By Malka Fraiman and Paulien Nuyts

Green-covid

The COVID-19 pandemic has had a profound impact on countries across the world and, in the absence of any known therapies, galvanized a global race to find safe and effective treatments and vaccines. Regulators have responded swiftly to help expedite drug development and approval. This blog focuses on two of the geographies most affected by COVID-19, Europe and the United States of America (US), and specifically the response of the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA). It considers the challenges and opportunities that arise from the changes in the regulatory landscape and the implications for the future of medicines regulation.

How have the EMA and FDA responded

Both regulatory agencies have exerted extraordinary regulatory efforts in responding to the crisis, including streamlining their regulatory frameworks to facilitate a faster path to approval while maintaining the focus on safety and efficacy (see figure 1).

Figure 1. Timeline of crucial regulatory measures
Fig1
In Europe, the EMA activated its emerging health threats plan in early February to expedite the development of vaccines and treatments for COVID-19.1 This built on the EMA’s existing pandemic planning processes while identifying a number of new crucial steps:

  • The EMA’s 2006 pandemic crisis management plan for the evaluation of vaccines was enhanced in December 2018 to deal with serious cross border health threats (the “EMA plan for emerging health threats”). This details the principles under which the Agency operates, provides a framework for coordinating scientific and regulatory activities throughout Member States, and gives the EMA a mandate to convene specific expert groups.2
  • In response to the COVID-19 pandemic, the EMA convened the “COVID-19 EMA Taskforce” to provide scientific advice, evaluate COVID-19 related products and collaborate with drug developers and other stakeholders including the European Commission and the World Health Organization (WHO).3 It also introduced initiatives to accelerate the development of treatments and vaccines including rapid scientific advice, rolling reviews, accelerated marketing authorisations and compassionate use programmes.4
  • The EMA issued guidelines for Member States and companies to manage and prevent medicinal shortages in general and in relation to COVID-19,5 including developing the European Medicines Regulatory Network COVID-19 Business Continuity Plan (EMRN COVID-19 BCP) to ensure that essential public and animal health regulatory activities continue during the pandemic.6

In the US, a health emergency was declared by the Health and Human Services Secretary (HHS) on January 31, and introduced several critical regulatory steps:

  • The FDA issued Emergency Use Authorizations (EUA), which allow unapproved medical products or unapproved uses of approved medical products during an emergency.7 These included EUAs for:
    • Hydroxychloroquine Sulfate/chloroquine phosphate (rescinded on June 16th), Remdesivir for acute COVID-19, Propoven 2%, to maintain sedation and MultiFiltrate PRO System and MultiBic/MultiPlus solutions to provide continuous renal replacement therapy.
  • The FDA established a special emergency programme for fast tracking medicinal COVID-19 treatments “Coronavirus Treatment Acceleration Program” (CTAP)8 to:
    • cut red tape, deploy FDA staff effectively, rapidly, and interactively, and provide early regulatory and scientific support
    • encourage collaboration with researchers and share and streamline protocols.
  • The FDA also leveraged and expanded the “compassionate use” access programme, through the emergency investigational new drug application (eIND) process for patients with an immediate life-threatening disease.9 The collection and utilisation of convalescence plasma was administered through this program.10
  • The National Institutes of Health (NIH/FNIH) has established the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) programme, a consortium bringing together leading private biopharma companies together with international regulators to develop a coordinated research response.11
  • In May, the FDA issued two new guidance documents to improve efficiency of regulatory pathways for pre-clinical and clinical studies for COVID-19 therapies.12

What industry responses are we seeing?

The publication of the genetic sequence of SARS-CoV-2, on January 11, stimulated industry efforts to identify a vaccine candidate and develop effective and safe treatments and led to a marked increase in collaborations between the pharma industry, academia, and governments, for example:

  • Developers from around the world are using numerous platforms to develop vaccines, from tested approaches to induce immunity (such as live attenuated virus vaccines) to innovative platforms never used before (such as RNA- and DNA-based vaccines). Each type offers unique benefits and challenges but given requirement to vaccinate everyone around the globe, more than one vaccine will likely be needed.13
  • Likewise, drug developers, academic labs, and other organisations globally are developing many different kinds of medical products to treat COVID-19, such as antibodies, antivirals, anti-inflammatory drugs, including repurposing clinically-approved drugs.14

The above partnerships and collaborations coupled with the regulatory accommodations have helped accelerate the progression of vaccine and medicinal candidates through the clinical development pipeline line from years to weeks (see figures 2 and 3). Indeed, as of 19 June, 169 potential vaccines are in development with 11 in clinical testing and some 251 potential treatments are undergoing review.15

Figure 2. Vaccine development process and overview of most advanced COVID-19 vaccines, as of June 19, 2020.16,17 

Figure 2

Figure 3. Medicinal therapy development process and overview of most advanced COVID-19 therapies per type, as of June 19, 2020.18

Figure 3

What are the current industry and regulatory challenges?

In the race to develop the above therapies, challenges are quickly emerging, in particular the fine balance between speed and patient safety that must be weighed by developers and regulators. With so many medicines and vaccines in development, prioritising the funding of promising candidates is also important. Partnerships to target funding and scientific resources are therefore needed. For example, Johnson & Johnson and the Biomedical Advanced Research and Development Authority (BARDA) have established a ‘landmark’ partnership, investing more than one billion dollars for the development of a COVID-19 vaccine.19

In the US, Operation ‘Warp Speed’ a private/public partnership is identifying and funding what they have highlighted as the most promising vaccines.20 So far, five leading candidates have been chosen: Moderna, Johnson & Johnson, Oxford-AstraZeneca group, Pfizer and Merck.21 Partnerships have also been developed to focus on early and at-risk manufacturing to ensure rapid production and distribution to the global population. It remains to be seen how patents will be utilised and if governments will expect a return on investment for their support. Moreover, acceleration of vaccine developments has raised some ethical issues given it requires trial participants to be deliberately infected to examine the vaccine effectiveness. However, clarity on the ethical issues are pending.22

What are the opportunities for the future of regulation?

One benefit to emerge from the COVID-19 pandemic is likely to be the emergence of a new drug family or vaccine category that can improve the chances of treatment for other diseases, for example, RNA vaccines. The more collaborative relationships between industry and regulators should also set the scene for more effective and speedier regulatory processes going forward.

The global alignment of regulations and the use of technology and advanced data-driven approaches are all trends predicted in our 2018 report, “A bold future for life sciences regulations: Predictions 2025”.24 However, COVID-19 has accelerated the realisation of many of our predictions. For example, CURE ID, an internet data repository application was developed collaboratively by the FDA, the NIH, the Centers for Disease Control and Prevention (CDC) and the WHO. It gives clinicians across the world a channel for reporting novel uses of existing drugs and is being piloted during the COVID-19 response.25

Indeed, the proactive steps taken by regulators during the COVID-19 crisis has provided opportunities to develop more efficient and agile processes in the regulation of vaccines and treatments and apply them globally. Innovations such as remote patient monitoring and use of telehealth in clinical trials, access to electronic medical records and novel endpoints; and use of advanced data analytics in collaborations between regulators and industry can all serve as a blueprint for the future of regulation. Digitalising the regulatory approval process and management of clinical trials will make processes even more efficient and therefore faster enabling novel therapies to be fast-tracked and globally coordinated.

Fraiman_Malka

Malka Fraiman - Advisory Specialist Master, Deloitte Risk and Financial Advisory Group

Malka is a Specialist Master (manager) within the Deloitte Risk and Advisory regulatory transformation practice focused on Life Sciences. Prior to Deloitte she worked as a freelance consultant within the MedTech industry for over 10 years and at a large IVD medical device company for over 15 years. Malka has a vast experience in quality and regulatory compliance within the medical device and pharmaceutical industry. 

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Paulien

Paulien Nuyts – Consultant, Deloitte Risk Advisory

Paulien is a consultant within the Deloitte Regulatory Risk practice, with a particular focus on the Life Sciences and Health Care sector. She has an educational background in biomedical sciences and health sciences and obtained her PhD in public health at Amsterdam University. She has extensive experience in policy research including policy making processes and policy evaluations within the Dutch and European context.

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1 https://www.ema.europa.eu/en/documents/press-release/ema-support-development-vaccines-treatments-novel-coronavirus_en.pdf
2 https://www.ema.europa.eu/en/documents/other/ema-plan-emerging-health-threats_en.pdf
3 https://www.ema.europa.eu/en/documents/other/mandate-objectives-rules-procedure-covid-19-ema-pandemic-task-force-covid-etf_en.pdf
4 https://www.ema.europa.eu/en/documents/other/ema-initiatives-acceleration-development-support-evaluation-procedures-covid-19-treatments-vaccines_en.pdf
5 https://www.ema.europa.eu/en/human-regulatory/overview/public-health-threats/coronavirus-disease-covid-19/availability-medicines-during-covid-19-pandemic#guidelines-for-eu-member-states-section
6 https://www.ema.europa.eu/en/documents/other/european-medicines-regulatory-network-covid-19-business-continuity-plan_en.pdf
7 https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization#covidtherapeutics
8 https://www.fda.gov/drugs/coronavirus-covid-19-drugs/coronavirus-treatment-acceleration-program-ctap
9 https://www.fda.gov/news-events/public-health-focus/expanded-access
10 https://www.uscovidplasma.org/
11 https://www.nih.gov/news-events/news-releases/nih-launch-public-private-partnership-speed-covid-19-vaccine-treatment-options
12 https://www.fda.gov/emergency-preparedness-and-response/coronavirus-disease-2019-covid-19/covid-19-related-guidance-documents-industry-fda-staff-and-other-stakeholders
13 https://milken-institute-covid-19-tracker.webflow.io
14 Ibid.
15 Ibid.
16 Ibid.
17 https://www.covid-19vaccinetracker.org/
18 https://milken-institute-covid-19-tracker.webflow.io
19 https://www.jnj.com/johnson-johnson-announces-a-lead-vaccine-candidate-for-covid-19-landmark-new-partnership-with-u-s-department-of-health-human-services-and-commitment-to-supply-one-billion-vaccines-worldwide-for-emergency-pandemic-use
20 https://www.hhs.gov/about/news/2020/05/15/trump-administration-announces-framework-and-leadership-for-operation-warp-speed.html
21 https://www.nytimes.com/2020/06/03/us/politics/coronavirus-vaccine-trump-moderna.html
22 https://www.nytimes.com/2020/05/02/us/politics/vaccines-coronavirus-research.html
23 https://apps.who.int/iris/bitstream/handle/10665/331976/WHO-2019-nCoV-Ethics_criteria-2020.1-eng.pdf?ua=1
24 https://www2.deloitte.com/uk/en/pages/life-sciences-and-healthcare/articles/life-sciences-predictions-2025.html
25 https://www.fda.gov/media/138725/download
26 https://www.fda.gov/media/136238/download

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