By Matt Jones
NEW YORK (GenomeWeb News) – The US Food and Drug Administration expects that companies developing drugs or in vitro companion diagnostic tests that depend on each other will file applications for the drug and the test concurrently, according to a guidance document FDA is still developing.
FDA's new draft guidance on "In Vitro Companion Diagnostic Devices" is aimed at drug developers who are developing a therapeutic that depends on the use of an IVD companion test, and for those planning to develop an IVD companion test that is intended to be used with a corresponding therapeutic product.
FDA undertook the review in response to the increased development of drugs and tests that are linked or depend on the use of the other.
The release of the draft guidance kicks off a 60-day comment period, during which the agency will collect thoughts and responses on its plans from industry and other interested groups.
"The rationale of the guidance was to let people know before we approved these kinds of drugs – where you actually have to select the population with a test – that we need to know that the test actually works," Elizabeth Mansfield, FDA Director of Personalized Medicine Staff in the Center for Devices and Radiological Health, told GenomeWeb Daily News today.
"This type of development of targeted drugs is becoming more and more common, and so it came to be time to make this widely known," she said. "As drug manufacturers are going down this road, they need to know ahead of time [that] you're going to have to have the diagnostic test approved."
The proposed rules will cover diagnostic tests that identify patients who are most likely to benefit from a certain treatment, those who are at increased risk for serious adverse reactions as a result of a particular treatment, and tests used to monitor response to treatments.
Although the new FDA plan does not overhaul the review processes for the drugs or their companion devices — both of which would still follow the processes they already do under the different therapeutic and device pathways — approval of the drugs or devices could depend on each other, and information about the IVD companion test will be requested and shared between parts of the agency.
"The way we've been handling it so far is that we're using the two different regulatory mechanisms as they already exist," Mansfield told GWDN. "But where the information from a drug study provides information that's needed for the device about clinical validity … then we just take that information from the drug study.
"We don't require the device company to do a whole separate trial. We're using the same regulatory pathways as ever, we're just able to tell the different companies what parts of it they need to fulfill, and what parts, if any" they don't, she explained.
"When results from a diagnostic device are a determining factor in patient treatment, healthcare professionals must be able to rely on those results," FDA said in the guidance, stating that inadequate performance of an IVD companion test "could have severe therapeutic consequences."
These devices could fail analytically by incorrectly measuring a quantity of protein, for example, or they could fail clinically by not identifying patients who are at serious risk for adverse events, according to the draft guidance.
Under the proposal, FDA will plan to review each IVD companion device submission within the context of, or in conjunction with, its corresponding drug product.
For novel therapeutic products, IVD companion tests should be developed and approved contemporaneously to support the treatment's safe and effective use, and FDA will determine if it is properly validated and meets safety and effectiveness standards.
In two types of cases FDA said that it may approve a drug even though the related IVD companion device has not yet been cleared or approved. One such situation would include the approval of new therapeutic products to treat serious or life-threatening conditions for which no satisfactory alternative treatment exists, and in which the benefits are deemed to outweigh the risks of using the drug without the approval of its companion test. Another situation would include therapeutic products that have already been approved and which require changes to the labeling to address safety issues.
Because FDA expects to use review mechanisms that are already in place, Mansfield said, it is likely that this guidance will not stir much concern among companies applying for review of co-dependent drugs and IVD companion tests.
"I think most of the companies who are doing this actually realize that without the test we can't say whether their drug is safe and effective until we know what population the drug is going to be given to," she said. "I think they grasp that and they understand that that's actually important for approving a drug. We say in this guidance that we may not approve your drug if we don't have a test to approve."
She said that after the two-month comment period FDA will review the comments and the draft guidance, adding that it may be optimistic to expect the final guidance by the end of the year.