Cell and Gene Therapy: BIO Comments on Preclinical Assessment of Investigational Cellular and Gene Therapy Products



Dear Sir/Madam: 
The Biotechnology Industry Organization (BIO) thanks the Food and Drug Administration (FDA) for the opportunity to submit comments on the Guidance for Industry: Preclinical Assessment of Investigational Cellular and Gene Therapy Products.
BIO represents more than 1,100 biotechnology companies, academic institutions, state biotechnology centers and related organizations across the United States and in more than 30 other nations.  BIO members are involved in the research and development of innovative healthcare, agricultural, industrial and environmental biotechnology products, thereby expanding the boundaries of science to benefit humanity by providing better healthcare, enhanced agriculture, and a cleaner and safer environment.  
BIO believes this document will be very helpful for developers of novel biologics and we appreciate the efforts of the Center for Biologics Evaluation and Research/Office of Cellular, Tissue, and Gene Therapies (CBER/OCTGT) in producing this Guidance.  In support of the Draft Guidance, we offer several general comments.  
A. Analogy to Drugs
BIO appreciates the analogy to the activity, safety, and kinetics of drug/protein therapeutics utilized in the Guidance.  We believe this is a useful starting point for explaining the key objectives of all preclinical translational programs.
B. Organization of Guidance Document
Overall, we suggest that it would help the readability and improve the clarity of the document if this Guidance were made more succinct.  A practical way to accomplish this without losing content is to consolidate comments that apply to all three product types, and place them in Section III.B.2-3.  As a result, each of the specialty product subsections would then focus on program design aspects that are unique to the particular product class.  
C. Novel Delivery
BIO believes guidance on co-development of novel formulations or devices used for delivery of cells or gene therapy is necessary, as many investigators are working with novel delivery methods.  
D. Scope
The Draft Guidance document indicates that it will address expectations to support both Investigational New Drug (IND) and Biological Licensing (BLA) applications.  However, the Draft Guidance focuses primarily on INDs.  We believe that consideration should be given to expanding the discussions in the Draft Guidance to include non-clinical assessments relevant for a BLA filing (e.g. Developmental and Reproductive Toxicology (DART) studies).  While we expect that treatments for lethal genetic disorders will be exempt from these tests, the expectations for treatment of milder conditions, such as connective tissue damage in athletes, or even more severe conditions, such as burn injury, are unclear.
E. Cell Therapy
Nomenclature – It is especially important to distinguish the risks associated with “stem cell” therapies (such as embryonic stem cell and induced pluripotent stem cell (iPSC) therapies) from those of adult tissue-derived and somatic cell therapies (e.g. bone marrow-derived mesenchymal cells).  To better illustrate this distinction, please utilize the term, “somatic cells” and make reference to prior somatic cell Guidances.  This will help readers to appreciate and define the attributes of their cell-based therapy (CBT).
Sections Section IV, C & D (Overall Study Design and Safety) - Please consider combining the considerations for “study design” and “potential safety concerns.”  Many of the aspects listed could be removed and considered in the Section III.B.2. as mentioned above.  Of the remainder, many aspects listed apply equally well to both safety and efficacy studies, since often both aspects are evaluated in the same or similar models.  We have included detailed comments on this topic on pages 19-21 of the chart below.
BIO appreciates this opportunity to comment on the Guidance for Industry: Preclinical Assessment of Investigational Cellular and Gene Therapy Products.  Specific, detailed comments are included in the following chart.  We would be pleased to provide further input or clarification of our comments, as needed.