Validation · Stability
Process validation (PV)
Confirms that manufacturing steps and in-process parameter control deliver products that meet requirements and are repeatable. CQAs and CPPs are assessed · batch size equals commercial batch size · minimum 3 lots · performed for new processes, changes to existing processes, or site transfers.
Prospective
Performed before the product is released to market.
Concurrent
Emergencies only, with a documented risk assessment and prior FDA approval.
Retrospective
No longer accepted · plus on-going process verification.
Cleaning validation (CV)
Confirms equipment cleaning effectiveness, focusing on cross-contamination from product residues, detergents and microorganisms.
- Visual inspection — failure fails the CV; no further testing needed
- Active ingredient residue (MACO — carry-over from product A to B)
- Detergent residue by total organic carbon (TOC)
- Microbial contamination checked twice, after DEHT and CEHT
Swab sampling
For active ingredient residue.
Rinse sampling
Equipment rinse water for detergent and microbial residue.
Media fill
Verifies aseptic processing by simulating the routine process as closely as possible with culture media instead of drug, including interruptions and worst cases such as power failure. The first media fill requires three consecutive simulations.
Environmental monitoring
Clean rooms such as sterile production areas are monitored for microorganisms; results are recorded and deviations corrected immediately.
Settle plate
Culture plates exposed to capture airborne microbes.
Air sample
Air drawn onto a culture plate.
Contact plate
Plate pressed onto working surfaces.
Glove print (5 fingers)
Five gloved fingers pressed onto a plate.
| Grade | Air sample (cfu/m³) | Settle plates ⌀90 mm (cfu/4 h) | Contact plates ⌀55 mm (cfu/plate) | Glove print 5 fingers (cfu/glove) |
|---|---|---|---|---|
| A | < 1 | < 1 | < 1 | < 1 |
| B | 10 | 5 | 5 | 5 |
| C | 100 | 50 | 25 | — |
| D | 200 | 100 | 50 | — |
Product Quality Review (PQR)
A report compiling data from several departments to review product quality: starting/packaging materials, QC and stability trends, non-conformities, deviations and CAPA, change control, regulatory information, complaints/recall/returns, CAR/PAR, registrations, validation/qualification status, technical agreements, supplier complaints and retention samples.
| Risk level | Frequency | Products |
|---|---|---|
| High | Every 1 year | Injectables, cytotoxic drugs |
| Medium | Every 2 years | Penicillins, cephalosporins, products with API < 2 mg |
| Low | Every 3 years | Other products |
Stability testing
| Type | Storage condition | Frequency (months) |
|---|---|---|
| Long term | 30 °C / 75% RH | 0, 3, 6, 9, 12, 18, 24 |
| Accelerated | 40 °C / 75% RH | 0, 3, 6 |
- If 24-month long-term and 6-month accelerated data pass, the FDA approves a tentative shelf life of 2 years at registration; long-term testing can continue to extend shelf life.
- On-going stability: at least one production batch per year for every strength and container type.
- In line with Thai GMP (Chapter 6, Quality Control) under the Drug Act B.E. 2559.
Water and HVAC
The water, wastewater and HVAC systems are covered under Facilities.
