Validation and Qualification
What the domain tests
Validation and Qualification tests the evidence that a facility, utility, equipment, or process consistently does what it claims. The exam distinguishes qualification of equipment from validation of processes, and expects a risk-based, lifecycle approach rather than a one-time documentation exercise.
Core rules
- The V-model links user requirements (URS) to design qualification (DQ), installation qualification (IQ), operational qualification (OQ), and performance qualification (PQ). Each stage must trace back to the URS.
- Process validation follows three stages under the FDA guidance: Stage 1 process design, Stage 2 process qualification (including PPQ), and Stage 3 continued process verification. Three consecutive successful PPQ batches is a common expectation, not a universal rule.
- Risk assessment determines the depth of testing. A direct-impact system needs more qualification than an indirect-impact utility.
- Cleaning validation uses a health-based or dose-based limit. Common acceptance criteria are 10 ppm of previous product in the next batch, 1/1000 of the minimum daily dose, and visually clean. The lowest limit controls.
- Change control must trigger revalidation when the change affects product quality or the validated state.
Worked example
Shared equipment makes Product A (smallest daily dose 100 mg) then Product B (batch size 200 kg, maximum daily dose 400 mg). Use a safety factor of 1,000 and a 10 ppm limit. Dose-based MACO = (0.001 × 100 mg × 200,000 g)/400 mg = 50 g. The 10 ppm limit = 10 mg/kg × 200 kg = 2 g. The lower limit, 2 g, controls. For 10 m² of product-contact surface, the surface limit = 2 g/10 m² = 0.2 g/m² = 20 µg/cm². If the visual limit is 4 µg/cm², visual cleanliness is the controlling criterion. The reasoning is to calculate both limits and use the most stringent.
Traps
- Calling IQ/OQ “validation” for a process.
- Using a single cleaning limit without a health-based rationale.
- Setting PPQ batches without a statistically based sampling plan.
- Forgetting utilities and computerized systems in the qualified state.