PCR technique of genomic fragments from endogenous and adventitious viral agents

The European Medicines Agency have issued a document entitled “Detection by a highly sensitive new PCR technique of genomic fragments from endogenous and adventitious viral agents in live attenuated vaccines” (reference EMEA/H/A-5(3)/1269).

The document is concerned with the possible presence of nucleic acid sequences from endogenous and adventitious viral agents in live attenuated viral vaccines. The paper considers the potential of the analytical metagenomics approach (polymerase chain reaction (PCR) combined with pyrosequencing, for the detection of viral fragments.

In summary, the statement outlines the following position:

1. Whilst the presence of endogenous ALV and SRV DNA fragments is potentially linked to the cell lines used for the manufacture of the individual vaccines, the finding of PCV-1 DNA pointed towards the presence of non-endogenous viral DNA. The Committee is therefore asked to assess if there is any potential public health concern arising from all the findings described in the article.

2. It is understood that as more hi-tech analytical methods become available, new findings may reveal in medicinal products presence of substances at very low concentrations and/or hard to detect that were thus far not picked up because of limitations of the analytical instruments/methods declared and authorised in the marketing authorisation dossier. Specifically, the Committee is asked to indicate if the new test method described above applied to identify viral genomic nucleic acid fragments should be considered, if validated, for the development/qualification and/or routine testing of biological medicinal products, and particularly live attenuated vaccines. Recognising the limitations of this novel method, and in order to conclude on the presence or absence of specific risks, the Committee is also asked to consider whether additional tests would be needed to conclude on the presence of replication competent endogenous and adventitious viral agents.

3. The Committee should indicate if there is a need to update existing guidance related to the testing and elimination of such substances in the context of development and/or testing of live attenuated vaccines.

4. Depending on the outcome of these investigations, the Committee should consider the need for appropriate guidance for other vaccines and other biological products.

The statement can be found at: EMA

Posted by Tim Sandle