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Dilemmas are multiple and stakes are high as the framework for thinking about medicines development frequently fluctuates because of the COVID-19 pandemic, making it harder to foresee all implications for the future.
The COVID pandemic is shifting the framework for thinking about medicines development in so many ways and in so many places that it is difficult to keep pace with the immediate changes, and harder still to foresee all the implications for the future. In Europe, deep concerns have been raised about the arrangements granting immunity from liability for the half-dozen manufacturers that have forged supply deals with the European Union for vaccines they have in development, and the still-confidential aspects of these deals leave many unresolved questions for the coming months and years. At the same time, new flexibilities introduced in EU regulations for COVID-related products—notably in absolving manufacturers from the customary prior environmental impact assessment of GM-derived medicines—could be harbingers of a more pragmatic approach when tough realities confront regulators.
Another area where circumstances are demanding novelty of response is conditional authorization. The UK—which is going it more or less alone in its COVID regulation, since the transition period linking it with the EU expires at the end of December—is now finalizing its plans for modifications to its human medicines regulations to support the rollout of COVID-19 vaccines. These are essentially detailed changes—driven by some tough realities—which will cover conditional authorization and other issues. But a public consultation on the plans provoked nearly 200,000 responses, illustrating clearly the sensitivity and degree of concern over many of the planned amendments. Regulators—and drug developers—are likely to face not only the new evident challenges in innovation to combat COVID, but also new levels of public scrutiny and skepticism over the operations of the medicines sector.
The UK aim is to strengthen existing regulations that allow for the temporary licensing of medicines and vaccines, on an exceptional basis, pending the grant of a full license. The intention is also to extend the current immunity from civil liability to companies producing the vaccine, rather than just healthcare workers and manufacturers, so as to protect them from legal liability in civil cases (although the UK authorities insist that this does not give them blanket immunity from civil liability). At the same time, a wider range of trained personnel will be authorized to administer COVID-19 or flu vaccines, with a view to ensuring that vaccines and treatments for specific types of public health threat, such as a COVID-19 vaccine, can be promoted as part of national vaccination or treatment campaigns. The changes will also make short-term provisions to ease the swift and safe transfer of COVID-19 and flu vaccines under NHS arrangements by providing an exemption from the need for a wholesale dealer's license.
Explaining the changes to the many anxious respondents to its consultation, the UK government's formal response observes that many of the concerns expressed were not about the new provisions for a temporarily authorized vaccine, but about the very concept of conditional authorization. "The existing Human Medicines Regulations contain a provision (regulation 174) that enables the temporary authorization of the supply of an unlicensed medicine (including vaccines) in response to a public health emergency," it says. "Many respondents to the consultation expressed concern about this existing provision, rather than the proposal we consulted on, which is to clarify that conditions can be attached."
The government goes on to emphasize that "these conditions ensure product safety, quality and efficacy, and could range from specifying exactly whom the product is suitable for (eligibility criteria, both who can and who can't receive the product), setting standards, and ensuring appropriate storage is in place throughout the supply chain." It underlines that ensuring safety will be the central aim in applying any conditions to the authorization.
The government also notes concerns that temporary authorization meant fast-tracking a vaccine and therefore by-passing necessary processes to uphold safety standards, as well as concerns that methods for shorter and smaller clinical trials need consultation and review.
Some respondents sought clarification about how long a temporary authorization of an unlicensed vaccine would last.
To damp down these concerns, the government says that COVID-19 vaccines "are being developed in a strategic and coordinated way that allows some stages of the process to happen in parallel to condense the time needed, but it does not mean steps and the expected standards of safety, quality and efficacy have been bypassed." It also says that
the existing regulation makes clear than any such authorization must be temporary – suggesting that "one of the conditions that could be applied to an authorization could be a specific time limit." In any event, the government goes on, "we expect an authorization using regulation 174 to be short term, kept under review and to automatically cease when the product is granted a full license."
Responding to arguments that a temporary authorization of an unlicensed vaccine should only be used in exceptional circumstances where a licensed alternative is not available, or even that only licensed products should be used, it offers reassurance that "the government's preferred route to enable deployment of a COVID-19 vaccine remains through the usual licensing routes available. A decision to temporarily authorize the sale or supply of an unlicensed vaccine or medicine will be rare and only in exceptional circumstances." A product will only be supplied once the relevant government minister is satisfied, in light of advice from the Medicines and Healthcare products Regulatory Authority, that robust evidence demonstrates safety, quality and efficacy.
In addition, "many of the responses to the consultation raised issues around safety, risks, possible side effects and harm as a result of receiving a temporarily authorized unlicensed vaccine. Several respondents said that full testing was needed." The government repeats its commitment to safety as central to the development of any COVID-19 vaccines: "Unlicensed does not mean untested. All vaccines must undergo robust clinical trials in line with international standards, with oversight provided by the MHRA. No vaccine will be authorized for supply in the UK unless the expected standards of safety, quality and efficacy are met." To appease some of these anxieties, the new rules will now require a public review within a year of the first use of regulation 174 to evaluate the whole process.
The dilemmas are multiple—and the stakes high. Most obviously because of the pressing urgency of successfully developing effective and safe therapeutics to combat, contain and control COVID—and that is challenge enough for developers and regulators. But because public perceptions of the issues relating to medicines innovation are so heightened by understandable if over-ambitious hopes of miracle cures and magic protections, any underperformance or adverse effects of the products that are likely to be rolled out over coming months will receive massive attention. It has often been said that COVID is giving drug innovation an unprecedented, if unfortunate, opportunity to demonstrate its value to society. That remains the case. But it is becoming increasingly clear that anxiety-fueled public expectations are rising to an extent that makes the credibility of the entire medicines sector fragile if expectations are not met.