From Good to Great in GMP

Compliance

Conducting GMP Audits Effectively

Auditors Qualification Course Part I – Self-

Inspection Systems
“It is not enough to do your best; you must know what
to do, and THEN do your best.”
W. Edwards Deming
 Programme GOALS

Part – I Self-inspection Part – II Auditing

Systems essentials
Part – III Getting skin deep Part – IV The Mechanics
into the systems of operation

Discussions, experience
sharing and Q & A ongoing !
2
 What is an audit ?

A planned and systematic

examination and check of a
system,
procedure or
operation
in order to monitor compliance with
and the effectiveness of established
standards and to allow for
improvement and corrective
measures where required.
 Understanding audits....

A systematic investigation of the intent,

implementation, and effectiveness of
selected aspects of systems of an
organization or department / function.
It is a formal activity , carried out against
audit criteria to independently examine
objective evidence ( collection of facts )
and verify compliance with specified
requirements ( for management
notification ).
 Understanding terms

Systematic = Not random but usually planned and scheduled

Independent = Auditors mostly independent of the area audited.
Documented = Written procedure and recorded findings.
Evidence = Objective evidence.
Evaluating it objectively = Comparing evidence with the audit
criteria using facts rather than perceptions, opinions and
feelings.
Audit criteria = Grading the audit and observations according to
audit type.
Fulfilled = getting the desired results
 New approach per PQS

• A systematic independent examination of a

manufacturer‟s quality system that is performed
at defined intervals and at sufficient frequency to
determine whether both quality system activities
comply with quality system procedures are
implemented effectively and that these
procedures are suitable to achieve quality
system objectives.
 Self-inspection

• A systematic independent and

documented process performed
by internal staff (or by
subcontracted third party
auditors) for obtaining evidence
and evaluating it objectively, to
determine the effectiveness and
applicability of the required
quality assurance system within
the company
 Meaning….

• It is a documented, systemic tool used by

management and done periodically by
independent, qualified people to verify and
evaluate an organisation‟s use of the
principles of good manufacturing practices
and compliance to applicable GMP
regulations
GMP Risk Based
Inspection process

An objective inspection planning

process that allows the relative
risk of sites to be determined and
a suitable re-inspection period set
to ensure proportionate
surveillance.
 Regulatory Requirements

All regulations / guidelines specify this

requirement ……
There is a procedure for self- inspection and / or
quality audit that regularly appraises the
effectiveness and applicability of the quality
assurance system;
Product Quality Reviews: There should be
management procedures for the ongoing
management and review of corrective and
preventative actions and “the effectiveness of
these procedures verified during self-inspection.”
 Audit types

Audit Type Aspect Auditor

Internal First Party Self inspection by the team of the
organisation on itself

External Second party Conducted by supplier / customer

Independent Third party Independent of the organisation
External conducted by a private agency /
firm
Regulatory GMP / Regulatory Conducted by inspectors from
External Inspections regulatory agencies
 Audit Types and details

Internal Audits
Specific against company
standards and Government
Regulations
Auditors may ( team ) or may not
be directly responsible to the
auditing area
Focus on state of control
Objective is „improvement‟
 Why Internal Audits

Audits aim to establish, by unbiased

means, factual information on some
aspect of performance.
Audits are performed as a safeguard
against a deterioration in standards.
Audits are performed to establish
facts rather than faults.
 Understanding Internal
Audits....

An internal audit is a periodic examination of the Quality

Management System (QMS) conducted by an internal team
or a third party to ensure that an organization‟s concepts,
principles, and procedures are properly maintained.
Internal audit more often is done by in-house personnel.
What, then, is an ,outsourced internal audit?,
Outsourcing is often sought when there are shortages of
skilled staff, or there is a need to improve upon the
processes that an organization is currently using.
 Outsourced Audits....

Outsourcing the internal auditing – the benefits

Allows for an exchange of information,
The external auditor can focus completely on the
task at hand.
Trained professionals within a company deal
with multiple job requirements - often leading to
an inability to put the auditing functions first.
More cost-effective.
 Audit Types and details

External Audits
Regulatory agencies
Other Companies
Specific against GMP and
regulatory compliance
Focus on Consistency
Objective is Consistent Quality
Standards
 Why External audits

• The Three Voices

VOICE of Customer
VOICE of Business
VOICE of the Best
 Audit Styles

Vertical – audit of several

systems in one department
Horizontal – audit of one
system spread across several
departments
 Audit reasons

Start-up : To review adequacy of new facilities or manufacturing

process to full scale production.
Here we provide feedback to the senior management on quality issues
Follow-up : To assess and maintain progress with implementation
actions.
Here we prevent quality failures based on data review
Routine : To monitor and maintain an adequate level of GMP
compliance.
Here we review weak points in advance
For cause : Investigation of specific quality failures or deviations or
for preparation of regulatory inspections.
Here we identify unsatisfactory trends
 In Summary

An audit collects information

about current practice and
analyses the information
according to stated /
expected / required practice.
Audits, like errors, should be
seen as „improvement
opportunities‟ and
encouraged not feared
 Audit Process Management

Tracking
Reports
Audit Planning
Audit Resolution
Define Audit Process
Standards Action Plans

Develop Notify Perform Audit Follow Up

Criteria Management Audits Findings

Set Audit Implement

Schedule

Review Write Up Audit Wrap Up

Procedures / Audit Meeting /
Observe Findings Present
Practices Findings
 GMP - product of
management and operator
behavior

Management Behaviors /
Techniques

Top-Down Analysis
Bottom-Up Analysis

Operator Behaviors
 Drawback

Audits
are
samples
SYSTEM OF INTERNAL
AUDITS
 Internal Audits / Self-
inspections .... the
requirements

Establish a comprehensive SOP

Designate an audit team
Train the audit team
Design an audit checklist
Let the process be meaningful
 Internal Audits /
Self-inspections ....
the requirements

Conduct audits at predetermined

frequency
Establish audit scheduling
Use balanced reporting
Assure confidentiality of reports
Plan for action and target date of
completion
 The SOP....

Objective
Scope
Frequency and time frames
Responsibilities
Evaluation Criteria
Reporting and record retention
Management notification and review
Corrective action policies / schedules
Procedural deviations
 The Scope of self-inspection

Pharmaceutical Quality Systems

Personnel
Premises
Equipment
Documentation
Sanitation and Hygiene
 The Scope of self-inspection

Production and state of control

Lab controls
Good distribution practices
Validation and revalidation programmes
Vendors and suppliers
Outsourced activities
Results of previous self-inspections and any
corrective steps taken.
 The purpose of self-
inspection

Monitoring GMP implementation

Assessing effectiveness of GMP
Detection of shortcomings in GMP
implementation
Recommending necessary corrective
action
Allowance for improvement
Ensuring regulatory compliance
Maintaining the GMP continuum
 The frequency of self-inspection

Generally annual
Based upon previous audit findings
Indication of problems
Repeated rejects
Repeated market complaints
Recalls
Product Quality Reviews
Before inspections of regulatory
agencies
 A different approach

Aspect Tier One Tier Two Tier Three

Auditors Staff of a section or Local Quality assurance Corporate Compliance
department of company Group Group and External
resource
Objective Of Short duration with Of longer duration with More focus on
Focus on house more focus on systems sustainable compliance
keeping and than housekeeping and initiatives and
documentation documentation assessment of readiness
for regulatory inspection
Frequency More Less than Tier one Less than Tier two
Qualification Education, Experience, Formally trained and Trained and experienced
training and training in qualified auditors or SME s with knowledge
Basic auditing skills and experience in GMP
auditing
Goal Immediate Correction Improve Systems Confirm Compliance
AUDITING TOOLS
 Checklist : advantages and
disadvantages

Advantages Disadvantages
Keeps proper track Inconsistent interpretation
Keeps the auditor Variable outcomes
focussed Not a substitute for
Helps the auditor in being planning
systematic Could be intimidating for
Could serve as a the auditees or outdated
compliance and ( overwhelmed by actions )
educational tool Documents non-
Objective as prepared in compliances without
advance solutions
Quick and simple
 For instance :A checklist
on self-inspection itself !

Are written procedures available : Y/N/NA

Are they current : Y/N/NA
Is self-inspection conducted at regular intervals : Y/N/NA
Is a team for self-inspection designated and trained : Y/N/NA
Do inspections cover all the aspects of GMP
compliance : Y/N/NA
Is follow-up action recorded : Y/N/NA

Remarks : ___________________________
 Checklists – How to
Use Them

Follow : Flexibility vs. rigidity works and pays !

Preferred use is during preparation stage
Use to collect information and chart progress
Preparation for the exit meeting
Preparation of the report
During follow-up
REMEMBER – offers guideline on questioning but
not on what is an acceptable answer
 Plan for the Audit:

REMEMBER - A successful audit does

not just happen; it is planned.
There are four points to keep in mind
when planning for the audit:
Determine the scope of the audit
Gather and review the
documentation needed for the audit
Prepare the audit time schedule
Notify the people to be audited
 Plan for the Audit:

To prepare the department(s)/ functions/

people that will be audited, the auditor
should make sure they understand the …
Scope of the audit
Date(s) of the audit
Audit time schedule
Requirements and requests of the
auditor (i.e., key personnel needed,
access to records, etc...)
 Plan for the Audit:

Audit is 90%preparation
No plan = waste of time
More no of auditors = attention to
details
Nothing is readily available , so

SEARCH
 The Meeting approach

FOR AGAINST
Effectively used by some Requires training of
firms specialists to act as
High quality output through chairperson/ interpreter
participation of variety of
competent individuals Resource intensive
Consistent interpretation
Requires more planning
when led by specialists
and co-ordination
Immediate and effective
communication of gap Progress appears to be
Immediate assignment of slower
actions
Immediate cost / benefit HAYWIRE
evaluation
 Some concerns …..

GMP upgradation ? Not an immediate goal

Gap between deficiencies identified by the self-
inspection team and regulatory inspectors / customer
auditors
Too generic self-inspection plans – could be used
anywhere
Very few GMP observations on the self-inspection
systems in recent years
 Some concerns …..

Direct GMP guidance on self-inspection / audit

types (e.g. horizontal, vertical, systems-based,
process-based, department-based ) not available
No consideration given to process or system
complexity
No structured risk-based approach
 Some concerns …..

Certain areas that would be important to self-inspect are not

mentioned in regulations and guidelines :
Deviations Management
Change Control
Batch Release activities and arrangements
Arrangements in place with external Reg. Affairs for
ensuring MA-compliance e.g. communicating variation
and manufacturing commitments
Good storage practices
Qualification of Contract Labs and Manufacturers
 Self – Inspection and Value
addition

A critical review of the self-inspection system itself!

Self-inspections are performed in the right areas, at the right
intervals and by the right people
Deficiencies identified during regulatory inspections can also
be identified by the self-inspection team
Issues that can lead to batch recalls and the cessation of
batch release can also be identified
Opportunities for continuous improvement are identified
during self-inspections, and can be realised thereafter
 GOOD END

GOOD
Science +
Systems +
Documentation +
People
= GOOD Results