EU GMP Annex 2 - Manufacture of Biological Active Substances and Medicinal Products

What it says

Manufacture of biological active substances and medicinal products, including products derived from cell culture, fermentation, and other biotechnology processes, requires GMP principles adapted for the specific characteristics of biological starting materials, including their inherent variability, and the specialised control strategies these products require.

Paraphrased for plain-language clarity. Always verify against the current published regulation text.

What it means in practice

• This annex applies GMP principles specifically adapted for biological manufacturing's unique characteristics, including the inherent variability of biological starting materials and the more complex, multi-step nature of many biological manufacturing processes.
• Cell banking systems, master and working cell banks used as the foundation for biological manufacturing, require their own specific characterisation, qualification and ongoing control expectations distinct from starting material control for small-molecule products.
• Viral safety, including viral clearance and inactivation validation, is a specific and significant control category for many biological products that has no direct equivalent in small-molecule manufacturing.

What inspectors look for

• Whether cell banking systems are adequately characterised, qualified and controlled, with clear traceability from the master cell bank through to commercial production.
• Whether viral safety control strategies, including clearance and inactivation validation, are appropriately designed and validated for the specific biological product and process.
• Whether the inherent variability of biological starting materials is genuinely accounted for in process design and control strategy, rather than assumed away as if biological materials behaved with small-molecule consistency.

Related regulations