Safeguarding global drug supply chains: new recommendations for life sciences manufacturers and authorities

Following a series of disruptions to worldwide supply chains, regulators across the globe have initiated fresh guidelines for manufacturers in the Life Sciences sector and those responsible for marketing authorisations. The aim is to safeguard uninterrupted global availability of crucial medication supplies. Juan Torrijos Lopez, GMP consultant at Rephine, discusses the regulatory requirements set by the FDA and EMA regarding the maintenance of robust supply chains, while also suggesting the subsequent steps that companies should consider.

In the wake of the COVID-19 pandemic, not to mention other high-profile challenges to supply chain continuity (including the Ukraine war, and the Suez Canal obstruction of March 2021, as well as Brexit in the UK/EU), major health authorities around the world have been issuing new recommendations to Life Sciences manufacturers and their supply chain partners to ensure that in the future vital drug supplies remain continuously, safely and conveniently available to the patients that need them, right around the world.

In addition to unforeseen major national or international events, supply disruption can also be caused by poor oversight of location-specific production issues, or incomplete or inadequate real-time demand and stock status information.

Although the situation internationally in terms of regulatory guidance continues to evolve, details of the latest expectations from FDA and EMA around maintaining supply continuity are set out below, along with recommended next steps for manufacturers and their international distributors/local marketing authorisation holders for fulfilling these expectations.

Mitigating drug shortage risk

In the US, the FDA announced new guidance on risk management to mitigate the potential for drug shortages more than a year ago now. The recommendations are derived from a 2020 US law - 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 the International Council for Harmonization (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 marketing authorisation holder (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 contract manufacturing organisations (CMOs) and active pharmaceutical ingredient (API) manufacturers would be considered secondary stakeholders.

2. 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 https://www.fda.gov/media/143406/download for the full FDA list).

3. 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 (it provides a comprehensive list of these https://www.fda.gov/media/158487/download).

Considerations include:

1. a) Identifying potential risks to drug availability, e.g. supply chain disruption or lack of manufacturing backup.
2. b) Analysing the risk for severity/probability/detectability;
3. c) Defining and implementing control, additional control measures to reduce the identified risk to an acceptable level; and
4. d) Reviewing the risks thereafter.

New European guidelines

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.

Together, these cover:

• Early notification of the relevant National Competent Authority - by MAHs, manufacturers and wholesalers - of a potential or actual shortage as early as possible;
• Increased transparency related to shortage information;
• The development of 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
• Increased resilience – and communication - in the supply chain, taking into account known vulnerabilities.

Key steps

To ensure brand reputation and patient safety, companies should acknowledge their respective role in the supply chain and identify the products to be assessed. The next step is to 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. Finally, evaluate the risks, identifying current control measures and, if necessary, define and implement additional controls.

The evolving US and EU requirements currently take ‘guidance’ rather than ‘mandate’ form, but there is no time to waste in developing a methodology to identify products and assess the risks of shortages.