EU regulators and industry have begun in earnest to focus on how to prevent and manage medicinal product shortages. Stakeholders have come together to assess the root causes of and potential solutions for such shortages and have proposed strategies. The European Medicines Agency (EMA) Draft Reflection paper on Good Manufacturing Practice (GMP) and Marketing Authorization Holders (MAHs) of January 14, 2020 (the Draft GMP Reflection Paper), has devoted an entire chapter to the maintenance of supply of medicinal products. And EU regulators have highlighted the fact that medicinal product shortage prevention is one of their key priorities in 2020 (and informs the broader discussion of medicinal product pricing). In light of these developments, MAH should consider now conducting a careful review of their shortage management procedures.
Stakeholder Initiatives to Identify Root Causes of Shortages
The European Federation of Pharmaceutical Industries and Associations (EFPIA) recently published a Policy Proposal to Minimize Medicine Supply Shortages in Europe, calling, in particular, for the use of the repositories being set up in the context of the Falsified Medicines Directive as additional intelligence about the root causes and drivers of shortages.
Further, supply chain stakeholders from EFPIA, Medicines for Europe and other industry associations recently published a paper addressing the root causes of medicines shortages. The document identifies a variety of causes, including regulatory-related root causes, such as specific national packaging requirements, and manufacturing- and quality-related root causes, such as manufacturing capacity and GMP issues. It suggests:
- Harmonizing and monitoring medicines shortages at the EU level and, in that context, clearly defining a “risk of shortage”;
- Creating regulatory incentives for essential, low-priced medicines to ensure they remain on the market;
- Allowing regulatory flexibility, such as allowing different pack sizes or multicountry packages in the event of a confirmed shortage and improving regulatory efficiency to mitigate shortages; and
- Ensuring market stability and sustainability in the form of a predictable and sustainable pricing and reimbursement environment.
The Draft GMP Reflection Paper
The EMA’s Draft GMP Reflection Paper for the first time consolidates general MAH GMP responsibilities into one comprehensive document. In an important chapter, on the maintenance of supply of medicinal products, the EMA reiterates MAHs’ “public service obligation” under Article 81 of Directive 2001/83/EC to “ensure appropriate and continued supplies of [a] medicinal product to pharmacies and persons authorised to supply medicinal products so that the needs of patients in the Member State in question are covered.” The EMA reminds MAHs that they have a responsibility to report restrictions in supply to competent authorities and that they must therefore ensure that their manufacturers notify them of potential supply problems in a timely manner. MAHs “should ensure that the communication arrangements between it and the manufacturer on potential supply issues are agreed and clearly documented in a technical agreement.”
The Draft GMP Reflection Paper identifies as possible reasons for supply disruptions, in particular, highly complex supply chains associated with globalization of manufacturing and distribution activities as well as poor management of marketing authorization transfers between companies, resulting in unavailability of the correct product artwork following such transfers.
The Draft GMP Reflection Paper emphasizes the importance of MAHs being proactive in their approach to supply chain management and recommends that MAHs carry out detailed risk assessments of their manufacturing, regulatory and supply chain processes and work to address any identified weaknesses in those areas.
Making Medicinal Product Shortage Prevention a Key Priority
These developments tie in with the public announcement on the EMA website as well as by EU regulators at various events in the past few weeks that medicinal product shortage prevention is a key priority of EU policy in 2020 and beyond. In addition to the documents that we reported on previously , EU regulators have upped their efforts to improve information sharing among competent authorities. In particular, the Heads of Medicines Agencies/EMA Task Force on the Availability of Authorised Medicines for Human and Veterinary Use has been running a pilot program on establishing a single point of contact (SPOC) network through which member states, the EMA and the European Commission can share information on important medicine shortages. In a first phase, the pilot program tested the functioning and usefulness of the SPOC network. In a second phase, in 2020, the pilot program will test the criteria for identifying cases deserving EU-wide coordinated action and for network alerts of upcoming public communications that could have a high impact on patients.
Conclusion
There have been several important developments over the past few months that focus on medicinal product shortages and their prevention. MAHs should expect these developments to gain momentum in 2020 and beyond and for EU regulators to more clearly define, and pay closer attention to, MAH GMP responsibilities with respect to medicinal product supply management.
MAHs should therefore closely monitor the developments set out in this Update, consider carrying out detailed risk assessments of their manufacturing, regulatory and supply chain processes and work to address any identified weaknesses in those areas.
