L6 - Pharmaceutical Inspection Topics of Special Interest Flashcards
Types of Inspection
1) On-site inspection
- inspectors phy present
2) Remote inspection
- e-technology, aims to mimic on-site inspection in terms of format, time-frame & overall rigour
3) Desktop inspection
- mainly “paper-based”
Arrangement of Remote inspection
- Agree on virtual conference (inspection) platform
- Strong internet/wifi
- Know the parties involved & their roles
- Agree on time & duration, time zones
- Confidentiality, security & access
- Agree on safety arrangements
- Deal with document system
Challenges of Remote inspection
- E-tech limitations
- Slower response time
- Lack of body language
- Limited resources at manufacturing sites
- Difficult to inspect utilities & manufacturing operations
ASEAN MRA & its benefits
- PIC/S framework as benchmark
- Covers pharmaceutical products in FINISHED dosage forms
- Prescription & OTC meds
- -> Does NOT cover biopharmaceutical products & APIs
Benefits:
- Avoids duplication of inspections within ASEAN
- Save time resources $$$
- Facilitates trade & quicker access to med products
- Harmonise inspection standards with that of PICS
- Increases attractiveness of ASEAN to regulators & investors
Objective of forming ASEAN JSC on GMP Inspection
To establish a register of ASEAN Listed Inspection Services (LIS)
- Implements PICS fully
- SG, MSIA, Thailand, Indonesia, Philippines
- -> Ready to expand scope of MRA to include APIs & biopharmaceuticals
MRA (Mutual recognition agreement) vs mra (mutual reliance approach)
MRA:
- Takes relatively long time to conclude
- Negotiated under Free Trade Agreements (FTAs)
- Involves regulators, lawyers/AGC, trade & industry representatives
- Considerations given to pharm import/export volumes, political, legal, social & other trade/services impacts
PICS GMP Inspection Reliance
- Have a MRA on GMP inspection in place
- Recognition of GMP compliance status of a facility located within territory of a PICS Participating Facility
- Recognition of inspection outcome by a hosting inspectorate which has been assessed under a robust framework
WHO Good Reliance Practices
- Covers reliance activities in REGULATION of medical products
- Spans entire product life cycle
- Intended for all national regulatory authorities
- Various approaches to reliance
What is reliance as described in WHO Good Reliance Practices?
Hall mark of an efficient regulatory authority & smart regulation
- does not represent less stringent form of regulation
- relying NRA remains independent, responsible & accountable
Benefits of remote inspections & reliance
- Enables business continuity during Covid-19 (Only options for overseas manufacturers)
- Decrease travel time
- Accord for more flexibilities
What is Nanomedicines (& Nanotechnology)
Emerging group of therapies which aim to achieve breakthroughs in diagnosis & treatment of diseases
Advantages of Nanomedicines
- Effective in targeting difficult-to-reach (tumour) sites
- Reduced side effects
- Smaller doses
- Improved solubility & bioavailability
–> Due to its size shape & surface chemistry
GMP & Safety concerns of Nanomedicines
Free nanoparticles released into envt during manufacture & are a potential health & cross-contamination hazard
- -> h/w they provide promising breakthroughs
- -> Need a clear & globally acceptable regulatory framework to facilitate acceptance
Limitations of Conventional Product Testing
- Only test on ‘representative’ sample size
- Test only if you know the analyte & have a test method
- Test only if test method is specific accurate & reliable
Limitations of Conventional QC Tests (QbT)
- Only test on ‘representative’ sample size
- Defaults only picked up at end of manufacturing process
- QC tests not conducted in real time
- -> $ of storage space during quarantine of bulky products
THEREFORE…
Developement of parametric release of terminally sterilised LVPs & QbD of other dosage forms by PAT
Advantages of QbD/PAR
- Non-destructive
- Higher Qa, deeper process understanding & better control
- Real time release of products
- Cost-savings for industry
Challenges to QbD/PAR implementation
- Limited understanding of QbD/PAR
- High financial investment (though long-term savings)
- Industry not accustomed to reviewing a validated process
- Regulators not ready for QbD/PAR submissions
(Used to older paradigm of QbT)
Advantages of Continuous Manufacturing
- Higher QA through at-line testing using non-destructive PAT/other technologies
- Real time release of finished product (Save warehouse space)
- Shortened batch processing time (Save $)
- Smaller equipment & facilities
- Integrated process (fewer steps)
OVERALL $ REDUCTION
What is “batch”
Specific Qty of a product with uniform quality regardless of mode of manufacture
Why is managing/inspecting API quality impt?
Quality of APIs, Purity
Why is assuring API supply chain integrity impt?
- Many players in supply chain
(Increased chances for potential points of interference of APIs/product –> Falsified medications) - GMP/GDP compliance can help to:
Assure quality, deter manipulation & detect adulterated products - International efforts to protect API supply chain integrity are ongoing & evolving
