PR3145 CA1 To Memorize Flashcards
What does PICS stand for?
Pharmaceutical Inspection Coorperation Scheme
When did Singapore join PICS?
2000
How many PICS members are there?
53 (as of 1 Jan 2020)
What are the 9 chapters of the PICS GMP standard?
Chapter 1 - Pharmaceutical Quality System 2 - Personnel 3 - Premises and equipment 4 - Documentation 5 - Production including packaging 6 - Quality Control 7 - Outsourced Activities 8 - Complaints and Product Recall 9 - Self inspection (IQA)
What is the usual flow of inspection?
Warehouse Weighing Room Production Areas Packaging Room QC Laboratories Documentation audit
What are the 4Ms and 1P for inspection?
Machine
Method
Manpower
Materials
Premises
What is a good quality medicinal product?
- identity and potency of API
- critical quality attributes (CQA) of dosage form
- Purity, stability and homogenity of final product
What is parametric release?
Release of terminally sterilized LVPs based on key parameters of a validated sterilization process, instead of results from batch sterility testing.
- temperature
- pressure
- sterilisation time or cycle
- bioburden of pre sterilized parenteral product
What is quality risk management?
- risk identification
- risk analysis
- risk reduction
- risk communication
what are the diff types of contaminants?
- intrinsic contaminants (impurities): present inherently in API, excipients and packaging materials -> often specific in nature
- extrinsic contaminants (cross contaminants) -> originate externally, often non specific in nature
What are some APIs with polymorphs?
Ampicillin, Carbamezapine, Cimetidine and Mefenamic acid
What are some APIs with stereo isomers?
- dopamine
- propranolol
How are extrinsic contaminants controlled?
Through GMP compliance, bc they are non specific in nature.
What are the different types of stability studies?
- real time studies (6 months) under controlled storage conditions
- accelerated studies under stressed conditions
- continual stability studies (after granting of MA)
How is homogeneity demonstrated?
Process validation
How is process validation carried out?
On at least three consecutive full scale batches.
What are the steps of process validation?
1) establish critical quality attributes (CQA)
2) identify critical processes parameters (CPP)
3) design sampling plan
4) design testing plan
5) set acceptance criteria
6) perform statistical analysis (intra and inter batch) for the 3 batches
What is a herbal medicine?
- herbal medicine is a medicinal product
- contains 1 or more herbal substances as active ingredients eg ginseng and lingzhi
- active ingredients not synthetic, herbal in nature
- inert ingredients can be synthetic
What is a traditional medicine?
- traditional medicine is a medicinal product
- contains one or more traditional substances as active ingredient
- traditional substance include herbal animal and mineral material.
- herbal medicine is a subset of traditional medicine
What is the current regulatory status of THMP?
- lack of harmonized GMP standard for THMP
- minimal product quality requirements (only have limits for microorganisms and toxic heavy metals)
What are the challenges in regulating THMP?
- harmonization of GMP standard for THMP (PICS GMP standard annex 7 us a good starting point for global harmonization)
- harmonization of quality standard for THMP -> EMA guidance note is a good starting point for harmonizing quality (impt to control water quality)
- combatting adulterated THMP
- levelling up cottage THMP industry
What are the 2 biotechnologies used?
- recombinant DNA technology involving bacterial cell
- hybridoma technology using mammalian cell
What are the major steps in manufacturing a biotech medicinal product?
- cell banking: MCB and WCB
- cell cultivation: fermentation for microbial cells and culturing for mammalian cells
- harvesting: lysis for microbial cells and centrifugation/filtration for mammalian cells
- purification: remove impurities via chromatography
- viral clearance - need to validate viral clearance process
- batching and storage of bulk biological API - can produce in sub lots and pooled as bulk batch ; store in refrigerators or freezers
- formulation, packaging and release of finished product (injection) - into injection only
What do we test for at cell banks?
- genetic stability
- endogenous viruses (for mammalian cell lines)
- residual DNA (mammalian cell line)
- adventitious vriuses introduced during sampling or transfer process
When to split upstream vs downstream processes?
Cuts off after harvesting and clarification.
What are the types of fermentation?
- batch fermentation (closed system)
- continuous fermentation (open system)
- fed batch fermentation (in between)
what are the types of cell culturing?
- anchored system
- suspension system
what should nutrient media not contain?
BSE prions
what are some things to note about the ASEAN biopharmaceutical industry?
- still at nascent stage
- mainly produce vaccines
- biopharmaceuticals are currently excluded from the scope of the ASEAN Mutual Recognition Agreement on GMP inspection
What is ALCOA
Attributable, Legible, Contemporaneous, Original and Accurate
How long to retain records for?
batch manufacturing records - 1 year after batch expiry
for clinical trial products, at least 5 years after clinical trial
What are the types of documents?
Instructional: SOP, batch manufacturing formula and site master file
Evidential: Records and reports (most DI problems)
What is metadata?
Metadata describes data (data of data)
what does the ASEAN sectoral MRA on GMP inspection not include?
Biopharmaceuticals and APIs
What are the ASEAN Listed Inspection Service (LIS)?
singapore malaysia indonesia thailand philippines
