FDA asks manufacturers to develop risk management plans to avert shortages

Regulatory NewsRegulatory News | 20 May 2022 |  By 

The US Food and Drug Administration (FDA) has issued draft guidance that spells out which types of drugs and medical devices are vulnerable to shortages and should be subject to risk management plan (RMP) reporting. The guidance also recommends risk factors to consider when developing the content of the RMPs.  
Under the Coronavirus Aid, Relief, and Economic Security Act (CARES Act), FDA was given 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 said that RMPs are a “useful tool to facilitate compliance with a firm’s regulatory requirements. As a general matter, the agency believes that RMPs are a good practice to help ensure reliability of supply of drug products and APIs” and recommends these plans even be in place for drugs that are not subject to the requirements of 506C(j).
The draft guidance aligns with the principles in the International Council for Harmonization (ICH)’s Q9 guidance on quality risk management.
Drug shortages have been a concern even before the pandemic, and in recent years there has been increased focus on the issue from FDA and Congress.
The Food and Drug Administration Safety and Innovation Act of 2012 (FDASIA) gave the agency new authorities to prevent or mitigate shortages. Yet FDA said that even with those new authorities, it has not been successful in eradicating the problems that cause drug shortages. “Although the number of new drug shortages has declined significantly since the peak in 2011, reaching a low in 2015 and 2016, this downward trend did not continue in subsequent years. Drug shortages continue to occur and at roughly the same levels since 2018,” said the guidance.
FDA proposes that three types of drug product 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, including drugs used in emergency medical care or during surgery, or any drug that is critical to the public health during a public health emergency;
  • Any active pharmaceutical ingredient (API) included in the above-listed drug products.
  • Any medical device used to prepare or administer prescription drug products listed above, including any device constituent part of a drug-led, drug-device combination product or biologic-led, biologic-device combination product.
The agency recommends that products across seven categories be subject to voluntary RMPs:
  • Drug products intended to treat rare diseases or conditions;
  • Drug products that lack appropriate interventions;
  • Medical countermeasures used to end a potential public health emergency stemming from a terrorist attack;
  • Sole source products;
  • Drug products with only one API manufacturer in the product’s supply chain that’s been qualified by the finished dosage form manufacturer’s quality unit;  
  • Drug products with only one finished dosage form in the supply chain;
  • Drug products that are manufactured in a facility that was classified as official action indicated (OAI) following an inspection in the last five years.
The RMP should consist of three elements: a risk assessment, risk control and risk review. The risk assessment should identify any associated hazards, evaluate the risk of each hazard, estimate the likelihood that something will go wrong, and measure the consequences if something goes wrong.
The risk control components are the steps manufacturers can take to mitigate the risks of a disruption to an acceptable level. These include “building redundancy into manufacturing operations, establishing adequate controls in the supply chain, strengthening relationships with suppliers (e.g., contract manufacturers, ingredient suppliers), and/or identifying alternative suppliers.”
Lastly, a risk review should document these risk assessment and risk control strategies. FDA proposes that manufacturers conduct an annual internal review to revise the RMP. The guidance says that “in some instances, it may be useful to quickly integrate the additional identifies risk and migration strategies into the RMP rather than waiting for the next annual review cycle.”
The guidance includes an appendix listing certain risk considerations for RMPs. For example, weaknesses in inventory management, whether drug manufacturing relies on incapable or unreliable equipment, and whether the drug’s safety and efficacy can be demonstrated beyond the labeled expiration date are some factors that can predict a drug’s chance of going into shortage.
Other risk factors include whether sites are located in areas prone to natural disasters, whether the manufacturer relies on sole source suppliers for critical components, and whether the equipment or systems at the site is vulnerable to cybersecurity threats.
The deadline for commenting is 19 July 2022.


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