Viral Safety of Raw Materials Used in Production of ATMPs (On-Demand)

Curriculum

Course Description:
Foetal Bovine Serum is commonly used at cell culture supplement for production of vaccines and viral gene transfer vectors. However, at production animal sera are increasingly being replaced by human raw materials such as pooled human sera or pooled human platelet lysates (HPL). The aim of this presentation is to review the experience from Paul-Ehrlich-Institut (PEI) at assessment of virus and prion safety of cell based medicinal products (CPMP) where most concerns were about the use of human sera or human platelet lysates. Cases will be discussed in light of the current regulations. Repeated cases of blood derived infectious transmissions have been found historically with pooled not-virally inactivated or insufficient virally inactivated plasma preparations. Recent reports on the transmission of hepatitis E virus or parvovirus B19 from blood products also supported the opinion of the PEI that pooling increases the risk for patients to be infected. In addition there is a risk of spread of emerging viruses via pooled components where specific donor testing has not yet been introduced The risk from pooled, non-virus inactivated raw materials has been outlined in the European Pharmacopoeia (Ph. Eur. 5.2.12). In general, the PEI’s guidance to HPL manufacturers and users of HPL is a recommendation to switch to smaller pool sizes, or use virus inactivation methods when pool size exceeds 16 donations (Blümel et al., 2020., Strategies toward virus and prion safe human platelet lysates, Transfusion 60:219-220). If viral inactivation is required, at least one effective (i.e. ≥ 4 log10) inactivation step targeting a wide range of lipid-enveloped and non-enveloped viruses should be applied, while two steps would be preferable. Few cases of prion transmission of the variant form of Creutzfeldt-Jakob disease (vCJD) by transfusion of blood components have been reported, but no case for the sporadic form of CJD (sCJD). However, some published experimental data indicate that the risk for sCJD transmission by blood or blood products cannot be completely ruled out. In addition, microvesicles and exosomes from platelets contain prion proteins suggesting that HPL could be a carrier of pathogenic prions. Smaller pools and younger donors might mitigate the risk. In general, the need for human material for application in cell culture or the possibility to use fractionated HPL/plasma or defined growth factors to reduce the risk for virus and TSE transmission should be evaluated.

The live version of this recording took place on April 14, 2021 and features
a presentation by Johannes Blümel

Who should participate:

  • Analytical chemists
  • QA/QC analysts
  • R&D scientists, managers
  • Team members in CMC development projects
  • Manufacturing scientists, managers
  • Regulatory affairs specialists
  • Contract research organizations
  • Contract ma