By: Daniel Logan and Justine Lenehan
The Coronavirus Aid, Relief, and Economic Security Act, or “CARES” Act (Pub. L. No. 116–136) makes numerous changes to the Federal Food, Drug, and Cosmetic Act (FDCA). The CARES Act made substantial changes related to the regulation of over-the-counter (OTC) drugs (see KKB’s alert here dedicated to summarizing these changes). Here, however, we describe other notable changes made to the FDCA.
The amendments made by sections 3111 and 3112 of the CARES Act will take effect 180 days after enactment of the CARES Act; however, the amendments made by sections 3121 and 3302 of the CARES Act ostensibly take effect immediately.
Section 3111 – Prioritize reviews of drug applications; incentives.
The CARES Act subtly tweaks the language relating to the expedited reviews and inspections in order to mitigate or prevent shortages or discontinuances of life-supporting and life-sustaining drugs. FDCA § 506C(g). Whereas, the FDCA previously stated that the Food and Drug Administration (FDA), acting through authority delegated from the Secretary of Health and Human Services, “may” expedite the review of supplemental NDAs, ANDAs, and supplemental ANDAs in response to a notification of the discontinuance or interruption of life-supporting or life-sustaining drugs, the CARES Act changes this to a “shall, as appropriate.” This slight shift changes the calculus for expediting certain drug applications by mandating that FDA speed-up crucial reviews and inspections. It also requires FDA to “prioritize,” as well as expedite, reviews of applications and inspections of establishments in the same context.
Section 3112 – Additional manufacturer reporting requirements in response to drug shortages.
Section 3112 of the CARES Act amends numerous sections under the FDCA regarding manufacturer reporting requirements and related provisions to anticipate and address drug shortages in the future.
Discontinuation or Interruption in Manufacture of Life-saving Drugs
The CARES Act expands the reporting requirement for the discontinuation or interruption of life-supporting or life-sustaining drugs or drugs intended to prevent or treat a debilitating disease or condition under section 506C(a) of the FDCA to expressly include “any such drug that is critical to the public health during a public health emergency” declared under the Public Health Service Act (PHSA). Further, the CARES Act extends the reporting requirement to capture any discontinuance or interruption in the manufacture of an active pharmaceutical ingredient (API) contained in these life-supporting or life-sustaining drugs.
When applicable, notification to the FDA must also include: the source of the discontinued or interrupted API and any alternative sources known to the manufacturer; whether any associated device in the preparation or administration of the drug is the reason for the drug’s discontinuation or interruption; and the expected duration of the interruption.
The CARES Act also requires that each manufacturer of a life-supporting or life-sustaining drug or an API or associated medical device used in the preparation or administration of such a drug implement a redundancy risk management plan that identifies the supply chain risks for each establishment where such drug or API is manufactured.
Drug Shortage List
The CARES Act imposes a new requirement under section 506E of the FDCA that FDA submit a quarterly report to the Administrator of the Centers for Medicare and Medicaid Services on the then-current drug shortage list.
The CARES Act imposes a new, additional obligation at the conclusion of inspections. FDCA § 704(b). To the extent an establishment subject to inspection manufactured a drug listed on the drug shortage list under section 506E in the prior 5 years, a copy of the inspection report will also be sent to an FDA office with expertise in drug shortages.
Under the CARES Act, any person registered under section 510 of the FDCA with regard to a drug must annually report to the Secretary the amount of each drug listed under section 510(j)(1) of the FDCA that was manufactured by such person for commercial distribution. FDA may also require this information to be submitted upon the declaration of a public health emergency under the PHSA. Further, FDA may determine that certain biological products regulated under section 351 of the PHSA are exempt from the foregoing reporting requirement.
Section 3121 – Discontinuation or Interruption in the Production of Medical Devices.
New to the FDCA is section 506J, which largely applies the framework of FDCA § 506C (governing discontinuance or interruption in the production of life-saving drugs) to medical devices.
Discontinuation or Interruption in Manufacture of Medical Devices Critical During Public Health Emergency
This provision requires manufacturers of medical devices for which FDA requires information about supply disruptions or that are critical during a public health emergency (including devices that are life-supporting, life-sustaining, or for use in emergency procedures or surgery) to provide advance notice to FDA of permanent discontinuances or manufacturing interruptions likely to lead to “meaningful disruptions” in the supply of such devices. FDCA § 506J(a). This would include changes in production likely to appreciably reduce the supply of the device. Notification would not be required for: short-term disruptions (less than six months) due to routine maintenance; temporary disruptions attributable to interruptions in manufacturing of components or raw materials; and disruptions in the manufacture of multiple use diagnostic devices that would not reduce procedures or diagnostic tests performed by that device. FDCA § 506J(i). When notice is required, it must be provided at least six months prior to the date of the discontinuance or as soon as practicable. FDCA § 506J(b). FDA must distribute information regarding the discontinuance to physicians, health care providers, patient organizations, and others, unless doing so would be adverse to the public interest. FDCA § 506J(c). Failure to provide notice will result in a letter from FDA which, along with any response, will be made publicly available. FDCA § 506J(e).
Prioritization of Device Reviews and Inspections
Further, the new provisions direct FDA to expedite reviews of De Novo classifications, PMAs, 510(k)s, and Humanitarian Device Exemptions (HDEs) for devices that could help mitigate a shortage. It may also prioritize and expedite establishment inspections or reinspections. FDCA § 506J(f).
Device Shortage List
Finally, FDA must establish, maintain, and publish a Device Shortage List, that lists medical devices that are determined to be in shortage in the United States. FDCA § 506J(g)(1), (3). The list must include information describing the name of the device, the name of any manufacturers, the reason for the shortage, and the estimated duration of the shortage. The statute prohibits the publication of trade secrets, confidential information, and information that would adversely affect the public health (i.e., increasing the possibility of hoarding). FDCA § 506J(g)(3).
Section 3302 – Priority Zoonotic Animal Drugs.
Also new to the FDCA is section 512A, which is intended to expedite the development and review of certain new animal drugs. At the request of a drug sponsor, FDA may expedite the review of an application for a new animal drug under FDCA § 512(b)(1) or conditional approval of a new animal drug under FDCA § 571 if the preliminary clinical evidence suggests that the drug may prevent or treat a zoonotic disease in animals that has the potential to cause serious health consequences in humans. Section 3302 of the CARES Act lays out the process for designating a new animal drug candidate as a “priority zoonotic animal drug” and what steps may be taken to expedite this development and review.