For Industry
Background and overview: CMA Pilot 1 Evaluation and Pilot 2 Preliminary Evaluation Studies -- Final Report
In 1992, Congress passed the Prescription Drug User Fee Act (PDUFA) authorizing the FDA to collect fees from companies for the review of drug applications as well as for providing regulatory oversight of manufacturing plants. Congressional funds and industry user fees, established under the PDUFA legislation, fund additional resources that allow the FDA to meet drug-review performance goals. In accordance with the 2002 PDUFA Reauthorization Performance Goals and Procedures (PDUFA goals), the FDA agreed to meet specific performance goals to improve the effectiveness and efficiency of FDA review of New Drug Applications (NDAs) and Biologic Licensing Applications (BLAs).
Overview of Continuous Marketing Application Pilots 1 & 2
As part of the current Fast-Track program, the FDA allows for the submission of Rolling Reviews-pre-submitted portions of marketing applications. There is however, no commitment for early review, which depends on resource availability. When reviewers are available, deficiencies of early-submitted sections can be identified earlier, providing in some instances an opportunity for resolution prior to first review action, and ultimately reducing the time for important drugs to reach the market.
| The Continuous Marketing Application (CMA) Pilot 1 program, introduced in PDUFA III, formalizes the commitment for early review of complete sections of marketing applications. Eligible Fast-Track applications can be submitted in up to four pre-determined sections called Reviewable Units (RUs) within one year of complete application submission. Under this Pilot, the FDA commits to reviewing these pre-submitted portions and issuing a discipline review letter within six months of receipt of each RU. In addition to the early feedback commitment, other goals of Pilot 1 included increasing review efficiency (e.g., eliminate the need for resubmission and multiple review cycles) and possibly reducing time to market (e.g., focused RU submissions may increase application quality; early issue resolution may help increase first cycle approvals). Exhibit 2–1 illustrates the differences in Pilot 1 to a traditional Fast-Track application. |
General CMA Pilot 1 program criteria: |
Exhibit 2–1. Comparison of the Fast-Track/Rolling Review and CMA Pilot 1 Programs
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A second CMA Pilot was also established under the PDUFA III legislation, which allows applicants with eligible Fast-Track products to enter into an agreement with the FDA that ensures frequent scientific feedback and interaction during the investigational new drug (IND) phase of product development. The intent of the early interaction is to ensure that the FDA's and sponsors' expectations for the clinical development program are aligned, preventing the need for re-work, and eliminating unnecessary trials. To be eligible, applicants must have a Fast-Track designated product, engage with the FDA at an End-of-Phase 1, or equivalent meeting, and demonstrate that the product has the potential to significantly benefit the public health. Applicants are required to draft an agreement for proposed feedback and interactions with FDA, defining the timing and frequency of FDA-sponsor contacts, the general types of submissions that will stimulate feedback, and the forms of communication requested. Exhibit 2–2 provides an overview of the key differences between a Fast-Track versus a CMA Pilot 2 product. |
General CMA Pilot 2 program criteria: |
Exhibit 2–2. Illustrative Differences between a Fast-Track IND and a CMA Pilot 2 Product
CMA Pilot Evaluation and Report
Under PDUFA III, the FDA agreed to retain an independent, expert consultant to evaluate the value and costs of the CMA Pilots 1 and 2, both from the perspective of the FDA and participating sponsors. This report presents the full evaluation of CMA Pilot 1 and a preliminary evaluation of CMA Pilot 2 which is currently still in early stages.
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The scope of the evaluation included 11 Pilot 1 and 9 Pilot 2 products (see Overview of CMA Pilots 1 & 2). A product comparison cohort was selected from the Fast-Track products submitted between 2002-2004 that were not enrolled in the Pilot programs. In that time frame, there were 12 non-pilot, Fast-Track products, and of those products 8 were selected as the comparison cohort. The 8 products were selected because they had Rolling Review submissions (i.e., portions of the application submitted prior to the submission of the full NDA/BLA) and did not have a special designation (e.g., 505(b)(2)), to ensure the comparison cohort was similar to the eligible Pilot products. Exhibit 2–3 below depicts details of the Pilot 1, Pilot 2 and comparison cohort products as of January 10, 2006. All comparison products have reached first action; 10 of the 11 Pilot 1 products reached first action, with one sponsor withdrawing after Pilot program enrollment. Because Pilot 2 targets products that are in earlier phases of development, only one of the products in this cohort has advanced to the stage of application submission. |
Comparison cohort selection criteria included: |
Exhibit 2–3. Status of the Pilot 1, Pilot 2 and Comparison Cohort Products
|
Pilot 1 |
Status |
Pilot 2 |
Status |
Comparison Cohort |
Status |
|---|---|---|---|---|---|
|
Retisert |
Approved |
8 Products |
IND |
Aldurazyme |
Approved |
|
Tarceva |
Approved |
1 Product |
NDA |
Apokyn |
Approved |
|
Macugen |
Approved |
|
|
Iressa |
Approved |
|
Exjade |
Approved |
|
|
Alimta |
Approved |
|
Kepivance |
Approved |
|
|
Fuzeon |
Approved |
|
Orencia |
Approved |
|
|
Velcade |
Approved |
|
Nexavar |
Approved |
|
|
2 Products |
Approvable |
|
2 Products |
Approvable |
|
|
|
|
|
1 Product |
Not Approvable |
|
|
|
|
|
1 Product |
Withdrawn |
|
|
|
|