L1 Flashcards
What is GMP?
Good Manufacturing Practice(s)
GMP is a __________ implemented by pharmaceutical manufacturers to ensure that:
(1) a medicinal product is __________ manufactured & controlled
(2) to the __________ appropriate for its intended use(s), and
(3) as required by its __________ (aka __________)
Quality System Standard
(1) consistently
(2) quality
(3) market authorisation; product license
How many chapters does PIC/S GMP Standard consists of?
9 Chapters
How many annexes does PIC/S GMP Standard consists of?
20 Annexes
- Of which, 4,5,16 and 20 are not compulsory in Singapore
Are all chapters of PIC/S GMP Standard mandatory? Which are not mandatory?
Yes, all 9 chapters are mandatory.
Are all annexes of PIC/S GMP Standard mandatory? Which are not mandatory?
Not all annexes are mandatory.
Not mandatory in SG:
- Annex 4
- Annex 5
- Annex 16
- Annex 20 (voluntary)
What is the conventional manufacturing flow?
- Input @ Warehouse
- Production and Packing @ Weighing Room; Production Areas; Packaging Room
- QC Testing @ QC Laboratories + Documentation Audit (SOPs, Records, Reports)
- Output of Products in finished dosage forms after QC (Product Batch release)
What are the 6+1 areas to be inspected during a GMP inspection?
(1) Warehouse
(2) Weighing Room
(3) Production Department
(4) Packaging Room
(5) QC Department
(6) Other areas
- Ancillary premises (Engineering workshop, restroom, corridors)
- External premises; Outsourced activities (e.g. Contract testing labs)
(7) Documentation Audit
What are the 5 areas covered during inspection of the Production department and Packaging rooms?
- Production rooms (Premises)
- Production equipment (Machine)
- Production Process (Method)
- Starting Materials
- Personnel (Manpower)
What is the 4M+1P?
- Production rooms (Premises)
- Production equipment (Machine)
- Production Process (Method)
- Starting Materials
- Personnel (Manpower)
What are the objectives of Documentation Audit?
Assess that the manufacturer conforms to legal & regulatory requirements and PIC/S GMP Standards (ie the 9 chapters)
cGMP is
Current Good Manufacturing Practices
Roles of a Pharmaceutical Inspector?
To inspect compliance to PICS GMP standard
Under Singapore Medicines Act/Health Products act, a manufacturer’s licence is required for manufacture of medicinal products (therapeutic pdts)
Compliance with PIC/S GMP standard is prerequisite for issuance and retention of manufacturer’s license
GMP compliance assessed through periodic audits by HSA inspectors
When did Singapore join PIC/S member in?
1 January 2000
Goal of PIC/S?
To lead the international development, implementation and maintenance of Harmonised GMP Standard (for manufacturers) and Quality System (For inspectorates) in the field of medicinal products
What is the conventional manufacturing flow?
Materials (input) → Processes → QC testing → Finished dosage forms (output)
Number of Chapters and Annexes in PIC/S Guide to GMP?
9 Chapters + 20 Annexes
Annex 4,5,16 and 20 not mandatory
What is assessed during Warehouse Inspection?
Mainly Storage and Production Materials, specifically:
- Starting materials (API, packaging materials, finished pdts have approved specifications, materials are purchased from approved suppliers)
- Procedures (SOP) are in place for handling receipts, quarantine, sampling (includ. Availability of sampling room), release of materials and for handling rejected materials and products
- Environment of Warehouse (e.g. Temperature, RH monitoring and pst control programs) preserves quality of materials and products stored
PIC/S Guide to GMP on Warehouse is found in
Chapter 3 (Storage) and 5 (Production Starting Materials)
What is assessed during Weighing Room Inspection?
- Calibrated, Accurate and reliable weighing balances are used
- Weighed materials are of correct identity, quantity and quality
- Authorised persons wear appropriate PPE and cross contamination is controlled (may have multiple substances weighed in the same weighing room)
PIC/S Guide to GMP on Weighing Room is found in
Chapter 5 (Production: Dispensing)
What is assessed during Production Department Inspection?
- Premises designed to prevent cross contamination
- Equipment cleaned and maintained regularly
- Personnel control programs to restrict access to authorised personnels + wear appropriate PPE/gown
- Materials of correct identity, quantity and quality
- Process controls in place (Critical Processes validated)
=> 4M+ 1P (Materials, Manpower, Method, Machines, Premises)
PIC/S Guide to GMP on Production Department is found in
Chapter 5 (Production Paragraphs 5.1 to 5.71)
What are the other areas inspected? (For Areas Inspected by Inspectors, other than Warehouse, Production Facilities, QC Department etc.)
Engineering Workshop
Restrooms
Corridors
Contract Testing Laboratories
What is the accepted ISO Certification for Contract Testing laboratories?
ISO17025 Certification by SPRING Singapore
From Wikipedia:
ISO/IEC 17025 General requirements for the competence of testing and calibration laboratories is the main ISO standard used by testing and calibration laboratories. In most countries, ISO/IEC 17025 is the standard for which most labs must hold accreditation in order to be deemed technically competent. In many cases, suppliers and regulatory authorities will not accept test or calibration results from a lab that is not accredited.
What is inspected for QC Testing Laboratories?
- Properly trained analysts
- QC methods approved by HSA (Robust, Sensitive, Accurate and Reliable)
- Procedures for maintenance, calibration, status labelling and assuring integrity of QC test equipment
- Procedures for receipt, storage, security, record keeping of test samples, reagents and reference stds
PIC/S Guide on QC Department is found in
Chapter 6 (Paragraphs 6.1 to 6.41)
What is Documentation Audit?
Check that: Manufacturer conforms to legal and regulatory requirements + PIC/S GMP Standard, follows all SOP + No data integrity issues
- Compliance to legal requirements under Medicines and Health products act
- Regulatory Commitments to HSA are complied (e.g. Composition and specifications, test methods, process validation/stability studies are correct)
- Manufacturing SOPs are followed
- Manufacturing Records are authentic (No falsifications)
Documentation Audit includes many things, but it notably includes (3 things)….
- SOP and records on product quality review (Ch 1)
- SOP and records of product complains and recalls (Ch 8)
- SOP and records of Self inspection (Internal Quality Assurance) program (Ch 9)
Documentation Audit - Self Inspection is found in Chapter
Chapter 9
Documentation Audit - Complaints and Product recalls is found in Chapter
Chapter 8
Documentation Audit - Product Quality Review is found in Chapter
Chapter 1
What is done with the results of Product Quality Review under PIC/S GMP Guide (Chapter 1)?
In general, Product Quality Review (PQR) results are:
- Trended (detect a trend for a particular reported quality issue),
- Investigated, with
- CAPAs (Corrective Action and Preventive Action) taken based on Root Cause Analysis
For Complaints and Product Recalls (Chapter 8), the Competent Authority (Regulatory Authority) should be notified if….
…. if manufacturer is considering Product Recall following serious quality defects, faulty manufacture and evidence of counterfeit products
(HSA will help the manufacturer with the product recall through consumer education)
The Process Validation Program consists of three main items… (name them)
Process validation: The act of providing documentary evidence that a manufacturing process is capable of consistency producing a finished product of the required quality. It consists of three main
- Protocols
- Acceptance Criteria
- Validation Master Plan (The long term plan?)
What is PIC/S?
Pharmaceutical Inspection Co-operation Scheme
How often does HSA inspect GMP compliance of manufacturers?
Periodic audits every 18 - 36 months
