✕
☰

Maintaining Robust Supply Chains: How to Meet FDA and EMA Expectations

by ,

Regulatory authorities across the world have been focusing on safeguarding global supply chains. Juan Torrijos Lopez, GMP consultant at Rephine provides some practical pointers as to how pharmaceutical manufacturers and their partners should respond to evolving expectations.

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.

Fulfilling Regulatory Expectations

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 here 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).

Considerations include:

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

European Good Practice Provisions

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:

US and EU regulatory recommendations so far are largely guidance rather than mandates, but there is no time to waste in developing a methodology to identify products and assess the risks of shortages.

Keep on the Front Foot

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. These steps will keep companies on the front foot when it comes to being prepared for changing regulation, while at the same time mitigating the real risk of shortages.

Back to topbutton