FDA Issues Draft Guidance on Risk Management Plans to Assist in Preventing Drug Shortages

On May 19, 2022, FDA issued a draft guidance intended to assist drug manufacturers in developing Risk Management Plans (RMPs) required under section 506C(j) of the Federal Food, Drug, and Cosmetic Act (FDCA). Section 506C(j) is one of the provisions Congress added to the FDCA in March 2020 as part of the Coronavirus Aid, Relief, and Economic Security Act (CARES Act). It requires manufacturers of certain drugs to develop RMPs that identify and evaluate risks to the supply of those drugs, with the aim of supporting industry’s efforts to prevent shortages of critical medical products. FDA’s draft guidance provides recommendations for the development and implementation of RMPs, and clarifies how FDA proposes that different entities in the supply chain fulfill this requirement.

Am I required to implement an RMP?

You are required to implement an RMP if you manufacture any of the following products:

• Prescription drug products that are life-supporting, life-sustaining, or intended for use in the prevention or treatment of any such drug used in emergency medical care or during surgery, or any such drug that is critical to the public health during a declared public health emergency.
• Any active pharmaceutical ingredient (API) included in the above-described prescription drug products.
• Any associated medical device used for preparation or administration included with the above-described drug products.

These requirements apply to both “primary stakeholders” (i.e., the holder of the drug application or license or, for products without an application or license, the entity with the understanding and capability to make changes to the supply chain for the finished product) and “secondary stakeholders” (i.e., finished product manufacturers that are not primary stakeholders, API manufacturers, and entities that physically process or package API).

While FDA recognizes that only manufacturers of the above-listed products are required to implement RMPs, the Agency recommends that manufacturers of the following products voluntarily implement RMPs:

• Drug products intended to treat rare diseases or conditions.
• Drug products that lack appropriate alternatives.
• Medical countermeasures used in the event of a potential public health emergency stemming from a terrorist attack with a biological, chemical, or radiological/nuclear material, or a naturally occurring emerging disease and other threat agents.
• Sole source products.
• Drug products with only one API manufacturer in the product’s supply chain that has been appropriately qualified by the quality unit of the finished dosage form (FDF) establishment.
• Drug products with only one FDF manufacturer in the product’s supply chain.
• Drug products that are manufactured in a facility (including packaging facilities and laboratories) with an inspection in the last 5 years that was classified as official action indicated (OAI) and there is no other manufacturing facility that is qualified in the product’s supply chain to conduct that operation.

Importantly, FDA recognizes that stakeholders will play different roles in developing and implementing RMPs based on their position in the drug supply chain. FDA recommends that primary stakeholders develop broader risk management plans that establish “overarching approaches” to identifying, assessing, and mitigating risks, and to repairing the supply chain after disruption. The Agency recommends that primary stakeholders share their RMPs with secondary and other stakeholders, as appropriate. This will allow stakeholders across the supply chain to align on broad risk mitigation strategies, contextualize risks, and develop product-specific mitigation and avoidance strategies.

How should I develop a risk management plan?

FDA recommends that stakeholders develop risk management plans in accordance with the risk management framework outlined in the International Council for Harmonisation guidance for industry Q9 Quality Risk Management (ICH Q9). This framework includes the following six steps:

1. Initiating an RMP: Stakeholders should proactively initiate the development of RMPs, rather than waiting for supply disruptions to occur.
2. Risk Assessment: Stakeholders should identify hazards that have the potential to cause a supply disruption, assess the risks associated with each hazard, and evaluate the probability of each risk.
3. Risk Control: Stakeholders should identify strategies for mitigating or avoiding identified risks and evaluate the acceptability of any risks that remain after applying these strategies. At the end of this step, stakeholders should develop a report to document their risk assessment and risk control strategies.
4. Risk Review: Stakeholders should review their RMP at least annually throughout the product’s life cycle.
5. Risk Communication: Stakeholders should proactively communicate with regulators and other external stakeholders about their RMPs. This might include, for example, leveraging an RMP when notifying FDA of drug product and API permanent discontinuances or manufacturing interruptions under section 506C of the FDCA.
6. Risk Management Tools: Stakeholders may consider using various off-the-shelf risk management tools when developing and maintaining RMPs.

The appendix of the draft guidance provides a detailed list of the risk factors stakeholders should consider when developing RMPs. These include factors applicable to all stakeholders, as well as risk factors specific to primary, secondary, and other stakeholders.

What actions should I take next?

Stakeholders who wish to comment on FDA’s draft guidance should do so by July 19, 2022. While FDA works to finalize the guidance, stakeholders who are required to develop RMPs should ensure general alignment with the principles outlined in the draft guidance. Stakeholders who are not required to develop RMPs, but who manufacture products for which FDA recommends an RMP, should assess the potential benefits of developing voluntary RMPs.

If you have any questions concerning the material discussed in this client alert, please contact the members of our Food, Drug, and Device Practice.