Presentation Transcript

Slide 1:
PROCESS VALIDATION FERMENTATION PROCESS By: Iti Som (Lecturer)

Validation: Definition :
Validation: Definition Validation is the documented act of proving that any procedure, process, equipment, material, activity or
system actually leads to the expected result.

Validation studies :
Validation studies Analytical test Equipment Facility systems (air, water, steam) Process- manufacturing processes, cleaning,
sterilization, sterile filling, lyophilization) Separate validation for lyophilizer/ lyophilization process cleaning of glassware/
cleaning of facility sterilization process/ sterility test

Validation studies :
Validation studies verify the system under test under the extremes expected during the process to prove that the system remains
in control. Critical equipment and processes are routinely revalidated at appropriate intervals to demonstrate that the process
remains in control.

Type of validation :
Type of validation Prospective pre-planned protocol Concurrent base on data collected during actual performance of a process
already implemented in a manufacturing facility suit manufacturers of long standing, have well-controlled manufacturing process
Retrospective for production for a long time, but has not been validated according to a prospective protocol and concurrent
validation is not realistic option is not generally accepted

Type of validation :
Type of validation Laboratory-and pilot-scale validations some production processes cannot be carried out in production facility
removal of impurities by individual purification steps in process -- not acceptable to bring high levels of unacceptable impurities
(endotoxin, unwanted protein, contaminating bacteria and viruses) spike into process.

Facility systems and equipment: Stage of validation :
Facility systems and equipment: Stage of validation Design qualification (DQ) Installation Qualification (IQ) Operational
Qualification (OQ) Performance Qualification (PQ) Systems and Equipment; PQ=validation

Facility systems and equipment :
Facility systems and equipment Design qualification (DQ) necessary when planning and choosing EQ or systems to ensure that
components selected will have adequate capacity to function for the intended purpose, and will adequately serve the operations or
functions of another piece of EQ or operation.

Facility systems and equipment :
Facility systems and equipment Installation Qualification (IQ) written for critical processing EQ and systems list all the
identification information, location, utility requirements, and any safety features of EQ verify that the item matches the purchase
specifications

Facility systems and equipment :
Facility systems and equipment Operational Qualification (OQ) outlines the information required to provide evidence that all
component of a system or of a piece of EQ operate as specified. should provide a listing of SOPs for operation, maintenance and
calibration define the specification and acceptance criteria include information on EQ or system calibration, pre-operational
activities, routine operations and their acceptance criteria

Facility systems and equipment :
Facility systems and equipment Performance Qualification (PQ) performed after both IQ and OQ have been completed, reviewed
and approved describes the procedures for demonstrating that a system or piece of EQ can consistently perform and meet
required specification under routine operation and, where appropriate, under worst case situations include description of
preliminary procedures required, detailed performance tests to be done, acceptance criteria other supporting EQ used during
qualification have been validated.

Facility systems and equipment :
Facility systems and equipment pH meter, incubator, centrifuge, freezer-IQ,OQ System: air (HVAC), compressed air, pure steam,
raw steam, purified water, WFI, central vacuum-IQ, OQ, PQ EQ: autoclave, oven, lyophilizer, continuous flow centrifuge- IQ,
OQ, PQ

OQ of a fermentor :
OQ of a fermentor Sterile envelope hold test SIP (sterilize in place) Heat distribution tests Power shortage tests Alarm tests
Environmental condition testing Control system Security testing

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Thermostat circulation pump Agitation control loop operation Foam control loop pH control loop operation Aeration control loop
operation Dissolved oxygen control loop operation Feed loop control Temperature control loop operation

Process validation :
Process validation A process is a series of interrelated functions and activities using a variety of specified actions and Equipment
which is designed to produce a defined result.

Process validation studies :
Process validation studies examine a process under normal operating conditions to prove that the process is in control re-
validation modification to the process problems occur EQ or systems are changed

Process validation :
Process validation To validate the reproducibility and consistency of a process full defined process is carried out using validated
EQ at least 3 times, under established procedure process must successfully and consistently meet all acceptance criteria at all
steps throughout the procedure at least 3 times consecutively Validated process Worst case: to ensure that process is acceptable in
the extreme case

Process validation :
Process validation Example cleaning sanitization fumigation depyrogenation sterilization sterile filling fermentation bulk
production purification inactivation filling, capping, sealing lyophilization

Process validation :
Process validation specific process clearly described in Master formula or in SOP all EQ; identity, code number, construction,
operation capacity, actual operating range processing parameter; sufficiently detailed to permit complete reproducibility (time
period, pH, volume, temperature etc.) specification at each step

Process validation :
Process validation Very important specifications for a process undergoing validation be pre-determined all critical processing
parameters for which specifications have been set, there must be equipment to measure all of those parameters during the
validation study

Typical content requirements for process validations :
Typical content requirements for process validations Cleaning, Fumigation, Sanitization Process collecting liquid and swab
samples for testing of residual product Test for residual protein endotoxin tests microbial tests (bioburden) chemical tests
(chlorine and phosphoric acid) residual levels of cleaning agents conductivity tests pH tests As relevant to the cleaning process
All analytical tests must be validated before

Typical content requirements for process validations :
Typical content requirements for process validations Sterilization sterilization filtration of solutions microbial challenge -Filter
integrity tests -Performance tests

Typical content requirements for process validations :
Typical content requirements for process validations Depyrogenation process (dry heat, column chromatography, other)
Validation of - limits of detection Quantitation of endotoxin assay Process performed atleast 3 times endotoxin content reduction
of 3 logs

Typical content requirements for process validations :
Typical content requirements for process validations Sterile filling Tests filling process for maintenance of aseptic condition
perform filling process with nutrient media (supporting bacterial & fungal growth) run at full scale for at least one fill size worst
case; large volume and number of vials

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Validated sterility test Process must be sterile for 3 consecutive runs to be considered validated. media fill performed twice a year
size of run must be large enough to detect low levels of contamination e.g. contamination rate of 1/1000, 3000 units are needed to
provide 95% confidence

Typical content requirements for process validations :
Typical content requirements for process validations Mock fermentation full scale fermentation of a representative fermentation
process to validate the parts of process involving connections, sampling, and additions of nutrients etc. fermentor prepared and
operated in a simulated process with uninoculated nutrient media process must follow the Master formula procedure 3
consecutive runs at each stage

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Production processes (Fermentation, Bulk production, Purification, Filling, Lyophilization) run according to approved Master
formula Including- raw material, personnel, equipment, facility preparations, in-process tests, processing, final testing of the
batch lot.

Slide 28:
all facility systems (water, steam, autoclave, environmental monitoring) must be monitored on prescribed schedule. 3 consecutive
lots must be produced all facility, EQ, support systems, product spec, and process being validated must pass at all steps.

Analytical assay Validation :
Analytical assay Validation

Type of Documentation :
Type of Documentation Validation master plan (VMP) Validation protocol (VP) Validation reports (VR) Standard operating
procedures (SOPs)

Master validation plan (MVP) :
Master validation plan (MVP) is a document pertaining to the whole facility that describes which EQ, systems, methods and
processes will be validated and when they will be validated. provide the format required for each particular validation document
(IQ, OQ, PQ for EQ and systems; process validation, analytical assay validation)

Master validation plan (MVP) :
Master validation plan (MVP) indicate what information is to be contained within each document indicate why and when
revalidations will be performed who will decide what validations will be performed order in which each part of the facility is
validated

Master validation plan (MVP) :
Master validation plan (MVP) IQ,OQ,PQ must be performed in order. indicate how to deal with any deviations state the time
interval permitted between each validation

Validation: MVP :
Validation: MVP Enables overview of entire validation project List items to be validated with planning schedule as its heart like
a map

Validation: In summary, VMP should contain at least :
Validation: In summary, VMP should contain at least Validation policy Organizational structure Summary of facilities, systems,
equipment, processes to be validated Documentation format for protocols and reports Planning and scheduling Change control
Training requirements

Validation: Protocol :
Validation: Protocol Objectives of the validation and qualification study Site of the study Responsible personnel Description of
the equipment SOPs Standards Criteria for the relevant products and processes

Validation: Report :
Validation: Report Title objective of the study Refer to the protocol Details of material Equipment Programmes and cycles use
Details of procedures and test methods

Validation: changes that require revalidation :
Validation: changes that require revalidation Software changes; controllers Site changes; operational changes Change of source
of material Change in the process Significant equipment changes Production area changes Support system changes