Good Manufacturing Practice (GMP)
What the domain tests
Good Manufacturing Practice tests the operational controls that prevent contamination, mix-ups, and cross-contamination: facility classification, HVAC, personnel and material flows, cleaning, aseptic technique, and documentation on the floor. EU GMP Annex 1 and FDA aseptic guidance are key references for sterile operations.
Core rules
- Cleanroom grades: Grade A is the critical zone (ISO 5 at rest and in operation); Grade B is the background for Grade A (ISO 5 at rest, ISO 7 in operation); Grades C and D correspond to ISO 7 and ISO 8 at rest, with defined in-operation limits. Do not quote ISO 5 for a Grade B in-operation condition.
- HVAC must maintain differential pressure, air changes, temperature, and humidity. Typical Grade B air change rates are 40–60 per hour; Grade A is unidirectional flow at 0.45 m/s ± 20% at the supply.
- Environmental monitoring includes viable and non-viable particles, settle plates, active air, and surface sampling. Alert and action limits are site-specific but must be justified.
- Personnel flow goes from lower to higher grade; material flow uses pass-throughs, and simultaneous open doors are controlled.
- Cleaning validation must demonstrate removal of product, detergent, and microbes; worst-case product, hardest-to-clean location, and hold times are required.
- Media fills qualify aseptic processing; acceptance criteria depend on fill size, and any contaminated unit requires investigation.
Worked example
A Grade B room has a volume of 30 m³. To achieve 50 air changes per hour, supply flow = 30 × 50 = 1,500 m³/h. If the HEPA terminal filters are rated at 0.9 m³/s each (3,240 m³/h), one filter is more than enough for flow, but coverage matters: a 30 m³ room with a 3 m ceiling has 10 m² floor area; one terminal may create dead zones. The reasoning is to calculate flow first, then check filter coverage and air distribution, not just the air-change number. The exam may ask why increasing ACH alone does not guarantee Grade B recovery.
Traps
- Confusing “at rest” and “in operation” limits.
- Treating Grade A and ISO 5 as interchangeable in all conditions.
- Relying on particle counts alone without viable monitoring.
- Accepting a media fill with no growth without checking fill volume and incubation.