FDA’s Guidance on Successful Development of Rare Disease Products
[Thursday, October 18, 2018] Drug and biologics intended to treat rare diseases require better planning and due diligence due to unique challenges posed by smaller target populations. In a new guidance document released this week, FDA lists several common sense measures for sponsors prior to conducting the first-in-human studies with such products and suggests that these be discussed at pre-IND meetings. FDA’s primary concerns for products in early stages of development are regarding the nature of the product, the relevant non-clinical information to support safe starting doses, and the endpoints to be used in the proof-of-concept clinical trials. The sponsor should have reasonable description of the drug substance and drug product, the manufacturing process, potency assays related to the proposed mechanism of action, description of release assays, and other critical information that would appear in the CMC sections of the IND. The non-clinical studies to be completed before the IND include in vitro and in vivo pharmacology, mechanism of action and toxicology studies to support the doses selected and the delivery methods for the first-in-human trial. The sponsor is expected to conduct the minimum amount of non-clinical studies deemed critical to support the first trial and discuss with FDA additional non-clinical studies in the pre-IND meeting. For rare diseases, FDA may waive studies or defer them to pre-NDA or post-market stages based on the nature of the disease and the product. For example, products intended for life-threatening diseases with no available therapies may get more flexibility. The guidance goes on to list issues related to clinical pharmacology and clinical endpoints, expedited approval, companion diagnostics, pediatric studies and electronic submissions. Pre-IND meetings are strongly suggested to discuss the development program with FDA. This guidance should be used to build a checklist for pre-IND meeting preparation and early stage product development. All the issues discussed in the guidance document potentially apply to all products, not just those intended for rare diseases. None of the topic discussed in the guidance should be new to experienced developers; this guidance document is a great primer for developers of all drugs and biologics.
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