GMP aims to ensure quality, safety and efficacy of medicines by requiring manufacturers to follow quality standards and comply with marketing authorizations. Inspections verify compliance and identify any deviations between dossiers and actual practices. Quality assurance, GMP, quality control, and quality risk management are interrelated aspects of quality management that are important for producing pharmaceuticals to the required standards.
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Gmp Guidelines by HCP
1.
2. 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
3. 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
4. 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)
5. 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
6. 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
7. 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
8. Good Manufacturing Practices
(cont'd)
11. Personal hygiene
12. Premises
General
Ancillary areas
Storage areas
Weighing areas
Production areas
Quality control area
13. Equipment
9. 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
10. 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
11. 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
12. GMP is actually Good Common Sense
Quality Management
Quality Assurance
GMP
Production and Quality Control
13. 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."
14. 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”
15. The five P's
• Premises
• Primary materials
• People
• Procedure
•
• Processes defined•
and recorded
16.
17. 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
18. 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
19. The position of QA
Director
Production QC lab Other Depts
QA
20. 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
21. 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
22. 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
23. 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
24. 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
25. 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)
26. 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
27. 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
28. GMP = continuous urge for
improvement
Involvement of the management
Annual Product Quality Review
Quality risk management
Complaints handling
Self-inspection
29. 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
30. 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
31. 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
32. 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)
33. 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.”
34. 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)
35. 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
36. 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
37. 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
38. 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
39. 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
40. 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
41. 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