# Presentation: 706196

## An FDA Approach to the Pre-IND Meeting Between a Sponsor and the AgencyJonathan Wilkin, M.D.Director, Division of Dermatologic and Dental Drug Products, Center for Drug Evaluation and Research, FDA

## “The views expressed are those of the author and do not necessarily represent those of the Food and Drug Administration.”

## Early Communication

- “It’s often a combination of problems that prevent approval.  Close communication with the FDA early on in a drug’s development reduces the chance that an application will have to go through more than one cycle of review.  But it’s no guarantee.”
- John Jenkins, MD
- Meadows, M. (July-August 2002) The FDA’s Drug Review Process: Ensuring Drugs are Safe and Effective. _FDA Consumer Magazine._

## Resources

- Code of Federal Regulations	21 CFR 312.47 & 312.82
- Guidance for Industry
- 	-  Formal Meetings with Sponsors and
- 		   Applicants for PDUFA Products (1995)
- 	-  Content and Format of IND Applications for	   Phase 1 Studies of Drugs... (2000)
- Manual of Policies and Procedures
- 	MaPP 4512.1 : Formal Meetings Between CDER and CDER’s External Constituents (3/7/96)

## 21 CFR 312

- 312.47 Meetings	(a) *General.* Meetings between a sponsor and the agency are frequently useful...
- ...during the course of a clinical investigation.
- 312.82 Early consultation	For products intended to treat life-threatening or severely debilitating illnesses, sponsors may request to meet with FDA-reviewing officials early in the drug development process...

## Guidance for IndustryFormal Meetings With Sponsors and Applicants for PDUFA Products 

- Types of Meetings (A, B, C)
- Procedures for Requesting Meetings
- Information Package
- Procedures for the Conduct of  Meetings
- Documentation
- Dispute Resolution

## Meeting Request

- Should include adequate information for the Division to determine the utility of the meeting and to identify Agency staff necessary to discuss proposed agenda items

## Meeting Request

- Type of meeting
- Meeting objective
- Proposed agenda
- Listing of specific questions that are categorized and grouped by discipline, viz., CMC pharmacology/toxicology, clinical pharmacology and biopharmaceutics, clinical microbiology (if any), clinical and biostatistics.
- List of sponsor participants

## Meeting Request

- Quantitative composition (all ingredients by percent composition) of the drug proposed for use in the study(ies) to be discussed
- Proposed indication and dosing regimen, viz., concentration (for topicals), amount dosed and frequency and duration of dosing
- For Pre-IND meetings, please specify one for each of the following:
- 		-  Phase 1/2, or End of Phase 2/Pre-Phase 3
- 		-  Rx Product, or OTC Product
- 		-  505 (b)(1), or 505 (b)(2)

## Meeting Request

- FDA meeting attendees are determined based on this information.  If briefing submitted does not reflect the information provided in your request, the meeting will be subject to delay.

## Pre-IND Meetings can be especially helpful when:

- novel indication
- no current Guidance Documents
- avoid clinical holds and/or protocol changes
- new sponsors or new to area of drug development
- sponsor has questions
- problematic pharm/tox signals
- new molecular entity
- serious or life-threatening disease is target

## Regulatory Elegance

- “Elegance” understood in
- organic chemical syntheses
- mathematical proofs
- Elegance implies doing only
- 	what is both necessary and
- 	sufficient

## Example of Regulatory Elegance

- Topical products intended for use on sun-exposed skin undergo phototoxicity and photoallergy testing.
- If no absorption by any ingredient in 290-700nm, then much phototesting can be waived.

## Discussion by Discipline

- Chemistry
- CMC Microbiology
- Pharmacology/Toxicology
- Clinical Pharmacology and Biopharmaceutics
- Clinical Microbiology
- Clinical
- Biostatistics
- Administrative/Regulatory

## Pre-IND Chemistry

- CMC information absent or minimal
- no CMC questions
- helpful if sponsor would state that IND would comply with CMC expectations in the two IND Guidances:
- 		-  Content and Format of IND Application
- 		    for Phase 1 Studies of Drugs
- 		-  INDs for Phase 2 and Phase 3 Studies CMC
- 		   Information

## Pre-IND CMC Microbiology

- sterility considerations for products applied to open wounds, lesions

## Pre-IND Pharmacology/Toxicology

- 505 (b)(1) vs. 505 (b)(2) can make a significant difference in the nonclinical data recommendations
- need to adequately characterize the toxicity of excipients

## Pre-IND Clinical Microbiology

- tendency to overlook the need to conduct microbiological studies in accordance with recent methods and standards
- lack of supportive information regarding the spectrum of activity against targeted pathogens
- tendency, esp. with topicals, to ignore exposure- antimicrobial activity relationship for relevant pathogens
- no Clinical Micro questions

## Pre-IND Clinical

- seeking End-of-Phase 2-type agreements too early
- tendency to overlook the need for bridging studies for many formulation changes, especially topicals
- rushing to Phase 3 without adequate learning in
- 	Phase 2
- insufficient attention to exposure-response relationships for safety as well as efficacy

## Pre-IND General

- pediatric development plan
- quality of life assessments
- problems with presenting new information at the meeting as an “update” to the briefing document

## Summary

- 	The Pre-IND meeting can serve a beneficial purpose for both the FDA review team and the sponsor to provide clarity and resolve issues related to the drug development and review processes.