Professional Documents
Culture Documents
Vipul Doshi
Warning letter
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10
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Yr 2011
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API API (Sterile) QC Solid Gel Injectables
Regulators Speak through
Regulations
GLP GAMP
Good Laboratory Practices Good Automated
21 CFR Part 58
40 CFR Part 160 ( EPA )
cGMP Manufacturing Practices
GAMP 5(ISPE) Guide
Current Good
Manufacturing Practices
21 CFR Part 211 ( Pharma )
21 CFR Part 820 ( Med devices)
21 CFR Part 110 ( Food )
21 CFR 600 680 Biologics GCP
GALP Good Clinical Practices
21 CFR 312 Sub part
Good Automated Laboratory Practices
EPA Directive 2185 ( 1995 Ed. )
Q1A(R2)
Q1B
Q1C Stability Testing
Q1D
Q1E
ICH Guidelines Q7 Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients
Quality, Efficacy, Safety, CTD / e CTD Q8(R1) Pharmaceutical Development
Q9 Quality Risk Management
Q10 Pharmaceutical Quality System
M4(R3)* Organization of the Common Technical Document for the Registration of
Pharmaceuticals for Human Use
Regulators Speak through
Regulations
GMP guidelines comprise strong recommendation on
Quality Management, Personnel Production, Facility and
Equipment, Documentation and Records, Product and in-
process Control, Packaging and Identification, Labeling,
Storage and Distribution, Laboratory Controls, Validation,
Complaint and Recalls, and Contract Manufacturers.
Schedule
M (1987): Good Manufacturing Practices and
requirements of Premises ,Plant and Equipment for
Pharmaceutical Products were regulated.
Challenges
FDA Today
FDA Today
FDA Today
Pillars of Compliance
Compliance
Man
Materials
Equipments
Environment
Operations R&D QA QC RA
Compliance Approach
Quality Assurance Systems
Analytical Control
Equipment Control
Process Control
Material Control
Supplier Management
Supplier Management
Your vendor qualification has not provided adequate evidence that the
manufacturer can consistently supply raw materials that meet appropriate
quality attributes
You did not specify how you intend to document and implement such audits
Your firm has not conducted at least one specific identity test and has not
established the reliability of the supplier's analyses through appropriate
validation of the supplier's test results at appropriate intervals"
In addition, you failed to appropriately validate your suppliers' test results (as
furnished to you on the suppliers certificates of analysis) at appropriate
intervals
Challenges in Assuring Supply Chain
Quality System Vulnerabilities
Often vendor audits restricted to the evaluation questionnaire and
obtaining TSE/BSE certifications
End Users
Are ultimately responsible for the use of appropriate ingredients and
assuring ingredient quality at every stage of the supply chain
Incoming Material Control
Purchasing important operation
Consignment checks
Integrity of package
Seal intact
Corresponds with the purchase order
Delivery note
Suppliers labels
Whats Involved
Materials
Man Methods
Medium Measurement
Machine
FAT
(To ensure for
functioning as per
Retirement expectation at
manufacturing site)
Usage Evaluation
SAT
(Receive at site
BM
In proper condition)
Breakdown
Maintenance
(Trending)
PQ IQ/OQ
PM Placebo run Qualify equipment
(Preventive Maintenance (Matrix approach to as per SOP
to maintain equipment qualify for
as per functionality) intended use)
Calibration
What ?
A set of operations that establish, under specified conditions, the relationship between the
values of quantities indicated by a measuring instrument or measuring system, or values
represented by a material measure or a reference material, and the corresponding values
realized by its standards.
Why ?
When process measuring instruments age and experience physical stress or temperature
variations, critical performance gradually declines. This is called drift.
The slow variation with time of metro logical characteristics of the measuring instruments.
As a result of this, the measurement results become unreliable and ultimately the production
quality can suffer.
Calibration:
Increases production yields,
Optimizes resources,
Assures consistency and
Ensures measurements (and perhaps products) are compatible with those made
elsewhere.
By making sure that measurements are based on international standards, promote
customer acceptance of the products around the world.
Validation Plan
Maintaining
Validate Status
Document
Evaluation & Risk
Assessment Validation
Report
System
Specification Validation
Documentation
Update
Cleaning Validation
Appropriate and sensitive method to determine low level to meet MACO
New FDA guidance on Process
Validation January 2011
Challenge Action Impact
3 Process Stage 1- Process design: (The Robust manufacturing
Validation: commercial manufacturing process process.
General is defined during this stage based
Principles and on knowledge gained through
Practices WEF: development and scale-up Compliance to the
activities). regulatory requirement.
Jan'11
Stage 2 Process Qualification:
(During this stage, the process
design is evaluated to determine if
the process is capable of
reproducible commercial
manufacturing).
Stage 3 Continued Process
Verification: (Ongoing assurance is
gained during routine production that
the process remains in a state of
control).
Analytical
Good Quality Control Practices-
- Personnel, Premises and Equipment in Laboratories should be
appropriate as per the tasks.
- Laboratory Controls Documentation ,Sampling ,Testing
A management system to assure the quality and integrity
of data underlying a study
Glassware
Controls
Analytical
Current Issues
OOS
Quality by Inspection
Inspect Approve / Reject
Pharmaceutical Quality System
Change
Control
Training
Internal Event
Quality Audit Investigation
Market
CAPA
Complaint
Effective Tools for Compliance
An Integrated Risk
Management Process
(for all phases of the life of the product)
Risk
Culture on Risk
Risk Hazard
Communication
Graph Cause
Implementation of Residual
Training Verify Post
Of
Risk Control Risk Production
Effectiveness
Personnel Measures Monitoring
Road to Compliance
Road to Compliance
When it comes to ensuring drug product quality and ultimately
Consumer/Patient Safety . . . We need to think and act globally!