9-9-2013 - Inside Health Policy - Device Center to Expand, Codify Measures to Speed Up Breakthrough Dx | Friends of Cancer Research

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9-9-2013 - Inside Health Policy - Device Center to Expand, Codify Measures to Speed Up Breakthrough Dx

9-9-2013 - Inside Health Policy - Device Center to Expand, Codify Measures to Speed Up Breakthrough Dx

September 9, 2013

By Nanci Bompey

FDA's device center will expand and codify actions it is already taking under its current authority to speed up the development and approval of diagnostics used alongside breakthrough therapies while deciding if it needs Congress to propose additional legislation in this area, agency officials said. Stakeholders are proposing FDA prioritize review of companion diagnostics used in conjunction with a breakthrough therapy, use a risk-based approach to determine what types of data are necessary for approval, and ensure more laboratories have timely access to the tests.

Agency officials on Friday (Sept. 6) described several ways they hope to speed diagnostics approvals using the agency's current authority, including:

  • Expand a pilot innovation pathway program that includes early, extensive collaboration between FDA and sponsors.
  • Give companies greater flexibility on an ad-hoc basis to assess analytical validity by allowing some data to be submitted postmarket.
  • Establish a formal framework to shift some pre-market data requirements to the post-market side.
  • Expand use of a product development protocol mechanism allowing sponsors and FDA to agree early on required submission elements.
  • Let devices be shipped to labs under an investigational label as long as they are not used to report patient results.
  • Allow companies to file a supplement investigational device exemption rather than a new IDE for the same test being used for different drugs.
  • Clarify in upcoming guidance that all companion diagnostics are automatically granted priority review.

But FDA officials also said that addressing changes to quality system requirements pose greater hurdles because inspectors in the field may not be attuned to decisions made at FDA headquarters. But even then, while the law does lay out certain preapproval device quality system requirements, there may be enough flexibility in the law that the agency can develop policy within its existing regulations, an agency official said.

The agency officials' comment came in response to proposals unveiled Friday (Sept. 6) by a working group of industry, patient, provider and federal agency stakeholders led by the Friends of Cancer Research and the Alexandria Center for Life Science. The group proposed FDA modify the standard drug-device co-development process to expedite the development of in vitro companion diagnostic devices intended for use with a breakthrough therapy.

About three-quarters of the 26 breakthrough designations FDA has awarded since the pathway was created last year involve a companion diagnostic, and stakeholders expect the majority of future designations will involve these types of devices. However, the FDA Safety and Innovation Act creating the breakthrough designation for drugs did not include any provisions aimed at speeding up development of these companion diagnostics, stakeholders said.

The working group proposed five areas where FDA could expedite companion diagnostic development for use with a breakthrough drug.

  • The working group urged FDA to automatically grant priority review to these devices.
  • FDA should ensure there is extensive interaction between sponsors and the agency, and involvement of senior management across the drug and device centers.
  • Further, FDA should use a risk-based process to determine which analytical studies a sponsor is required to submit in its pre-market application and which could be submitted after approval, the working group said. For example, FDA could use a risk-based approach to decide what kinds of samples should be used in a study and if the sponsor could use artificial samples instead of actual patient samples to validate an assay.
  • The agency also could use a risk-based approach to determine what data and testing requirements are necessary for validating quality systems, manufacturing processes and software. For example, FDA could allow for some application elements to be submitted after an initial PMA, or waive inspections for manufacturers who have a good inspection history, the working group said.
  • Lastly, the working group called for FDA to broaden its “continued access” mechanism to allow sponsors to make devices available to laboratories that were not used in the clinical study. It can take months of training, developing procedures and testing before these labs are ready to receive the device after it has been approved, stakeholders said.

The proposals are not designed to lower any FDA standards for safety and efficacy. “Meeting with device and therapeutic review divisions as early in development as possible is already in practice and the question is, with breakthrough medicine, can this be any further expedited,” said Barbara Conley, associate director of the cancer diagnosis program in the division of cancer treatment and diagnostics at the National Cancer Institute, a member of the working group.

The proposals echo many strategies FDA has already undertaken or is working on to speed up the development of companion diagnostics, FDA officials said. The agency plans to expand and codify some of these mechanisms in policy and guidance, they said.

“I think at the present time there is a lot we can do with our current authority,” said Jeff Shuren, head of FDA's device center. “Certainly a push from Congress for doing this sometimes can be helpful. But we are also looking at how far we can take it under our current authority and whether we may be able to take it further if there were changes in the law. That is something we are currently exploring.”

The device center is looking at expanding a pilot innovation pathway program that includes early, extensive collaboration between FDA and sponsors to bring breakthrough devices to market faster, Shuren said. The center also has worked with companies on an ad hoc basis to allow greater flexibility in assessing analytical validity by allowing some data to be submitted postmarket rather than premarket -- a procedure analogous to the drug center's accelerated approval pathway, he said. The device center's risk-benefit framework released last year makes explicit this idea of accepting more uncertainty in some instances, Shuren said.

Stakeholders are concerned that the device center does not have the same post-market authorities as the drug center, which could make implementing some of the recommendations difficult. But FDA officials said the agency believes it has some authority under its 522 post-market authority, where FDA can order a study following a product's approval to address public health questions.

The medical device law allows FDA to consider whether data collected to support effectiveness can be done after a device is marketed, but the agency has never fully implemented the policy, Shuren said. The device center's entrepreneur-in-residence program has recommended FDA establish a formal framework for shifting some pre-market data requirements to the post-market side, and the device center is working on that policy, he added.

“You can anticipate that that also include opportunities and features of accelerated approval or an accelerated approval-like framework and breakthrough therapy components in that as well,” Shuren said. “And what is coming out of the recommendations today from the white paper are considerations we would look to potentially fold into that draft policy.”

Elizabeth Mansfield, director of personalized medicine staff in FDA's device center, said the administrative proposals outlined by the working group are “relatively easy to do” as the agency has flexibility in this area and is already working to figure out efficiencies. Mansfield said the agency could possibly expand use of its product development protocol mechanism that allows sponsors and FDA to meet early in the development process to decide what elements will be needed in a submission.

The more difficult proposals for FDA to implement could be the ones around quality systems because inspectors in the field may not be attuned to decisions made at FDA headquarters, Mansfield said. She said implementing that provision may require more coordination, but other specific proposals -- like reducing inspections and reductions in documentation -- are already being done or could be implemented easily.

Lastly, Mansfield said lawyers have determined that the agency can allow devices to be shipped to labs under an investigational label as long as they are not used to report patient results, which could address the proposal about pre-positioning devices. The agency is working on a policy that would allow companies to file a supplement IDE rather than a new IDE for the same test being used for different drugs. Further, all companion diagnostics are automatically granted priority review, a policy the agency plans to include in upcoming guidance.

“We don't believe that we need new legislation for any of this,” she said. Mansfield noted although the law does lay out certain quality system requirements before a device is approved, there may be enough flexibility in the law that the agency can develop policy within its existing regulations.

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