Best Practices for Communication Between IND Sponsors and FDA During Drug Development

In December 2015, FDA issued a draft guidance for industry and review staff describing best practices and procedures for communication between investigational new drug application (IND) sponsors and FDA at critical junctures in drug development.

The draft guidance describes:

• FDA’s philosophy regarding timely interactive communication with IND sponsors as a core activity
• The scope of appropriate interactions between the review team and the sponsor
• The types of advice appropriate for sponsors to seek from FDA in pursuing their drug development program
• General expectations for the timing of FDA response to IND sponsor inquiries
• Best practices and communication methods to facilitate interactions between the FDA review team and the IND sponsor during drug development
• Expectations for appropriate methods, including the frequency, of such communications

FDA’s recommendations particularly relevant to RPI’s areas of expertise include:

• Because sponsors are ultimately responsible for managing the overall development program for their proposed drug, sponsors should closely monitor for advances in the field and/or changes in FDA guidance, and inquire if those changes may necessitate changes in prior FDA recommendations for their development program.
• Sponsors should only submit milestone meeting requests when drug development has progressed to the point where a full discussion of issues germane to that development stage is possible. Premature meeting requests are often denied by FDA.
• Sponsors should submit a limited number of clearly worded and targeted questions that directly address concerns about the drug and development program. The number of questions in a meeting package should not exceed what can be reasonably discussed within the duration of allotted meeting time.
• Sponsors should provide sufficient data to support the questions being asked. If the meeting package is determined to be inadequate or too voluminous, the meeting may be rescheduled.
• Sponsors’ meeting packages should be well-organized and indexed to enhance the readability of the background information both before and during the meeting.

Find out more about how RPI can optimize your communication with FDA.

Nonclinical Safety Evaluation of Reformulated Drug Products and Products Intended for Administration by an Alternate Route

In October 2015, FDA issued a guidance for industry and review staff providing nonbinding recommendations for the nonclinical evaluation of previously approved drug substances when a new formulation or a new route of administration for a previously approved formulation is proposed by the sponsor.

The goals of the guidance are to:

• Communicate to industry the FDA’s current thinking pertaining to safety data needed to support approval of these drug products
• Increase uniformity within CDER on recommendations for the nonclinical development of reformulated drug products and products being used by an alternate route

The guidance presents general considerations, systemic toxicity considerations, and route of administration considerations. Notable recommendations include:

• The ICH guidance for industry M3(R2) Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals or S9 Nonclinical Evaluation for Anticancer Pharmaceuticals and the appropriate review division should be consulted regarding the timing of submission of nonclinical data relative to clinical development.
• The adequacy of the available systemic toxicity information should be evaluated based on a comparison of the systemic exposure obtained after administration of a proposed new formulation to the systemic exposure with use of the previously approved formulation.
• In general, durations of the toxicity studies should follow the recommendations outlined in ICH M3(R2) or ICH S9. For a new formulation that will be used by the same route as the previously approved product, shorter duration toxicity studies than those outlined in ICH M3(R2) may be appropriate.
• In addition, the route-specific recommendations should be considered for all new formulations, whether they are proposed for a new route or the same route as a previous formulation.

For further assistance in preparing submissions for reformulated and other drug products, contact RPI.

FDA to require electronic submission by 2017

In May 2015, FDA finalized the guidance for industry requiring that all new drug and biological product submissions, including drug/device combination products, be sent electronically and in the format specified by FDA.

Submissions that are not sent electronically or in a format that FDA can process, review, and archive will not be filed or received, unless exempted from the electronic submission requirements.

The electronic submission requirements will go into effect on:

• May 5, 2017 for NDAs, ANDAs, BLAs, and master files.
• May 5, 2018 for commercial INDs. (Noncommercial INDs are exempt.)

A notable change from the draft guidance document is the inclusion of master files under the electronic submission requirements. FDA considers master files to be submissions to an NDA, ANDA, BLA, or IND, such as DMFs (new drug master files), BPFs (new biological product files), and any amendments to or annual reports on previously submitted DMFs or BPFs.

This guidance document outlines electronic submission specifications and provides links to technical specification documents. Further and more detailed technical instructions will be included in a separate eCTD technical conformance guide.

Contact RPI for assistance in meeting FDA’s new electronic submission requirements.

Formal Meetings Between the FDA and Sponsors or Applicants of PDUFA Products Guidance for Industry

In March 2015, FDA issued a draft guidance providing recommendations to industry on formal meetings between FDA and sponsors or applicants relating to the development and review of drug or biological drug products regulated by the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER). This guidance does not apply to abbreviated new drug applications, applications for biosimilar biological products, or submissions for medical devices.

This draft guidance discusses the principles of good meeting management practices (GMMPs) and describes standardized procedures for requesting, preparing, scheduling, conducting, and documenting such formal meetings. These GMMPs are intended to provide consistent procedures that will promote well-managed meetings and to ensure that such meetings are scheduled within a reasonable time, conducted efficiently, and documented appropriately.

This draft guidance revises the guidance for industry Formal Meetings Between the FDA and Sponsors or Applicants issued in May 2009. After it has been finalized, this guidance will replace the May 2009 guidance. Significant changes from the 2009 version include:

• Addition of the written response meeting format for pre-investigational new drug application (pre-IND) and Type C meetings
• Designation of a post-action meeting requested within 3 months after an FDA regulatory action other than approval as a Type A meeting
• Designation of a post-action meeting requested 3 or more months after an FDA regulatory action other than approval as a Type B meeting
• Designation of a meeting regarding risk evaluation and mitigation strategies (REMS) or postmarketing requirements that occur outside the context of the review of a marketing application as a Type B meeting
• Inclusion of a meeting package in Type A meeting requests
• Designation of meetings to discuss the overall development program for products granted breakthrough therapy designation status as a Type B meeting

Contact RPI for assistance with FDA interactions, including meeting preparation and representation at FDA meetings.