LEC 6 Flashcards
Onsite inspection
- inspectors are physically present at manufacturing site
Remote inspection
- mimics onsite inspection in terms of format, time-frame & overall rigor
- desktop inspection is a type of remote inspection
Desktop inspection
- a form of remote inspection based on review of documentary evidence
- paper-based remote inspection
Challenges of remote inspection (4)
- poor internet connectivity
- limited resources at manufacturing sites due to split teams
- overall slower response time to complete remote inspection
- difficult to inspect utilities and manufacturing operations
Hence, now adopt hybrid inspection + mutual reliance program
Benefits of ASEAN MRA on GMP inspection (6)
- avoid duplication of inspection within ASEAN
- save time, resources and costs for manufacturers and regulators
- facilitate trade in medicinal products across ASEAN
- quicker access of medicinal products by ASEAN patients
- harmonisation of ASEAN inspection system to that of PIC/S
- increase attractiveness of ASEAN to regulators & investors
MRA
Mutual Recognition Agreement
MRA vs mra
MRA
- Mutual Recognition Agreement
- legally binding
- can take relatively long time to negotiate and conclude
mra
- mutual reliance approach
- not legally binding
- only involve regulators and inspectors only
Framework for PIC/S GMP inspection reliance (3)
- have MRA on GMP inspection
- recognition of GMP compliance status by a facility within the territory of PIC/S participating authority
- recognition of inspection outcome by a hosting inspectorate which has been assessed under a robust framework
NRA reliance by WHO Good Reliance Practices
- an act whereby an NRA takes into account an assessment performed by another NRA (or a trusted institution) in reaching its own decision
- the relying NRA remains independent, responsible and accountable for his decision
- doesnt mean less stringent regulation
- mutual reliance is a hallmark of a modern and efficient regulatory authority and smart regulation
Limitations of conventional product testing (3)
- req “representative” sample
- can only test if you know the analyte and have a test method
- test method must be accurate, reliable and specific (validated)
Advantages of QbD/PAT (4)
- non-destructive
- deeper process understanding, better control and higher QA
- real time release of product
- cost saving
Challenges of QbD/PAT (4)
- limited understanding of QbD/PAT
- high financial investment in PAT
- old habits
- not ready for QbD/PAT submissions
Disadvantages of traditional manufacturing (4)
- need to collect intermediate product for testing
- need to collect end-product for testing
- need to quarantine products in the meantime of testing (cost of storage space)
- increased total batch processing time (costly)
Advantages of continuous manufacturing (4)
- fewer steps, fewer contamination
- shorter batch processing time
- smaller equipment and facilities
- online monitoring and QC (higher quality and real time release)
mra
mutual reliance approach
PIC/S GMP Inspection Reliance
- with “complexity of global supply chains”, demands for inspections far exceed what any one inspectorate can accomplish alone
- hence, PIC/S published a guidance on GMP Inspection Reliance on 1 June 2018
Advantages of Post-Covid increasing trend towards (2) :
- remote inspection
- reliance (MRA/mra)
- decrease travel times (both domestic and local)
- accord flexibilities to inspectors and inspectees regarding timeframes and inspection pace
Impact of 5 LIS on ASEAN MRA
- can now expand the scope of MRA to include API and biopharmaceuticals
5 LIS (ASEAN)
- Singapore
- Malaysia
- Indonesia
- Thailand
- Philippines
Nanotechnology and Nanomedicines
- nanoparticles can interact with biomolecules to treat pathologic problems even before the expression of the disease symptoms
Advantages of Nanomedicines (3)
- Effective in targeting difficult-to-reach site (tumors)
- Improved solubility, bioavailability and reduced side effects
- Achievement of same therapeutic effect with smaller doses
Disadvantage of Nanomedicines
- shown to accumulate in organs
- haemolyze erythrocytes
- safety concerns
Hence, a clear, globally acceptable framework is needed to facilitate the development and public acceptance of nanomedicines
QbT
- Product/batch tested only at the end of manufacturing process
- If product passes the test, it was deemed to be of good quality
Batch definition
Refers to a specific quantity of product with uniform quality regardless of mode of manufacture
Advantage of GMP/GDP compliance and vigilance in the industry
- Assure quality of API/pharmaceutical products
- Detect manipulation by unscrupulous supply chain players
- Detect adulterated products, counterfeit and falsified medicines
