# Sample Statement of Work for the Evaluation of First Cycle Review Performance

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This document, as currently written, is a sample Statement of Work. FDA
will consider all comments received in the Federal Register Notice of
Availability about this statement of work before finishing it prior to
awarding any task order under the related contract.

This sample task order is a model of a task order that will be
representative of those a prospective contractor should expect to
receive under the contract. This sample task order is included only to
assist in the selection of a contractor based upon proposal responses
received in accordance with the RFP.

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# A. Background 

> In conjunction with the 2002 PDUFA Reauthorization Performance Goals
> and Procedures (PDUFA goals) FDA agreed to meet specific performance
> goals (See 2002 PDUFA Reauthorization Performance Goals and Procedures
> [www.fda.gov/oc/pdufa/PDUFAIIIGoals.html](http://www.fda.gov/oc/pdufa/PDUFAIIIGoals.html)).
> Under the PDUFA goals, FDA agreed to create a joint guidance for
> review staff and industry on good review management principles (GRMPs)
> that apply to the first cycle review of NDAs, BLAs and efficacy
> supplements. These GRMPs clarify the roles and responsibilities of
> review staff in managing the review process and identify ways in which
> NDA and BLA applicants may enhance the effectiveness and efficiency of
> the review process. Under the PDUFA goals, FDA also agreed to provide
> applicants with early notification of issues identified during the
> filing review (filing review issues). The PDUFA goals specify that
> training must be provided to FDA staff in association with the
> implementation of these programs.
>
> These programs are intended to improve the effectiveness and
> efficiency of the first cycle review of new product applications.
> During the first review cycle, a well-managed review process allows
> sufficient time for careful regulatory decision-making, and if needed,
> time to work with the applicant to resolve readily correctable
> deficiencies in the application. For applications that otherwise meet
> the standards for approval, the process allows for finishing the
> review of the labeling and other regulatory issues (e.g., negotiation
> of postmarketing commitments) and issuance of an approval letter on or
> before the PDUFA goal date, thereby eliminating unnecessary,
> inefficient additional review cycles.
>
> Such a well-managed review process fulfills the Agency's public health
> mission to make safe and effective products available to the public in
> a manner that is timely, while making the most efficient use of the
> Agency's limited resources.
>
> Under the PDUFA goals, FDA agreed to retain an independent expert
> consultant to evaluate first cycle reviews of NDAs for NMEs (new
> molecular entities), and BLAs. The analysis will include a study of
> the impact of the new programs associated with drug review.

B.  **[Key Objectives of the PDUFA III Evaluation of First Cycle Review
    Performance]{.underline}**

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1)  Determine current performance including a retrospective analysis of
    the cycles necessary for approval and the reasons for multiple cycle
    reviews for NDAs for NMEs and BLAs submitted in FY 2002. This
    retrospective analysis will determine the factors that have led to
    successful first cycle outcomes as well as the factors that have
    contributed to the need for multiple cycle reviews. Where possible,
    it should identify the underlying root causes for multiple reviews.

2)  Track the steps of the first review cycle and determine whether
    there are correlations with the outcome of the first review cycle
    for NDAs for NMEs and BLAs submitted during PDUFA III, FY 2003
    through FY 2007.

3)  Determine the impact of the implementation of the GRMPs on the first
    cycle review process for NDAs for NMEs and BLAs submitted during
    PDUFA III. Performance before and after implementation of the first
    cycle initiatives, including notification of filing issues, will be
    compared. Also, determine the effectiveness of the training program
    for GRMPs.

# Scope of Work 

The primary goal of this study is to evaluate the impact of FDA's
implementation of initiatives to enhance first cycle review performance
during the five-year period of PDUFA III. The evaluation will include
prospective and retrospective analyses of review process management,
communication between FDA and applicants, and other factors that
contribute to first review cycle outcomes, such as the quality of NDAs
for NMEs and BLA submissions. The standards for scientific and
regulatory decision-making are not the subject of this evaluation. The
evaluation will be conducted from the perspective of both FDA and
applicants.

> The evaluation of first cycle review programs will include all
> original NDAs for NMEs submitted to CDER, and for all original BLAs
> submitted to CBER in FY 2003 through FY 2007 (October 1, 2002 through
> September 30, 2007). Review performance will be measured for each
> application and reported by receipt cohort.
>
> For the first cycle review of applications, the contractor should
> assess the interactions between FDA and the applicants by examining
> documents and by observing events in the review process. The
> contractor should draw on many sources of information, such as FDA
> tracking databases, participation in review events, direct feedback
> through interviews with FDA and applicant staff, and other records of
> review activity.

C.  **[Key Tasks]{.underline}**

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1)  Assess baseline review performance for PDUFA applications (NDAs for
    NMEs, BLAs) submitted to FDA in FY 2002. This analysis will include
    the number and length of cycles for each review, and the primary
    reasons and root causes for multiple review cycles.

2)  Assess the first cycle review activity for all NDAs for NMEs and all
    BLAs submitted during PDUFA III, FY 2003 through FY 2007, evaluating
    the events that occurred between submission and approval. Identify
    the best practices of FDA and industry that increased the
    effectiveness and efficiency of the review process, and identify the
    root causes of multiple review cycles. Sample evaluations include:

    a.  Quality and effectiveness of FDA-applicant interactions,
        including use of information request and discipline review
        letters

    b.  Characteristics of the product, application, applicant, and
        review team

3)  Identify and describe the sources of variation in review practices
    by review divisions for tasks 1 and 2 above.

4)  Investigate correlations between review actions and outcomes of the
    first review cycle. For a sample of applications, evaluate the
    impact of the use of GRMPs in product review.

5)  Assess the effectiveness of the training program on GRMPs that FDA
    will give to review staff during implementation of the GRMPs.

6)  Recommend actions on a continuous basis that would improve first
    cycle review performance. The contractor will provide
    recommendations that can be used to increase the quality of
    FDA-applicant interactions, the quality of applications, early
    notification of application deficiencies, and timely resolution of
    deficiencies.

> These improvements should increase the quality and efficiency of
> reviews, and eliminate unnecessary multiple reviews without
> compromising patient safety and product efficacy standards.
> Preliminary recommendations will be summarized for FDA management on a
> yearly basis and final recommendations will be included as part of the
> final study report.

The contractor will prepare annual reports of the findings of the study
and a final study report at the end of the five-year study period. The
full (unredacted) study reports will be provided to the FDA Commissioner
and a version of the study reports redacted to remove confidential
commercial information or other information exempt from disclosure will
be made available to the public.

E.  **[Deliverables]{.underline}**

    1.  Quarterly written progress reports to the Project Officer, with
        monthly oral reports. (If needed, written reports may be
        required monthly.)

    2.  Periodic briefing(s) to the PDUFA III Implementation Steering
        Group

    3.  Annual reports and briefings to the PDUFA III Implementation
        Steering Group in December of each year, 2004 - 2006

    4.  Draft final report for FDA review and comment 60 days before due
        date of unredacted, final report

    5.  Final reports (two versions) addressing FDA comments, due in
        September, 2007

    6.  Electronic versions of all presentations, reports, databases,
        methodologies, and models in formats compatible with IBM PC
        Systems, preferably Microsoft Office