Drug compounding, sterile and non-sterile preparations, hospital manufacturing and quality assurance (GMP, pharmacopoeia)
This domain tests whether you can run and defend in-house production: cleanroom design, validation, documentation and pharmacopoeial limits. Expect one calculation and one deviation scenario.
Sterile compounding
- Grade A (ISO 5) at the critical filling zone, Grade B background for aseptic processing, C/D for lower-risk operations; pressure cascade, HEPA H14 filters, defined air-change rates, and continuous non-viable particle monitoring in Grade A.
- Personnel qualification includes gowning and media fill (aseptic process simulation); environmental monitoring covers settle plates, active air and surface sampling; sterility assurance level 10⁻⁶ underpins the whole system.
- Bacterial endotoxin testing (LAL) has product-specific limits; pyrogen control matters most for intrathecal and high-volume parenteral products.
- Hazardous drugs (cytotoxics, some antivirals and hormones) are prepared in negative-pressure isolators with closed system transfer devices, dedicated gowning and validated cleaning with documented residue limits.
Non-sterile compounding
Balance calibration with a defined minimum weighable quantity, geometric dilution, homogeneity, appropriate excipients, packaging and a beyond-use date derived from stability data or pharmacopoeial guidance - not copied from the commercial product's expiry.
Quality assurance
Work under PIC/S-derived GMP: master formulae, batch records, in-process controls, deviation and CAPA systems, change control, supplier qualification, validation (IQ/OQ/PQ), periodic review, recall handling, and self-inspection. Ph. Helv. monographs and the general methods chapters are your legal reference.
Worked example
Order: cytarabine 75 mg/m² for a patient of 2.1 m² BSA = 157.5 mg; vials contain 100 mg. Reasoning: two vials are required; after reconstitution you calculate the volume for 157.5 mg, document the exact withdrawal, and define the beyond-use date from the reconstitution data (typically 24 h refrigerated for a preservative-free solution). Surplus drug handling and sharps/waste disposal follow the hazardous-drug procedure. A dose rounded down to 100 mg would be a dosing error.
Traps
- Treating a beyond-use date as identical to the manufacturer's expiry date.
- Forgetting that a media fill failure triggers batch rejection and a formal investigation, not a repeat run.
- Omitting the pressure cascade and gowning rationale when describing cleanrooms.
- Ignoring documentation of deviations - an undocumented deviation is a GMP finding.