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A Seminar On Quality Audit
M.Pharm (Quality assurance)
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Prepared by :Paras Shah
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Guided By :Mr. Dhaval Rathod
Contents
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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
Periodic Evaluation
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
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
 Audit is the function of Quality
assurance
 Periodic evaluation is a function of
Quality control department
Conti….
Conti….
Quality audit
Periodic Evaluation
 To verify on a regular basis that a
firms procedures and practices are in
conformity with established SOPs and
applicable GMPs
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 Periodic Evaluation determine the
need for change in product,
specification or control procedures
and implement it if necessary
 Auditors reviewed Sops, Employee
practices And behavior to see how
well they follow established SOPs
It plays a primary role in Day-to-Day
decision-making process used by QC
unit
Report is prepared by Q.C personnel
 Quality control management
personnel usually prepared Periodic
evaluations
4.Self Inspection
Principle: To evaluate the manufacturer’s 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 product recalls
or repeated rejections
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.…
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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-GMP’s 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
or department of
company
Local Quality
assurance Group
Corporate
Compliance Group
And External
Consultant
Purpose:-
Require Short time
and Focusing on
house keeping and
documentation
Require Longer
period and more
focus on system
than housekeeping
More focusing for
asses the readiness
of regulatory audit
Frequency:-
More
Less
Less than tier two
Qualification:-
Receive Some
basic training
More exclusive
training
Highly trained and
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
External Audit
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….
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Carried Out by a company on its vendors or sub
contractors
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No legal requirement for to conduct audit
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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 483”is 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….
Benefits which 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
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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
Firm’s 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 firm’s 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….
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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
Pharmaceutical Dosage 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)
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