By Phil Crooker, VP - Technical, Regulatory & Access, Parexel
On March 27, 2020 the president of the United States signed into law the Coronavirus Aid, Relief and Economic Security (CARES) Act in response to the emerging pandemic (a copy of the public law may be found here - https://www.congress.gov/bill/116th-congress/house-bill/748/text). The legislation included several amendments and additions to the Federal Food, Drug and Cosmetic Act (FDCA) that expands the Food and Drug Administration’s (FDA) authority in areas that have a connection with emergency drug shortages.
The section of the act which addressed mitigating emergency drug shortages – Section 3112 – included several important pieces of information.
- The definition of critical drugs defined in FDCA § 506C was amended to include drugs that are life-supporting, life-sustaining, or intended for use in the prevention or treatment of a debilitating disease or condition, including those used in emergency medical care or during surgery.
- Manufacturers of active pharmaceutical ingredients (API) that are used to formulate critical drugs must now have a risk management plan for each establishment involved in the API production that identifies and evaluates risks to the supply of the API.
- Likewise, manufacturers of critical drug products must also have a risk management plan for each establishment in place.
- FDA will have the authority to inspect these risk management plans or request copies of the plans in advance of or in-lieu of an inspection.
Other than changing the statutory definition of critical drugs, the legislation did not offer any more specific information about what specific drugs that they can expect FDA to scrutinize for these new risk management plans. And FDA has yet to draft any type of policy statement, including guidance, much less publish any type of rulemaking such as a final interim rule. Now industry is faced with two questions: (1) which “critical” drug products and API are going to need risk management plans; and (2) what will FDA expect to be in a fit-for-purpose risk management plan? If a manufacturer is involved with these of these types of drugs (and the definition of manufacturer in the CARES Act did not change the broad definition in the regulations), then it’s fair to expect that the level of FDA (and public and political) scrutiny will increase (emphasis added). I’ll address the first question in this blog and then cover the second one in a later blog.
Some insight will come from the National Academy of Sciences (NAS) study included in Section 3001 of the CARES Act. Congress required the NAS to assess the security of the US medical supply chain and make recommendations to promote supply chain redundancy and contingency planning. The report may identify critical drugs necessary for responding to public health emergencies. But the legislation did not have a timeline for completion of the report and the NAS may choose to hold public meetings prior to issuing its report.
In the meantime, are there any other sources of information that could help provide some parameters for what specific drugs the FDA could designate as critical and then require risk management plans. Some hints could be found in a recent solicitation/contract/order for commercial items published by the Health and Human Services (HHS) Office of the Assistant Secretary for Preparedness and Response (ASPR) – Biomedical Advanced Research and Development Agency (BARDA). The solicitation can be found here - https://beta.sam.gov/opp/4b51ebae8a80475c914641ecebe3aaa8/view?keywords=75A50120R00038&sort=-relevance&index=&is_active=true&page=1. Since FDA is an operating division of HHS, the information in the solicitation can reasonably be used to gauge FDA’s thinking and perspectives.
The solicitation lists several API including:
There are also a variety of finished dosage forms such as oral solid, oral liquid and injectable.
Time will tell if or how well this list eventually aligns with any recommendations from the NAS report and FDA policy statements or rulemaking. Firms who are involved with the manufacturing of these drugs – and those firms and activities are broadly defined (have a look at the definitions of manufacturer and manufacturing in 21 C.F.R. § 207.1) are well advised to use this information as an early opportunity to raise awareness for the potential requirement to perform comprehensive assessment of supply chain risks and eventually develop and implement risk management plans that will widen the FDA’s scope and authority during inspections.
Parexel’s Regulatory & Access team encompasses more than 1,000 consultants, including over 80 former regulators / inspectors from around the globe. Our deep understanding of regulatory guidelines and in-depth GxP/cGMP compliance experience means that we are well equipped to assist companies in the identification, evaluation, expansion and compliant-ready manufacturing operations.