"Continuous Marketing Applications (CMA) Pilot Programs"
Continuous Marketing Applications (CMA) Pilot Programs Michael Folkendt Special Assistant to the Director Office of New Drug Chemistry CDER Continuous Marketing Applications (CMA) “To 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 2 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 3 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. 4 June 13, 2004 CMA - Pilot 1 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 6 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. 7 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. 8 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 9 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 10 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. 11 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 12 June 13, 2004 CMA - Pilot 2 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 14 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 15 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 16 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 17 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) 18 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 19 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 20 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. 21 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 22 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 23 June 13, 2004