Learning Regulatory Lessons in Times of a Crisis

Editor’s Note: This article was published in Pharmaceutical Technology Europe’s July 2020 print issue.

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Numerous industries around the world have been significantly impacted by the current global COVID-19 pandemic and have been required to adapt in order to ensure continued commercial success. The bio/pharma sector is an industry that has probably been most affected by the pandemic, not only is there an expectation for bio/pharma companies to step up and develop appropriate treatments quickly, resulting in regulatory flexibility and unprecedented collaborations, but there have also been concerns around supply chain security.

Focusing on how regulatory authorities have reacted to the COVID-19 pandemic within the bio/pharma sector and the potential ramification of actions taken in a crisis situation for the long-term, Pharmaceutical Technology Europe sat down with a roundtable of experts to get an in-depth view of current regulatory enforcement trends. These experts include Gabriela Marton, regulatory affairs director at Arriello; Remco Munnik, associate director at Iperion; Darren Mansell, regulatory affairs manager, Owen Mumford Pharmaceutical Services; and Denis Gross, vice-president delivery at ProductLife Group.

Adapting to a pandemic

PTE: In light of the current climate (COVID-19 pandemic), what changes have regulatory authorities been making to accommodate for industry disruption and/or to accelerate any potential treatment development?

Marton (Arriello): Regulatory authorities around the world started adapting to the COVID-19 pandemic and adjusting ways of working by primarily changing submission conditions. For example, many authorities, which usually require physical submission of documents or parts of documents, have now made submission available by electronic means. It is hoped that these solutions (electronic submission) will be continued in the future.

Additionally, adapted rules on handling clinical studies and product approvals have been published. Most authorities have adopted a flexible approach regarding product registration; clinical trial rapid review, advice, or management; audits; extending deadlines where needed; readability user tests; and so on. All of the changes being made by regulatory authorities could accelerate solution development for a COVID-19 treatment or help reduce the risk of the infection spreading.

Munnik (Iperion): In the current pandemic situation, industry is facing a reality that most people are working remotely or from home. Regulators, on the European level, did share information that systems are running; however, it is also believed that the current situation demonstrates the need for more transparency within industry. How can real-life information about the availability of medicines be provided? In case one country faces problems with medicines (or medical devices), how can the industry and regulators track products that are registered on a European level and those that are available for supply from another country? The same could apply on an even smaller scale, with information of availability between regions and/or hospitals. The current process of checking availability of medicines involves the appointment of a single contact to collect information by sending out spreadsheets, which need to be filtered and completed (1).  

With regards to potential treatments, a large number of activities are ongoing to stimulate the development of vaccines and treatments. For pharmacovigilance purposes, at the level of adverse event reporting, new terms for COVID-19 were added to the MedDRA [Medical Dictionary for Regulatory Activities] (2).

Mansell (Owen Mumford): There has been discussion by regulatory authorities on the fast-tracking of particular products that could be used to diagnose or treat the COVID-19 virus. In addition to accelerated pathways, regulatory authorities have been accepting scans of documents instead of ‘original’ paper documents where notarization and legalization services are currently unavailable. 

However, there have been negative impacts too, where regulatory authorities are either currently short-staffed or prioritizing emergency products, meaning non-emergency products are currently ‘de-prioritized’.

Gross (ProductLife): Regulators in the United States and the European Union, as well as other major authorities, have been focused on streamlining clinical research for potential medical solutions against COVID-19 by prioritizing resources on these activities. Agencies have prioritized protocol consultations, shortened the timelines for clinical trial application review and approvals, and there is some focus on implementing fast-track and priority review processes for the evaluation of marketing authorization applications.

Global efforts

PTE: Have the approaches been vastly different around the world (Europe versus US versus rest of the world)? Or is there general harmonization?

Gross (ProductLife): Members of the European Medicines Agency (EMA) have written a paper asking for a worldwide coalition to concentrate the efforts on the set up of adequate clinical trials to treat COVID-19. They have listed seven points for consideration to achieve streamlined efforts, which, broadly speaking, call for cooperation between all stakeholders-agencies, the research community, ethics committees, the development of infrastructure to support clinical trials, and efforts by patient organizations to encourage clinical trial coordination.

Marton (Arriello): Authorities that have more experience in evaluation of data adapted quickly, while other authorities, such as those in the Commonwealth of Independent States area, stopped all activities for a period of time or adapted along the way. The Medicines and Healthcare products Regulatory Agency (MHRA) and EMA are good examples, and they were immediately followed by other EU authorities. 

The challenge was perhaps greater for authorities in the eastern EU where they needed to adopt reduced contact rules and make it possible for marketing authorization holders (MAH) to approach authorities by virtual means. 

The US Food and Drug Administration (FDA) started signalling what was happening in the world before the pandemic reached the US and coming up with changes and solutions slightly more openly than EU authorities, but overall, more experienced authorities around the world [have been] harmonized in their approach to the pandemic situation.

An opportunity to prepare

PTE: How might the approaches being taken at the moment (whether different or more harmonized) impact regulation of the global pharma industry in the future?

Mansell (Owen Mumford): There has been discussion of more ‘fast track’ options for devices that need rapid movement to market in the future. There could also be more allowance for electronic regulatory dossiers rather than the old-fashioned paper copies containing legalized documents, as a result of the acceptance of digital documents during the COVID-19 pandemic.

Munnik (Iperion): It is my opinion that the current situation should be used as an opportunity to prepare for the future. As a network, both industry and regulators need to have current information on which products are registered and available on a global level. This requirement is true for products that are new developments (new treatments), and those that are already existing medicines, which are critical in treatment and/or new clinical trials to test medicines for new indications.

Marton (Arriello): At the moment, as the pandemic is not yet over, it is hoped that some changes will be maintained in the future, but it’s hard to predict if most of the measures will be maintained or if the industry will encourage authorities to maintain some of the new measures and embrace the changes.

From the perspective of a regulatory affairs and quality professional, I would say that some of the rules, relaxations, or changes in communication adopted during this period are welcome and have accelerated processes. In some cases, especially those related to products proven to have a clinical effect on the virus or on associated symptoms of the virus, it was demonstrated that collaboration between professionals and authorities can be very effective.

Whereas, I recognize that the pharma industry needs to remain very strictly regulated and legislation needs to fit the times that we live in when the necessity is to have safe, high quality, and efficacious medical products on the market.

In conclusion, I’m hoping that both regulatory authorities and the industry will learn from this pandemic. 

Gross (ProductLife): There is already some cooperation between the US and Europe, especially in the regulatory development process and in the evaluation process, so it’s possible the current situation could reinforce those efforts and lead to some further joint assessments for clinical trial protocols and marketing authorization reviews. However, there are many issues that would have to be overcome, including the regulatory burden, competition between agencies and countries, as well as economic and political considerations.

Potential ramifications

PTE: Are there any potential legal ramifications that could arise from the current regulatory approaches?

Gross (ProductLife): There is likely to be a push to relocate manufacturing of certain strategic products-such as vaccines, active substances, and finished products, in addition to medical equipment-to Europe, rather than China and India where most manufacturing currently takes place. There may also be a crackdown on investigator-initiated trials and more control over the design of clinical trials to avoid resource shortages, although this could be difficult to enforce.

Marton (Arriello): If the question implies potential new legislation being introduced in areas not regulated until now, I would say probably not, but I think that changes resulting from COVID-19 will enrich current legislation in the EU or US. I believe that the pandemic has made both authorities and industry players see that it is possible to speed up some processes by slightly changing the approach, as in the case of clinical trials, and that access to medicine can be improved.

Munnik (Iperion): I would assume that on regional level, more guidance will be made available with regards to working in pandemic situations, which included better tracking on availability and shortages of medicinal products.

Impact on existing regulations 

PTE: Have any existing regulations been affected by the pandemic?

Mansell (Owen Mumford): The EU’s Medical Device Regulation (MDR) has been delayed by 12 months to May 2021, as a direct result of the COVID-19 pandemic (3).

Gross (ProductLife): The most obvious one is the MDR, which has been delayed by a year due to the impact of the pandemic. Beyond that, the fact that agency staff can’t work together will have an impact on the development of new guidance documents.

Marton (Arriello): Many rules set by regulators have been affected by the pandemic because of contact restrictions and because treating COVID-19 infected people was every government’s priority. Setting regulations was affected, as legal work started before the pandemic was postponed. Instead the focus is on adopting measurements to help the population and industry during the COVID-19 pandemic. Probably, during this month, the issues that were raised before the pandemic happened will start to once again become the topic of discussion. 

Learning lessons

PTE: Do you believe EMA (and other regulatory authorities) will reassess their approach to ‘health crises’ as a result of lessons learned from COVID-19?

Marton (Arriello): The COVID-19 pandemic has definitely been a lesson of sorts. How much will be learned remains to be seen, as measures that were introduced in a period of change need to be endorsed by both authorities and industry.

There is no doubt that crisis management, as well as business continuity planning, will be different as a result of the pandemic, and both authorities and industry will have to consider these changes. Plans to support continuity for employees working from home or from adapted working places will trigger the need for change. 

Furthermore, there has been an immediate response needed in light of COVID-19, with regards to supply, advice, and approval. Everyone-government, authorities, and industry-must be better prepared to take action in the instance of a future crisis.  

Munnik (Iperion): Undoubtedly regulatory authorities should be learning lessons from the current pandemic! There should be efforts made to ensure the latest regulatory status on new clinical trials, as well as existing products and their availability, is available. I do hope that everyone realises the importance of having one (preferably) global set of regulatory data that can be used in crisis situations. 

It is currently unknown as to how long the impact of COVID-19 will last. In my opinion, it is better to start assessing regulatory approaches to pandemic and crisis situations as soon as possible to make systems future proof.

Gross (ProductLife): It is certainly the hope that lessons will be learned, but success will require harmonization between countries, which is a political issue, and extends beyond the oversight of health products. It is possible regulatory harmonization could start with alignment on certain activities, for example, France and Germany are collaborating on a proposal for a recovery fund for regions and sectors hardest hit by the pandemic, but this still requires agreement from other European countries. 

One challenge that could undermine clinical research into COVID-19 vaccines and therapies particularly is the proliferation of isolated, poorly controlled clinical trials that create a strain on patient resources. To combat this issue there is a need for greater coordination across agencies, as well as private and public stakeholders, to concentrate their efforts on setting up conclusive, well-designed clinical trials to avoid these patient shortages.

References

1. EMA, “Update on EU Actions to Support Availability of Medicines During COVID-19 Pandemic,” ema.europa.eu, Press Release, 10 April 2020.
2. MedDRA, “MedDRA Version 23.0 Update to be Produced,” meddra.org, Press Release, 10 April 2020.
3. European Parliament, “Parliament Decides to Postpone New Requirements for Medical Devices,” europarl.europa.eu, Press Release, 17 April 2020.

Article Details

Pharmaceutical Technology Europe
Vol. 32, No. 7
July 2020
Pages: 24–26

Citation 

When referring to this article, please cite it as F. Thomas, “Learning Regulatory Lessons in Times of a Crisis,” Pharmaceutical Technology Europe 32 (7) 2020.