The CDER Medical Policy Council’s review of “breakthrough therapy” designation requests for specific products and indications marks a departure from the council’s charge to take a big picture approach to addressing broader, non-product-specific policy challenges.

Nevertheless, the task of reviewing the growing number of breakthrough requests has been handed to the council to ensure consistency of decisions under the new regulatory pathway created by the FDA Safety and Innovation Act.

CDER is seeking public input on medical policy issues that should be brought before the council.

In announcing the council’s establishment in January 2012, Center for Drug Evaluation and Research Director Janet Woodcock said the group would provide a “senior-level forum for deliberations about medical policy issues in CDER (and its application to the new and generic drug review process, as well as other CDER programs) and will help to ensure that medical policy is implemented in a consistent manner throughout the center” Also see "Senior CDER Management Panel Could Facilitate Novel Therapy Approval" - Pink Sheet, 1 January, 2012..

A newly enacted Manual of Policies and Procedures governing the council’s operations provides more insight into the group’s membership and focus, as does a Federal Register notice announcing the creation of a docket for comments on potential matters for council consideration.

Senior-Level Membership

The council’s organization, membership, responsibilities and procedures are described in a MAPP that took effect on March 19.

The council comprises senior officials from across the drugs center (see box). The Center for Biologics Evaluation and Research, the Center for Devices and Radiological Health and other relevant agency offices will be invited to send a representative to attend council meetings of known interest, the MAPP states.

CDER’s Medical Policy Council

Chair:

Rachel Sherman, director, Office of Medical Policy

Members:

Janet Woodcock, director, CDER
Robert Temple, deputy center director for clinical science
John Jenkins, director, Office of New Drugs
Gerald Dal Pan, director, Office of Surveillance and Epidemiology
OND review division director to participate for a one-year term (current representative: Ann Farrell, Division of Hematology Products)
OND review division medical officer to participate for a one-year term (current representative: Aliza Thompson, medical team leader, Division of Cardiovascular and Renal Products)

The MAPP makes no mention of the council’s review of breakthrough therapy requests. Rather, it characterizes the council’s work as one of broader policy development that is not focused on specific products.

“Although the issue discussed by the council may have been triggered by a specific product, the policy established by the council will be applied to all similar products,” the MAPP states. “Product-specific decisions will be remanded to the appropriate review division and/or office for follow-up and implementation.”

The MAPP lists nine general areas of medical policy that fall within the council’s domain:

Clinical evidence of effectiveness or safety;
Clinical study/trial design;
Professional and patient labeling;
Prescription drug promotion;
Human subjects protection;
Bioresearch monitoring;
Good clinical practice;
Counter-terrorism drug development (such as application of the “animal rule”); and
Post-marketing surveillance.

To be considered by the council, a medical policy matter typically would meet one or more of the following criteria: a novel issue requiring senior management input; an issue on which CDER seems to have taken inconsistent positions; an existing policy position that should be reconsidered in light of scientific or regulatory advances; a complex safety management issue requiring senior management input; a policy that may be triggered by a specific product, but that will be applicable to other products; or strategies for implementation of a new policy.

The MAPP includes an attachment listing examples of medical policy issues and challenges that the council may address (see chart).

Issues may be submitted for consideration by any CDER staff member and may be developed from issues raised by the medical products industry, academia, political bodies or other interested parties and brought to the attention of CDER staff, the MAPP states. The medical policy issue that is presented to the council will not be product-specific.

In a March 18 Federal Register notice, FDA announced the opening of a public docket to receive “suggestions, recommendations and comments for topics from interested parties, including academic institutions, regulated industry, patient representatives and other interested organizations” on medical policy issues for council consideration.

“These comments will help the agency identify and address medical policy issues that need clarification through guidance, notice and comment procedures, or other means,” the notice states. The comment deadline is July 16.

Busy With Breakthroughs

FDA said the council meets approximately once a month on topics other than breakthrough therapy requests. Although the MAPP is silent on the council’s role in the breakthrough therapy program, the early industry enthusiasm surrounding the expedited development pathway has surely created a lot of additional work for the group in recent months.

As of April 10, CDER had received 36 requests for breakthrough designation and had taken action on 21 of those (see related story, [A#06130501025]).

The council considers breakthrough therapy designation based on the review division’s recommendation of the sponsor’s request. “The council will either agree or disagree with the review division’s recommendation by consensus,” FDA explained.

CDER officials have pointed to the council’s review of such requests in highlighting efforts to ensure that FDASIA’s new drug development and review provisions are consistently applied across the center ([A#00121224003]).

During an April 11 address to the World Orphan Drug Congress, former FDA Deputy Commissioner for Medical and Scientific Affairs Scott Gottlieb, now a resident fellow at the American Enterprise Institute, said the center-level oversight will help to smooth out any differences in how the review divisions are implementing the breakthrough program.

“Some divisions have been more proactive, more aggressive, about implementation of it and using the measures afforded by the new pathway to try to accelerate development than others,” he said, noting that the oncology review divisions have been particularly proactive. “I think there’s going to be a sort of shaking out. We’re going to get a sense of which divisions have interpreted this differently than others and there’ll be some standardization.” A framework at the center level will “get some standardization, harmonization between the different divisions in how they apply these new provisions.”

Obstacles to development of a non-inferiority margin (e.g., historic data outdated or historic data unavailable on current endpoint, or efficacy data unavailable on proposed comparator or non-inferiority margin undefined when new drug must be used in combination with other active agents)

Obstacles to development of an appropriate control regimen (e.g., the new product has already been adopted by the medical community as the standard of care for a new off-label indication)

Ethical obstacles to studying a drug in a high prevalence area where drug may not be deployed in the future (e.g., malaria prophylaxis)

Standards for use of the animal rule

Approach to new indications proposed by sponsors, principles in deciding on medical relevance.

Approval of products that may benefit the community but not the individual (e.g., combinations to prevent emergence of microbial resistance, transmission blocking vaccines, interventions to reduce transmissibility of tuberculosis)

Standards of evidence for prophylaxis where efficacy may not be testable in man (e.g., prevention of anthrax, countermeasures to prevent poisoning)

Defining surrogate endpoints (e.g., when does a surrogate become a validated clinical endpoint)

Source: FDA Manual of Policies and Procedures 4303.1, CDER Medical Policy Council

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