good manufacturing practices purpose and principles of gmp tony gould
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Good Manufacturing PracticesPurpose and Principles of GMP
Tony Gould
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Why GMP?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
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Why inspect?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
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WHO GMPWHO GMP
Quality assurance of pharmaceuticals
A compendium of guidelines and related materials
Volume 2, 2nd updated edition
Good manufacturing practicesand inspection
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Guidelines and referencesGuidelines 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)
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Other WHO GMP GuidelinesOther WHO GMP Guidelines
Pharmaceutical excipients Sterile pharmaceutical products Biological products Pharmaceutical products containing hazardous
substances Investigational pharmaceutical products for clinical trials iHerbal medicinal products Radiopharmaceutical products Water for pharmaceutical use HVAC for non-sterile pharmaceutical dosage forms Validation
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Good Manufacturing Practices (FPP):Good Manufacturing Practices (FPP):
1. Quality assurance2. Good manufacturing practices for pharmaceutical products 3. Sanitation and hygiene4. Qualification and validation5. Complaints6. Product recalls7. Contract production and analysis
– General– The contract giver– The contract accepter– The contract
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Good Manufacturing Practices (cont'd)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
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Good Manufacturing Practices (cont'd)Good Manufacturing Practices (cont'd)
11. Personal hygiene
12. Premises– General
– Ancillary areas– Storage areas– Weighing areas– Production areas– Quality control area
13. Equipment
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Good Manufacturing Practices (cont'd)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
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Good Manufacturing Practices (cont'd)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
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Good Manufacturing Practices (cont'd)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
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GMP is actually Good Common SenseGMP is actually Good Common Sense
Quality Management
Quality Assurance
GMP
Production and Quality Control
Section 1 and 2
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Quality management in the drug industryQuality 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."
Glossary
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Quality ManagementQuality 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”
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The five P'sThe five P's
Premises
Primary materials
People
Procedures
Processes defined and recorded
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Quality AssuranceQuality 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 1.1
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Quality AssuranceQuality 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 design1.1
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The position of QAThe position of QA
DirectorDirector
QAQA
ProductionProduction QC labQC lab Other DeptsOther Depts
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Quality Assurance means to assure: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
1.1 a- d
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Quality Assurance means to assure: (cont'd)
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
1.1 e - h
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Quality Assurance means to assure: (cont'd)
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 improvement1.1 i - l
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Quality Assurance includes: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
1.3
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Good Manufacturing PracticesGood 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) 2.1
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Basic requirements for GMP:Basic requirements for GMP:
Clearly defined and systematically reviewed processes
Qualification and validation is performedAppropriate resources are provided:
– Qualified and trained personnel– Premises, space, equipment and services– Materials, containers, labels– Procedures, storage, transport– Laboratories and in-process control
2.1 a - c
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Basic requirements for GMP: (cont'd)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 2.1 d - j
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GMP = continuous urge for improvement GMP = continuous urge for improvement
Involvement of the management
Annual Product Quality Review
Quality risk management
Complaints handling
Self-inspection
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Involvement of the managementInvolvement 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
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Product Quality ReviewProduct 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
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Product Quality Review (cont'd)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
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Annual Product Quality Review (cont'd)Annual Product Quality Review (cont'd)
Review of Marketing Authorization variations submitted, granted or refused (incl. third countries)
Review of stability programme and trendsReview of adequacy of previous decisions on changes
or improvements or corrective actionsFor new Marketing Authorizations (plus new
variations) a review of post marketing commitmentThe qualification status of all relevant equipment and
utilities (like water, HVAC, gases, etc.)Review of Technical Agreements (if applicable)
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5.1
Complaints handlingComplaints 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.”
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5.2 – 5.3
Complaints ProcedureComplaints 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)
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5.4 – 5.6
Complaints Procedure – cont'dComplaints 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
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5.7 – 5.9
Complaints Procedure – cont'dComplaints 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
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5.10
Complaints - other actionsComplaints - 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
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Self-InspectionSelf-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 routinelyAlso on special occasions such as
– Recalls– Repeated rejections 8.1
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8.3, 8.4
Self-Inspection (cont'd)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
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8.5, 8.6
Self-Inspection (cont'd)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
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Summary and conclusions:Summary and conclusions:
GMP compliance is not an option Quality should be built into the productGMP's are very similar and are really
Good Common SenseGood Practices cover all aspects of
manufacturing activities prior to supplyThe role and involvement of senior
management is crucial
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http://www.who.int/prequalhttp://www.who.int/prequal
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