pre-IND Meeting for Individualized ASOs

Food and Drug Administration (FDA) recommends that sponsors request a pre-IND meeting with the appropriate review division as soon as a participant and at least one potential individualized ASO drug product (with proof-of-concept data) are identified.

Pre-IND meeting is a Type B meeting under the Prescription Drug User Fee Act (PDUFA) and can be in person face-to-face, virtual face-to-face (video conference), teleconference, and written response only (WRO). The written response only (WRO) meeting format would be the preferred format for individualized ASOs. FDA will provide response to the listed questions within 60 days of receiving the full Meeting Package.

To request a WRO meeting, a written request must be submitted to the FDA via the electronic gateway, along with a meeting package to provide background information on the proposed IND.

Upon receiving the request, the FDA will notify the requester of the date it intends to send the written response (generally within 60 days). For individualized ASOs, FDA generally will not grant more than one pre-IND meeting per potential IND application..

For individualized ASOs dosed through the intrathecal route, the appropriate review division would be Rare Diseases and Medical Genetics (DRDMG), Chief Project Management Staff (CPMS), Michael White. [email protected]

Meeting Request

The meeting request should include adequate information for the FDA to assess the potential utility of the meeting and to identify FDA staff necessary to discuss proposed items.

Sponsors should only request meetings with FDA after fully consulting available guidelines and should anticipate future needs and address relevant issues in the fewest meetings. Furthermore, there should generally be no more than 10 total questions to the FDA in a single meeting request.

Content of the meeting request should cover：

1. The application number (if previously assigned).
2. The product name.
3. The chemical name, established name, and/or structure.
4. The proposed regulatory pathway (Non-commercial).
5. The proposed indication(s) or context of product development.
6. The meeting type being requested (i.e. Type B).
7. Pediatric study plans, if applicable.
8. Human factors engineering plan, if applicable.
9. Combination product information (e.g., constituent parts, intended packaging, planned human factors studies), if applicable.
10. Suggested dates and times (e.g., morning or afternoon) for the meeting. Dates and times when the requester is not available should also be included.
11. A list of proposed questions, grouped by FDA discipline. For each question there should be a brief explanation of the context and purpose of the question.

The meeting request must contain the following information:

• The proposed meeting format (i.e., in person face-to-face, virtual face-to-face, teleconference, and WRO).
• The date the meeting package will be sent by the requester.
• A brief statement of the purpose of the meeting.

The numbering of each question in the meeting request should be identical to numbering in the meeting package.

Pre-IND Meeting Package

The meeting package content should support the intended meeting objectives and should contain: summary information relevant to the product; any supplementary information needed to develop responses to issues raised.

FDA and ICH guidelines should be fully consulted when planning, developing, and providing information needed to support a pre-IND meeting. If a product development plan deviates from current guidelines or existing precedent, the deviation should be identified and explained. For Type B meetings, the sponsor should submit the meeting package no later than 30 days before the scheduled date of the WRO response.

The package should justify the proposal to develop an individualized ASO drug product and to include:

• proposed clinical protocol,
• product manufacturing and quality information,
• bioinformatic (information related to the design of the oligonucleotide) and nonclinical pharmacology data to support in-human efficacy of the candidate ASO,
• the design of toxicology studies to support the safety of initiating administration to a participant.

The meeting package should be a sequentially paginated document with a table of contents with appropriate electronic linkage, appropriate indices, appendices, and cross references. Meeting packages should include the same first nine items provided for the meeting request, and in addition, should include:

1. A list of all individuals who will attend the requested meeting.
2. Background section that includes the following:
   a. A brief history of the development program and relevant communications with the FDA before the meeting.
   b. Substantive changes in product development plans when applicable.
   c. The current status of product development.
3. A brief statement summarizing the purpose of the meeting and identifying the type of meeting, if applicable.
4. A list of the final questions for discussion grouped by FDA discipline and with a brief summary for each question to explain the context.
5. Data to support discussion organized by FDA discipline and question. Protocols, full study reports, or detailed data generally are not appropriate for meeting packages.

Links to original guidelines are here and here.

Definitions commonly used during pre-IND communication with FDA for individualized ASOs:

Agency	The Food and Drug Administration
Applicant	Any person or company who submits an application to obtain FDA approval for an individualized ASO and any person who owns an approved application.
Drug Product	A finished dosage form, for example, solution, that contains a drug substance (ASO), generally in association with one or more other ingredients.
Drug Substance	The antisense oligonucleotide chemical, usually in lyophilized powder form and is intended to furnish pharmacological activity, but does not include intermediates used in during synthesis.
DMF	Drug Master File. A Drug Master File (DMF) is a submission to the Food and Drug Administration (FDA) that may be used to provide confidential detailed information about facilities, processes, or articles used in the manufacturing, processing, packaging, and storing of one or more human drugs.
IND	Investigational New Drug application.
Sponsor	An individual, partnership, corporation, or Government Agency and may be a manufacturer, scientific institution, or an investigator regularly and lawfully engaged in the investigation of new drugs, who assumes responsibility for an investigation of a new drug, including responsibility for compliance with applicable provisions of the Federal Food, Drug, and Cosmetic Act and related regulations.