Manufacturing Flashcards
What are the 9 chapters in PIC/S GMP Standard
1) Pharmaceutical Quality System (includes Product Quality Review and Quality Risk Management)
2) Personnel
3) Premises & Equipment
4) Documentation
5) Production
6) Quality Control
7) Outsourced Activities (Contract Manufacture & Analysis)
8) Complaints & Product Recall
9) Self-inspection (IQA)
What is GMP
Good manufacturing practice
A quality system standard implemented by pharmaceutical manufacturers
Ensures that medicinal product is consistently manufactured and controlled to a quality appropriate for its intended use and as required by its MA/product license
How often should product quality review (PQR) be carried out
Annually
PQR should be carried out on:
1) Quality of starting materials
2) Quality of finished products and critical in-process controls
3) Failed batches
4) Manufacturing process / QC deviations
5) Changes to manufacturing process and analysis methods
6) Changes to MA (product license)
7) Stability testing program
8) Complaints and product recalls
9) Adequacy of CAPA
10) Qualification status of key equipment and utilities
PIC/S GMP Standard for complaints
1) A designated person should be responsible for handling complaints and deciding on action(s) to be taken
2) SOP in place for handling complaints
3) All complaints should be recorded, investigated and closed out, with decisions taken documented
4) Complaint records should be reviewed regularly for any recurring trend
5) Regulator should be notified if considering product recall following serious quality defects, faulty manufacturing or evidence of counterfeits
PIC/S GMP Standard for product recalls
1) Designated person (independent of Sales & Marketing) should be responsible for coordinating and executing product recall
2) SOP in place for product recall
3) Distribution records should be available to designated person
4) Regulator should be notified if considering product recall
5) Progress of product recall should be recorded and final report issued, including reconciliation between delivered and recovered products
6) Recalled products should be stored securely while awaiting its fate
7) Effectiveness of recall procedure should be evaluated regularly
PIC/S GMP Standard for self-inspection
1) Should be carried out periodically
2) Areas covered should include all 9 chapters & relevant annexes in PIC/S GMP standard
3) Should be carried out in an independent and detailed way by designated competent person
4) Independent audits by external experts can also be useful
5) Should be recorded, including observations made and proposed CAPAs
6) Statement(s) of eventual action(s) taken should be recorded
How are inspections carried out
Follows conventional manufacturing flow:
1) Warehouse (starting materials)
2) Weighing room
3) Production room
4) Packaging room
5) QC laboratories (QC testing)
6) Document audit
Inspection of warehouse - Objective
Assess that:
1) Starting materials have approved specifications and were purchased from approved suppliers
2) SOPs in place for (1) handling, receipt, quarantine, sampling (including availability of sampling room), release of materials (2) handling of rejected materials and products
3) Environment of warehouse preserves quality of materials/products during storage - Check that temperature & RH are monitored, pest control programs in place
Inspection of warehouse - Relevant chapters in PIC/S GMP Standard
Chapter 3: Premises - Storage area
Chapter 5: Production - Starting materials
Inspection of weighing room - Items/Areas to be inspected/assessed
1) Weighing balance
- Weighing balance should be calibrated, reliable, accurate
2) Materials
- Inspect labelling of starting materials
- Weight materials must be of correct identity, quality, quantity
3) Weighing process
- SOP for weighing methods, records of weighing
4) Personnel
- Only authorized personnel allowed
- PPE, proper gowning
5) Premises
- Environment controlled to prevent cross-contamination
- Inspect dust extraction system and housekeeping of weighing room
Inspection of weighing room - Relevant chapters in PIC/S GMP Standard
Chapter 5: Production - Dispensing
Inspection of production room - Items/Areas to inspect
1) Production room
- Design/Construction
- Partition/Segregation; Air-handling & containment
- Maintenance & cleaning (including records)
- Connecting pipe-work (stainless steel) and drainage pipes (no back flow)
- Environmental / Microbiological monitoring
- Change room (appropriate class & air showers)
2) Production equipment
- Design/Construction
- Cleaning/Maintenance, calibration, usage records
- Status labelling of equipment
3) Production process
- Labelling/Control of starting materials
- Batch production records
- Gowning of personnel
- Process deviation & investigation
- Process validation, re-validation and change control
4) Personnel
- Appropriate PPE, gowns
- No jewelry, cosmetics
Inspection of production room - Objective
Assess that:
1) Production room
- Premises are designed to prevent cross-contamination
2) Production equipment
- Effectively cleaned and regularly maintained
3) Personnel
- Restricted access to authorized personnel
- Appropriate gowns, PPE
4) Process controls
- Critical processes are validated / re-validated
- In-process QC
- Comprehensive batch manufacturing records kept
Inspection of production room - Relevant PIC/S GMP Standard chapters
Chapter 5: Production - Paragraphs 5.1 - 5.71
Inspection of packaging room - Items/Areas to inspect
1) Packaging room
- Design/Construction
- Maintenance/Cleaning & calibration
- Environmental/Microbiological monitoring
2) Packaging equipment
- Maintenance/Cleaning, calibration, usage records
- Status labelling of equipment
3) Packaging process
- Control of labels and packaging material, bulk and finished products
- Batch packaging records
- Process validation, re-validation, control change
4) Personnel
- Appropriate PPE, gowns
Inspection of QC department - Objective
Assess that:
1) Trained analysts available
2) Independent authority for head of QC
3) QC test methods are approved by HSA and are robust, sensitive, accurate & reliable for testing (as evident from records of analytical method validation and routine QC testing)
4) Procedures in place for maintenance, calibration, status labelling and assuring integrity of QC test equipment
5) Procedures in place for receipt, storage, security, record keeping of test samples, reagents, reference standards
Inspection of QC chemistry testing laboratories - Items to be inspected
1) Test samples
2) Prepared reagents
3) Retained samples
4) Reference standards
5) Test methods - types of tests, validation, calibration of equipment, raw data records & print-outs
6) OOS investigation
7) Stability testing
Inspection of QC department - Relevant PIC/S GMP Standard chapters
Chapter 6: Quality Control - Paragraphs 6.1 - 6.41
Other areas to inspect
1) Ancillary premises
- Restrooms
- Corridors
- Engineering workshop
2) Outsourced activities / External premises (contract testing laboratories)
- Check for quality agreement stipulating roles and responsibilities of manufacturer and contract testing laboratories
- ISO 1702S Certification by SPRING Singapore is acceptable by HSA
Inspection of documentation - Objectives
Assess that:
1) Manufacture complies to legal requirements under Medicines Act & Health Products Act
2) Manufacture complies to regulatory commitments to HSA
- Composition of finished product, specifications of starting materials
- Test methods used
- Process validation / Stability study reports (protocols & acceptance criteria)
3) Manufacturing SOPs are followed
4) Manufacturing records are authentic
4) Manufacture follows PIC/S GMP standards
Inspection of documentation- Items to be inspected
1) Document control system
- SOP on preparation of SOP
- SOP on document control
- SOP on records control
2) SOP & records on:
- Pest control program
- Temperature & RH monitoring
- PQR
- Complaints & product recalls
- Self-inspection
3) Batch manufacturing records
4) Stability testing reports
5) Process validation reports
- Protocols
- Acceptance criteria
- Validation master plan
20 Annexes
1) Manufacture of sterile products
2) Manufacture of biological products
3) Manufacture of radiopharmaceuticals
4) Manufacture of non-immunological veterinary products
5) Manufacture of immunological veterinary products
6) Manufacture of medicinal gases
7) Manufacture of herbal medicinal products
8) Sampling of starting and packaging materials
9) Manufacture of liquids, creams, ointments
10) Manufacture of inhalations
11) Computerized systems
12) Use of ionizing radiation in manufacturing
13) Manufacture of investigational medicinal products
14) Manufacture of blood products
15) Qualification and process validation
16) Qualified person and batch release
17) Parametric release
18) EMPTY
19) Retention and reference samples
20) Quality risk management
