Design and Analysis of Shedding Studies for Virus or Bacteria-Based Gene Therapy and Oncolytic Products
In August 2015, the US Department of Health and Human Services (HHS), the Food and Drug Administration (FDA) along with the Center for Biologics Evaluation and Research, produced a guidance document titled 'Design and Analysis of Shedding Studies for Virus or Bacteria-Based Gene Therapy and Oncolytic Products, (Guidance for Industry)'.
The HHS, FDA and CBER | FDA are aware that Virus-Based Gene Therapy (VBGT) Vaccines produce shedding
This "Guidance for Industry" report issued in August of 2015 by the U.S. Department of Health and Human Services, the Food and Drug Administration, and the Center for Biologics Evaluation and Research, shows quite clearly that the U.S. Federal Government must be aware that "shedding" of the Virus-Based Gene Therapy (VBGT) vaccines does occur. For example, in Section VI, B.: 'Route of Administration', it clearly says that:
"In addition to the tropism of the VBGT or oncolytic product, the route of product administration should be considered in the selection of sample types to collect in a shedding study. For example, to assess shedding in patients administered an oncolytic virus by the intradermal route, we recommend the collection of skin swabs at the site of injection, in addition to the other samples routinely assessed for shedding (e.g., urine, feces, and saliva). Similarly, we recommend the collection of nasopharyngeal washes when an oncolytic virus is administered by inhalation or via the intranasal route.s occur. For example, in Section VI, B 'Route of Administration'
Documents on Shedding Recommendations Non-Binding
It is notable that the recommendations for shedding studies in pre-clinical studies, clinical studies and also in untreated individuals in population/s, are non-binding.
Feces, Urine and Nasal Swabbing Samples determine Shedding Capability
In Chapter VI. 'DESIGN OF SHEDDING STUDIES: GUIDING PRINCIPLES', the key aspects in the design of shedding studies are: the choice of clinical samples that are collected from subjects in a trial (e.g., feces, urine, nasal swabs); the frequency of sample collection and duration of the monitoring period; and the assay methodology selected to test for the presence of the shed VBGT or oncolytic product in the clinical sample wherein which Replication competence, wherein which the ability of the VBGT or oncolytic product to multiply and amplify in the human host greatly affects how it is disseminated in the body and may increase the extent and duration of shedding; Immunogenicity, wherein the VBGT or oncolytic product is derived from viruses or bacteria that elicit a strong immune response, the product may be more rapidly cleared from circulation than a poorly immunogenic product, and may be shed for a shorter duration; Persistence and latency, wherein which the duration of a shedding study may be longer if the VBGT or oncolytic product exhibits persistence or latency-reactivation in the host; and Tropism where the tropism of the product may affect what samples should be collected to assess shedding. For example, VBGT or oncolytic products that are engineered to carry tropism modifying gene(s) or mutation(s) may exhibit an altered shedding profile than the parent virus because of retargeting of the product to different tissues or organs.
Full Document on the Non-Binding Recommendations to Design & Analyze Shedding Studies on Virus or Bacteria-Based Gene Therapy (VBGT or BBGT) and Oncolytic Products
CLICK HERE to go directly to the document on the FDA's website
CLICK HERE to download from this website
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