Basic Understanding of Good Manufacturing Practices ... · PDF fileBasic Understanding of Good...
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1 Minda Chiang Minda Chiang Hong Kong Society for Quality Hong Kong Society for Quality Jan 2006 Jan 2006 Basic Understanding of Basic Understanding of Good Manufacturing Practices Good Manufacturing Practices Requirements and Execution Requirements and Execution
Transcript of Basic Understanding of Good Manufacturing Practices ... · PDF fileBasic Understanding of Good...
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Minda ChiangMinda ChiangHong Kong Society for Quality Hong Kong Society for Quality
Jan 2006Jan 2006
Basic Understanding of Basic Understanding of
Good Manufacturing Practices Good Manufacturing Practices
Requirements and ExecutionRequirements and Execution
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Outline
� To know why GMP� To know what GMP is� To know how to comply with it� To know what difficulties will be encountered
Let’s begin… .
Why GMP
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Why GMP
n …n …n …n Eventually …n for Qualityn …n for Total Quality Management (TQM)
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Quality is
n "A subjective term for which each person has his or her own definition. In technical usage, quality can have two meanings:
1. the characteristics of a product or service that bear on its ability to satisfy stated or implied needs
2. a product or service free of deficiencies"
[ASQ, American Society for Quality]
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TQM is
n Chain Reactionn Improve Quality … improve procedure
improve products / services
NDecrease Cost … less rework, fewer delayless contingency feeless cost of warranty
NImproves ProductivityNCapture the market with better quality & priceNStay in business
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n Failure driven companiesn “if it breaks, we’ll service it”
n Quality excellence approachn “no defects, no problems, essentially
moving toward perfect work processes”
TQM is [cont]
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n Key elements:n Employee involvementn Customer satisfactionn Continuous improvementn …
n Tools:n ISOn HACCPn Six Sigma
How to comply with quality
n Control Chartn GMPn …
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Why GMP
n Ensure public safety n Identity, Safety, Purity, Efficacy, Potency,
Stability, Consistencyn Achieve top quality pharmaceutical products: free of
errors and risksn Increase efficiency: i waste, rejects, reworks,
complaints & recallsn Increase competitiveness
n Regulatory requirementn Minimum standard for drug manufacturing
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Remember …
GMP is a tool
v to comply with a certain quality level
v to help to stay in business
What GMP is
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GMP is
l Good Manufacturing Practicesl Quality System ¡ Ensuring products are consistently
produced and controlled to the quality standards appropriate to their intended use
¡ Ensure that things are done right first time, every time and on time
¡ Supported by scientific evidence
l Lifestyle in drug manufacturing
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WHO GMP GuidelinesTherapeutic Good Act (TGA) Food & Drug Administration (FDA)GMP Guidance for Pharmaceutical ProductsGMP Guidelines for Pharmaceutical Products, 1995GMP Guidelines for Proprietary Chinese Medicines, 2003
GMP Guidance
l WHO: l Australia:l USA:l China:
l HK:
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HK GMP Guidelines 1995
l Part 1: Quality Management in the Drug Industry ¡ Section 1: Quality Assurance¡ Section 2: GMP for Pharmaceutical Products¡ Section 3: Quality Control¡ Section 4: Sanitation & Hygiene¡ Section 5: Validation¡ Section 6: Complaints
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¡ Section 7: Product Recalls¡ Section 8: Contract Production and Analysis¡ Section 9: Self-inspection & Quality Audit¡ Section 10: Personnel¡ Section 11: Premises¡ Section 12: Equipment¡ Section 13: Materials¡ Section 14: Documentation
HK GMP Guidelines 1995 [cont]
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l Part 2: Good Practices in Production & Quality Control¡ Section 15: Production¡ Section 16: Good Practices in Quality Control
l Part 3: Supplementary Guidelines¡ Section 17: Sterile Pharmaceutical Products¡ Section 18: GMP for Active Pharmaceutical
Ingredients
HK GMP Guidelines 1995 [cont]
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GMP is
1. An appropriate quality system¡ encompassing the organizational structure,
defined procedures, competent personnel, validated equipment and materials
2. Systematic actions¡ building confidence that a product is safe,
consistent and reliable
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Remember …
GMP diminishing risks, inherent in any pharmaceutical production, that cannot be prevented completed through the testing of final products
v Cross-contamination
v Mix-up
How to comply with GMP³ Organization³ Personnel & Training³ Design & construction Features³ Environment Cleanliness³ Equipment³ Product Components & Vendor Evaluation³ Testing & Re-testing³ Labelling³ Documentation & Recording³ Validation³ Self-Inspection³ …
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Organization
l Top management commitmentl Providing resources, personnel, time
l Quality Unitl Separated from Production Departmentl Having responsibility and authority l to approve or reject all procedures or spec.l to approve or reject all components,
in-process materials, packaging material, labeling and drug products
l to review production recordsl to investigate and correct any error occurred
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l Sufficient qualified & competent personnel to carry out all tasks
l Clear job description & responsibility for each key function & personnel
l Authorized Personl Responsible for the release of every batch of
finished products for salesl Sufficient training conducted on a continuing basis and
with assessment to assure that employees remain familiar with GMP requirements applicable to them
Personnel & Training
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Design & Construction Features
l Operations performed within specifically defined areas of adequate size
l Construction permit effective cleaning, maintenance and proper operationsl Floors, walls and ceilings of smooth, hard surfacesl Temperature and humidity controlsl Air supply filtered through HEPA filters under
positive pressurel The flow of materials and personnel through the
premises designed to prevent contamination
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l Separate areas forl Materials receivingl Materials pending sampling and testing before release
for manufacturing or packaging l Released components, drug product containers, closures
and labelingl Rejected components, product containers, closures and
labeling before dispositionl Storage of in-process materials, drug products before
releasing (Quarantine), drug product after releasingl Different manufacturing process: mixing, packaging,
labeling, etcl Laboratory operationsl Rest
Design & Construction Features [cont]
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l System forl Drains of adequate size, provided with an air
break or other mechanical device to prevent backflow
l Room cleaning and disinfectingl Pest controllingl Ventilation for air filtration and air exhausting l Lightingl Environmental monitoring
Design & Construction Features [cont]
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Environment Cleanliness
l Particles & Microbiall Controlled byl Filtering out particles from the air before it enters
the clean areas by using HEPA filtersl Adequate air flow of at least 10-20 changes per
hourl Differential pressure between roomsl Temperaturel Relative humidity
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Equipment
l Appropriate design to facilitate operations, cleaning and maintenance
l Surfaces that contact components, in-process materials or drug products shall not be reactive, additive or adsorptive
l Substances required for operation (such as lubricants, coolants, etc.) shall not come into contact with components, drug product containers, in-process materials or drug products
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Product Components & Vendor Evaluation
l Containers and closures shall l Not be reactive, additive or absorptivel Provide protection against foreseeable external
factors in storage and usel Be clean, and where appropriate, sterilized and
processed to remove pyrogensl Be specified and tested before use
l Vendor Assessment: Professionalism, Technical Support, Material Quality, Quality System, …
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Testing
l Examine each lot of incoming materials before release for use
l Representative sampling from each shipment of each lot shall be collected
l Sample collection precautions:l Prevent contamination of contentsl Use aseptic techniques when neededl Identify samplesl Mark containers which have been sampled
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Re-testing
l Retest for identity, strength, quality and purity, as deemed necessary, i.e.,l After storage for long periodsl After exposure to air, heat or other conditions that
might have adverse effects
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Labelling
l Identity labels: for every material and product l Quarantinel Approved / Releasedl Rejected, Recalled, Returnedl …
l Status labels: for every stage of productionl Weighing l Mixing, Filtration, Filling, Tabletting, Capsulation l Cleaning, Sterilization, Disinfectionl …
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l Apparatus / equipment / room status shall be identified:l Cleaned / to be cleanedl Disinfected / to be disinfectedl Under maintenancel Out of orderl Validatedl Calibratedl Process in progress
Labelling [cont]
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Documentation & Recording
l Establish written procedures to assure uniformity from batch to batchl Instruction: specification, master formulae, manufacturing,
packaging, operation, maintenance…l Maintain records, including production, control, and
distribution, all components (drug product containers, closures and labelling) and disposition of rejected components, …l Generally retained for at least 1 year after the expiration
date of the batchl Control unauthorized copyl Critical Documents: Site Master File, Drug/Food Master File,
Batch Record, Testing Record, Complaint Record, Recall Record, Distribution Record, Training Record, …
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l Laboratory Record shall includel Description of samplel Statement of the testing methodl Statement of weight or measure of sample used for each
testl All data and test resultsl Initials / signature of individual who performed the testl Initials / signature of second person who checkedl Testing date, approving date
Documentation & Recording [cont]
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l Batch Record shall includel Product information: name, batch number, registration
number, …l Each significant manufacturing stepl Date of each processl Identity of individual major equipment and linel Identity of components and in-process materialsl Weights and measures of components usedl In-process and labeling control recordsl Sampling records and laboratory control resultsl Statement of actual yieldl Responsible signature: preparing and checkingl Divergence and investigation (w conclusions and follow-up)
Documentation & Recording [cont]
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l Complaint Files shall includel Name and strength of drug productl Lot numberl Name of complainantl Nature of complaintl Reply to complainantl Investigation results l Lab test results, if anyl Corrective actions, if anyl Conclusion l Follow-up, if any
Documentation & Recording [cont]
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Validation
l To demonstrate reliability of the processl To show the process consistencyl To build confidencel Re-validation
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Validation Sequence & Items
l Validation Master Planl Items include1. Facility & Utilities (Installation & Operational Qualification)
l Cleanrooms / Clean Boothsl Purified Water System / WFI Systeml Stem Generation Systeml Compressed Air Systeml Dust Collection Systeml HVAC Systeml Industrial Steam Generation Systeml …
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2. Equipment (Installation, Operational & Performance Qualification)l Production Equipment
l Granulator, Mixer, Drying Ovenl Tabletting Machine, Encapsulation Machine, l Primary Packaging Equipment: Filing, Cappingl Sterilizerl …
l Testing Equipmentl Stability Chamber, Spectrophotometer l Chromatography: HPLC, GCl …
Validation Sequence & Items [cont]
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3. Testing Methodl Accuracyl Precisionl Specificityl Detection limitl Quantitation limitl Linearity and rangel Ruggednessl Robustness
Validation Sequence & Items [cont]
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4. Process (Prospective, Concurrent, Retrospective Validation)l Solid Dose: Granulation Mixing, Blending,
Compression, …l Liquid Dose: Mixing, Storage, Filtration, Filling, …l Cream: Homogenization, Mixing, Filling, …l Cleaning: Visual Inspection, Product Residue,
Detergent Residue, …l Other Process: Sterilization, Washing, Capping, …
Validation Sequence & Items [cont]
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Self-inspection
l To evaluate the system effectivenessl To re-allocate resourcesl To detect the weakness and potential improvement
areas, including training needsl To develop continuous improvement plan
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Key Elements for GMP Compliance
v Management Commitmentv Organization Structure & Quality Systemv Qualified Personnel & Continuous Trainingv Facility & Equipment Design & Maintenancev Components from Qualified Vendorv Laboratory Testing & Proper Labellingv Documentation & Recordingv Validationv Self-Inspection & Continuous Improvementv …
Common Problems in GMP Execution
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u Organization
u Lack of commitment u Lack of resources for executionu …
u Layout & Construction
uNo quarantine areau Insufficient environmental monitoring uCracked flooru …
Common Problems in GMP Execution
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u Equipment
uNo calibrationuNo performance check of balance before
useuRustyu Parts not kept improperly
Common Problems in GMP Execution [cont]
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Common Problems in GMP Execution [cont]
u Documentation & Recordingu No signature; no counterchecku Improper correction made, e.g. use of
correction fluidsu No written procedureu Incomplete complaint recordu No up-to-date training recordu No document reviewu Not legible u Not traceable
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u Personnel
u Improper gowning u No continuous trainingu No training assessmentu No job description
u Laboratory Testing
u Poor reference standard keepingu Poor data recordingu Reagent with no label
Common Problems in GMP Execution [cont]
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u Labellingu Status not defined clearlyu Poor labelling controlu Release label not kept securelyu Inadequate reconciliation of batch labelu Defective equipment with no label
u Validationu Insufficient validationu Insufficient raw datau No validation programme
Common Problems in GMP Execution [cont]
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u Others
u Dirty apparatus/cleaning toolsu Fiber shedding towel/mop used for
cleaningu Rejected materials not segregatedu Poor disposal handlingu Fail the principle: “Do what you say”
Common Problems in GMP Execution [cont]
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Reaction
1. Establish Quality Policy by top management2. Design and build proper facilities and equipment3. Maintain the facilities and equipment4. Have approved procedures5. Follow the written procedures6. Document your work7. Validate your work8. Staff Competence (training & experience)9. Control for quality10. Audit for compliance11. …
Keys …
Attitude & Knowledge
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More information
l ICH Documentsl www.ifpma.org/ich1.html
l FDA Documents (21 CFR 11)l Parts 210 and 211: Current Good Manufacturing
Practices for Finished Pharmaceuticalsl Part 820: Quality System Regulationsl www.fda.gov
