Why GMP?

 Provides a high level assurance that medicines

are manufactured in a way that ensures their
safety, efficacy and quality
 Medicines are manufactured to comply with their
marketing authorization
 Quality is built in
 Testing is part of GMP, but alone does not
provide a good level of quality assurance
 Why inspect?
 Verify compliance with GMP
 Verify compliance with marketing authorization
 Dossier: "Dedicated equipment is used"
Inspection: Observation that this means
"dedicated while used for the product or not being
used for another product"
 Dossier: "The vials are removed from the
lyophilliser and crimped in a grade A
environment"
Inspection: Correct, but before crimping they are
stored in an uncontrolled corridor
 Guidelines and references
• GMP applies to both Active Pharmaceutical
Ingredients (APIs) and Finished Pharmaceutical
Products (FPPs)
• FPP:
WHO Good Manufacturing Practices for
pharmaceutical products: main principles. WHO
Technical Report Series, No. 908, 2003, Annex 4.
• API:
WHO good manufacturing practices for active
pharmaceutical ingredients - Annex 2, WHO
Technical Report Series 957, 2010 (Based on
ICH Q7)
Other WHO GMP Guidelines
• Pharmaceutical excipients
• Sterile pharmaceutical products
• Biological products
• Pharmaceutical products containing hazardous
substances
• Investigational pharmaceutical products for clinical
trials i
• Herbal medicinal products
• Radiopharmaceutical products
• Water for pharmaceutical use
• HVAC for non-sterile pharmaceutical dosage forms
• Validation
Good Manufacturing Practices (API):
1. Quality assurance
2. Good manufacturing practices for pharmaceutical
products
3. Sanitation and hygiene
4. Qualification and validation
5. Complaints
6. Product recalls
7. Contract production and analysis
• General
• The contract giver
• The contract accepter
• The contract
Good Manufacturing Practices (cont'd)
8. Self-inspection and quality audits
• Items for self-inspection
• Self-inspection team
• Frequency of self-inspection
• Self-inspection report
• Follow-up action
• Quality audit
• Suppliers’ audits and approval
9. Personnel
• General
• Key personnel
10. Training
 Good Manufacturing Practices
(cont'd)
11. Personal hygiene
12. Premises
 General
 Ancillary areas
 Storage areas
 Weighing areas
 Production areas
 Quality control area
13. Equipment
 Good Manufacturing Practices
(cont'd)
14. Materials
 General
 Starting materials
 Packaging materials
 Intermediate and bulk products
 Finished products
 Rejected, recovered, reprocessed and reworked
materials
 Recalled products
 Returned goods
 Reagents and culture media
 Reference standards
 Waste materials
 Miscellaneous
 Good Manufacturing Practices
(cont'd)
15. Documentation
 General
 Documents required:
 Labels

 Testing procedures

 Specifications for starting and packaging materials, for

intermediate and bulk products and for finished
products
 Master formulae and Batch Processing Records

 Packaging instructions and Batch Packaging Records

 Standard Operating procedures (SOP's) and records

 Logbooks
 Good Manufacturing Practices
(cont'd)
16. Good practices in production
 General
 Prevention of cross-contamination and bacterial
contamination during production
 Processing operations
 Packaging operations
17. Good practices in quality control
 Control of starting materials and intermediate,
bulk and finished products
 Test requirements
 Batch record review
 Stability studies
GMP is actually Good Common Sense
Quality Management

Quality Assurance

GMP

Production and Quality Control

 Quality management in the drug
industry
Philosophy and essential elements:
 "The concepts of quality assurance, GMP, quality
control and quality risk management are interrelated
aspects of quality management, and should be the
responsibility of all personnel. ……their relationship
and their fundamental importance to the production
and control of pharmaceutical products."
 Quality Management
 The basic elements are:
 An appropriate infrastructure or “quality system”
encompassing the organization structure, procedures,
processes and resources

 The systematic actions necessary to ensure adequate

confidence that a product (or service) will satisfy given
requirements for “Quality”

The totality of these actions is referred to as “Quality

Assurance”
The five P's
• Premises

• Primary materials

• People

• Procedure
•

•• Processes defined
and recorded
 Quality Assurance
 Quality assurance is a management tool

 In contractual situations, it also serves to generate

confidence in a supplier

 QA, GMP and Quality Control are interrelated

aspects of Quality Management

 They are described on the following slides in order

to emphasize their relationship and their
fundamental importance to the production and
control of pharmaceutical products
Quality Assurance
 Wide-ranging concept
 covers all matters that individually or
collectively influence the quality of a product
 Totality of the arrangements
 to ensure that the drug is continuously of the
right quality for the intended use
 Quality Assurance incorporates GMP
 and also includes product design and
development, with special focus on process
design
The position of QA

Director

QA

Production QC lab Other Depts

 Quality Assurance means to
assure:
 Products are designed and developed correctly
 Complying with, e.g. GMP, GCP, GLP
 Production and control operations are defined
 Managerial responsibilities are defined
 In job descriptions
 The manufacture, supply and use of correct starting
and packaging materials
 Quality Assurance means to assure:
(cont'd)

 Controls are performed, including

intermediates, bulk, calibration and validation
 Correct processing and checking of the
finished product
 Products are sold/supplied only after review by
the authorized person
 Complying with marketing authorization,
production and QC requirements
 Proper storage, distribution and handling
 Quality Assurance means to
assure: (cont'd)
 Procedures for self-inspection and quality audits are
applied
 Deviations are reported, investigated and recorded
 System for change control is applied
 Regular evaluation of product quality to verify
consistency and continued improvement
 Quality Assurance means to
(cont'd)
 Procedures for self-inspection and quality audits are
applied
 Deviations are reported, investigated and recorded
 System for change control is applied
 Regular evaluation of product quality to verify
consistency and continued improvement
Quality Assurance includes:
 Responsibility of the Manufacturer for the quality of
the product
 Fit for intended use
 Comply with marketing authorization
 Safety, efficacy and quality
 Commitment of senior management and
involvement of all staff
 Comprehensively designed and well implemented
quality system
 Full documentation and monitoring of effectiveness
 Competent personnel, sufficient premises,
equipment and facilities
Good Manufacturing Practices
 That part of QA that ensures that products are
consistently produced and controlled
 Quality standards
 Marketing authorization
 Aim: Diminishing risks that cannot be controlled by
testing of product
 Contamination and cross-contamination
 Mix-ups (confusion)
Basic requirements for GMP:
• Clearly defined and systematically reviewed
processes

• Qualification and validation is performed

• Appropriate resources are provided:
• Qualified and trained personnel
• Premises, space, equipment and services
• Materials, containers, labels
• Procedures, storage, transport
• Laboratories and in-process control
 Basic requirements for GMP:
(cont'd)

 Clear, written instructions and procedures

 Trained operators
 Records of actions, deviations and investigations
 Records for manufacture and distribution
 Proper storage and distribution
 Systems for complaints and recalls
 GMP = continuous urge for
improvement
 Involvement of the management
 Annual Product Quality Review
 Quality risk management
 Complaints handling
 Self-inspection
Involvement of the management
• The senior management is responsible to attain
the company's quality objectives
• All different departments and all levels within
departments should be involved; and it's the senior
management who should facilitate this
• Also suppliers and distributors should be involved
• The senior management should make available
the required resources
• The basis of the quality system is the quality
statement and quality policy, by the senior
management
Product Quality Review
Objectives of Product Quality Review:
 To review and verify the consistency and
appropriateness of the existing process
 To identify and highlight any trends in the
process, e.g. in analytical results, yields etc.
 To identify any possible product or process
improvements
Product Quality Review (cont'd)
• Review of starting materials/ packaging
materials, especially from new sources
• Review of in-process control results and finished
product analytical control results
• Amount of batches and packaging units
produced and their yields
• Reviews of:
• Out-of-spec situations, rejections,
deviations, changes
• Plus investigations and analysis of causes
Annual Product Quality Review
(cont'd)
• Review of Marketing Authorization variations
submitted, granted or refused (incl. third
countries)
• Review of stability programme and trends
• Review of adequacy of previous decisions on
changes or improvements or corrective actions
• For new Marketing Authorizations (plus new
variations) a review of post marketing commitment
• The qualification status of all relevant equipment
and utilities (like water, HVAC, gases, etc.)
• Review of Technical Agreements (if applicable)
Complaints handling

Complaints: Principle
“All complaints and other information concerning
potentially defective products must be carefully
reviewed according to written procedures and
corrective action should be taken.”
Complaints Procedure
 Designated responsible person:
 To handle complaint
 Decide on measure to be taken
 May be authorized person - if not, must
advise authorized person of results
 Sufficient support staff
 Access to records
 Written procedure (SOP):
 Describes action to be taken
 Includes need to consider a recall (e.g.
possible product defect)
Complaints Procedure – cont'd
• Thorough investigation:
• QC involved
• With special attention to establish whether
"counterfeiting" may have been the cause
• Fully recorded investigation – reflect all the
details
• Due to product defect (discovered or
suspected):
• Consider checking other batches
• Batches containing reprocessed product
Complaints Procedure – cont'd
 Investigation and evaluation should result in
appropriate follow-up actions
 May include a "recall"
 All decisions and measures taken should be
recorded
 Referenced in batch records
 Records reviewed - trends and recurring
problems
Complaints - other actions
 Inform competent authorities in case of
serious quality problems such as:
 Faulty manufacture
 Product deterioration
 Counterfeiting
 Have a thorough recall procedure that is
consistent with the complaints handling
procedure
 Trend complaints, their investigations and
results
Self-Inspection
• Purpose is to evaluate whether a company’s
operations remain compliant with GMP
• The programme should
• cover all aspects of production and quality
control
• be designed to detect shortcomings in the
implementation of GMP
• recommend corrective actions
• set a timetable for corrective action to be
completed
• Should be performed routinely
• Also on special occasions such as
• Recalls
• Repeated rejections
Self-Inspection (cont'd)
 Performed by team appointed by management,
with:
 authority
 sufficient experience, expertise in their own
field. knowledge of GMP
 may be from inside or outside the company
 Frequency should normally be at least once a
year
 May depend on company requirements
 Size of the company and activities
Self-Inspection (cont'd)
 Report prepared at completion of inspection,
including:
 results
 evaluation
 conclusions
 recommended corrective measures
 Follow-up action
 Effective follow-up programme
 Company management to evaluate both
the report and corrective actions
Summary and conclusions:
• GMP compliance is not an option
• Quality should be built into the product
• GMP's are very similar and are really Good
Common Sense
• Good Practices cover all aspects of
manufacturing activities prior to supply
• The role and involvement of senior management
is crucial