WHO Technical Report Series, No. 878, Annex 1 (1998)

This Annex (now superseded by WHO TRS 978, 2013) set out principles and expectations for selecting, establishing, and controlling animal cell substrates used to manufacture biological medicines (e.g., vaccines and other biologicals). It defines the cell-banking framework (Master and Working Cell Banks) and the testing and quality controls needed to mitigate risks from adventitious agents and to ensure consistent, safe production.

Although foundational in shaping global regulatory approaches to cell substrates, TRS 878 is now of historical interest only and has been replaced by more current WHO recommendations.

Applies to qualification and control of cell substrates (primary, diploid, and continuous lines) used as manufacturing platforms for biological products.

Addresses the establishment and characterization of cell banks, including documentation of origin and history, species confirmation, and genetic stability considerations.

Cell substrate categories & selection criteria: definitions, provenance, and suitability assessments for primary, diploid, and continuous cell lines.
Cell-bank system: recommended practices for creating, storing, and qualifying Master Cell Banks (MCB) and Working Cell Banks (WCB), with traceability and change control expectations.
Adventitious agent safety testing: sterility and mycoplasma testing; in vitro and in vivo viral assays; approaches for retrovirus detection; and virus-safety controls throughout culture and production.
Tumorigenicity/oncogenicity evaluations: guidance for testing continuous cell lines and interpreting risk in relation to product type.
Manufacturing controls: expectations for media and reagents (including animal-derived materials), culture conditions, contamination control, and batch documentation supporting consistent processing.

TRS 878 should be referenced only for historical perspective; WHO TRS 978 (2013) provides the applicable expectations.