Shoring up medicines supply: new Regulatory expectations

Juan Torrijos, GMP Consultant Rephine


In the wake of the pandemic, on top of other challenges to supply chain continuity (including the Ukraine war, and the Suez Canal obstruction of March 2021), major health authorities around the world have been issuing new recommendations to Life Sciences manufacturers and their supply chain partners to ensure that vital drug supplies are not interrupted in the future.

Below are details of the latest Regulatory expectations, specifically FDA and EMA guidance around maintaining supply continuity, and what this means in practice.

US market/FDA

In the US a year ago, the FDA announced new guidance on risk management to mitigate the potential for drug shortages. This is derived from a 2020 US law – specifically the Coronavirus Aid, Relief, and Economic Security Act (CARES Act) – which proposes that manufacturers should develop a redundancy risk management plan. This should identify and evaluate risks to the supply of the drug, as applicable for each establishment in which such drug or active pharmaceutical ingredient thereof drug is manufactured.

The new guidance, specific to the Life Sciences industry, is designed to prevent and mitigate medicine shortages under ‘ICH Q9 Quality risk management – Scientific guideline’, to reduce any associated risk to patient safety. It provides a methodology/recommendations for assessing the risks of drug shortage in a brand or MAH’s portfolio, so that they can implement control strategies as needed.

The FDA requires stakeholders to develop risk management plans for products designated as ‘critical’, ideally using ICH Q9 principles. It suggests the following steps:

  1. Identifying the stakeholders – ultimately any person or entity with oversight and control over the manufacture of drugs. That includes contract facilities; applicants with an approved new drug application/abbreviated new drug application/approved biologics licence application; manufacturers of drug products marketed without an approved application; manufacturers of components, including APIs, intended for use in the manufacture of drug product; and manufacturers of drug-led, drug-device or biologic-led, biologic-device combination products.

The MAH is seen as the primary stakeholder, while CMOs and API manufacturers would be considered secondary stakeholders. Other stakeholders include packagers, distributors and non-active ingredient manufacturers. Each entity has its own part to play.

  1. Identifying drug products (and their active ingredients) for which potential shortage assessments are necessary. These include prescription drug products that are life-supporting or life-sustaining; those intended for use in the prevention or treatment of a debilitating disease or condition, in emergency medical care, or during surgery; along with associated medical devices. Controls are also recommended for drugs intended to treat rare diseases or conditions; those that lack appropriate alternatives; sole-source products; and so on. (See for the full FDA list).
  2. Developing a risk mitigation plan (RMP).

While ICH Q9 provides the methodology for risk management the FDA is particularly clear on the potential risks to consider, by type of stakeholder, and provides a list of these (

Considerations include:

  • Identifying potential risks to drug availability, e.g.
    • Supply chain disruption
    • Lack of manufacturing backup
    • Unique supplier of API
    • Old and unreliable equipment
    • Regulatory issues (import alert)
    • Forecast issues
    • Natural disaster
    • Cyberattack
    • Communication errors
  1. Analysing the risk for severity/probability/detectability;
  2. Defining and implementing control additional control measures to reduce the identified risk to an acceptable level; and
  3. Reviewing the risks thereafter.


In the EU, the European Medicines Agency has also issued new guidelines. Simpler than those of the FDA, and designed more as guidance for the industry on “good practices to ensure continuity in the supply of human medicines, prevent shortages and reduce their impact”, the provisions take the form of 10 recommendations.

These span early notification of the relevant National Competent Authority  – by MAHs, manufacturers and wholesalers – of a potential or actual shortage as early as possible; increasing transparency related to shortage information; devising a shortage prevention plan specific to the company’s role; optimising pharmaceutical quality systems to strengthen the reliability and resilience of supply chains throughout the lifecycle of a medicine; and increasing resilience – and communication – in the supply chain, taking into account known vulnerabilities.

Stakeholders that follow the more prescriptive FDA guidance should by default be in compliance with EMA’s recommendations.

What to do now

Even though the evolving US and EU requirements take ‘guidance’ rather than ‘mandate’ form, for the sake of brand reputation and patient safety we recommend that companies take the following steps today:

  1. Acknowledge their respective role in the supply chain.
  2. Identify the products to be assessed (for non-primary stakeholders, communication with the primary stakeholder is advised to understand the need for a risk management plan).
  3. Identify the risk factor (by viewing the current FDA guidance and the latest version of ICHQ9, to ensure all potential risk factors are in scope), with input from supply chain, manufacturing, quality/regulatory, engineering and production functions.
  4. Evaluate the risks, identifying current control measures and, if necessary, define and implement additional controls.

How Rephine can help

We can help companies in the development of the methodology to identify products and assess the risks of shortages. To find out more, or to discuss a specific requirement, please get in touch with our expert consultants 

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