A Seminar On Quality Audit

M.Pharm (Quality assurance)

Prepared by :-
Paras Shah
Guided By :-
Mr. Dhaval Rathod
 Contents
Definition
Objectives
Difference between Quality audit and Periodic
evaluation
Self inspection
Types of Quality Audit
Role OF GMP Audit in QA and QC programmes
Elements of a Systemic Audit program
 1.Quality Audit
Quality Audit

Quality audit is defined as a systematic and

independent examination to determine whether
activities and related results comply with
planned arrangements and whether these
arrangements are implemented effectively and
are suitable to achieve objectives
 Quality audit means a systematic examination of
a quality system.
Quality audits are typically performed at defined
intervals
Any failure in their proper implementation may
be published publicly and may lead to a
revocation of quality certification
 2.Objectives Of Quality Audit
Pharmaceutical manufacturers commonly use
audits as an effective mechanism to verify
compliance with GMP regulation (GMP).GMP
audits with two important goals
Audis are intended to verify that manufacturing and
Control systems are operating under a state of
control.
Audits permit timely correction of potential
problems.
Audits can be used to establish a high degree
of confidence to remain under an adequate
level of control by managements
 3.Difference between Audit and
Periodic Evaluation
Quality audit
Quality audit is Periodic, independent,
and documented examination and
verification of activities, records,
processes, and other elements of a
quality system to determine their
conformity with the requirements of a
quality standard such as GMP
Auditors should not have direct
responsibilities for the operations
they review
Audit is the function of Quality
assurance
Periodic Evaluation
Periodic evaluations are routine
reviews and assessments of the
quality standards of each drug
product that are made to determine
the need for changes in drug product
specifications or manufacturing or
control procedures
Employees who are directly
responsible for system under review
normally perform periodic evaluations
Periodic evaluation is a function of
Quality control department
Conti.
Conti.

Quality audit Periodic Evaluation

To verify on a regular basis that a Periodic Evaluation determine the

firms procedures and practices are in need for change in product,
conformity with established SOPs and specification or control procedures
applicable GMPs and implement it if necessary

Auditors reviewed Sops, Employee It plays a primary role in Day-to-Day

practices And behavior to see how decision-making process used by QC
well they follow established SOPs unit

Report is prepared by Q.C personnel Quality control management

personnel usually prepared Periodic
evaluations
 4.Self Inspection
Principle:-
To evaluate the manufacturers
Compliance with GMP in all aspects of
production and Quality control.

Designed to detect any shortcomings

in the implementation of GMP and to
recommend the necessary corrective
actions

Performed routinely as well as on

special occasions, e.g. in the case of
 Items of Self inspection

Personnel
Premises including personnel
facilities
Maintenance of buildings and
equipment
Storage of starting materials
and finished products
Equipment
Production and in-process
controls To be Continued
Quality control
Conti.

Documentation
Sanitation and hygiene
Validation and revalidation
programmes
Calibration of instruments or
measurement
systems
Recall procedures
Complaints management
Labels control
Results of previous self-inspections
and any corrective steps Taken
 5.Types Of Quality Audit

The quality audit system mainly classified

in three different categories:

i Internal Audits
ii. External Audits
iii. Regulatory Audits
 i.Internal Audit

Purpose of Internal audit:-

To Ensure that adequate Quality systems are
maintained
To asses compliance with the C-GMPs and firms
standard operating procedure
To achieve consistency between manufacturing
and testing facilities
To identify problems internally and Correct
problems prior to a FDA inspection
 Types Of Internal Audit
Tier One Tier Two Tier Three
Carried out:- Staff of a section Local Quality Corporate
or department of assurance Group Compliance Group
company And External
Consultant

Purpose:- Require Short time Require Longer More focusing for

and Focusing on period and more asses the readiness
house keeping and focus on system of regulatory audit
documentation than housekeeping

Frequency:- More Less Less than tier two

Qualification:- Receive Some More exclusive Highly trained and

basic training training experienced or

specialist with the
expert knowledge
of GMP
Designing of the Internal Audit
System
In a pharmaceutical facility for internal
auditing, you require to check mainly two
things namely
Activities carried out by different departments
Documents maintained by these departments
Implementing the Internal Audit
Program
Constitute a small team of experts

Provide Initial training

Fix Audit schedule (Carried out at least once in Six months)

Report the Audit finding and report given to top management

and Shows corrective actions

Repeat the audit as per preplanned

Schedule
 ii.External Audit
External Audit
Purpose of External Audit:-

Confidence in the partnership arrangement

Ensuring that requirements are understood

Enabling reduction of in-house QC testing of

starting materials

Reducing the risk of failure

Conti.
Conti.

Carried Out by a company on its vendors or sub

contractors

No legal requirement for to conduct audit

External auditors have experience of GMP and as

well as regularly audited by their certification
body
 iii.Regulatory Audit
Purpose of Regulatory audit:-
Networking and confidence-building between
national inspection authorities

Development of quality systems

Work towards global harmonisation of GMP

Conti.
Conti.
Carried out by regulatory bodies such as
MCA(U.K),USFDA(USA) for manufacturing and
supply of pharmaceutical product
Audits may be unannounced
Failure of regulatory audit
withdrawal of a manufacturing or import/export
license
After regulatory audit,a formal report will be
delivered
For MCA:- verbal feedback report is given at
the exit meeting
For USFDA:- Provides Form 483is given at
the exit meeting
 6.Role of GMP Audits in Q.A And
Q.C programmes
What is to be audited:-
Auditors review
SOPs
Employees Pracices and behaviour
Compare master specifications against
compendial and regulatory requirements
Verify the test data and validation testing
Validation test reports are compared against raw
data
Verify Corrective actions taken inreaction to audit
finding Conti
Conti.

Benefitswhich are derived from

Audits are given below:

Assuring GMP compliance

Detecting Potential Problems
Effecting
Programme
improvement
Increasing management
awareness Conti.
 Assuring GMP Compliance

FDA conducts routine inspections of all

pharmaceutical manufacturers to determine if
manufacturing and control procedures conform
to GMPs
FDA investigators make unannounced visits to
the manufacturing facilities to examine facilities
, equipments, personnel and records
 Detecting Potential Problems

GMP audits find objectionmable condition that is

unknown to responsible production , QC ,QA or
mangement personnel.

The auditor will see whether such actions are

frequent or not .From this he can signal other
GMP problems.
 Effecting Programme
Improvements

Changing SOPs
Modifying maufacturing equipment or
procedure
Upgrading equipment or procedure
Improiving emplyee training programme
Developing new or revised documentary system
 Increasing Management
Awareness
For any given audits there are two outcomes,either
problems are found or not
If the problems are found , management takes
an approprioate step to eliminate the problemn
An audit is not finding any objectionable
conditions
Either there were no problems to be found
Auditor failed to detect objectionble
condition that were actuaslly present
 7.Elements of a Systemic Audit
Program
Key Elements
i. Expectations and Philosophies
ii. Audit Formats and Approaches
Checklist format
GMP regulation approach
System analysis methods
iii. Checklist written criteria and Standard
Operating Procedures
iv. Planned periodic frequency for audit
v. Specially trained personnel
vi. Finding Written Audit reports
 i.Expectations and Philosophies

Senior management establishes the fundamental

expectations of audit
Upper level management must establish the
realistic goals and objectives
Use of Formal Written Master Plan approved
by management
 ii.Audit Format And Approaches

Manual GMP audit methods can be divided in

to categories
Checklist format
GMP regulation approach
Systems analysis method
 Checklist Format

Use checklist as GMP audit guides and reporting

finding.

Series of questions or instructions are grouped in to

logical order.

Blocks may be used to record answer and space

may be provided to make comments.

Conti
.
Conti.
Advantages:-

Simple, convenient and easy to use for any

desired subjected area
Knowledgeable personnel may develop
questions and guideline
Questions are in logical order that help
auditor to detect problems
Report can be prepared in a minimum
amount of time.
Conti.
Conti.
Disadvantages:-
Question may be interpreted in more than one
way because of bias or hidden meaning
Solve the devising questions is not easy task
Limited content
The amount and type of questions that are
provided limited .
Not every issue will be covered
Each auditor must apply sound judgment when
evaluating system.
 GMP Regulation Format
The basic elements are derived from the
following subpart of regulations
Subpart B: Organization and personnel
Subpart C: Building and facilities
Subpart D: Equipments
Subpart E: Production and Processing Controls
Subpart F: Production and Packaging control
Subpart H: Holding and Distribution
Subpart I: Lab controls
Subpart J: Records and Reports
Subpart K: Returned and Salvaged drug
 Systemic Potential Problem
Analysis

Likely to Affect the Quality Of the Product

These FDA investigators describe the

organized method for determining of
potential problem
 iii.Written Criteria And SOP
Need to be established defining which audit
data or elements are to be considered in the
assessment of program performance
Formal written SOPs should fully describe the
details for carrying out the various audit functions.
Effective use of written criteria to ensure that
conditions and practices remain under a suitable
state of control
SOPs should establish
The responsibility for audit data review
Personnel responsible for recommendations
Decisions concerning corrective actions.
 iv. Planned Periodic Frequency
Each firm must establish the optimum time interval
between audits based on several important factors
like
Intended purpose
Objectives, scope and depth
Prior history of audit finding.
Two types of visit Can be done depending on
the type of audit:-
Announced Visit
Unannounced Audit
Conti.
Announced Visits:
Advanced notice is given before the audit.
It is not persuasive for two reasons
The employee covers up the problem.
The person makes major adjustment in
their behavior
Benefits :-
Audit efficiency is improved from advance
notification
Necessary records may be organized and
retrieved in the preparation for the audit.
Key personnel become available
Conti.
 Conti.
Unannounced Audits
To view conditions and practices that is normal
or customary (representative) as possible.
For observing employees behavior as well as
observation of equipments and facilities.
Benefits :-
Allows observation of normal condition
and practices
 v. Specially Trained Personnel

The following personnel factors deserve systemic

attention
Defining auditor Qualification

Documentation training skills and Experience.

Selecting audit teams

Maintaining auditor awareness levels

 Defining Auditor Qualification
Selected based
On their knowledge
Experience in manufacturing and QC
principles as well as years of first hand
experience dealing with GMP matters.
Essential auditor skill is aware of
Firms SOPs and Knowledge
Integrated by various departments.
 Documentation Training Skills
And Experience
Two formats
Scientific Principles
Training under chemistry, engineering,
statistical and pharmaceutics
GMP
GMP training may include the cumulative
knowledge from years of experience
This knowledge comes from
Daily activities
Formal training sessions
 Selecting Audit teams
Limitations of Personnel audit
Experience and knowledge, which is
individual.
Emphasize on familiar issues as well as
particular area
Team is required for cover many different
systems and large amount of data.
Composition of team will vary depending upon
the nature and scope of the audit

Conti.
Conti.
Leader is usually a senior auditor who has
extensive knowledge of the firms operations and
exhibit strong leadership qualities.
Team size depends upon

Firm size
Total no of products manufacturing
and control system
Breath and depth of the audit.
The Audit objective
 vi. Reporting Audit Finding
Audit reports should contain complete
details of the program detected.
Corrective action is taken to eliminate
problems and to measure the overall adequacy
of the audit program uses reports.

There are two important reporting phases:-

1) Preliminary reports during the audit
2) Final report to the management

Conti.
Conti.

Preliminary reports during the audit:

1) Benefits can be gained from having dialogues
with employees

2) Finding is communicated with affected

personnel.

3) Discussion may help the employees to learn

why problems happened.

Conti.
Conti.

Final report to the management

Management must review the final reports and
determine what steps need to be taken to eliminate
deficiencies.
Management should sincerely encourage detection of
problems and express appreciation for being able to
improve quality operations.
The audit reports may be shared with manger
supervisor who may discuss finding with
employees.
The workers and supervisory personnel should be
given the opportunity to explain their views and
ideas about the audit findings.
 References

PharmaceuticalDosage forms:Parenteral
medication,Revised and Expanded.Edited by
Kenneth E.Avis,Herbert A.libermann and Leon
Lachmann,Volume 3, Second edition ,
Page no:-363-420

Pharmaceutical Quality group mpnograph no:-5

(revised): Pharmaceutical Auditing ,
IQA2001,ISBN 0906810 68X

Conti
Conti.

Quality asuurance And Quality management in

pharmaceutical Industry By
Y.Anjaneyulu,R.Marayya,Pharma Book syndicate,
Page no:-209-218
Provisional Guideline ON the inspection of the
pharmaceutical manufacturers in: WHO Expert
committee on specification for Pharmaceutical
Preparations:
32ndreport,Geneva,WHO,1992,Annex-2(Who
technical report seried. No:-823)