Pharma groups: FDA is exceeding its authority in risk management plan guidance

Regulatory NewsRegulatory News | 01 September 2022 |  By 

The US Food and Drug Administration’s (FDA) draft guidance on risk management plans (RMPs) has overstepped the agency’s statutory bounds in requiring manufacturers of active pharmaceutical ingredients (APIs) as well as prescription drug manufacturers to submit risk management plans (RMPs) to avert drug shortages.
This requirement could impose the very drug shortages it is designed to prevent, instead of just targeting those products at risk of drug shortage, pharmaceutical stakeholders told the agency.
The comments were submitted in response to FDA’s call for feedback on its draft guidance outlining which types of drugs and medical devices are susceptible to shortages and should be subject to a risk management plan (RMP). (RELATED: FDA asks manufacturers to develop risk management plans to avert shortages, Regulatory Focus 20 May 2022)
Others said the guidance should be more aligned with the International Council for Harmonisation’s (ICH) Q9 guideline on quality risk management.
FDA issued the draft guidance under a mandate of the Coronavirus Aid, Relief, and Economic Security Act (CARES Act), which gave the agency new authorities to collect information from manufacturers in responding to pandemic-prompted shortages. The law added a new section 506C(j) to the Federal Food, Drug, and Cosmetic Act (FD&C Act) requiring certain manufacturers to develop and implement a “redundancy risk management plan” to evaluate the potential for drug shortages.
FDA proposed that three types of drug products be required to have an RMP: prescription drug products that are life-supporting, life-sustaining, or intended to prevent or treat a debilitating diseases or condition; any active pharmaceutical ingredient (API) included in the above-listed drug products; and any medical device used to prepare or administer the prescription drug products listed above.
Twenty-five comments were submitted on the guidance from a range of pharmaceutical industry groups, drugmakers and one medical device manufacturer.
Serious concerns expressed
The Biotechnology Innovation Organization (BIO) that while the group “agrees with the systematic approach for establishing risk management plans (RMPs) laid out in the draft guidance, we have serious concerns related to the scope and timing oof the guideline.”
The Association for Accessible Medicines (AAM) said the draft guidance “advances an unnecessarily broad interpretation of the statute that requires individual’s product specific RMPs for prescription drug products. Further the draft guidance recommends the development of RMPs for products not included in the statute as requiring an RMP – a recommendation that many manufacture will interpret as a requirement. As a result, the guidance as written is unnecessarily burdensome and may cause unintended product discontinuations and contribute to, rather than mitigate, drug shortages.”
Statutory authority
The major criticism from groups and companies including the Biosimilars Forum, AAM and BIO is that the agency exceeded the bounds of the law by requiring RMPs for a more extensive range of products than what was written in the law.
The Biosimilars Forum wrote that “Congress’s requirement for industry to implement a redundancy risk management plan (RMP) under section 506C(j) of the Federal Food, Drug, and Cosmetic Act (FDCA) is limited and does not require the broad product and detailed framework called for in the draft guidance.”
The group asserts that the law states that “each manufacturer of a drug described in [section 506C(a)] or of any active pharmaceutical ingredient or any associated medical device used for preparation or administration included in the drug, shall develop, maintain, and implement, as appropriate, a redundancy risk management plan that identifies and evaluates risks to the supply of the drug, as applicable, for each establishment in which such drug or active pharmaceutical ingredient of such drug is manufactured. A risk management plan under this section shall be subject to inspection and copying by the Secretary pursuant to an inspection or a request under section [704(a)(4)] of [the FDCA].”
The Forum wrote that “from these two sentences FDA has proposed a very prescriptive draft guidance detailing comprehensive regulatory requirements and expectations that go far beyond what Congress contemplated and provided for in section 506C(j).”
AAM concurred that “the list of products that must be included in RMPs already is so broad that it could be read to encompass almost all prescription drugs. Furthermore, the development, maintenance, and implementation of RMPs for individual drug products and APIs will place a tremendous financial and resource burden on stakeholders that could lead to product discontinuation and potentially drug shortages, which is counter to the intent of the CARES Act.”
BIO also expressed its concerns with requiring API manufacturers to submit RMPs.
BIO writes that “such a requirement would be highly burdensome to manufacturers of API intermediates or drug product intermediates (e.g., milling operations, granulation operations) and could be non-value added since manufacturers of intermediates might not have knowledge of the information needed to provide a meaningful RMP.”
The Bulk Pharmaceutical Task Force (BFTF) also requested clarity on whether API manufacturers should submit RMPS.
“It also is not clear whether API manufacturers are required to develop their own RMP or whether an API manufacturer RMP should be considered a component of the primary stakeholder RMP. Because API manufacturers have such incomplete information regarding the downstream supply chain for their products, it presents a significant challenge to develop a meaningful and accurate RMP.”
PhRMA calls for alignment with ICH Q9
In its comments, the Pharmaceutical Research and Manufacturers of America (PhRMA) urged FDA to align the guidance with the ICH Q9 guideline. (RELATED: Pharmaceutical industry groups suggest modifications to ICH Q9 guideline, Regulatory Focus 19 July 2022)
“The draft guidance uses terminology and presents concepts that differ from those in the revised Q9(R1) draft guidance. For example, the ICH Q9(R1) guideline refers to ‘hazard identification’ whereas the FDA draft guidance refers to ‘risk identification.’ Rather than using different terms and concepts that could create confusion or introduce inconsistency, PhRMA recommends that, in finalizing this guidance, FDA align with the terminology and concepts as presented in the Q9(R1) guideline, once finalized, and that to the extent practicable FDA ensure harmonization with existing ICH guidelines.”
PhRMA also suggested the guidance be modified to allow manufactures submit their RMPs on an as-needed basis; this change would also be aligned with ICH Q9. The guidance specifies that RMPs undergo annual revisions thought-out the life cycle of a drug.


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