cleaning and/or sanitizing.
9.4.2.16 Maintenance of the State validated.
9.4.2.17 Should include a programme of activities, which must be updated with the frequency required.

9.5 Qualification and validation protocols.

Is must count with protocols written where is specify how is will be the qualification and validation, this should
specify the stages critical and include the criteria of acceptance.
9.5.1 These protocols should include the process parameters that can affect the attributes of the quality of
the drug.
9.5.2 You must specify intervals of acceptance of each critical process parameter of manufacture of routine.
9.5.3 You must specify the number of repetitions for qualification or validation study.
9.5.4 You must set the type of validation that will take place, which may be prospective or concurrent.
9.5.5 Reports of qualification and validation.
Must have written reports of the qualification and validation that demonstrate traceability to the Protocol
corresponding, they should include the results obtained, the deviations observed and conclusions. Any change
to the Protocol during the execution must document it and justify is.
9.6 Qualification.
The qualification must be made through the following four consecutive stages:
9.6.1 Should count with qualification of design based on them requirements of user, where is check that the
design of facilities, equipment and systems critical is suitable for the use to which are destined.
9.6.2 Must have qualification of installation based on the manufacturer's requirements, which is checks that
the equipment and systems installed to comply with the approved design and the recommendations of
the manufacturer or user requirements.
9.6.3 They must have qualification of operation or operation based on conditions and intervals of operation
established by the manufacturer and user.
9.6.4 Must have performance ratings showing that critical systems and equipment interconnected work
so effective and reproducible under routine conditions, for a particular process and approved specifications.
9.6.5 To proceed with the next stage of qualification must successfully conclude the precedent. You can start
the next stage, only when they demonstrate that critical deviations there are no and there is a evaluation
documented that there is a significant impact in the next stage.
9.6.5.1 Measurement instruments involved in the qualification, must be calibrated with traceability to the
national standards.
9.6.5.2 Standards used should be traceable to a certificate pattern.
9.6.5.3 Keep records of calibrations.
9.6.5.4 Instruments which do not meet calibration should not be used in any part of the process.
9.6.5.5 Deviations from the standards of calibration on critical instruments should be investigated to
determine if these could have impacted on the quality of the intermediate or manufactured drugs in that team
from the last successful calibration.
9.7 Qualification of HVAC system and/or ventilation.
9.7.1 The HVAC system should be described as in accordance with the FEUM taking into account at least
the following parameters: temperature and HR of them areas that feeds, volume of injection of air, differential of
pressure between the areas, number of changes of air, count of particles, flows of air, levels of cleaning, speed
of flow and tests of integrity of those filters HEPA.
9.8 Water systems score.
9.8.1 The qualification of the systems of water for use pharmaceutical must perform is according to the
FEUM and their supplements.
 9.9 Validation of processes.
9.9.1 Validation of the processes must be done with an approach to risk management for quality.

9.9.1.1 Should there be a document system that supports knowledge and continuous improvement of the
process throughout the entire life of the product cycle.
The approach must support scientifically, according to the characteristics of the process and its control should
be be provable by the manufacturer.
9.9.2 Stages of validation of process.
The validation of process consists of three stages within the cycle of life of the product:
9.9.2.1 Design of the process (stage 1).
9.9.2.1.1 Based on solidly scientific, including the BPD, principles and methods must be defined the
processes of manufacturing and their records of control.
9.9.2.1.2 At this stage must be defined the strategy for the control of the process, which
must documented. This must include the quality of the materials, the monitoring of critical parameters of
the process and the critical quality attributes that have been identified, including the results during the execution
of the Protocol for the transfer of technology.
9.9.2.1.3 Records planned for production and Control that contains the operational limits and the strategy
total control must be confirmed in the next stage.
9.9.2.2 Qualification process (stage 2).
This stage can be made with prospective approach or concurrent, release and consists of two elements:
9.9.2.2.1 Facilities design and qualification of equipment and services.
9.9.2.2.1.1 Facilities, equipment and services must be qualified.
9.9.2.2.1.2 Each of these elements can be described as individual plans or all together with a general plan.
9.9.2.2.2 Rating of the performance of the process.
9.9.2.2.2.1 At this stage should be defined and confirmed the conditions of manufacture. It is the
combination, with the manufacturing process for the production of commercials, all the elements previously
lots qualified that integrate it, including the qualified personnel, control procedures, and inputs.
9.9.2.2.2.2 It must establish methods objectives of measurement applying tools statistics.
9.9.2.2.2.3 During this phase should be surveys, additional tests and greater scrutiny of the performance of
the process than would be typical in commercial production.
9.9.2.2.2.4 The level of monitoring and testing should be sufficient to confirm the uniformity of quality whole
lot product.
9.9.2.2.3 The qualification of processes must be done with batches commercial size, using at least three lots
of consecutive in a defined period of time, which should provide the sufficient data to demonstrate that the
process is capable, stable and consistent.
9.9.2.2.4 Batches produced to this end may be marketed if they comply with: all the requirements of GMP,
the acceptance criteria, the conclusions are satisfactory and the previously established release specifications.
9.9.2.2.5 Release concurrent of them lots of the qualification of the process.
9.9.2.2.5.1 The release concurrent in the stage of qualification of the process only is acceptable in cases such
as: demand limited, half-lives short, by health emergencies, among others; this decision should be previously
justified and approved since the Protocol responsible for health or person authorized. Documentation
requirements should be the same as for prospective validation.
9.9.2.2.5.2 This allows that though the validation with the minimum of batches needed to complete the
not concluded, se you can make the release of these meet all of their critical attributes of the quality.
9.9.2.2.5.3 Manufactured under this condition, lots may be released and marketed if they meet: all the
requirements of the GMP, the acceptance criteria set out in the Protocol of validation, the validation of each lot
and specifications report satisfactory conclusions of previously established release.
 9.9.2.2.5.4 Any report of non conformity or coming event of customers, must be investigated to determine
root cause and correct it immediately.
9.9.2.2.5.5 Batches released concurrently should be included in the stability program.
9.9.2.2.5.6 Concurrent qualification process batch release must not be a common practice in the validation
of processes.
9.9.2.3 Continuous verification of the process (stage 3).
9.9.2.3.1 Must ensure on an ongoing basis that the process remains in a State of control during the
commercial manufacturing.
9.9.2.3.2 Should establish is systems of control that detect the changes in the variability of them processes
in order to correct them immediately and take them back to their validated conditions of operationn. Estos must
be defined in procedures that include the data to collect, the frequencies collection, the calculations and
interpretation of the results obtained, as well as actions that they derived. When the nature of the measurement
allows apply statistical tools.
9.9.2.3.3 Variability can also be detected through timely complaints assessment related to the process and
the product, reports of non-conforming product deviation reports, variations yields, review of records of the lots,
records of receiving inputs and reports of adverse events.
9.9.2.3.4 This information should contribute to the continuous improvement of processes.
9.9.2.3.5 Once established the status of a process qualification, this must be maintained by the definition of
programs of preventive maintenance to facilities, equipment and services, as well as for periodic calibration of
critical instruments of measurement. These aspects will also contribute to the maintenance of the validated state
of the process.
9.10 Validation of cleaning.
9.10.1 Is must perform the validation of cleaning with the objective of demonstrate the effectiveness of
the procedures of cleaning.
9.10.2 Cleaning methods must be appropriate to the nature of products.
9.10.2.1 Where the cleaning method includes processes of sanitization, sterilization and/or decontamination,
these must be validated.
9.10.2.2 Interactions between the different agents, sanitizers must be evaluated and be included
in validation.
9.10.3 Analytical methods validated considering sampling, to detect technique should be used traces of
pollutants, detergents or sanitizers.
9.10.4 Is must validate the procedures of cleaning of the surfaces that are in contact with the product and
must go to those stages of the process where contamination or drag of materials represent the greatest risk to
the quality of the drug.
9.10.5 If several products are processed on the same computer, and it is cleaned using the same procedure,
a representative product may be used for validation or criteria of the ""worst case. This selection may be based
on the solubility and difficulty of cleaning and the calculations of the residual limits based on a combination of
concentration, toxicity and stability.
9.10.6 The validation of cleaning must make is in three applications consecutive of the procedure of cleaning
with results satisfactory.
9.10.7 The number of applications may be increased depending on the complexity of the process of cleaning
to validate.
9.10.8 Is should use methods analytical validated with the sensitivity appropriate to detect traces
or contaminants.
9.10.8.1 The limit of detection of each method should be sufficiently sensitive to detect those limits of
acceptance established for traces of the drug or contaminant.
9.10.8.2 You should set the level of recovery that the method is able to reach.
9.10.8.3 The limits can be set based on the minimal pharmacological activity, toxicological or physiological
drug.
 9.11 The effect of the cleaning of them teams of manufacturing, accessories, utensils and all the pipes must
establish is with base on the results of the validation.
9.11.1. General Cleaning validation Protocol should describe the equipment, the detailed procedure
of cleaning, materials, acceptable levels of cleaning parameters to be controlled, analytical methods,
techniques of sampling and identification of samples.
9.12 The procedure of sampling must include, the technique to collect it shows, the material to use, the size
of the surface and sampling points.
9.12.1 Studies validation of cleaning and decontamination of equipment must take into account
the microbiological or contamination by endotoxin for those processes where a level is specified of microbial
count or endotoxins, particularly those drugs used in the manufacture of sterile drugs.
9.12.2 You must set a program of periodic for the determination of trace amounts of products
including cleaning validation.This frequency must be set based on risk assessment.
9.13 Validation of analytical methods.
9.13.1 When is used methods compendial, is should demonstrate the applicability to the product, under
the conditions of operation of the laboratory and depending on the desired analytical method.
9.13.2 When compendial methods are used, it must demonstrate applicability to the product, under
the conditions of operation of the laboratory.
9.13.3 The proper analysis equipment qualification should be considered before validation of methods
analytical.
9.14 Validation of processes aseptic.
9.14.1 In products that claim to be sterile and that are not subject to terminal sterilization, each one of the
unit operations involved must be independently validated and confirmed altogether.
9.14.2 Aseptic process validation should be performed in accordance with the FEUM and its supplements.
9.15 Validation of computer systems.
9.15.1 Computer systems that have an impact on the quality of the product and data integrity, must be
validated.
9.15.2 Should count with an inventory of all the systems computer.
9.15.3 Computer systems should be considered software components, instruments and
equipment infrastructure of the information technology, among others.
9.15.3.1 Must have a system of protection, integrity and information support, which should be determined
based on the documentation of risk assessment of the computer system. He access and readability of the data
must ensure is during all the time of retention.
9.15.3.2 The access to these must be controlled.
9.15.3.2.1 Apply controls physical and/or logical to restrict access to users with different levels of
authorization. Security code must be defined according to predetermined criteria and be modified periodically.
9.15.3.2.2 The system should block a user after a quantity defined from attempts of entrance failed.
9.15.3.3 When a computerized system to generate electronic records or electronic signatures using these
should be considered in the validation:
9.15.3.3.1 Electronic records are considered documents and records which are created, modified,
maintained, archived, retrieved or transmitted through systems electronic.
9.15.3.3.2 If you determine that a system generates and maintains data electronic regulated, documentary
evidence must exist to ensure their traceability, easy access and integrity.
9.15.3.4 If they carry out critical data capture manually there should be a further review in the accuracy of
the data that can be carried out by a second person or through a medium electronic validated.
9.15.3.5 Data should be protected by tools such as backups made with frequencies according to a procedure
defined.

9.15.3.6 The ability to restore data, as well as the integrity and accuracy for their support, must be checked
during validation and monitored on a regular basis.
 9.15.3.7 Based on a risk assessment to determine the need that the system include a system data audit,
scheduled to independently record the date and time of entry of the users, as well as the actions create, modify,
or delete electronic records.
9.15.3.7.1 Data audit system (also known with the technicality in English as Audit trail) you must prevent
alteration and it must be available and convertible in an understandable way, during their retention period, to
provide evidence of the chain of events.
9.15.4 The validation process should cover all relevant phases of the life cycle according to the category and
architecture of the system, to ensure the accuracy, completeness, and consistency in the performance planned
computer systems.
9.15.4.1 Risk management should be applied to the validation complete cycle, including phases of planning,
specifications, testing and release of the system, maintenance and removal of system.
9.15.4.2 Components of the infrastructure of the information technology and any instrument or relevant
equipment must be qualified.
9.15.4.3 For the validation, process can be executed tests by the supplier, without However it acceptance of
them records of test delivered by the supplier not must replace the tests of validation made in their facilities,
equipment and personal, such as Plan of validation, requirements of user, analysis of risk, rating of performance,
report of validation, between others.
9.15.4.4 If a centralized multi-site system is used, the validation process should include the verification of the
processes executed through the system at each individual site.
9.15.5 Should count with a matrix of traceability where document the multiple stages of specifications
(including revisions) and the evidence once they have fulfilled in a way satisfactory.
9.15.5.1 All changes to a computer system should be in accordance with control system of changes, including
configurations of system, should apply is according to a process predefined and controlled that understand the
definition of the impact of the change and the activities of verification resulting, including testing regressive
9.15.5.2 Control procedures, which ensure the review of the audit must be implemented in data regularly, the
frequency and the method will be determined, according to the risk.
9.15.5.3 The functionality of data auditing systems should be issued information enabling verify if any data
has been altered since its original entry.
9.15.5.4 If the data are transferred to another system or data format, validation must include the review that
data are not altered in value or definition during the migration process
9.15.6 For electronic signatures:
9.15.6.1 E stas must be unique to each individual and non-transferable.
9.15.6.2 When the use of signatures electronic is adopted, is should set the date starting from which the
signatures electronic are valid and equivalent to the signatures autograph.
9.15.6.3 Electronic signatures are required to have at least two different such as a code elements ID and a
password.
9.15.6.4 The signatures electronic should be linked to their respective records electronic that ensure that the
signatures not have been altered, copied or of any way, transferred to a record electronic to be falsified by means
ordinary.
9.15.6.5 In case that the electronic signature is performed using tokens or biometric devices, the system
should ensure that another person can not use it and that measures have been implemented in necessary
control.
9.15.6.6 If electronic signatures are used in documents, must be authenticated and secure.
9.16 Maintenance of the State validated.
9.16.1. brief Should be periodically checked the validated state and you will be based on an evaluation of risk
analysis. You must include a revision to the facilities, systems, equipment and processes.

9.16.2. detailed Where a significant change affects the quality or characteristics of the drug, it should be
performed a new validation.
9.17 Guidelines for qualification and validation.
 9.17.1. photographs May be used as support for the qualification and validation, national guidelines
and International described in the bibliography of this standard.
10. production systems
10.1 Generalities.
10.1.1 Them drugs or principles active can be obtained by processes of manufacturing such as the synthesis
chemical or enzyme, extraction, growing cell, fermentation, obtained from sources natural, or by combination of
these processes.
10.1.2 The manufacture of drugs or active ingredients that are prepared by the processes outlined in
the previous point must follow provisions of this standard.
10.1.3 The establishment engaged in the manufacture of intermediates that are incorporated as a structural
fragment characteristic of a drug; must distinguish and technically, justify the stage of process in which is defined
the structure and chemical properties of the molecule.
10.1.3.1 From the stage in which it is defined the structure and chemical intermediate properties and/or drug
must follow provisions of this standard.
10.2 Supplies control.
10.2.1 Generalities.
10.2.1.1. must have written procedures for the receipt, inspection, sampling, identification, storage, control,
release and management of all inputs that are used in the manufacture of drugs.
10.2.1.2 Inputs must be purchased, when possible, directly from the manufacturer.
10.2.1.2.1 Must have the certificates of analysis issued by the manufacturer supplies.
10.2.1.3 Inputs in any of the stages of manufacture, should be handled and stored in so prevent
contamination and alteration.
10.2.1.4 Those inputs, must be identified with a number of lot internal according to each shipment received.
10.2.1.4.1 When a shipment is received different batches, each batch must be considered by separate for
sampling, analysis and release.
10.2.1.4.2 In the case of a game already received lots of criteria should be established for evaluate or analyze
inputs.
10.2.1.5.1 Must have a system for the identification of the status of each batch (quarantine, approved or
rejected).
10.2.1.6 Before mixing input with an already existing inventory, it must be approved.
10.2.1.7 When using containers not dedicated to the storage of inputs, you must implement a system to
ensure that risk of cross-contamination there is no. This system can include, validation of cleaning, qualification
of suppliers, among other measures.
10.2.1.8 There must be a system of control inputs liquid storage tanks of great volume that includes the
application and coding of lines and valves.
10.2.1.9 Is must count with a system that secure that those inputs are used under the criterion of Early
expiration dates first outputs or first innings first outputs. It must be justified and approval of the non-use of this
system for inputs which by their nature are mixed a time approved.
10.2.1.10 When CRSs, are used in the control of inputs must be validated, and ID managed via tags or
codes.
10.2.1.12 May not be reanalyzed nor used inputs whose date of expiry given by manufacturer finished.

10.2.1.13 Rejected inputs, must be identified and segregated to prevent their use in the manufacturing.
10.2.1.14 Them inputs of origin animal or in which is used for the manufacture, derivative of origin animal,
they must submit the certificate which shows that they are free from risk of encephalopathy transmissible (for its
acronym in English, Transmissible Spongiform Encephalopathies), spongiform encephalopathy BSE (for its
acronym in English, Bovine Spongiform Encephalopathies), fever FMD, enzootic bovine and others representing
a health risk, regardless of use published by the World Health Organization viral inactivation methods.
10.2.2 Reception.
 10.2.2.1 In the reception of inputs are must check that each container or group of containers, are full,
identified with at least name, quantity, number of batch and date of expiration, when apply.
10.2.2.2 The inputs must be identified for storage indicating at least the following information:
10.2.2.2.1 The name assigned by the receiving establishment and the international denomination,
when apply.
10.2.2.2.2 Internal batch number.
10.2.2.2.3 Quantity and number of containers.
10.2.2.2.4 The status.
10.2.2.2.5 The date of expiration or reanalysis, when you apply.
10.2.3 Sampling.
10.2.3.1 Those inputs, must be stored in quarantine, until they have been, sampled, analysed or evaluated
and released by the quality unit for use.
10.2.3.1.1 In the case of highly toxic materials may exempt the analysis if the supplier has been qualified and
the material received counts with a certified analytical. The evaluation in site of the manufacturer shall make is
periodically, the frequency must be sustained in a valuation of the risk.
10.2.3.1.2 The number of containers to sample, and the amount of material taken from each
container, should be based on statistical criteria of variability of the component, levels of trust, history of quality
of the supplier, and the quantity required for the analysis and required retention sample.
10.2.3.2 Sampling should be performed by considering the following:
10.2.3.2.1 Containers must be cleaned or sanitized, to prevent the introduction of contaminants.
10.2.3.2.2 For the sampling of sterile supplies, instruments sterile, areas and techniques should be
used aseptic sampling.
10.2.3.2.3 The samples taken must be identified.
10.2.3.2.4 Sampled containers must indicate in their identification.
10.2.3.2.5 Prior authorization of the Secretariat, the manufacturer of drugs may carry out a reduction in
frequency and/or analytical tests for the inputs used in the manufacture of the drugs, the analysis referred to in
this point is made in the country, the frequency can be reduced and analytical evidence in the analysis carried
out by the manufacturer.
10.2.3.2.5.1 For the reduction analytical of an input used in the manufacture of a drug must be submit to the
Secretariat the following information:
10.2.3.2.5.2 Certificate of current BPF of the place of manufacture of the applicant.
10.2.3.2.5.3 Support of rating of the manufacturer and the supplier or suppliers involved in the supply chain.
10.2.3.2.5.4 Risk assessment which contains technical and scientific justification supporting the frequency
and analytical to reduce test application.
10.2.3.2.5.5 Study statistical made between the results obtained by the manufacturer and those obtained in
Mexico, with a minimum of 20 lots of the input used in the manufacture of the drug, to demonstrate that not exists
difference statistically significant. Analytical certificates that support should be included the study batches.

10.2.4 Storage of inputs.

10.2.4.1 Them inputs must store is in conditions to avoid risks of contamination cross, degradation or
pollution of the environment.
10.2.4.2 The inputs are stored in boxes, bags, or any material that by its nature represent a risk your shelter,
should be placed on pallets and not directly touch with the floor.
10.2.4.3 When justify some materials you can stored outdoors always this not represent a risk of
contamination or degradation for the input and its identification is kept readable.
10.2.5 Assortment.
10.2.5.1 Traceability must be ensured for lot of quantities received against the numbers assorted.
 10.2.5.2 Inputs must be weighed or measured in accordance with written procedures and the instruments
used must be calibrated and their precision and accuracy correspond to the intended use.
10.2.5.2.1 Is should check that those inputs assorted have been previously approved by the unit of Quality
and have the date of expiration or reparse force.
10.2.5.3 Refill amounts should be verified before use in production and correspond to the order of production
or packaging and labelling.
10.2.5.4 If a component is removed from the container original to another, the new container must
be identified in the same way.
10.2.5.5 Printed materials must be stored and transported separately in containers closed to avoid mixtures.
10.2.5.6 Assorted manufacturing inputs must be separated by a lot of product in which will be used.
10.3 Production control.
10.3.1 A system must be set to ensure control of the critical stages of the process of production, some stages
may require direct supervision for their control.
10.3.2 Production operations must be performed by qualified personnel and supervising staff has the
experience, knowledge and qualifications that correspond with the activity that oversees.
10.3.3 Each lot of drug should be controlled from the assortment by the order and instructions of production.
10.3.4 Before production must verify the cleaning of areas and equipment, and that there matter prima,
product, residue of product or documents of the operation earlier and that not be required for the operation.
10.3.5 All those equipment and areas used, should be identified with the data of the product,
the number batch and production or establish a system that avoids risk of confusion or pollution crusade.
10.3.6 Based on history, lots of proof or validation, studies the yields should be established expected for the
stages of process that it required.
10.3.7 Deviations to the yields in the critical stages of the process should be investigated and to determine
its impact on the quality of the final product.
10.3.8 You should investigate any deviation or out of trend to the production process, classify such deviation
and determine the corresponding corrective or preventive actions.
10.3.9 The addition and the order of the inputs during manufacture must perform and verify agree to the
manufacturer's instructions, these instructions should be included in the critical process controls and
the frequency of the monitoring.
10.3.10 In process controls will be performed by the production staff, these should register is in the order of
production and be part of the record of the lot.
10.3.11 When an intermediate product is not used immediately, it should be stored in validated conditions
ensuring their conservation.

10.3.12 You must set procedures for product sampling process, intermediate and drug, the number of
containers to sample, and the amount and integrity of material taken from each stage, these should be based
on statistical criteria of variability of the component, levels of trust, and the quantity required for analysis.
10.3.13 Sampling procedures should not represent a risk of contamination cross for the product sampling or
pollution to the environment and the environment.
10.3.14 Mixture of intermediate products or drugs.
10.3.14.1 Controls that ensure the homogeneity of the mixture of lots should be established or fractions of
lots of intermediate products or drugs. Only fractions of lots or batches you can mix intermediates or drug
complying with established quality specifications.
10.3.14.2 The mixture of intermediate products or drugs ensuring traceability must be documented batch
mixed, assigning a new issue of lot to the resulting mixture and that it complies with the established quality
specifications.
10.3.14.3 Is not mixing the resulting fractions of a same stage of production that is coupled to a later stage
of production.
10.3.14.4 The mix between products intermediate or drugs out of specification and approved not is allowed.
 10.3.14.5 Mixing of intermediate products or drugs should be validated when the characteristics physical as
the distribution of the particle size, bulk density, among others, are critical for the process in which will be used
as the manufacture of dosage forms sorwarm or suspensions.
10.3.14.6 The impact of mixing in the stability of the intermediate product or drug must be evaluated and if
required stability studies must be carried out.
10.3.14.7 The date of expiration or reanalysis of the intermediate product or drug must be set with base on
the date of the lot or oldest fraction used in the mix.
10.3.15 Pollution control.
10.3.15.1 Measures should be established for the manufacturing operations that minimize the risk of cross-
contamination.
10.3.15.2 At each stage of the process, products and materials should be protected from
contamination microbial or otherwise.
10.3.15.3 It must be ensured that in the subsequent purification operations others are not managed drugs
simultaneously in the same equipment or areas.
10.3.15.4 The remnants of the product, must count with a procedure for its management that considers as a
minimum the following:
10.3.15.4.1 Characteristics of the remnant to be incorporated at any stage of the process.
10.3.15.4.2 In no case may use these remnants to integrate or integrate directly to the finished product.
10.3.15.4.3 The traceability of each one of the remnants.
10.3.15.4.4 Disposal of the remnants, if applicable.
10.4 Control of the production of drugs manufactured by cultivation or classical fermentation.
10.4.1 Generalities.
10.4.1.1 The manufacture of products intermediate and drugs manufactured by culture or fermentation
involves conditions and precautions additional by the employment of organisms live, however is applied
them same principles of BPF contained in this standard. In this section will address them processes that employ
microorganisms existing in the nature and/or modified by methods mutagenic traditional, combined with methods
physico-chemical to produce drugs between which is found products oflow weight molecular as them antibiotics,
amino acids, vitamins e hydrates of carbon. The biotechnology processes requirements and specifications will
be established in the NOM-059 -good practices of drug manufacturing, SSA1-2013.
10.4.2 When required biological load, viral load controls should be established and/or endotoxin in them
inputs and in different stages of the manufacture of those drugs.

10.4.3 Controls should be established in the production process that minimize the risk of contamination of
equipment, facilities and environment.
10.4.4 Must be adequate in all stages of manufacture to ensure controls the quality intermediate product or
drug. The steps leading to the stage of fermentation/cell culture, such as the preparation of a vial of the cell Bank
for use in the manufacture, must be done under the adequate process controls.
10.4.5 Should be the phenotypic characterization master banks and/or work.
10.4.6 Must document is the origin and history of the banks cell.
10.4.7 Information on genetic stability of the cell banks should be documented.
10.4.8 It must demonstrate the purity of cell banks using controls that demonstrate that are free of agents
microbial adventitious and of contaminating cell.
10.4.9 Records of use of conditions and cell banks vials should be stored storage.
10.4.10 The cell banks should be kept separately from other materials, under storage conditions designed in
order to maintain its viability and prevent its pollution.
10.4.11 The units of storage of them banks cellular and/or lots seed must be sealed, labeled and maintained
at the set temperature. The temperature of storage freezers must be recorded continuously. You must register
any deviation from the established limits and any corrective measures taken. As well as having a plan
of contingency in the event of failure of cryopreservation systems.
10.4.12 Access to seed lots or cell banks should be restricted to the Personal authorized.
 10.4.13 Is must count with a procedure that ensures the control of use, handling and maintenance of seed
lots or cell banks.
10.4.14 Controls in fermentation processes should include at least:
10.4.14.1 Count with a procedure for the inoculation and growth of the crop.
10.4.14.2 It should monitor the critical parameters during the cell culture or fermentation, such as pH, oxygen
content, speed of agitation among others.
10.4.14.3 Will need to monitor the process of cell growth and viability.
10.4.15 Harvest procedures should be established.
10.4.16 Purification procedures that remove cells, cellular waste should be established and components from
the inputs used in the manufacture of the drug.
10.4.17 Fermentation.
10.4.17.1 The addition of cell substrates, buffer solutions and gases must be checked in fermentation
processes to minimize the risk of contamination. Should be preferably used closed systems.
10.4.17.2 When a process has operations in environments open, these activities you should perform under
conditions ensuring the purity of the crop.
10.4.17.3 Production staff must be trained in the use of cell cultures and carry the clothing required according
to the type of product.
10.4.17.4 Used in cell culture and fermentation equipment should be cleaned and sterilized with validated
procedures.
10.4.17.5 If the process requires it media must be sterilized prior to use in a fermentation process.
10.4.17.6 Procedures for cleaning and sanitizing or sterilizing equipment should be established used in the
fermentation process.
10.4.17.7 When it detects a pollutant in the equipment used in fermentation, this is should identify and
maintain records of these pollution events.

10.4.17.8 When is use equipment multiproduct is must establish controls that minimize the risk of pollution
cross. In these cases you should set production campaigns.
10.4.17.9 Critical operating parameters (e.g., temperature, pH, agitation speeds, addition of gases, pressure)
should be monitored to ensure consistency with the established process. He growth cell, the feasibility (for the
most of them processes of cultivation of cells), and, in his case, it productivity also must be monitored. Them
parameters critical can vary of a process toanother, and for the fermentation classic, certain parameters (of
viability cell, for example) may not be supervised.
10.4.18 Harvesting, isolation and purification.
10.4.18.1 Isolation and purification phases must be validated and performed in facilities and
equipment designed to minimize the risks of contamination.
10.4.18.2 Is must establish procedures for the stages of harvesting, isolation and purification that ensure the
elimination or inactivation of the producing organism, cellular waste disposal and the elimination of the culture
medium components.
10.4.18.3 Equipment used in these stages must be cleaned and decontaminated according to the validated
process.
10.4.18.4 When a process has operations in open environments, purification should be in controlled areas
to ensure the quality of the drug.
10.4.18.5 If is uses an equipment for processes multiproduct, for the stages of purification is must controls
such as resins dedicated chromatographic or further evidence that minimize the risk of contamination.
10.4.19 Removal and viral inactivation, when you apply.
10.4.19.1 The process of removal and inactivation viral must be validated.
10.4.19.2 Validation of these processes must be done outside areas of manufacturing.
10.4.19.3 Deviations in these processes should be investigated and the impact should be evaluated in
the finished before release product safety.
 10.4.19.4 For the stages of inactivation and viral removal the air handling units must be dedicated when the
process is exposed to the environment.
10.4.19.5 There should be a system for clear identification of the product subject to removal and viral
inactivation - and those who have not gone through this process.
10.5 Packaging control.
10.5.1 Packaging of drugs in areas classified in accordance with the normative appendix A should be of this
standard.
10.5.2 The materials of the container primary of them products intermediate or the drug not should
be reagents, additives, absorbents, adsorbents, in such a way that they can affect the quality of these.
10.5.3 Printed materials should be handled separately once they have been assigned to an order from
packaging to minimize the risk of pollution cross.
10.5.4 Not be packaged simultaneously two or more different products in the same area.
10.5.5 Should be a reconciliation of printed materials under each packaging order.
10.6 Labelling control.
10.6.1 There must be procedures and records for the receipt, identification, sampling, inspection, release,
handling and storage of labels and packaging materials.
10.6.2 Conditioning materials.
10.6.2.1 Packaging materials must be protected to the drug's contamination and the deterioration during
storage and transportation.
10.6.2.2 If containers are re-used, they should be cleaned according to procedures and the pre tags deleted.

10.6.3 Tags control.

10.6.3.1 Access to the label storage areas should be restricted to Staff authorized.
10.6.3.2 Must be a reconciliation of tags under each packaging order.
10.6.3.3 Should investigate and assess the impact of any difference in the reconciliation of
tags. The conclusions must be approved by the quality unit.
10.6.3.4 Surplus already printed labels with any specific data of the lot or batch number or departure must
be destroyed and have evidence of this activity.
10.6.3.5 Obsolete labels should be destroyed and have evidence of this activity.
10.6.3.6 The print operation of lot, expiration or other specifics on the label must be documented.
10.6.3.7 Verification of the printed data must be against your specification labels.
10.6.3.8 A printed label must be included in the record of the batch of the drug.
10.6.4 Packaging and labelling.
10.6.4.1 Should exist procedures for the operations of packaging and labelling.
10.6.4.2 Is should make the clearance of line in them areas of packaging and labelling, for ensure that foreign
material for the operation there is no. This operation should be documented in the the batch record.
10.6.4.3 Is should implement those controls to prevent the pollution cross in the packaging and labelling.
10.6.4.4 Must have physical separation in the packaging and labelling of different batches of drugs or
intermediates.
10.6.4.5 Drugs or intermediates labels should indicate at least the name or identifier code, the lot number of
the product, quantity, date of expiry or reanalysis and the storage conditions, as well as the number of container
when you apply to several recipients of the same lot or game.
10.6.4.6 Is should establish controls during the process of packaging and labelling, these they must be
documented and the results should be part of the batch record.
10.6.4.7 Containers of drugs or intermediate products that are transported out of the control of
the manufacturer, must be sealed in such a way that if the seal is missing or has been forced, can be put on
alert to the receiver considering that the content has been altered.
 10.7 Storage and distribution.
10.7.1 Is must count with facilities to store the drugs and products intermediate in the conditions appropriate
and when is required, count with conditions controlled in HR and/or temperature. Is must keep records of HR
and/or temperature when the drug storage conditions or intermediate product so specified it.
10.7.2 You must assign a separate areas for the storage of drugs and intermediates quarantined, rejected,
returned or withdrawn from the market, unless there is an alternative system for prevent its unintended use or
unauthorized, before a decision is taken upon your fate end.
10.7.3 Drugs and intermediates can only be released for distribution after a have been approved by the
quality unit and released by the responsible health or person by writing has been designated.
10.7.4 Drugs and intermediates should be transported so that is it not affected negatively their quality.
10.7.5 The special conditions of storage or transport drugs and intermediates must be stated on the label.
10.7.6 Manufacturer must ensure that the carrier hired to send drugs and products intermediate knows and
follow the instructions for transport and storage appropriate.

10.8 Rejection, reproceso, rework, recovery and return.

10.8.1 Reject.
10.8.1.1 Intermediate products and drugs that do not comply with stated specifications should be identified
and segregated to prevent their improper use.
10.8.1.2 Should be investigating the causes and documenting the final destination of the intermediates
and drugs that do not comply with stated specifications.
10.8.1.3 If as a result of the research is determined that an intermediate product or drug can be reprocessed
or emerged, they should clearly identify and satisfy at least the conditions stated in this.
10.8.2 Reprocessing.
10.8.2.1 Is should implement those controls in process that ensure that the stage of the process that
is repeats does not affect the quality of the intermediate product or drug and that it meets the
specifications established.
10.8.2.2 If a stage of the process is often repeated, should not be considered as reprocessing and shall be
included as one stage of the process and documented according to the change control.
10.8.2.3 The repetition of a reaction or the reinstatement to a stage of the process of an input that not has
reacted also is considered reproceso and must establish is the controls that ensure that not affects the quality of
the intermediate or drug and that this meets them specifications established.
10.8.2.4 A batch of a drug can only be reprocessed one time. When the reprocessing is repeated in several
batches, should be included as part of the operation and be validated again.
10.8.3 Rework.
10.8.3.1 Be sure to lots of drug undergoing a rework to meet with the established quality specifications and
that their stability will not be affected, it shall be necessary to stability studies.
10.8.3.2 One should compare the profile of impurities from a batch emerged against the produced lots of way
to regulate to ensure that this is maintained in accordance with the limits laid down.
10.8.3.3 A batch of a drug can only be emerged one time.
10.8.4 Recovery of supplies.
10.8.4.1 Is an acceptable recovery of inputs used in the manufacturing process of intermediates and drugs
always to ensure that these recovered inputs conform with the specifications set forth for reuse in a new process
of production and not affect the quality of the intermediate product or drug.
10.8.4.2 Are considered inputs that can be subject to recovery to the solvents, reagents, water mothers,
filtered, among others.
10.8.4.3 In the case of recovery of solvents make sure that it complies with the specifications established
before mixing with other approved solvents qualities not recovered or to be used in stages of process.
10.8.4.4 Is should establish a procedure for the use of inputs recovered and register is in what process are
being used.
 10.8.4.5 Solvents and reagents recovered and new can be combined if they have been the tests that
demonstrate their suitability for all manufacturing processes in which can be used.
11 Quality Control Laboratory
11.1 General information
11.1.1 Quality Control activities include the Organization, documentation and procedures that ensure that the
tests are carried out according the BPL, according to the methods and specifications in force, so that the inputs
and outputs are not released for use or sale until their quality has been assessed.

11.1.2 Quality of drug manufacturers drives should have a control laboratory of quality corresponding to the
type of products manufactured. The quality unit must be independent and under the authority of a qualified
person.
11.2 Should exist procedures for the realization of the sampling, analysis, release, register and shelter of the
data generated in the laboratory.
11.3 Sampling should be performed in accordance with point 10.2.3 of this standard.
11.4 Is must retain samples of retention of them drugs in quantity sufficient for the realization of two analysis
complete according to the specification approved in the system of documentation of the establishment.
11.5 Retention samples should be kept under the conditions set out in the record up to one year after the
date of revocation or reanalysis of the drug or up to 3 years after the full distribution of the batch, use the period
that is longer.
11.6 Retention samples should be stored in primary packaging and packaging of the same characteristics or
equivalent that is conditioned the drug to market.
11.7 The specifications and methods of analysis should correspond to those indicated in the EMSF.
11.8 Drugs and intermediates specifications should be established according to accepted standards and be
in accordance with the manufacturing process.
11.9 The specifications must correspond to the recognized standard reference or when they do not exist
according to those laid down by the manufacturer, which should also include: profile and concentration of
impurities and identity. The impurities may come of the same process of manufacturing or well of the process of
degradation of the drug or them intermediate.
11.10 Profile of intermediates and impurities of the drug should be compared on a regular basis against data
historical or them profiles established in the record of the drug, with the purpose of detect changes in the process
of manufacture, equipment or supplies used in its manufacturing.
11.11 If the specification of the drug include a microbiological control, you must set limits of action for the
total microbial count, pathogenic microorganisms or endotoxins.
11.12 Must exist a procedure that indicates the actions to follow in the case of results analytical outside
specifications.
11.12.1 The same analysis of a sample when one of the results is out should not be repeated specification
and can either be average when one of them is out of specification.
11.12.2 The procedure for analytical out of specification results must consider at least the Next:
11.12.2.1 Verification of the results to rule out analytical errors clearly identified, this research should be
documented and reported.
11.12.2.2 If an analytical error is discarded must be justified as part of the investigation.
11.12.2.2.1 You must start an investigation that involves all areas related to the manufacture product, and
establish a plan of testing considerandor repetitions of sampling or reanalysis of the sample to confirm the result.
11.12.2.3 You must set the evaluation and interpretation of the results, considering all findings from the
research, re-evaluation or re-muestreos to determine the acceptance or rejection of the researched lot.
11.13 The research and conclusions from those results analytical out of specification should be approved by
the responsible health.
11.14 The samples taken must have an identification indicating at least: name, number batch, date of
sampling, storage conditions and the containers of which have been taken samples.
 11.15 The solutions reagent, solutions pattern and means of cultivation must be prepared according to a
procedure, the FEUM and supplements existing. A date must be set usage limit for these solutions when you
apply.

11.16 The date of expiration of the reagents, solutions pattern and culture media should be stated on the
label along with the storage conditions. For volumetric solutions should be indicate the date of valuation, real
concentration and indicate the person who prepared it.
11.17 Primary and secondary reference substances should be dated, stored, handled and used so that their
quality is not affected. Is must register the origin, lot, identification, any information relative to their preparation
and characterization, the date in that is used and your life useful.
11.17.1 For controlled substances, these should be recorded in the book of authorized control by the
Secretariat.
11.18 Primary patterns or primary reference substances may be used without being scanned if they
are obtained from a recognized national or international provider.
11.19 You can get a substance of reference primary or pattern primary, when not is has of a pattern
recognized officially, in this case it must characterize this substance and determine clearly the identity and purity
of this.
11.20 The substance of reference secondary or patterns side can determine is starting from a pattern
primary, each pattern secondary must evaluate is periodically according to a procedure for ensure their correct
use.
11.21 Records of the results of the tests shall include at least the following data:
11.21.1 Name of the product, presentation and where applicable concentration.
11.21.2 Lot number.
11.21.3 Name of the manufacturer or provider.
11.21.4 Specifications and analytical methods references.
11.21.5 Results of the tests, including observations, calculations, printed outputs of teams.
11.21.6 The date of testing.
11.21.7 Testing is performed by that person or people.
11.21.8 The person or persons who supervised the tests and calculations.
11.22 Them certificates of analysis of those drugs must contain at least:
11.22.1 The name of the drug or product intermediate when apply, the grade, batch, date of release, date of
expiry or reanalysis and analytical tests carried out in accordance with methods or the FEUM internal,
acceptance limits, results and references used.
11.22.2 Certificates of analysis of the manufacturer should include, name, address of the plant,
telephone, release date, date of issue and be signed by the responsible health or its equivalent in the stranger.
11.22.3 If the analysis is performed by an establishment other than the manufacturer, this should also include
the name, address and phone of the latter.
11.22.4 When the testing is carried out by an authorized, external laboratory the certificate of analysis should
include also the reference of the certificate of analysis issued by the laboratory external.
11.23 The release of each batch of the drug by the responsible health or person must be Authorized a
procedure-based.
11.24 All process control tests must be carried out according to the methods approved by the quality unit.
11.25 The stability, according to the NOM-073-SSA1-2005, stability studies should be dad drugs and drugs.
11,26 Dates of expiry or reanalysis of drugs and intermediates should be established based on stability
studies.
11.27 Preliminary revocation or reparse dates can be based on studies with lots pilot, however must be
confirmed with studies of stability batches industrial scale.
11.28 There should be procedures for the cleaning, maintenance and operation of each of the instruments
and equipment of analytical laboratory with corresponding records.
 11.29 An impurity profile describing the identified impurities should be established as well as also the
unidentified present in a typical batch obtained by a controlled manufacturing process under conditions
validated. The impurity profile should include the identity or any analytical designation qualitative (e.g., retention
time), each impurity observed range and classification of each identified impurity (e.g., inorganic, organic,
solvent). The profile of impurities depends on of the process of production and the origin of the drug. When this
is not required, must be scientific justified.
12. removal of product from the market
12.1.1 A procedure for removal of the product from the market, indicating what must be set cases will take
this decision and its justification. This procedure should involve the distributors of the drugs and clearly define
the responsibilities of the manufacturer and Distributor.
12.1.2 The responsible health must appoint the person responsible for managing the process of
withdrawal product from the market.
12.1.3 The Secretariat should be informed the decision to withdraw a product from the market, the
report should contain:
12.1.3.1 The name of the drug.
12.1.3.2 Lot or lots involved.
12.1.3.3 Reason.
12.1.3.4 Amounts.
12.1.3.5 Distributors and manufacturers of drugs involved and distribution dates.
12.1.3.6 Site of concentration of the product withdrawn.
12.1.3.7 Final disposal.
12.1.4 When the reason for removal of the product from the market represent a risk to the health of the
population, immediate contact with the Secretariat to determine the scope of the withdrawal process must be set
and the leading actions that may include notification to international authorities.
12.1.5 The effectiveness of the process of withdrawal of the product on the market must be evaluated by
means of drills, establishing the frequency of these.
12.2.6 The final report must include a reconciliation between the distributed amount and the amount
recovered, actions that must be taken to prevent recurrence.
13. outsourced activities
13.1 Fundamentals.
13.1.1 Any activity included in this standard that are subcontracted must be defined, agreed and controlled
to prevent inaccuracies that will result in a product or operation of quality unsatisfactory.
13.1.2 You must formalize in an agreement of quality by written between the agent contracting and the
agent contracted to establish clearly the responsibilities of each part.
13.1.3 The system of quality management of the contracting agent must reflect clearly the way in
which responsible for health or person authorizing the release of each batch of product includes the activities
subcontracted responsibility.
13.2 General information
13.2.1 All agreements for activities subcontracted including any modification of type technician or other
arrangements that are proposed must be in accordance with the provisions legal applicable.
13.3 Contracting agent
13.3.1 The contractor's quality management system must include the control and review of any outsourced
activity. The Contracting Party is the ultimate responsible for ensuring that there are established processes to
ensure control of the subcontracted activities. These processes should incorporate the principles of management
risks and include in particular:

13.3.1.1 Prior to the subcontracted activities, the Contracting Party is responsible for evaluating the legality,
suitability and competence of the contracted to carry out successfully the activities subcontracted. The contractor
is also responsible for ensuring the contract that followed the principles and guidelines of this standard.
 13.3.1.2 The contracting must provide to the hired all the information and in your case the
knowledge necessary to perform the operations correctly contracted in accordance with the legal
provisions applicable to the product in question.
13.3.1.3. The contractor should be responsible for the review and evaluation of the generated documentation
and results related to subcontracted activities.
13.4 Contracted agent.
13.4.1 The contract must be able to satisfactorily perform the work commissioned by the contractor, having
adequate facilities, equipment, knowledge, experience and competent staff.
13.4.2 The contract must ensure that all products, materials, and knowledge that are delivered are suitable
for their intended purpose.
13.4.3 The hired not subcontract to a third any part of the work that you have been entrusted with regard to
the contract unless the contracting it has evaluated and approved previously. Agreements concluded between
the contract and any third party shall ensure that information and knowledge, including the assessment of the
suitability of the third, are available in the same way that you are between the original contractor and the contract.
13.4.4 The contract must not make changes without permission beyond the terms of the contract, which can
affect negatively to the quality of the activities subcontracted by the contractor.
13.4.5 The contract will be informed that the outsourced activities, including review of the contract, they may
be subject to inspection by the competent authorities.
13.5 Contract.
13.5.1 The contractor shall keep or have at his disposal, all related records with the activities outsourced,
such as: records of production, analysis and distribution, as well as the samples of reference. Any data important
for evaluate the quality of a product in case of claims or suspected of some defect, or to investigate for suspected
of product counterfeit must be accessible and specified in them procedures relevant of the contracting.
13.5.2 The contract should describe clearly who is responsible for each stage of the activity subcontracted,
such as: knowledge management, transfer of technology and analytical methodology, qualification and
validation, supply chain, subcontracting, quality and materials acquisition, analysis and release of materials,
responsibility for the production and quality control (including controls in process, sampling and analysis),
intermediate product release, shelter records.
13.5.3 The contractor shall keep or have at his disposal, all related records with the activities outsourced,
such as: records of production, analysis and distribution, as well as the samples of reference. Any important data
to assess the quality of the drug claim or suspected defect, or to investigate in the case of suspicion of counterfeit
product must be accessible and specified in the relevant procedures of the contracting.
13.5.4 The contract must allow the contractor audit outsourced activities, by means of the contracted or
subcontracted by mutual agreement.
13.6 Outsourced services.
13.6.1 All contractors for production services, laboratory analysis, systems services critics and teams that
impact the quality of the product, must be evaluated and qualified as suppliers.
13.6.2 Must be a procedure that describes the criteria to evaluate contractors before be approved.
13.7 Services to systems critical and equipment.
13.7.1 Is should evaluate the training academic, training technical and experience of the staff that pay such
services.
13.8 Are not considered as subcontracting or maquila change a drug manufacturing site.

14 destruction and final disposal of waste

14.1 Must have a documentary set in a procedure that ensures the fulfillment of the legal provisions on
ecological and health for the final destination of the waste.
14.2 Must be notified to the competent authorities of the fate of them.
15 distributors
15.1 Distributors of drugs must have accommodation that meets this standard, the FEUM, its supplements
and the applicable legal provisions.
 15.2 Distributors must ensure that he remains the traceability of each batch of the drug and must have at
least the following documentation:
15.2.1 Order of purchase or order in original.
15.2.2 Documents that demonstrate the possession legal of the drug to the freight or transportation.
15.2.3 Original Bill.
15.2.4 Certificate or certificates of analysis original signed by the responsible health or its equivalent in the
stranger.Certificate of analysis should comply as indicated in paragraph 11.25 of this rule.
15.2.5 Certificate of GMP of some agency recognized by COFEPRIS or the issued by COFEPRIS.
15.2.6 Documents of the reception of the drug at its facilities.
15.3 Quality management system.
15.3.1 The distributors must document and implement a system of management of quality according to
the point 5 of this standard, with the reach and data enabling the fulfillment of the BPF and ensure the quality
and purity of drugs.
15.4 Storage and relabelling.
15.4.1 Storage of drugs should be as described in section 10.7 of this standard.
15.4.2 Is must count with a system documented for the relabelling that set those controls necessary to ensure
the compliance of the BPF and that avoid confusion, mixtures, losses of identity or purity and any deviation that
impact the quality of the drug.
15.4.3 If the establishment carries out the transfer of the product received must be materials used are of the
same characteristics of the original container from the manufacturer.
15.4.4 If the material in which the transfer is made is different to the original characteristics of
the manufacturer, must have stability in accordance with the legal provisions applicable studies.
15.4.5 Being required for the transfer of drugs having areas according to the normative appendix A of this
norm and authorization of the Secretariat to carry out this activity.
15.5 Distributors should be transferred to its customers all the documentation and information received from
the manufacturer, relating to the quality of the drug.
15.6 Distributor must provide to the customer the original manufacturer's name and numbers of lot delivered.
15.7 The dealer must have legal authorization of OEM marketing of the drug.
15.8 When the distributors not buy the drugs directly to the manufacturers, must ensure the traceability of
the drug and have with the documentation original required in this chapter.
15.9 Drug dealers must have a record of complaints, refunds and withdrawals of product on the market.
15.10 If derived from a complaint, return or removal of product on the market is required to have
greater information or to make it extensive to other batches of the drug, should be a joint investigation with
the manufacturer or even with COFEPRIS.
15.11 Documentation and information collected for a complaint, return or recall you should take shelter by
the dealer and must include any response from the original manufacturer.
15.12 Distributors must comply with the relevant part of section 12 of this rule for the removal of product from
the market.
15.13 Returns should be treated as described in section 5.8 of this standard.

16. manufacturing of drugs for use in studies clinical

16.1 The manufacturing of drugs for use in clinical studies investigational requirements requires differentiated
in compliance with GMP due in good measure to various factors such as may be limited information about: its
activity and toxicity, limited manufacturing operations control, lack of validation of the manufacturing process and
primary packaging materials still in test.
16.2 These factors are not however limitations to ensure that drugs used in research clinic comply with GMP
and have the characteristics of quality expected.
16.3 This section describes the different requirements that must be observed in making drug for clinical use.
16.3.1 The already existing for use in clinical trials drugs hold a. n full compliance of this standard.
16.4 Quality control.
 16.4.1 Since the process of manufacturing can not be validated, the control of quality is relevant to ensure
that each batch of product in research complies with the specifications established.
16.4.2 You must set the responsibilities of quality control to evaluate the inputs used in the manufacture of a
drug under investigation to ensure that they are appropriate and comply with the features of quality expected.
16.4.3 Can exist a unit of quality specific to those products in research.
16.4.4 The inputs used for the manufacture of drugs in research for use in studies clinical, can be fully
analyzed or performed only the trial of identity to use.
16.4.5 In those cases in that is determine the use of an input with the acceptance of the certificate of
quality manufacturer must document and justify this use.
16.4.6 Samples of retention of investigational drugs manufactured in quantity should be stored such that the
same quality can be checked.
16.4.7 These samples should be kept under conditions which ensure its integrity and at least two years after
it concluded the study clinical in that was used.
16.4.8 Is should set period of revocation or of reanalysis for drugs known; for drugs new used at primary
stages of trials clinical is to ensure their quality characteristics during the time of the study.
16.4.9 Laboratory controls.
16.4.9.1 Them methods analytical developed to evaluate a lot of drug for those trials clinical may not be
validated, provided scientifically warranted.
16.5 Documentation.
16.5.1 Within the quality system established policies and guidelines that should be considered apply to the
drugs in research, with the aim that applied the basic principles of GMP.
16.5.2 You must set specifications, instructions and order of production for inputs and drug, however these
may change during the development of the product so you should ensure these changes are documented and
are available in the history of the product.
16.5.3 Should be clear instructions for each stage of production, packaging and conditioning.
16.5.4 Must have a record of the drug that must be updated, ensuring the traceability of them records earlier.
16.5.5 The record of the drug should include specifications, reference to those methods analytical used,
production, packing and packaging, process, control instructions tags approved, results of stability, conditions of
storage and distribution records.
16.5.6 The record must be kept at least five years since the trial concluded in which was used the product.
16.6 Staff.
16.6.1 There must be a person in charge of production and a manager of quality which are not dependent
on one of theother.

16.6.2 Staff involved in the production and control of investigational drugs must be the experience necessary
for the management of the drug undergoing research and be familiar with the principles of the BPF.
16.7 Facilities and equipment.
16.7.1 The manufacture of drugs in high risk or high power research shall be subject to the conditions
authorized in health license.
16.7.2 Equipment and instruments must be included in programs of maintenance,
calibration and qualification.
16.7.3 The equipment used in pilot scale manufacturing must be clean and must be suitable to the operations
to be carried out.
16.7.4 The procedures of use of them equipment and areas should ensure that not there is risk for
the personal that the uses and does not represent a source of contamination or pollution cross for the product to
manufacture.
16.8 Production.
 16.8.1 Specific instructions for the production of these drugs should be established. These instructions will
have information about the assorted production, equipment, facilities, supplies operations, controls and scientific
observations recorded during production.
16.8.2 Expected yields may vary and shall not be required to justify research the yields.
16.9 Validation.
16.9.1 It must validate the production process when being manufactured for commercial lots.
16.9.2 Validation of processes for the manufacture of drugs for use in clinical trials typically does not
apply. The combination of controls, calibration and, in its case, the qualification of the equipment ensures the
quality of the drug during this phase of development.
16.10 Release of investigational products.
16.10.1 There must be a system for the release of each batch manufactured from an investigational
drug based on the review of record manufacture, process, deviations or non-conformances controls.
16.10.2 The opinion of release must be endorsed by a qualified person.
16.10.3 The results out of specifications and deviations or non-conformances during manufacturing should
be investigated.
16.11 Packaging, labelling and distribution.
16.11.1 Drugs in research for use in clinical trials should be packaged for protect them from disturbance,
pollution, and damage during storage and shipping.
16.11.2 Must have procedures or instructions for the control of packaging, labeling, and the distribution
operations.
16.11.3 The label of the drug must indicate that is is of material in research.
16.12 Removal of product.
16.12.1 There should be a procedure for removal of the product in research for clinical use describes the
responsibilities of all members of the supply to the unit chain that you are using the drug, this must include the
manufacturer, to the sponsor, the investigator, the clinical monitor and the head of the unit of research.
16.12.2 The manufacturer and the sponsor should ensure that all those involved are trained in this procedure.
17. consistent with international and Mexican regulations
This standard is partially equivalent to the standard international:
17.1 EudraLex. Volume 4, Good manufacturing practice (GMP) Guidelines, Part II, Basic Requirements
for Active Substances used as Starting Materials. February 2010.
17.2 Pharmaceutical Inspection Convention/Pharmaceutical Inspection co-operation
Scheme. Explanatory notes for Pharmaceutical Manufacturers on the Preparation of a Site Master File. January
2011.

17.3 U.S. Foods and Drug Administration. Guidance for Industry Process Validation: General Principles and
Practices.Washington, January 2011.
17.4 ICH Q7 Good Manufacturing Practice Guidance for Active Pharmaceutical
Ingredients (November 2000).
17.5 ICH Q9: Quality Risk Management (November 2005).
17.6 ICH Q10: Pharmaceutical Quality System (June 2008).
17.7 U.S. Foods and Drug Administration. Guidance for Industry Investigating Out-of-Specification
(OOS) Test Results for Pharmaceutical Production. Washington, October 2006.
 18 bibliography
18.1 General health law.
18.2 Federal law on metrology and standardisation.
18.3 General Law of ecological balance and the protection of the environment.
18.4 Regulation of inputs for the health.
18.5 Regulation of the law Federal on metrology and standardisation.
18.6 Regulation of the Federal Commission for protection against health risks.
18.7 Pharmacopoeia of the United States Mexican, 11a. Ed. Mexico (2014).
18.8 ISO 9000:2005 Quality management systems-Fundamentals and vocabulary.
18.9 ISO 9001:2008 Quality management systems-Requirements.
18.10 ISO 9004:2009 Managing for the sustained success of an organization-A
quality management approach.
18.11 ISO 14644-1:1999. Cleanrooms and associated controlled environments - Part 1: Classification of air
cleanliness.
18.12 ISO 14644-2:2000. Cleanrooms and associated controlled environments-Part 2: Specifications
for testing and monitoring to prove continued compliance with ISO 14644-1.
18.13 ISO 14644-3:2005. Cleanrooms and associated controlled environments - Part 3: Test methods.
18.14 ISO 14644-4:2001. Cleanrooms and associated controlled environments - Part 4: Design, construction
and start up.
18.15 ISO 14644-5:2004 . Cleanrooms and associated controlled environments - Part 5: Operations.
18.16 ISPE. GAMP 5, A Risk-Based Approach to Compliant GxP Computerized Systems. 2008.
18.17 National College of pharmaceutical chemical biologists Mexico. The method validation
guide analytical. CNQFBM, 2002.
18.18 James Agalloco, Frederick J. Carleton . Validation of Pharmaceutical Process; 3th
edition. Reports Healthcare, 2008.
19 enforcement
The monitoring of the compliance of the present standard corresponds to the Secretariat of health and to
them Governments of the federative entities in the field of their respective competencies.
20 entry into force
This Regulation shall enter into force 180 days after its publication in the official journal natural of
the Federation.
TRANSIENT
Unique. The present standard gate to the standard official Mexican NOM-164-SSA1-2013, good practices of
manufacture for drugs, posted in the daily official of the Federation the 25 of June of 2013.
Mexico, D.F., January 4, 2016. - The Federal Commissioner for protection against Health risks and Chairman
of the Advisory Committee National standardization of regulation and health promotion, Mikel Arriola Pealosa
Andoni.-rubric.
20.1 normative appendix. Manufacturing areas.
Maximum allowable particle
number h Viable particles b
total / m 3: Differenti Air
Temperat
al chang
Classificati Static ure
Examples of processes to pressure es Clothing
on conditions g/ Frequency Frequency and
and per
dynamic of (UFC) of humidity
air flow hour i
0.5 5 monitoring monitoring
m m
CONTINUO >15 Pa
Jumpsuit,
US / with
CONTINUO < 1/plate b.1 hood,
Throughout respect to
US / 18 c to 25 go or pape
Class A 3 520 < 1 3 b.2 the adjacent
Packaging/filling of 20 / Throughout C rs, shoe
(ISO class / 3 < 1/plate b.3 recommend rooms, n.a.
principles sterile asset. 20 the 30 to 65% covers and
5) 520 < ed service applying
process of RH f gloves,
1/glove b.4 life of the a concept
filling sterile area
process of waterfall
aseptic.
filling c
>15 Pa
with
< 5/plate b.1 respect to
3 520 18 C to 25
29 / < 10/m 3 b.2 Daily / shift non Same as in
/ c / 3 20 to C
Class B ISO - 5 class environment 2 < 5/plate b.3 of aseptic ISO-class
352 months e 50 30 to 65%
900 < production areas, 5
000 RH
5/glove b.4 applying
a concept
waterfall
c / 6 months Uniform
to plant
<
exception of clean;
Mixed, homogenized ofprinciple 50/plate b.1
352 2 filling of 18 c to 25 hair, hair
Class C s assets that will besterile. solutions < facial and
000 / 900 / 100/m 3 b.2 20 to C
(ISO-class Extraction, purification of with Weekly > 10 Pa body
3 520 29 < 2 5/plate b 50 30 to 65%
7) drug obtained from sterilization covered,
000 000 .3 RH
cropscell/fermentation. Terminal surgical
which is face
make c/3(a)) masks and
months d gloves
> 5 Pa
Negative
pressure
where
generate Uniform
d are plant
<
powders
100/plate b. clean;
with hair, hair
Quarters of insulators. 1 18 c to 25
Class D regard to
3 520 29 < facial and
Mixed, homogenized ,packagin adjacent 10 to C
(ISO-class 000 / 000 / c / 6 months 200/m 3 b.2 Monthly body
g/filling of principles assets non- rooms 20 30 to 65%
8) n.a. n.a. < 50 /Placa covered,
sterile and RH surgical
b.3 positive face
with masks and
regard gloves
where are
not
generate
d
powders
Positive
pressure Uniform
35
293 with plant
200 18 c to 25
ISO-class 9 ISO - 8 class environment. 000 / Annually n.a. Annually with n.a. clean;
000 / C
n.a. respect to covered
n.a.
areas not hair.
classified.
NOTES:
to Examples listed here are guidance but not limited.
b The microbiological monitoring should be performed using the following methods:
b.1 Plate sedimentation of 90 mm in diameter, with not less than 30 minutes and not more than 4 hours exposure.
b.2 Air sampling.
b.3 Contact 55 mm diameter plate.
b.4 5-finger gloves sampling.
c Unidirectional flow area must comply with parameter of 0.45 flow velocity m/s 20%.
d Can make it with less frequency according to the maintenance of the State validated.
e May be made unless in ISO class 8, provided they support with validation studies.
f The rooms ISO class 5 classification must comply with these parameters, does not apply to one-way flow modules.
g The limits of particles given in the table for static condition can be reached after a short period of 15 to 20 minutes after cleaning to conclude the operation without
operators.
h Sample sizes taken for purposes of monitoring are given depending on the used sampling system and not necessarily the volume of sample of monitoring will
be the same as the amount of air taken during the formal classification of the quarter.
i This parameter can be an indicator of the appropriate design of the system, therefore if there is no compliance to the range established in the table, you
must investigated and carried out the technical justification that evidence that failures inherent in the design of areas there are no.

20.2 Appendix B normative. Review annual of the product.

Review annual of the product

Product name

International Nonproprietary name Concentration:

Review of the period of: Up to:

Total revised batches:

Approved

Approved deviation

Rejected

Total:

Total batches (export / national):

Review of documentation Performed by: Date:

Route of synthesis Information: Changes in the process.

Review of specification of the product Information: Changes to the specifications and analytical methods of the product.

Review of the history of additives /primary Information: review the history of inputs involved in the manufacturing of the batches of the RAP,
packaging material including changes in manufacturers, specification changes and analytical methods cross
references, reports and programs.

Review of the quality management system Performed by: Date:

Deviations or nonconforming product Information: Include cross references, reports and research of associated fault and layer.

Analytical results outside of specification Information: Include cross references, reports and associated fault research.
(OOS) / results analytical out trend (OOT)
 Review of the process data Performed by: Date:

Critical parameters Information: Review of process controls, including amendments.

Maintenance of the status validated Performed by: Date:

Validation of process Information: Review of status of the validation process, include verifications.

Validation of analytical methods Information: Review of status of the validation of analytical methods, including renewals.

Critical systems Information: Description and review of the validated state.

Review of samples of retention Performed by: Date:

Information: not there are observations adverse on a sample representative based in an

inspection visual.

<

Review of stability Performed by: Date:

Information: the product consistently meets the specification over the period expiration. Refer it
to the review of stability for the analysis of trends

Activities subcontracted analytical and process Performed by: Date:

of manufacturing

Actions arising from the review of the previous rap Performed by: Date:

Conclusion of the RAP Performed by: Date:

Information:

Actions related to the findings of the RAP Performed by: Date:

Overview of the annual product review

Performed by: Date:

Approved by: Date: