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Pharmaceutical Technology REGULATORY SOURCEBOOK MARCH 2020 7 It also established draft guidance to help clarify what will be needed in order for a new therapy to be eligible for orphan drug designation and its benefits, which include: • Tax credits for clinical testing • Exemption from some prescription drug user fees • The possibility of seven years of patent exclusivity. This designation is extremely important for gene therapies, because more than 70% of the current pipeline targets rare diseases (i.e., diseases that af- fect fewer than 200,000 patients) (4). The agency has asked for comments on this draft guidance from industry and will be accepting them until April 29, 2020. This article offers brief summaries from new draft and finalized guidance documents and com- piles initial commentary from legal and regulatory experts on their significance. Orphan drugs: from macromolecules to transgenes and vectors According to FDA's draft guidance (5), orphan drug designation can only be granted if the de- veloper can show that the new therapy is differ- ent from, and clinically better than, previously approved treatments (i.e., that it shows greater efficacy, improves patient safety, or significantly improves the level of overall patient care). Extrapolating language from traditional bio- pharmaceuticals to the gene therapy space and applying the principles behind orphan drug regu- lations (21 Code of Federal Regulations 316.3(b) (14) (ii)), which focus on the "macromolecule," and principal molecular structure, FDA is focusing on the transgene (genetic material that is being in- jected into the patient) and the vector (the carrier used to deliver the genetic material). When considering two gene therapies that have been designed to treat the same condition, FDA will currently consider a new gene therapy different from an existing one if: • The two products express different transgenes (encoding different enzymes) and have or use different vectors. • They have or use vectors from different viral classes (e.g., gammaretrovirus, as compared with adeno-associated virus), even if they ex- press the same transgene. If two therapies express the same transgene with or without the same vector, FDA may still consider them different depending on final product features and how they contribute to the overall therapeutic effect, according to the draft guidance. CMC information in the IND One of the most significant differences between the draft CMC guidance of 2018 and the final guidance is increased understanding that CMC data and core quality by design information, such as critical qual- ity attributes (CQAs) and manufacturing processes and controls, may not be available during the earli- est stages of an IND. The guidance states that not all sections of the common technical document (CTD) need to be completed before the IND is submitted and that sponsors can add material to their applica- tion as development progresses. "As your product progresses through development, the list of poten- If two therapies express the same transgene with or without the same vector, FDA may still consider them different.