Quality Assurance in product development and manufacture Flashcards
Recalls
Harm to consumers
Destroy reputation
Cost - refunds, replacements, communication
To avoid build a quality system
Quality Assurance
Planned and systematic production processes that provide confidence in a product’s suitability for its intended purpose
Set of activities intended to ensure product satisfy customer requirements - in a systematic, reliable fashion
QA cannot guarantee production of quality products but more likely in order to satisfy the customer
ICH Guidelines Q8: Pharmaceutical Development - Quality built by design
Quality cannot be tested into products - should be built into the product from the beginning of development
What are GMP?
Good Manufacturing Practices
- is a SYSTEM for ensuring products are CONSISTENTLY PRODUCED and CONTROLLED according to quality standards
- system is designed to MINIMISE THE RISKS involved in any pharmaceutical production that cannot be eliminated through testing the final product
Main risks involve:
- unexpected CONTAMINATION of products, causing damage to health or death
- INCORRECT LABELS on containers, which means patient receive wrong meds, insufficient meds, too much active ingredient
Resulting in INEFFECTIVE TREATMENT OR ADVERSE EFFECTS
GMP covers ALL ASPECTS OF PRODUCTION
Detailed WRITTEN PROCEDURES are essential for each process that could affect quality of finished product
Must have systems to provide DOCUMENTED PROOF that correct procedures are consistently followed at each step in the manufacturing process - EVERYTIME a product is made
Why is GMP important?
- health hazard
- Waste of money on government and consumers
- poor quality may damage health
- may contain toxic substances unintentionally added
- does not have intended therapeutic effect
One major difference in regulation
When submitting a new product to FDA, compliance to GMP is verified by Pre Approval Inspection (PAI)
If PAI is not satisfactory then FDA can hold the approval
If there are comments, ‘FDA 483’ are issued
If it is more important FDA sends out ‘warning letters’
EMEA - have no PAI
EMEA Quality Assurance
Attainment of this quality objective is the responsibility of SENIOR MANAGEMENT and staff commitment AT ALL LEVELS WITHIN THE COMPANY
To achieve this there must be a comprehensively designed and correctly implemented SYSTEM OF QUALITY ASSURANCE
QA is the SUM OF ORGANISED ARRANGEMENTS made with the objective of ensuring products are of QUALITY REQUIRED FOR THEIR INTENDED USE
Therefore QA incorporates GMP and OTHER FACTORS outside the scope of this guide
Chapter 2: Personnel
The satisfactory system of QA and good manufacturing RELIES UPON PEOPLE
There must be sufficient QUALIFIED PERSONNEL to carry out tasks responsible by the manufacturer
Individual RESPONSIBILITIES should be clearly understood by the individuals and RECORDED
All personnels should be aware of the GMP principles that affect them and receive initial and continuing TRAINING relevant to their needs
TRAINING should be provided with a WRITTEN PROGRAMME for all personnel required in MANUFACTURING areas or in CONTROL laboratories
All personnel should undergo HEALTH EXAMINATIONS prior to and during employment
Chapter 3: Premises and Equipment
Premises and equipment must be LOCATED, DESIGNED, CONSTRUCTED, ADAPTED and maintained to suit the operations to be carried out.
Design must aim to minimise the RISK OF ERRORS and allows effective CLEANING to avoid in general any adverse effect on quality of product
Clean room
- CONCENTRATION OF AIRBORNE PARTICLES IS CONTROLLED
- Used in a manner to minimise the INTRODUCTION, GENERATION AND RETENTION OF PARTICLES inside the room
- Supply air that is HEPA FILTERED
- INFILTRATION CONTROLS with slight pressure in the clean room to prevent entry of microbes from adjacent under pressured areas
- prevent PARTICLES FROM OPERATOR by gowning
Qualification and Validation WHO
In accordance with GMP, company should identify what qualification and validation work is required to prove that the CRITICAL ASPECTS of their particular operation are CONTROLLED
- key is to provide a clear and defined VALIDATION MASTER PLAN
Equipment requires qualification - design, installation, operation and performance
Product process validation - requires 3 CONSECUTIVE SUCCESSFUL batches with at least 10% of the industrial size
Cleaning validation - using cleaning procedures of KNOWN EFFECTIVENESS and verification by swabbing areas for testing
Chapter 4: Documentation
- ESSENTIAL PART of QA system
- Clearly written PREVENTS ERRORS from spoken communication
- Permits TRACING history
- SPECIFICATIONS, MANUFACTURING FORMULAE AND INSTRUCTIONS, PROCEDURES, RECORDS must be FREE FROM ERRORS and available in writing
- LEGIBILITY is of paramount importance
Chapter 5: Production
Production operations must follow CLEARLY DEFINED PROCEDURES
- must comply with GMP principles to obtain requisite QUALITY and be in accordance with relevant manufacturing and marketing authorisations
Control Charts - consists of measurements of a quality characteristic in samples with upper/ lower limits indicating the threshold (2 standard deviations from the normal)
Capable process - where almost all the measurements fall inside SPECIFICATION LIMITS
Cp - how big the measurements. 1 = normal
Chapter 6: Quality Control
Concerned with SAMPLING, SPECIFICATIONS AND TESTING with the ORGANISATION, DOCUMENTATION AND RELEASE PROCEDURES which ensure relevant tests are actually carried out and materials are not released until their quality has been judged to be satisfactory
Quality control is not confined to laboratory operations but must be involved in all decisions concerning the quality of the product
Principle - Independence of quality control from production is considered fundamental to satisfactory operation of Quality Control
