BIO submitted comments on the Food and Drug Administration’s (FDA) Draft Guidance, Human Gene Therapy for Rare Diseases. BIO says the guidance will assist stakeholders developing human gene therapy (GT) products to treat rare diseases. BIO reminds FDA that complex, innovative clinical trial designs might be fit-for-purpose to execute clinical trials of GT products for rare diseases. Consequently, BIO urges FDA to provide regulatory flexibility to allow for innovative clinical trial designs – and to not otherwise use limiting language, such as recommending a specific number of treatment arms, utilizing different doses but the same product administration procedures, or the inclusion of a sham control group. The use of innovative clinical trial designs can decrease unnecessary and unethical patient exposure to clinical procedures and experimental products while still advancing clinical development. BIO also requests additional guidance on what types of patient experience data would be most helpful to inform regulatory decision-making.  

BIO submitted comments on the Food and Drug Administration’s (FDA) Draft Guidance on Human Gene Therapy for Retinal Disorder and Human Gene Therapy for Hemophilia. BIO says the guidance will assist stakeholders developing human gene therapy (GT) products to treat rare diseases, including hemophilia and retinal disorders, and provided specific suggestions for the FDA to clarify both guidances. The topics discussed in BIO's comments include preclinical in vitro and in vivo proof-of-concept studies and disease-specific animal models, science-based regulatory flexibility when evaluating appropriateness of animal models, the use of the word "pharmacokinetics," biodistribution studies, reproductive/developmental toxicity studies, fit-for-purpose clinical trial designs, and patient experience.

BIO submitted comments on the Food and Drug Administration’s (FDA) Draft Guidance, Chemistry, Manufacturing, and Control (CMC) Information for Human Gene Therapy Investigational New Drug Applications (INDs). BIO says the comprehensive draft guidance effectively covers a range of chemistry, manufacturing, and control (CMC) topics relevant to gene therapy products. However, BIO notes the draft guidance is quite prescriptive and does not necessarily match modern manufacturing. BIO would like to see a better balance between the information FDA needs to see in order to allow an IND to move forward, and over-reporting of information that may be unnecessary. On the whole, it seems much of the information required by the draft guidance is more appropriate for a BLA filing, an approved product, or postapproval changes to a product rather than an IND. BIO suggests specific changes to avoid misinterpretation and clarify the scope, the stage of development the guidelines apply to, and testing expectations, among other topics.

BIO submitted comments on the Food and Drug Administration’s (FDA) Draft Guidance, Long-Term Follow-Up After Administration of Human Gene Therapy Products. BIO says the guidance reflects the FDA’s experience evaluating the safety of gene therapy products over the past decade. In addition, the guidance provides important recommendations on how to determine and develop long-term follow-up after the administration of human gene therapy products. BIO provides general and detailed comments on a number of issues, including the safety risk and viral vector of gene therapy products, logistical challenges of long-term follow-up periods and the need to work with sponsors to develop best practices, the importance of partnering with stakeholders on biodistribution questions, and the importance of harmonization with global, multilateral organizations in the field.

BIO submitted comments to the National Institutes of Health (NIH) regarding the Proposed Changes to the NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules. BIO applauds the NIH’s efforts to support and advance drug development for gene therapies, by streamlining protocol registration and reporting requirements and by modifying the roles and responsibilities of the Recombinant DNA Advisory Committee. BIO agrees with the goal to eliminate duplication and excess in regulation of gene therapy products, as these redundancies do not exist in most other areas of clinical research. BIO believes there is sufficient and robust regulatory framework already in place for safe and effective development of gene therapy products. BIO also proposes changes to the requirement for an Institutional Biosafety Committee (IBC) approval of a study site before initiation of a study.

BIO submitted comments on the Food and Drug Administration’s (FDA) Draft Guidance, Expansion Cohorts: Use in First-In-Human Clinical Trials to Expedite Development of Oncology Drugs and Biologics. BIO welcomes FDA’s efforts to provide clear guidance on the regulatory and scientific framework for designing and conducting adaptive trial designs in which different aspects of a drug can be assessed in a single clinical trial while enrolling the minimum number of study participants necessary. BIO’s comments cover topics including sample sizes, the need for flexibility, and balancing safety and efficacy. BIO encourages the FDA to consider expanding the use of the guidance beyond oncology.