# Presentation: 683961

## Continuous Marketing Applications (CMA) Pilot Programs

- Michael Folkendt
- Special Assistant to the Director
- Office of New Drug Chemistry
- CDER

## Continuous Marketing Applications (CMA)

- “_**T**__**o test**_ whether providing early review of selected applications and additional feedback and advice to sponsors during drug development for selected products can further shorten drug development and review times...”
*PDUFA Reauthorization Performance Goals and Procedures, June 2002*

- June 13, 2004

## CMA Pilot Programs

- Pilot 1 – Discipline Review Letters for Pre-submitted “Reviewable Units” of NDAs/BLAs
- Pilot 2 – Frequent Scientific Feed Back and Interactions During Drug Development

- June 13, 2004

## Scope of CMA pilot programs

- Only applies to _**some**_ products that have been designated to be Fast Track Drugs or Biologics (Section 112 of FDAMA)
- Serious or Life-Threatening Conditions, and
- Potential to Address Unmet Medical Needs
- Must have a written agreement with the review division
- Duration: October 6, 2003 – September 30, 2007.

- June 13, 2004

## Discipline Review Letters for Pre-submitted “Reviewable Units” of NDAs/BLAs

## CMA – Pilot 1Overview

- Must be for a product designated as a Fast Track Product.  Selection based on:
- Clinical Trials have demonstrated that the product has significant promise as a therapeutic advance
- Potential for enhancement of overall application review efficiency
- Must have had an EOP-2 or Pre-NDA/BLA meeting
- Based on an agreement between the review division and the applicant
- Review of a limited number of discrete pre-submitted portions of an NDA/BLA called “**Reviewable Units**” (RU)
- Discipline Review Letter will be issued for each RU within 6 months of receipt

- June 13, 2004

## CMA – Pilot 1Agreement

- Discussion at an EOP-2 or Pre-NDA/BLA meeting
- Plan for RU content and submission schedule.
- Generally,
- 1 RU per technical section
- No more than 4 RU per application
- RU submission should begin no earlier than 1 year in advance of the complete application.

- June 13, 2004

## CMA – Pilot 1Agreement (cont.)

- Clearly label the submission as “Reviewable Unit for CMA Pilot 1” and indicate Discipline
- PDUFA fee must be paid with submission of first RU.
- All facilities supporting the data and/or referenced in the RU should be ready for inspection at the time the RU is submitted.

- June 13, 2004

## CMA – Pilot 1Reviewable Unit

- A pre-defined logical portion of an NDA/BLA
- Complete CMC, Clinical, or Pharm./Tox. technical section (e.g., CMC, clinical, Pharm./Tox., etc.)
-  Other logical component OK _with prior agreement._  For example:_ _
- Drug substance portion (of the CMC technical section),
- one of the pivotal studies,
- Toxicology studies,
- pharmacology studies,
- Human Pk/Pd studies
- Based on FDA resources, generally no more than 4 RUs for an application

- June 13, 2004

## CMA – Pilot 1Process

- Each RU will undergo a 60-day “filing” review
- Substantially (or not) complete for review
- Content based on agreement
- No news is good news
- If “accepted,” FDA will issue a “Discipline Review” (DR) Letter within 6 months of receipt (unless extended).
- One DR per RU
- May be combined with the action letter for NDA/BLA

- June 13, 2004

## CMA – Pilot 1Amendments

- Only minor amendments to RUs are expected (e.g., in response to Information Request letters)
- Major amendments to RUs are strongly discouraged and may trigger a 3 month extension.
- Routine safety updates will be accepted
- Amendments in response to a DR letter will not be subject to Pilot 1 timelines and may not be reviewed until the complete application is submitted.

- June 13, 2004

## CMA – Pilot 1PDUFA Performance Goals

- Discipline Review Letter issued within 6 months of receipt of RU
- 30% of RUs submitted in FY 2004
- 50% of RUs submitted in FY 2005
- 70% of RUs submitted in FY 2006
- 90% of RUs submitted in FY 2007

- June 13, 2004

## Frequent Scientific Feed Back and Interactions During Drug Development

## CMA – Pilot 2

- FDA and applicant enters into agreement to engage in frequent scientific feedback and interaction during the IND phase of product development

- June 13, 2004

## CMA – Pilot 2Eligibility

- Limited to no more than one Fast Track product for each CDER & CBER review division over the course of the pilot program.
- Should have had an EOP-1 meeting (Pre-IND may qualify)
- Not on Clinical Hold

- June 13, 2004

## CMA – Pilot 2Application

- Pilot 2 application should include
- Past and projected milestones in drug development
- How the proposed development program could be significantly enhanced by frequent interaction with the FDA
- The potential for improvement in the efficiency of the development program to significantly benefit public health

- June 13, 2004

## CMA – Pilot 2Agreement

- Will outline
- Types of interaction (meetings, telecons, etc.)
- Types of feed back expected
- Tentative timeline
- Should be flexible enough to allow for adjustment during implementation
- Changes to the agreement can be made in subsequent discussions and must be documented
- Divisions will conduct an annual reevaluation of each agreement to ensure that it continues to promote the goals of the pilot

- June 13, 2004

## CMS-Pilot 2Interaction Agreement

- Frequency of contact
- Timelines and triggering events
- Types of submissions
- Evaluation of protocols, plans, reports, etc.
- Types of feed back expected
- Level of interaction with the FDA
- Regular meetings (face to face, telephone, secure emails)

- June 13, 2004

## CMA-Pilot 2Termination

- Product participation in Pilot 2 will be terminated when:
- An agreement can’t be reached
- The marketing application is submitted
- Applicant withdraws from the pilot
- Drug development changes such that it no longer promotes the goal of the pilot

- June 13, 2004

## Evaluation of the Pilot Programs

- Done by an independent expert consultant familiar with FDA process and regulations
- Done in consultation with the FDA
- Data collect began Oct. 1, 2003
- To assess value, cost, effects of the program in relation to the product development and review process
- Preliminary report to Commissioner by Sept. 30, 2006
- Final Report due after Sept. 30, 2007
- Redacted version of both reports will be available to the public

- June 13, 2004

## Current Status: CMA – Pilot 1

- The CMA Pilot 1 program is progressing well.
- We have already received Reviewable Units for various disciplines.
- Discipline Review Letters for these RUs have begun to be issued.

- June 13, 2004

## Current Status: CMA – Pilot 2

- As of March 9, 2004, 7 of 16 participating CDER review divisions have accepted CMA-Pilot 2 applications.
-  The remaining Divisions may receive applications for Pilot 2 enrollment through Sept. 30, 2004.
- Continuous Marketing Application (CMA) Pilot Programs web page: http://www.fda.gov/cder/pdufa/cma.htm

- June 13, 2004

## References

- Guidance for Industry
- Continuous Marketing Applications: Pilot 1 – Reviewable Units for Fast Track Products Under PDUFA
- Continuous Marketing Applications: Pilot 2 – Scientific Feedback and Interactions During Development of Fast Track Products Under PDUFA
- Continuous Marketing Application (CMA) Pilot Programs web page: http://www.fda.gov/cder/pdufa/cma.htm

- June 13, 2004