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Background and overview: CMA Pilot 1 Evaluation and Pilot 2 Preliminary Evaluation Studies -- Final Report

Table of Contents

EXECUTIVE SUMMARY

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:
•  Product must be Fast-Track
•  Typically, no more than four RUs per application
•  RUs can be submitted up to 12 months prior to complete submission
•  FDA commits to a 6-month RU review

 

Exhibit 2–1. Comparison of the Fast-Track/Rolling Review and CMA Pilot 1 Programs

link to long description of Exhibit 2-1D

 

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:
•  Product must be Fast-Track
•  Must have had an End-of-Phase 1, or equivalent meeting
•  Must not be on clinical hold
•  Only one Pilot 2 product per CDER/CBER review division

Other FDA considerations for applicants:
•  Potential value of enhanced interaction (public health benefit resulting from development of the product)
•  Likelihood that concentrated scientific dialogue will facilitate the availability of a promising novel therapy
•  Demonstration of commitment to product development

 

 

Exhibit 2–2. Illustrative Differences between a Fast-Track IND and a CMA Pilot 2 Product

The major difference between the CMA Pilot 2 program and the Fast-Track program is the number of scheduled FDA/sponsor interactions.D

 

 

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.

 

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:
•  Not a Pilot product
•  Designated Fast-Track and submitted a portion of the application as a rolling submission
•  Recent and available data
•  Products assigned to divisions similar to those of the pilot products

 

 

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

 

 

 

 

Methodology Analysis Overview