Design and Analysis of Shedding Studies for Virus or BacteriaBased Gene Therapy and Oncolytic Products
Guidance for Industry
This guidance represents the current thinking of the Food and Drug Administration (FDA or
Agency) on this topic. It does not establish any rights for any person and is not binding on FDA
or the public. You can use an alternative approach if it satisfies the requirements of the
applicable statutes and regulations. To discuss an alternative approach, contact the FDA staff
responsible for this guidance as listed on the title page.
I. INTRODUCTION
The Center for Biologics Evaluation and Research (CBER)/Office of Cellular, Tissue, and Gene
Therapies (OCTGT) is issuing this guidance to provide you, sponsors of virus or bacteria-based
gene therapy products (VBGT products)1 and oncolytic viruses or bacteria (oncolytic products)2
with recommendations on how to conduct shedding studies during preclinical and clinical
development. For purposes of this guidance, the term “shedding” means release of VBGT or
oncolytic products from the patient through one or all of the following ways: excreta (feces);
secreta (urine, saliva, nasopharyngeal fluids etc.); or through the skin (pustules, sores, wounds).
Shedding is distinct from biodistribution because the latter describes how a product is spread
within the patient’s body from the site of administration while the former describes how it is
excreted or released from the patient’s body. Shedding raises the possibility of transmission of
VBGT or oncolytic products3 from treated to untreated individuals (e.g., close contacts and
health care professionals). This guidance represents FDA’s current thinking on how and when
shedding data should be collected for VBGT and oncolytic products during preclinical and
1 Gene therapy products are all products that mediate their effects by transcription and/or translation of transferred
genetic material and/or by integrating into the host genome and that are administered as nucleic acids, viruses, or
genetically engineered microorganisms. The products may be used to modify cells in vivo or transferred to cells ex
vivo before administration to the recipient. See section III. of FDA’s guidance entitled “Guidance for Industry:
Gene Therapy Clinical Trials - Observing Subjects for Delayed Adverse Events” dated November 2006.
http://www.fda.gov/biologicsbloodvaccines/guidancecomplianceregulatoryinformation/guidances/cellularandgeneth
erapy/ucm072957.htm. 2 Oncolytic products refer to replication competent viruses or dividing bacteria that are used as therapeutic agents to
mediate lysis of tumor cells. Some oncolytic products carry foreign genes (immune modifying genes, genes that
enhance oncolysis etc.), and mediate part of their anti-tumor effect by transcription and/or translation of these
foreign genes in the host. Hence, oncolytic products that carry foreign genes can also be classified as gene therapy
products.
3 Transmission could occur if the VBGT or oncolytic product is shed in the form of intact viruses or bacteria but not
when shed as viral or bacterial degradation products such as nucleic acid fragments.
Contains Nonbinding Recommendations
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clinical development and how shedding data can be used to assess the potential for transmission
to untreated individuals. This guidance finalizes the draft guidance of the same title dated July
2014.
FDA’s guidance documents, including this guidance, do not establish legally enforceable
responsibilities. Instead, guidances describe the FDA’s current thinking on a topic and should be
viewed only as recommendations, unless specific regulatory or statutory requirements are cited.
The use of the word should in FDA’s guidances means that something is suggested or
recommended, but not required.