“We consider an assessment of the vector integration pattern to be relevant in subjects enrolled in gene therapy clinical studies when the vector has the potential for genomic integration (e.g., integrating retroviral vectors).

An assessment of integration sites may be useful if subjects demonstrate evidence of clonal expansion (e.g., a dominant clone representing a substantial proportion of the integration profiles).

Sponsors should test for vector sequences in surrogate samples (e.g., peripheral blood) by PCR at predetermined intervals during the long-term follow-up period. Depending on the nature of the product and the expected risks, sampling intervals may be no greater than every six months for the first five years and no greater than annually for the subsequent ten years.”

< Guidance for Industry: Long Term Follow-Up After Administration of Human Gene Therapy Products >

“Testing for evidence of replication-competent retrovirus (RCR) should be performed on vector lots used for clinical manufacture and on ex vivo–transduced cells prior to patient infusion.

Clinical samples obtained from subjects should be tested for RCR infection by PCR for RCR-specific sequences and/or by serologic testing for RCR-specific antibodies. Relevant clinical samples should be collected and tested upon the development of an adverse event suggestive of retrovirus-associated disease.”

< Guidance for Industry: Testing of Retroviral Vector-BasedHuman Gene Therapy Products for Replication Competent  Retrovirus During Product Manufacture and Patient Follow-up>