FDA Offers New Draft Guidance on How to Co-Develop IVDs, Therapeutics

The age of precision medicine, with treatments targeted to specific patients based on a companion test identifying the need for such a treatment, is pushing the US Food and Drug Administration (FDA) to release new and more detailed draft guidance on how companies can co-develop a therapeutic alongside what the agency is calling an in vitro companion diagnostic device, or IVD companion diagnostic.

The draft released Thursday, entitled "Principles for Codevelopment of an In Vitro Companion Diagnostic Device with a Therapeutic Product," is intended to be a practical guide to assist drug and IVD sponsors in developing these two products simultaneously.

The concept outlined in the guidance is not new, however, as in 2014, more than 20% of new drugs and biologics were approved alongside such a diagnostic test, and 2015 saw that portion rise even more, with 28% of new drugs and biologics approved alongside a diagnostic.

Amy Miller, PhD, executive vice president of the Personalized Medicine Coalition, told Focus that she expects that moving forward, about one-quarter of all new drug approvals will include the approval of an IVD companion diagnostic.

And though the release of the new draft guidance might be viewed as an attempt to increase support for President Barack Obama’s Precision Medicine Initiative, Miller explained that the draft had been in the works for almost a decade before the initiative materialized, though both he and FDA Commissioner Robert Califf have been vocal supporters of further expanding precision medicine.

FDA notes that the concept of co-development of a therapeutic and an IVD companion diagnostic was first applied in 1998, when Herceptin (trastuzumab) was paired with an immune-histochemical IVD companion diagnostic (HercepTest), which measures expression levels of human epidermal growth factor receptor 2 (HER-2; also known as ERBB2) in breast cancer tissue and identifies patients more likely to have a therapeutic response.

“Since that time, interest in identifying biomarkers that could be used as biological targets for therapeutic product development, prognostic indicators, or predictors of patient response to specific therapeutic products has grown tremendously,” FDA says, noting there are now numerous examples of therapeutics with an accompanying diagnostic.

Miller also noted that the guidance will be welcomed by those outside of the oncology space, where precision medicine has not caught on as quickly. She added that some of the major difficulties in co-developing drugs and companion diagnostics deal with logistical challenges as two centers at FDA (the Center for Drug Evaluation and Research and the Center for Diagnostic and Radiological Health) have to be consulted, and at times, two different sponsors (one for the IVD and one for the drug).

Draft Specifics

In general, the 48-page draft guidance describes the principles to guide co-development to support obtaining contemporaneous marketing authorization for a therapeutic and its corresponding IVD companion diagnostic, certain regulatory requirements that sponsors should be aware of as they develop such products, considerations for planning and executing a clinical trial that also includes the investigation of an IVD companion diagnostic, and administrative issues in the submission process for such co-developed products.

“Although there is significant flexibility in the type of test to be used, and test design changes are permissible between therapeutic product clinical trial phases, it is still important to understand the critical analytical performance characteristics of early prototype tests,” FDA explains. “The analytical validation studies that evaluate critical performance parameters should be completed in advance of using the test in a trial that is intended to provide the clinical evidence in support of IVD companion diagnostic claims. Using an analytically validated test is important to protect clinical trial subjects, to be able to interpret trial results when a prototype test is used, and to help to define acceptable performance characteristics for the development of the candidate IVD companion diagnostic.”

Miller also noted that often these types of companion products start out as an investigational drug and a lab-developed test that slowly improves with time in terms of precision and accuracy.

And as FDA notes, various approaches may be acceptable to obtain the data needed to support contemporaneous marketing authorization of a therapeutic and an accompanying IVD companion diagnostic, so “FDA strongly recommends that the sponsors of both the therapeutic product and the IVD meet with the appropriate FDA review centers prior to launching a trial intended to advance the development of the therapeutic product and the IVD companion diagnostic.”

And since the investigation of the IVD often occurs in the context of the therapeutic's clinical development program (where applicable regulations for both the investigation of the therapeutic and the investigation of the IVD must be met) FDA says information about the IVD might be required by the therapeutic product review center if it is needed to determine whether the trial can meet its stated objectives.

The draft is open for comment for the next 60 days.

Principles for Codevelopment of an In Vitro Companion Diagnostic Device with a Therapeutic Product Draft Guidance for Industry and Food and Drug Administration Staff