FDA urges manufacturers to develop risk management plans to avoid bottlenecks – Regulatory Focus | Region & Cash

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| May 20, 2022 | Through Joanne S Eglovitch


The U.S. Food and Drug Administration (FDA) has issued draft guidance that establishes which types of drugs and medical devices are prone to shortages and should be subject to risk management plan (RMP) reporting. The guidelines also recommend risk factors to consider when developing the content of the RMPs.

Under the Law on help, aid and economic security because of the coronavirus (CARES Act) gave the FDA new powers to collect information from manufacturers to respond to pandemic-related shortages. The law added a new Section 506C(j). Federal Law on Food, Drugs and Cosmetics (FD&C Act), which requires certain manufacturers to develop and implement a “Redundancy Risk Management Plan” to assess the potential for drug shortages.

The FDA said that RMPs are a “useful tool to facilitate compliance with a company’s regulatory requirements. In general, the Agency believes that RMPs are “good practice to ensure the reliability of drug and API supply” and recommends that these plans be in place even for drugs that are not subject to 506C(j) requirements.

The draft guideline conforms to the principles of the International Council for Harmonization (ICH) Q9 guideline on quality risk management.

Drug shortages were a concern before the pandemic, and in recent years the issue has received increasing attention from the FDA and Congress.

That Food and Drug Administration Safety and Innovation Act of 2012 (FDASIA) gave the agency new powers to prevent or mitigate bottlenecks. However, the FDA said that even with these new authorities, it has failed to address the issues causing the drug shortages. “Although the number of new drug shortages has fallen significantly since peaking in 2011 and bottoming out in 2015 and 2016, this downward trend has not continued in subsequent years. Drug shortages continue to occur and have been at about the same level since 2018,” the guidance reads.

The FDA proposes that three types of drugs must have an RMP:

  • Prescription drugs that are life-sustaining, life-sustaining, or intended to prevent or treat a debilitating disease or condition, including drugs used in emergency medical care or during surgery, or drugs used during a public health event of critical public health importance meaning are emergency;
  • Any active pharmaceutical ingredient (API) contained in the drugs listed above.
  • Any medical device used in the manufacture or administration of any prescription drug listed above, including any device that is part of a drug-based drug-product combination product or a biologically-based bioproduct combination product.

The agency recommends that products in seven categories be subject to voluntary RMPs:

  • medicines to treat rare diseases or conditions;
  • Drug products lacking appropriate interventions;
  • Medical countermeasures to end a potential public health emergency resulting from a terrorist attack;
  • single source products;
  • Drugs with only one API manufacturer in the product supply chain that has been qualified by the quality unit of the finished dosage form manufacturer;
  • Medicines with only one finished dosage form in the supply chain;
  • Medicines manufactured in a facility classified as OAI after an inspection in the last five years.

The RMP should consist of three elements: risk assessment, risk control and risk review. Risk assessment should identify all associated hazards, assess the risk of each hazard, estimate the likelihood that something will go wrong, and measure the consequences if something does go wrong.

The risk control components are the steps manufacturers can take to mitigate the risks of a failure to an acceptable level. These include “redundancies in manufacturing processes, establishing appropriate supply chain controls, strengthening relationships with suppliers (e.g. contract manufacturers, ingredient suppliers) and/or identifying alternative suppliers.”

Finally, a risk review should document these risk assessment and risk control strategies. The FDA suggests that manufacturers conduct an annual internal review to revise the RMP. The guidance states: “In some cases, it may be useful to quickly integrate the additional identified risk and migration strategies into the RMP, rather than waiting for the next annual review cycle.”

The guidance includes an appendix detailing certain risk considerations for RMPs. For example, weaknesses in inventory management, whether drug manufacturing relies on inappropriate or unreliable equipment, and whether the drug’s safety and efficacy can be demonstrated beyond the stated expiration date are some factors that can predict the likelihood of a drug shortage.

Other risk factors include whether sites are located in areas prone to natural disasters, whether the manufacturer relies on sole suppliers for critical components, and whether the equipment or systems at the site are vulnerable to cybersecurity threats.

The deadline for comments is July 19, 2022.


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