Orphan Drugs: BIO Comments on FDA Draft Guidance Clarification of Orphan Designation of Drugs and Biologics for Pediatric Subpopulations of Common Diseases
Re: Docket No. FDA-2017-D-6380: Clarification of Orphan Designation of Drugs and Biologics for Pediatric Subpopulations of Common Diseases
The Biotechnology Innovation Organization (BIO) thanks the Food and Drug Administration (FDA) for the opportunity to submit comments regarding FDA’s Draft Guidance, Clarification of Orphan Designation of Drugs and Biologics for Pediatric Subpopulations of Common Diseases.
BIO is the world's largest trade association representing 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. Specifically, BIO and its member companies are committed to conducting pediatric studies that lead not only to innovative therapies for children, but also provide important pediatric labeling information on efficacy, safety, and dosing. As FDA notes in the Draft Guidance, the Best Pharmaceutical for Children Act (BPCA) and the Pediatric Research Equity Act (PREA) are responsible for the addition of new pediatric information in labeling for over 600 products.
BIO appreciates the FDA’s efforts to clarify and provide notice of an FDA policy change intended, as stated in the Draft Guidance, to enable FDA to apply the Orphan Drug Law (ODA) and PREA to non-rare adult indications that correspond to orphan-designated pediatric subpopulations. However, in the paragraphs that follow, BIO details several general concerns and specific line edits regarding the draft guidance and policy changes:
We recognize that FDA’s interpretation and application of the ODA to grant Orphan Drug Designation (ODD) to drugs for use in pediatric populations based on prevalence/incidence alone preceded BPCA and PREA. As such, it may have inadvertently created a regulatory scenario in which PREA-required pediatric studies could be exempt by virtue of the designation. However, there are many examples of products that have been designated and are either being studied or have been approved for pediatric indications, reflecting that the regulatory scenario that may have been created has not kept innovator companies from investing in pediatric drug development for rare pediatric sub-population of a common disease. However, the terminology used by the FDA in the draft guidance implies that sponsors are acting inappropriately by taking advantage of a “loophole”. BIO respectfully disagrees and requests that the FDA adjust this language within the guidance to reflect that it has been FDA’s legal interpretation of the PREA that has allowed for such designations to be granted.
Throughout the Draft Guidance, the FDA references the terms “pediatric subpopulation(s)” and “pediatric-subpopulation designation(s)” as common lexicon, however, these terms have not been previously defined or described within Title 21: Food and Drugs PART 316—ORPHAN DRUGS, nor, have the terms been used in past FDA orphan drug guidance, or the associated FAQs on the FDA web-site. Specifically, these terms have not been described in question 14 of the FAQs, defining an “orphan subset”. To this end, BIO requests that the above terminology be more clearly defined within the text of the Draft Guidance. Additionally, to more clearly demonstrate the FDA’s thinking, BIO also requests that the FDA provide, in the Draft Guidance, specific examples as to what would constitute an “orphan subset” as defined by molecular characteristics, safety profile, and empirical evidence. BIO also asks for clarification of the term “different disease”, included in bullet two of FDA’s criteria for determining whether a product may receive orphan designation for a pediatric subpopulation (Draft Guidance, page 4). We also ask that specific examples be provided indicating what is meant by “different disease” as defined by endpoints, biomarkers, or other measures.
For clarity, we ask the FDA to revise references to prevalence to state the following:
- Orphan or rare diseases: less than 200,000 patients
- Common diseases or conditions: 200,000 or greater patients
BIO appreciates this opportunity to submit comments regarding FDA’s Draft Guidance, Clarification of Orphan Designation of Drugs and Biologics for Pediatric Subpopulations of Common Diseases. In addition to the comments above and the line edits include in the attached table, BIO strongly believes that multiple incentives work in tandem towards broader public health outcomes, and this is particularly true in the case for rare disease drug development. BIO asks the FDA to continue to strive towards an appropriate balance of incentives to encourage rare disease drug development. We would be pleased to provide further input or clarification of our comments, as needed.
 See FDA, Summary Review of NDA 22205, at 16 (“OCC interpreted the Act to mean that PREA does not apply to adult approvals in which the same indication has orphan designation in pediatrics.”).
 Food and Drug Administration FAQs, https://www.fda.gov/ForIndustry/DevelopingProductsforRareDiseasesConditions/HowtoapplyforOrphanProductDesignation/ucm240819.htm