FDA Final Rule and Draft Guidance on Orphan Drug Designation

A final rule amending the 1992 Orphan Drug Regulations became effective on August 12, 2013. The main change from the proposed rule was to add the definition of “orphan subset”.  In particular, “Orphan subset of a non-rare disease or condition (‘orphan subset’) means that use of the drug in a subset of persons with a non-rare disease or condition may be appropriate but use of the drug outside of that subset (in the remaining persons with the non-rare disease or condition) would be inappropriate owing to some property(ies) of the drug, for example, drug toxicity, mechanism of action, or previous clinical experience with the drug.” Additional changes include:

• Removing the language in the proposed rule that, to demonstrate clinical superiority, the drug must provide safety and effectiveness comparable to the approved drug
• Clarifying that a designation request need include only ‘relevant’ in vitro laboratory data, as well as data from ‘clinical experience’ with the drug in the rare disease or condition
• Stating that FDA’s publicly available posting of designated drugs will include whether a drug is no longer designated if the drug loses designation
• Clarifying that the scope of orphan exclusive approval is limited to the indication(s) or use(s) for which the designated drug is approved
• Clarifying that a designated drug that is otherwise the same as a previously approved drug receives 7-years market exclusivity upon approval only if the sponsor of the second-in-time drug demonstrates upon approval that its drug is clinically superior to the previously approved drug

A draft guidance published in April 2014 describes procedures for meetings with the Office of Orphan Products Development (OOPD), including timing:

• OOPD will aim to respond to a request for an informal or formal meeting within 5 working days of receipt. Before scheduling the meeting, OOPD may request a brief list of questions that the stakeholder hopes to have answered.
• If a formal meeting is scheduled, OOPD should receive a meeting package at least 2 weeks before the meeting. If OOPD fails to receive a meeting package on time, OOPD may postpone the meeting and work with the stakeholder to reschedule.
• If meeting minutes are warranted, the stakeholder should provide a draft of summary meeting minutes within 15 working days after the meeting.

For further assistance on preparation of orphan designation applications, contact RPI.

FDA Draft Guidance on Pediatric Study Plans

The FDA Safety and Innovation Act (FDASIA), signed into law on July 9, 2012, requires that the sponsor of a drug subject to the Pediatric Research Equity Act (PREA) submit an initial pediatric study plan (PSP) early in the drug development process. The intent of the PSP is to identify needed pediatric studies early in drug development and begin planning for these studies.

A draft guidance published in July 2013 specifies the timing of a PSP submission:

• The sponsor must submit the initial PSP before the submission of the required assessments and no later than 60 calendar days after the end-of-phase 2 meeting.
• In the absence of an end-of-phase 2 meeting, the sponsor should submit the initial PSP as early as practicable but before the initiation of any phase 3 studies, or any combined phase 2 and phase 3 study.
• If a phase 3 study, or a combined phase 2 and phase 3 study, will not be conducted, the sponsor should submit the initial PSP no later than 210 calendar days before the submission of a marketing application or supplement.

A sponsor should submit the initial PSP to its Investigational New Drug (IND) Application. In cases when there is no active IND for the drug, but the sponsor expects to include a phase 3 or combined phase 2 and phase 3 study, the initial PSP should be submitted as a pre-IND submission. In this situation, FDA encourages sponsors to schedule a pre-IND meeting before submission of the initial PSP.

For assistance on preparation of Pediatric Study Plans, contact RPI.

FDA Guidance on Providing Regulatory Submissions in Electronic Format — Receipt Dates

FDA Guidance on Providing Regulatory Submissions in Electronic Format — Receipt Dates

In February 2014, the FDA issued a guidance to assist sponsors, applicants, and others making regulatory submissions in electronic, paper, or hybrid format to the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER).

The guidance eliminates the 4:30 PM cut-off for electronic submissions received through the electronic submission gateway (ESG) Monday through Friday. Electronic submissions submitted up to 11:59 PM will now be assigned a receipt date corresponding to the same day of submission.

The FDA states that a regulatory submission’s receipt date is the date on which the submission is deemed to have arrived at the FDA. The receipt date may be used to determine important regulatory milestones, such as the end of the 30-day safety review cycle and the review performance goal date.

A paper submission is assigned a receipt date corresponding to the day on which it physically arrived at the appropriate receiving unit of the FDA center designated to review the submission, while the office is open for business.

Contact RPI to find out how your company can use electronic publishing to streamline the FDA submission process.