The European Medicines Agency (EMA), together with the Heads of Medicines Agencies (HMA), recently published new guidance for marketing authorization holders (MAHs) and regulators to address medicinal product shortages. This new guidance aims to clarify EU law obligations and puts a strong focus on the adequacy of companies’ supply management and shortage detection processes.
New Guidance for MAHs
Under EU law, MAHs of medicinal products are obligated to ensure appropriate and continued supply of medicinal products so that the needs of patients are covered. Further, MAHs should notify regulatory authorities at least two months before a product ceases to be placed on the market.
The recent guidance for MAHs on detection and notification of medicinal supply shortages (the MAH Guidance, available here) now provides more clarity on these MAH obligations. As an important first step (and for the first time), the MAH Guidance defines the term “medicinal product shortage” as an event that “occurs when supply does not meet demand at a national level,” recognizing that not having had a common definition in the past contributed to inconsistent detection and management of shortages in the EU.
The MAH Guidance clarifies that MAHs are responsible for detecting and reporting all current, impeding or anticipated shortages that affect (or are expected to affect) one or more EU Member States, regardless of the medicinal product’s perceived clinical importance and availability of alternative medicinal products. The MAH Guidance clarifies that such notifications should cover all current and impending shortages that have or will occur due to regulatory issues, quality defects and or any other causes, including good manufacturing practice/good documentation practice issues, batch failures and recalls.
To be able to fulfil this obligation, MAHs must continuously monitor the supply and demand situation of their medicinal products and have an open and continuous communication with all their operators in the supply chain, such as manufacturers and wholesalers. MAHs are expected to be particularly vigilant (i) with respect to medicinal products for which (a part of) the manufacturing process depends on a single facility or (ii) if no or only limited alternative medicinal products are available and where interruption of supply will result in a potential risk to public health.
The MAH Guidance stresses that MAHs should notify any identified shortages as early as possible and no later than two months before the interruption in the placing on the market of the medicinal product at issue. For all products, such shortage notifications must be sent to the affected national competent authorities. For centrally authorized products, the shortage notification should also be sent to the EMA. The MAH Guidance provides a template (Annex 1, available here) that should be included in notifications (to the EMA and to national competent authorities) in those cases where a reporting template is not available at the national level. The MAH Guidance advises that the content of the notification should be “as accurate and up-to-date as possible while being comprehensive and concise” and that outstanding or new information should be provided as soon as it becomes available.
New Guidance for Competent Authorities
MAHs should also be aware of the new guidance on competent authority communication to the public on medicines’ availability issues (the Regulator Guidance, available here). It provides an overview of what information, and when, competent authorities may make available on a shortage situation to the general public.
In particular, the Regulator Guidance states that competent authorities should not apply selection criteria for publication and should communicate on all shortages occurring within their jurisdiction. This means that for all authorized medicinal products, national regulators should report shortages on their website. Further, the EMA should report a shortage on its website if the shortage affects more than one Member State, and the EMA has given recommendations to healthcare professionals.
The Regulator Guidance recommends that the following information be published as early as possible once the MAH has confirmed the shortage: (i) details on the medicinal product such as trade name, MAH, active ingredient; (ii) details on the shortage, including the timeframe of the shortage and the reason for it; (iii) if applicable, advice to healthcare professionals; (iv) and updates to the current status of the shortage.
The new guidance is an important first step to providing greater clarity to MAHs on their obligations under EU law with respect to the management of supply and detection of shortages, and to regulators on their obligations to communicate on medicinal product availability issues.
MAHs should expect more scrutiny by regulators of their supply and potential shortage management. MAHs should consider reviewing their supply management and shortage detection processes and update those processes where necessary to bring them in line with the new guidance.