By Alberto Grignolo, Corporate Vice President, Regulatory Consulting
The COVID-19 pandemic is suddenly and unexpectedly presenting us with a unique moment in history. In a time of global crisis and desperate human suffering, the world needs treatments and preventive measures as urgently as ever.
Help is on the way.
At least 16 biopharmaceutical companies across the globe are feverishly working to develop treatments and/or vaccines for Coronavirus infections. These products are subject to regulation and to eventual regulatory approval before they can be administered to patients or to healthy people at risk of becoming infected. A number of Regulatory Authorities (FDA, EMA, MHRA, PMDA, ANVISA and many others) have recently and very quickly issued guidelines, positions, press releases and points to consider in response to this global emergency. These documents reflect a new reality that calls for flexibility, pragmatism, speed, diverse approaches but also adherence to established standards of quality, efficacy and safety to protect and promote the health of patients. These standards have been in place for decades and have proven to be beneficial to society. It is not likely or prudent that the current emergency should cause these standards to be abandoned. This would not be in the collective interest because releasing products that are of poor quality, ineffective or unsafe might be expedient but would be a gross disservice to humanity. No Regulatory Authority thus far has suggested lowering these standards below what is prudent and practical.
In the realm of regulation, the pandemic calls for a sensible balance between speed and quality. In this dramatically new and rapidly evolving environment, biopharmaceutical companies and regulators have to quickly learn how to work with each other in new ways, in order to speed effective and safe products to market while applying sensible regulatory standards.
The safety of patients remains the top priority of all concerned.
Because events are unfolding rapidly now, the role of regulatory intelligence is more important than ever. Different regulatory agencies are busily issuing documents and position papers related to the start and conduct of clinical trials, meetings with sponsors, conduct of inspections; more can be expected in the coming weeks, and they should be tracked daily if not hourly by regulatory intelligence personnel.
These actions have an impact on sponsors’ regulatory strategies, whether they be local or regional or global. Staying abreast of the actions of individual regulatory agencies and integrating those inputs into regulatory strategies will prove to be a success factor going forward. For many sponsors, it is likely that existing regulatory strategies will need to be updated, timelines and milestones revised, goals modified and the list of target countries revisited.
Clinical Trial Applications and Reporting
It stands to reason, and some authorities have confirmed, that clinical trial applications related to developing products for COVID-19 will be prioritized. But there are thousands of other products in development and many sponsors will want to continue such development by submitting clinical trial applications to the Authorities of the target markets for clinical development. Some authorities, but certainly not all, have discouraged sponsors from initiating any new clinical trials that are not related to COVID-19. It is likely that a number of Regulatory Authorities with relatively more limited resources will prioritize the review of clinical trial applications related to COVID-19, with a possible slowdown in the review of clinical trial applications for other indications. The EMA has urged a “pooling of resources” into large-scale, multi-center, multi-arm clinical trials to generate sound evidence against COVID-19 on the ground that such trials are more likely to generate actionable data than disparate and disjointed small trials. Industry will want to heed this call to action.
With regard to Authorities that are open to receiving new clinical trial applications, sponsors will want to be very familiar with the associated requirements and expectations of each Authority. Some authorities (FDA, MHRA) have stated their willingness to allow sponsors to monitor clinical trials remotely for the convenience of sponsor staff, and to conduct virtual/decentralized trials for the convenience of patients. The industry, including CROs, has already considered and developed these approaches for several years and has recently been in the process of implementing them.
Regarding protocol deviations and safety reporting, some Authorities have waived the requirement for preapprovals and timely reporting; but they have urged sponsors to keep good records and to inform the Authorities as soon as practical.
At this time, there is no explicit indication that the acceptance and review of marketing applications by Regulatory Authorities is affected by the current emergency. However, considering that some regulatory Authorities have limited resources and that those resources may be diverted to dealing with the COVID-19 outbreak, sponsors will need to be aware of the possibility that such constraints may slow down the review of pending applications. Effective communication with the assigned liaison officers at specific regulatory Authorities will be an important way to stay abreast of developments affecting specific marketing applications.
In this evolving environment, normal regulatory timelines may well be affected. This is particularly possible with regard to the review and approval of clinical trial applications and marketing applications, meetings and telecommunications with the Authorities, timing of inspections, and more.
The now widespread recommendation for “social distancing” will make it nearly impossible for sponsors to meet face to face with regulators for the foreseeable future. In addition, due to the distractions caused by COVID-19, some authorities may delay meetings of any kind (even teleconferences) with sponsors substantially or indefinitely.
FDA’s CDER now encourages meetings with external stakeholders to occur by teleconference, when possible.
Sponsors need to prepare to meet with regulators “remotely” and to adapt their goals, arguments, presentations and interactive discussions accordingly. Language may become more of an issue if meetings are conducted by phone rather than in person, possibly mandating the use of interpreters. In many cases the logistics of communications with regulators will have to be revisited and updated.
Both MHRA and FDA have announced that their regular GxP inspections are now drastically scaled back (e.g. limited to essential inspections associated with COVID-19 and other specific public health risks), or eliminated entirely, both domestically and internationally. For example, FDA has temporarily postponed all domestic routine surveillance facility inspections; all domestic for-cause inspection assignments will be evaluated and will proceed if mission-critical. Both agencies have urged sponsors to continue to comply fully with the GxP requirements even in the absence of inspections. This is sound advice for the purposes of ensuring that products are manufactured and developed according to the normal regulatory standards for the sake of patients’ health.
Other Authorities may adopt a similar stance and reduce or eliminate inspectional activities for extended periods of time.
How regulators are working
A number of regulatory Authorities are allowing or even ordering the majority of their staff to work at home. For example, FDA has directed all eligible FDA employees to begin teleworking. Authorities do understand that a majority of sponsors are doing the same. As a result, a number of Authorities have issued guidance to the effect that documents that are normally submitted to regulators in paper form can now be submitted electronically instead, with the paper versions to be submitted in paper form at a later date to be determined. This approach is intended to facilitate the work of sponsor staff who are compelled to work at home and may not have access to facilities the produce paper documentation for submission.
Email and telephone communications between regulators and sponsors are expected to increase and to become a standard mode of communication for the foreseeable future.
What does this all mean?
Regulatory best practices have developed and evolved over several decades. Suddenly, they have to be reexamined and adapted to a new environment. Monitoring and tracking developments at all regulatory Authorities is now imperative in order to inform industry’s strategies and actions and to help ensure that the development and availability of new products and the lifecycle management of existing marketed products are protected.
How can Parexel help?
With our 1,000+ consultants, including ~100 former regulators / inspectors / HTA assessors, our Regulatory & Access consulting group are optimally positioned both geographically and experientially to track and understand the views and evolving approaches of each local Regulatory Authority, to communicate clearly and to intervene effectively with each on behalf of sponsors and their patients, and to help sustain the supply chain for medicines, medical devices and diagnostics in this time of urgent global need. Our decades-long experience with thousands of clinical trial applications, hundreds of marketing applications, myriad Pre-Approval and Post-Approval inspections and thousands of scientific advice meetings helps protect and promote the regulatory and access interests of the biopharmaceutical industry and the patients who are waiting for treatments for COVID-19 and innumerable other diseases.
Particularly in a time of crisis, we are ready to serve.