A New Draft Guidance Provides In Vitro Diagnostic Device Requirements That May Impact Therapeutic Drug Trials

Did you know that an assay used in a clinical trial designed to study an investigational drug may be considered an investigational In Vitro Diagnostic (IVD) Device, and therefore subject to the requirements of an Investigational Device Exemption (IDE)? Potentially two separate investigational applications for one drug trial? This could be the case even if the assay is not intended for commercialization.

With the growth of personalized medicine and investigations for genetic diseases, the situation arises more frequently: more studies include novel assays. To raise awareness for sponsors and IRBs, and to clarify how to comply with the medical device regulations for an investigational IVD, the FDA published a draft Guidance entitled ‘Investigational IVDs Used in Clinical Investigations of Therapeutic Products’ in December 2017.

It is worth getting familiar with the requirements as the FDA can put your study on clinical hold if it considers that the investigational IVD represents an unreasonable risk to the safety of the study subjects.

What Is an Investigational IVD?

An IVD is a device used to collect, prepare, or examine specimens from the human body. The draft guidance defines an investigational IVD as an IVD “that is the object of an investigation” which includes a clinical investigation involving subjects to determine safety and effectiveness of a device.  However, this definition is extrapolated to IVDs that are used to guide therapeutic management within a drug product trial when:

• An IVD that is novel or not legally marketed in the US (this includes lab-developed tests [LDTs])
• An IVD that is legally marketed in the US, however, is being used for a new indication, sample type, or significant technological changes have been made that would impact performance characteristics
• IVDs that are used within their cleared/approved indications or label are not considered investigational

Investigational IVDs are subject to IDE regulation; however, the regulatory requirements are ultimately determined by the level of risk to subjects associated with the use of the IVD: significant risk (SR), non-significant risk (NSR), and exempt studies. Factors that may contribute to the finding of higher risk (and therefore SR) associated with an investigational IVD in a therapeutic drug trial include:

• Risk associated with the investigational drug (eg, adverse effects that cause serious harm)
• Results generated by the investigational IVD could change the dose (risk of over or under dosing) or treatment population for enrollment (both for inclusion for optimal efficacy or exclusion for safety)
• Results generated from the investigational IVD are used for monitoring for purposes of adjusting treatment (schedule, dose, discontinuation)
• Assigning subjects to a particular study arm (eg, stratification or adaptive study designs)
• Invasive sampling is used to collect subject samples that are not part of the standard of care treatment

Why Is This Important?

Determining if the investigational IVD may be considered SR is critical for preventing a clinical hold on a pending therapeutic drug product trial based on the new draft guidance recommendations. When a trial includes a SR investigational IVD, the draft guidance states that even if the therapeutic product trial does not require an IND, the sponsor must still have an approved IDE.  This may also include investigational IVDs that are solely used for providing information in the clinical trial without any intent to commercialize.

How Premier Consulting Can Help?

Therapeutic drug product trials will need to adhere to these provisions in order to prevent clinical hold.  Therefore, performing a risk assessment on the assays used in planned drug trials and presenting to FDA through a Q-submission meeting is pivotal to prevent delays and potentially a clinical hold.

Premier Consulting can conduct a risk assessment of the assay in your planned therapeutic drug trial to determine the relative risk and subsequent regulatory requirements. Our experts in medical devices, including in IVDs, combined with our unparalleled success in 505(b)(2) drug products give us a strong foundation in the strategic thinking required for effective risk assessments and interactions with both CDRH and CDER.

Premier Consulting can help you navigate IND and IDE regulations and meetings with CDER and CDRH to mitigate regulatory hurdles in your drug development program. Contact us to engage Premier Consulting’s team of drug and device experts.