Balancing Speed and Safety: The Authorisation of Covid-19 Vaccines and Medicines

Abstract

Click to increase image sizeClick to decrease image size Notes1 We are immensely grateful to Adela Williams (Arnold & Porter), Kelyn Bacon QC and Nick Saunders QC for their helpful suggestions on an earlier draft of this article. In the usual way, any errors are ours.2 The government guidance document entitled “Our plan to rebuild: the UK Government's Covid-19 recovery strategy” (first published 11 May 2020) describes two different vaccine strategies (at section 5.11) in the following terms: An epidemic modifying vaccine strategy aims to induce immunity to the infection at the population level and therefore stop the epidemic. To be epidemic modifying the vaccine has to be very safe (because it is used in the entire population) and highly effective. A disease modifying vaccine strategy aims to protect all or selected vulnerable parts of the population from the worst effects of the disease, even if the vaccine is not capable of complete protection against infection. It might for example ensure that those vaccinated are much less likely to die from the disease. The epidemic may continue but with significantly reduced mortality and long-term health effects.3 See <https://1daysooner.org/> (accessed 10 June 2020). See also <https://www.ft.com/content/e1e65c42-911b-11ea-bc44-dbf6756c871a> (accessed 10 June 2020) (free to view, at the time of writing).4 In particular, one of the medicines with most promise seems to be remdesivir, which is discussed further below. Other trials are considering whether antibody-containing plasma from a recovered patient may safely and effectively be given by transfusion to a patient who is suffering from Covid-19. The hope is that the donor antibodies could help shorten the length or reduce the severity of the virus. In the past, convalescent plasma has been used to treat a variety of illnesses from measles to polio, chickenpox, and SARS. See <https://www.health.harvard.edu/diseases-and-conditions/treatments-for-covid-19> (accessed 10 June 2020).5 See Art. 6(1) of Directive 2001/83/EC on the Community code relating to medicinal products for human use, as amended (“Medicines Directive”). The Medicines Directive is largely implemented in the UK by the Human Medicines Regulations 2012 (“Human Medicines Regulations”). It should be noted that there are some exceptions to this general rule such that, in certain very limited circumstances, unauthorised medicines can be placed on the market.6 Medicines Directive, recital 2.7 However, it is notable in the present context that it did not originally cover vaccines.8 Medicines Directive, Arts 28–29.9 Ibid.10 Ibid., Art. 26(1)(a).11 Human Medicines Regulations, reg. 58(4).12 See ibid., reg. 58(1). The period is extended if the MHRA requests the applicant to provide any further information or material (see reg. 58(2)).13 Regulation (EC) No. 726/2004 of the European Parliament and the Council laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency (“Centralised Procedure Regulation”), Art. 3 and Annex I.14 These are set out in the Centralised Procedure Regulation and include that the CHMP has up to 210 days to provide its opinion on whether the medicinal product in question ought to be authorised (Art. 6(3)); a further 15 days is then permitted for the EMA to communicate that opinion to the Commission (Art. 9(3)); it then usually takes around a further six weeks for the Commission to adopt a final decision on marketing authorisation (see the procedure set out in Art. 10(1)).15 The requirements are set out in the Medicines Directive, Art. 8 and Annex I. Generating the results and other data for this dossier is extremely expensive, and many of the judicial review proceedings concerning medicinal products to come before the Administrative Court in recent years centre on protection of those data. As explained in the next paragraph, there are some exceptions to the requirement to provide a full dossier of information.16 See the Medicines Directives, Arts 10–10c.17 Ibid., Art. 8(e).18 See <https://covid19vaccinetrial.co.uk/phase-i-trial-explained> (accessed 10 June 2020).19 See e.g. “Our plan to rebuild: the UK Government's Covid-19 recovery strategy” (first published 11 May 2020), section 5.11. There are reports that there are so many trials being conducted that it is becoming more challenging to recruit patients.20 Centralised Procedure Regulation, Art. 3(1), and Annex, para. 1.21 Ibid., Art. 3(2)(b).22 A further consideration relevant to this subject, but which there is not space to discuss in detail, is the Joint Procurement Agreement. This was adopted by the Commission on 10 April 2014 following the Swine flu pandemic. It has since been signed by the majority of Member States, including the UK. The Agreement provides a framework laying down common rules for the practical organisation of coordinated procurement procedures (for example relating to protective equipment, vaccines, treatments and medical devices) in the case of a serious cross-border threat to health. The aims of the Agreement include to secure more equitable access to specific medical countermeasures and an improved security of supply, together with more balanced prices for the participating countries. In circumstances where supplies of vaccine could be limited (in particular since unpredictability of production is a limitation on biological products), a central allocation mechanism, which is independent of the developer, may be important. Some EU countries have already made use of the Agreement, for example to coordinate the procurement of personal protective equipment. The Commission has clarified that under the terms of its Withdrawal Agreement, the UK is entitled to participate in such joint procurement. See generally the Commission's explanation of this at <https://ec.europa.eu/info/live-work-travel-eu/health/coronavirus-response/public-health_en> (accessed 10 June 2020). At the time of writing, there has been some press coverage of the question of whether the UK intentionally has not participated in the joint procurement procedure that has occurred to date, and whether it will do so in the future.23 This remains the case for centrally authorised products in the UK, even though the UK has formally left the EU, and pending the end of the transition period. The implications of Brexit and the ending of the transition period are discussed further below.24 The National Institute for Health and Care Excellence (Constitution and Functions) and the Health and Social Care Information Centre (Functions) Regulations 2013, reg. 7(6)–(8).25 The difference between the different sorts of documents published by NICE was explained in R (Fraser) v NICE [2009] EWHC 452 (Admin) at [13]–[14].26 “COVID-19 rapid guideline: critical care in adults” (first published 20 March 2020). A full list of NICE's guidelines published in response to the Covid-19 crisis is available at <https://www.nice.org.uk/guidance/published?type=cov,coa> (accessed 10 June 2020).27 The Exercise of Commissioning Functions by the National Health Service Commissioning Board (Coronavirus) Directions 2020, made under emergency powers conferred by s. 253 of the National Health Service Act 2006.28 See <https://www.gov.uk/government/groups/joint-committee-on-vaccination-and-immunisation> (accessed 10 June 2020). The agenda for the last JCVI meeting that appears on its website is from February 2020, and contains no item referring to Covid-19. The current chair of the JCVI is Professor Andrew Pollard of the University of Oxford.29 “Our plan to rebuild: the UK Government's Covid-19 recovery strategy” (first published 11 May 2020), section 5.11.30 See <https://ec.europa.eu/health/sites/health/files/human-use/docs/guidance_regulatory_covid19_en.pdf> (accessed 10 June 2020). This guidance covers potential exceptions to various rules that we do not have space to address, including those relating to the renewal of marketing authorisations, sunset clauses and good manufacturing practice. The guidance also mentions Art. 5(2) of the Medicines Directive, which we discuss briefly below.31 See <https://www.gov.uk/guidance/mhra-regulatory-flexibilities-resulting-from-coronavirus-covid-19#marketing-authorisations> (accessed 10 June 2020).32 Centralised Procedure Regulation, Art. 14(9). If the CHMP accepts that request, then the statutory long-stop date for it to produce its opinion is reduced from 210 days to 150.33 See EMA/213341/2020 “EMA initiatives for acceleration of development support and evaluation procedures for COVID-19 treatments and vaccines” of 4 May 2020, p. 4. The EMA is a member of the International Coalition of Medicines Regulatory Authorities (“ICMRA”). On 28 April 2020, ICMRA members committed to strengthening global collaborative efforts in order to facilitate the rapid development, approval and global roll-out of safe and effective medicines to prevent and treat COVID-19. The efforts focus in particular on increasing the efficiency of regulatory processes and decision-making: see <https://www.ema.europa.eu/en/partners-networks/international-activities/multilateral-organisations-initiatives/international-coalition-medicines-regulatory-authorities-icmra#supporting-the-development-of-covid-19-vaccines-and-treatments-section> (accessed 10 June 2020).34 MHRA Guidance, “Apply for a licence to market a medicine in the UK” <https://www.gov.uk/guidance/apply-for-a-licence-to-market-a-medicine-in-the-uk#fast-track-your-marketing-authorisation> (accessed 10 June 2020).35 See also Human Medicines Regulations, reg. 247.36 See n. 31 above.37 The MHRA is permitted to do so by Art. 22 of the Medicines Directive, implemented by reg. 60 of the Human Medicines Regulations. The EMA is permitted to do so pursuant to Art. 14a of the Centralised Procedure Regulation and pursuant to Commission Regulation (EC) No. 507/2006 on the conditional marketing authorisation for medicinal products for human use (“Conditional Marketing Authorisation Regulation”).38 See e.g. ibid., recital 2.39 Ibid., recital 2 and Art. 2.40 Ibid., Art. 4(1).41 See <https://www.ema.europa.eu/en/documents/other/mandate-objectives-rules-procedure-covid-19-ema-pandemic-task-force-covid-etf_en.pdf> (accessed 10 June 2020).42 See n. 30 above.43 See <https://www.ema.europa.eu/en/human-regulatory/overview/public-health-threats/coronavirus-disease-covid-19/treatments-vaccines-covid-19> (accessed 10 June 2020). Remdesivir was originally developed for use against EBOLA virus disease.44 See EMA/178637/2020, “Summary on compassionate use: Remedesivir Gilead”, 3 April 2020.45 See MHRA guidance available at <https://www.gov.uk/guidance/mhra-regulatory-flexibilities-resulting-from-coronavirus-covid-19> (accessed 10 June 2020).46 See MHRA press release at <https://www.gov.uk/government/news/mhra-approves-covid-19-vaccine-trial-in-7-working-days> (accessed 10 June 2020).47 The team at Oxford University working on a Covid-19 vaccine has stated that “the best-case scenario is that by the autumn of 2020 we could have an efficacy result from the phase III trial to show that the vaccine protects against the virus, alongside the ability to manufacture large amounts of the vaccine, but these best-case timeframes are highly ambitious and subject to change”: see <https://covid19vaccinetrial.co.uk/blog-how-long-will-it-take-get-oxford-vaccine-deployment> (accessed 10 June 2020).48 Also known as the “implementation period”.49 See <https://www.gov.uk/guidance/guidance-on-handling-of-decentralised-and-mutual-recognition-procedures-in-a-no-deal-scenario> (accessed 10 June 2020).

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