Professional Documents
Culture Documents
TRAINING COURSE
Darren Freestone
Senior Consultant
SeerPharma (Singapore) Pte,
Ltd
Aug. 1-2, 2012 @ FDA Alabang
ECHO SEMINAR
August 17, 2012
Audit Program
Audit Procedures
Lead Auditors
REFERENCE GUIDELINES
Inspectorates
PIC/S PI 037-1
Companies (Manufacturers)
PIC/S PE 009-9
ICH Q9
ICH Q10
GMP Guideline
Harmonized Tripartite
Guidelines
INSPECTORATE
Two Roles:
1.
Inspectorates meets
requirements of
PIC/S PI 037-1
2. Companies
(Manufacturers) program
meets requirements of
PIC/S PE 009-9
Audits types
GMP Compliance
Specific / focused (e.g. deviation or
customer complaint)
Analyzing process, environmental data
Corporate
Responsibility (1)
Senior Management (Q10)
Provide resources
Provide Authority
Responsibility (2)
Responsibility (3)
Lead Auditor (PIC/S and Q9)
Responsibility (3.1)
Additional
Responsibilities
(outside audits)
Organizing the
logistics
Travel
Accommodation
Liaising with the
Auditee
Working out time
and costs of the
audit
Vendor /
Supplier
Audits
API manufacturers
Sub-contract manufacturers
Contract test laboratories
Excipient suppliers
Warehouse and distribution train cold chain system
Pre-printed (coded) matter suppliers
Component/packaging suppliers
Processing aids providers (filters, resin)
Calibration service providers
Contract research organizations
Software developers
Etc..
Contract Manufacture
Clause 7.5 The Contract giver should ensure that all products and
materials delivered by the Contract acceptor comply with their
specifications or.
Requirements of Vendor /
Supplier Assurance Programs
Vendor / Supplier
Rating Example
Disqualified
New
Approved
Preferred
Certified
Building a
PROFILE
Workshop # 1
Workshop # 2
Using the example Supply Chain Quality
Factors (next slide) and the example
Risk Matrix Vendors/Suppliers
Recommended Actions in your workbook,
complete the 2012 profile for each of the
manufacturers previously identified.
Patient Risk
Factor
5.
4.
3.
2.
1.
Patient Risk
Factor
5.
4.
3.
2.
1.
Patient Risk
Factor
5.
4.
3.
2.
1.
No site assessment
No international GMP audits
International GMP audits
QA reviewed
QA vendor audited > 1 cycle
Workshop #4 Metrics
What metrics could we use for the
schedule?
How do we rate these metrics?
Example.
On-time Audits
1, 2, 3, 4, 5
Missed Audits
5, 4, 3, 2, 1
Closed on Time
1, 2, 3, 4, 5
Internal
Audits
Common Mistake
Manufacturers have the advantage of time.
Should not try to audit everything in one
large auditing session
WHY?
Be specific
For Example..
Quality System Elements (QSEs)
HVAC
Equipment
Personnel and Training
Customer Complaints
Market Authorization
Cleaning / Sanitation
Materials Storage and
Handling
Production Controls
Validation Programs
Laboratory Controls
Computer Systems
Solid Dose
Sterile aseptic filling
Preventive maintenance
Change Control
Purified water
Movement of Personnel
Document Control
CAPA
Product Quality Review
Validation Master Plan
Out of specification
Inwards Good receipt
Release for supply
Stability
Retention samples
management
Control of NCP
Housekeeping
Deviations
Risk Management
Sampling
Supplier Management
Workshop #5
Assume that the following QSEs are
applicable to your manufacturing
operations:
o Inwards Good and Sampling
o Validation
o Training
o Laboratory
o Calibration
o Maintenance
o Release for supply
o Purified water
o Deviations and CAPA
o Process Controls
o Marketing Authorization
Workshop #5 - continued
Refer to:
QSE Quality Risk Factors (next
slide)
Risk Matrix (QSE) Recommended
Actions (workbook)
1.
2.
Category 1
Category 2
Rx/Prescription products
Process not overly complex
Previous assessment satisfactory
Occasional deviation/complaint
Category 3
Facility Control
Direct Impact
Equipment
Personnel /
Training
Quality Systems
Market
Authorization
Cleaning /
Sanitation
Materials /
Supply
Production
Control
Validation
Programs
Laboratory
Controls
Computer
Systems
Compliance
Product
Exposure
Consequenc
es
Assessment
Schedules/Prior
ity
Mgmt
Likelihood
CAPA
Trends / History
Quality Assurance
Area Head
Area Head of audit
team members
c)
d)
Conducting audits
e)
f)
g)
h)
b)
Identifying
operations/objectives and
assessing the risk
Monitoring implementation
of schedule
c)
Escalation of findings
d)
Linkage to CAPA
e)
f)
Assessing / classifying
deficiencies
Monitoring effectiveness of
corrective actions
Establish Competencies of
Team and Lead
Requires review of
effectiveness (performance)
So far.
Vendor and Internal Audits
Pre-requisites in
place:
Company Policies
(Commitment)
SOPs (System)
Competencies
(Resources)
Schedule (Plan)
Internal
Audits
To improve
systems
Compliance Audit
Systems Audit
Document
Deficiencies
Document
Improvement
Standard
Operating
Procedures
Verify
Complian
ce
Practices and
Records
Verify
System
Audit Methodology
Systems and Compliance
A. Systems Audit
Prepare list of required SOPs
Compare SOPs to Regulations, Policies,
Guidelines
Verify system is documented
Has the system
been
deployed
C.
Training
Records
B. Compliance Audit
Choose SOPs of particular interest*
Review related or exhibit records
Verify compliance (evidence) of records to SOPs
*These could be used as checklists
1.
2.
3.
4.
5.
1. Audit
Intent
and
Purpose
2. Audit
Planning
Checklists
Advantages
Disadvantages
2.
3.
4.
5.
6.
7.
8.
9.
Doc
#
Title
and
Reco
rd
Record Review
Title
Engineering Change
Notes
Policy # - Change
Management
Critical
SOP Questions
# xxxx Change
Validation reports
Control
Is there
a documented change control program in place?
Critical Question
Construction and Development
Critical questions should be
probing,
Must be structured around the
audit intent and scope,
Regulatory guidance documents
are useful in developing
questions.
Questions usually begin with Is,
Does, Are, and usually the
following:
Effectiveness or adequacy
The presence / availability or
absence
Responsibilities
Mechanisms
Standards
Example QSE
Purified water (2)
Records
System description
As-built drawings
Specifications of the water, for Conductivity and TOC
Qualification and re-qualification reports and protocols
Trend reviews micro, chemical, conductivity, TOC
SOPs for operation, sanitation, maintenance + training records
SOPs for establishment and monitoring of Alert and Action
Limits
Questions
Workshop #6.1
Refer to your workbook.
Equipment
Sampling
Testing
Workshop #6.2
Refer to your workbook.
1.
2.
3.
4.
5.
By the way, you only have one (1) day to complete the
audit.
3.
Conducti
ng the
Audit
Tips and
Common
Mistakes
Audit Plan
Clipboard
Sharp mind!
Good Humor!
Audit checklist
Calculator
10
Leadership
11
Time Management
Communication
4.
Analyzin
g
Results
and
Preparin
g Audit
Listen to responses
10
5.
RESPON
SE:
Present
Results
Correctiv
e&
Corrective Action
Do the Actions meet the following:
Address the root cause and
contributing factors
Specific
Easily understood and
implemented
Developed by process owners
Measurable (Corrective
Action did in fact occur)
Audit Closure
verified as closed
Pro-active follow-up
Report missed timeliness to
management
Auditing a PRINTER
Generally:
Printers are NOT
required to follow GMP
Printers are NOT
required to have any
Quality certification
Good quality
printers are
Sometimes
hard to find
Generally more
expensive
Auditing a PRINTER
Generally, Printers need
to:
Understand company
requirements
Understand the RISKS
for customers and
company
Be educated / guided /
assisted to implement
the controls needed to
be in place
Auditing a PRINTER
What are the risks:
Death, serious injury
to consumers
Customer complaints
Product recalls
Continuity of supply
Rejected deliveries
Company profits
Auditing a PRINTER
What are the hazards:
Mix-ups with other
products
Mix-ups with different
strength of same product
Wrong version /text
Incorrect counts
Batch variation (Color,
missing text, faded,
illegible)
Auditing a PRINTER
Some points to consider:
Control of Master Plates and specifications
Control of color standards
Version control
Line clearances
Program of Maintenance
Print-run records and in-process checks
Segregation and control of WIP (un-cut
and cut)
Verification of count
Release to customer
Training / competencies
Auditing a PRINTER
IMPORTANT!!!
Dont forget Capability of the process
(variation)
Discuss your critical attributes and
variables
INSPECTORATE
Inspectorate
program meets
requirements of
PI 037-1
Overview: PI 037-1
Intrinsic Risk
(1st page)
A combination of:
sites
Number of different operations on site
Dedication of facility and equipment
Organizational (# staff)
Contract manufacturer or not
Sterile process
Number of unit operations and critical steps
Extent of rework and repackaging
Special storage
Criticality
Manufactures
Intrinsic Risk
(1st page)
After these points are considered:
Rated:
Complexity: 1, 2, or 3
Criticality: 1, 2, or 3
Criticality
Complexity
1 (low)
2 (low)
3 (med)
2 (low)
4 (med)
6 (high)
3 (med)
6 (high)
9 (high)
Intrinsic risk:
Compliance Risk
(1st page)
Simple Rating:
From the most recent inspection:
Low : No critical or major
deficiencies
Medium : 1-5 Major deficiencies
High : 1 or more Critical
deficiencies or more than 5
Major deficiencies
Low
Medium
High
Low
Risk Rating
=A
Risk Rating
=A
Risk Rating
=B
Medium
Risk Rating
=A
Risk Rating
=B
Risk Rating
=C
High
Risk Rating
=B
Risk Rating
=C
Risk Rating
=C
Risk Rating:
A: Reduced frequency, 2 3 years
B: Moderate frequency, 1 2 years
C: Increased frequency, <1 year
Scope of Inspection
Part F of PI 037-1
Recommendations of Lead Auditor for
the next routine inspection:
Focus and depth
Where deficiencies where found
Areas not inspected
Areas inadequately resourced at site
Areas where LA believes a more detailed
inspection is needed for next inspection
Duration
Number of inspectors
Specific expertise