On January 19, 2018, FDA announced the availability of a new draft guidance, titled “Material Threat Medical Countermeasure Priority Review Vouchers.” FDA’s publication of the draft guidance, which was issued by FDA’s Office of Counterterrorism and Emerging Threats (OCET) without a statutory mandate – reflects the commitment of FDA leadership to the development and approval of medical countermeasures (MCMs). In a question and answer format, FDA provides details about the Agency’s interpretation and implementation of the MCM priority review voucher (PRV) program, which was established in December 2016 by the 21st Century Cures Act (Section 565A of the Federal Food Drug, and Cosmetic Act (FD&C Act)). That provision, intended to incentivize the development of MCMs, requires FDA to award a PRV to the sponsor of a successful marketing application that meets certain statutory criteria.

Although much of the information in the draft guidance is not novel – for example, procedures for requesting and redeeming PRVs, fees associated with the use of PRVs, and transferability of MCM PRVs – FDA does provide several important clarifications and insights into the new program. As a threshold matter, FDA notes that MCMs include drugs, biological products, and medical devices that are intended to diagnose, prevent, or treat diseases or conditions associated with chemical, biological, radiological, and nuclear (CBRN) threats and emerging infectious diseases (or to mitigate, prevent or treat adverse events caused by such MCMs). The Agency correctly points out, however, that not all MCM applications will qualify for PRVs under 21^st Century Cures. Here are a few of the key limitations to keep in mind:

• Medical devices, including diagnostic products, are not within the ambit of the voucher program; only applications for human drugs, including biological products, are eligible for PRVs.

• The voucher program is available only for MCMs directed at CBRN agents that the Department of Homeland Security (DHS) has identified as material threats under Section 319F-2 of the Public Health Service Act.

• To qualify for a PRV for future use, the MCM application itself must be eligible for priority review under the standards set forth in FDA’s 2014 guidance, “Expedited Programs for Serious Conditions – Drugs and Biologics.

• Only applications approved after 21^st Cures was enacted (i.e., after December 13, 2016) are eligible for PRVs, although an application filed before that date, but not approved at the time of enactment, will be eligible.

FDA also notes that, to qualify for a voucher, the MCM must be for a drug, “no active ingredient (including any ester or salt of the active ingredient) of which has been approved in any other application.” In the spirit of incentivizing innovation in the MCM space, FDA has announced that, with respect to MCM drugs approved under the FD&C Act, it intends to apply the policy that it announced in 2014 guidance in the context of on new chemical entity (NCE) exclusivity for fixed‑combination drug products, “Exclusivity Determinations for Certain Fixed-Combination Drug Products.” Under this policy, a drug-drug combination product that contains “at least one active moiety that has not been approved in any other application under section 505(b) of the FD&C Act” will be eligible for an MCM PRV. FDA also indicates that applications for MCM combination products (presumably drug/device, drug/biologic, or drug/device/biologic) submitted under section 505(b) of the FD&C Act or section 351 of the PHS Act similarly may be eligible for a PRV, provided that the product contains at least one new active moiety. For biological products approved under section 351 of the PHS Act, however, FDA has announced that it will make MCM PRV eligibility determinations on a case-by-case basis.

The draft guidance also fleshes out some of the uncertainties associated with developing an MCM with the hopes of winning a PRV. One of the key risks is that certain criteria for eligibility must be met as of the time of approval of the marketing application. FDA states explicitly that “a drug product that meets the criteria at the time of submission may not meet those same criteria at the time of approval action and, in that case, would not be eligible to receive a PRV.” Some of the “watch outs” include the following:

• To be eligible to receive a PRV, the material threat must be listed by DHS as of the time of approval of the application, not at the time of filing. Thus, there is some risk that if the material threat is removed from the list before approval, the sponsor may not receive a PRV.

• Regardless of when a sponsor submits an MCM application, if another application for a drug containing the same active moiety is approved first, the sponsor is no longer eligible to receive a PRV upon approval of its application.

• Although a sponsor may submit a single application for an MCM indication and a non-MCM indication, a PRV will be awarded only if the MCM indication is approved first or approved simultaneously with the other indication. Thus, there is some risk that if approval of the MCM indication is delayed, the application could be approved without that indication, and the sponsor would no longer be eligible to receive a PRV for that application.

For these reasons, FDA notes that it cannot determine, prior to approval or licensure of an application, whether the application will be eligible to receive a PRV. To provide the potential for at least some regulatory certainty, FDA states that it may render a preliminary, nonbinding opinion, before approval, regarding whether at that time the application appears to meet the criteria for PRV eligibility.

Recognizing that the MCM PRV program is not as all-encompassing as it could be, FDA goes out of its way to highlight that some MCMs that might not be eligible for a PRV may qualify for other incentive programs. FDA notes, for example, that some MCM applications may be eligible for other PRV programs (although the same application may receive no more than one PRV), orphan drug designations, statutory exclusivity, tax credits, and exemptions from user fees.

The draft guidance closes by encouraging sponsors to contact the Agency to discuss questions relating to material threat MCMs as early as the pre-IND phase, stating that contacts are available within CDER, CBER, and OCET (which resides in the Office of the Commissioner). Notably, FDA also provides contact information for the Office of the Assistant Secretary for Preparedness and Response (ASPR) in the Department of Health and Human Services (HHS), indicating a high-level organizational commitment to the development and approval of MCMs.

Biotechnology and pharmaceutical companies that are developing MCMs should review the draft guidance carefully and consider the implications of FDA’s proposals on their product pipelines. Companies operating in this space also should assess whether there are areas of concern or ambiguity that FDA does not address in the draft guidance and consider proposing additional questions and answers. Comments to the docket are due on or before March 20, 2018.