All for one, one for all: An urgent call to harmonize global drug regulation against COVID-19
Guest Commentary: Why COVID-19 has created an urgency for a global regulatory framework
The COVID-19 pandemic has spurred enormous activity in the drug industry around the world with many companies pooling their expertise and technologies to develop vaccines and treatments. However, we have no visible global coordination of the responses among the national or regional regulatory authorities. Instead, regulatory decisions are happening only at the national -- or in some cases institutional -- level, resulting in fragmented efforts that waste valuable resources and time.
As of April 21, more than 2.5 million cases of COVID-19 and 180,000 deaths have been reported worldwide, according to the Johns Hopkins University COVID-19 data tracker. The disease has spread to over 200 countries and territories, and all major economies have felt its impact. There is still no definitive answer of which therapy would work effectively.
COVID-19 underscores the threat infectious diseases can pose to health on a global scale; it also highlights both the need for a harmonized global regulatory response to this global health crisis and the opportunity to streamline regulatory processes to meet the rapidly expanding pandemic and deliver safe, effective drugs to patients everywhere.
While biotechs and academics are significant drivers of innovation in the response to COVID-19, most do not have global regulatory experience. Because their regulatory engagement will likely be limited to national or regional agencies, this will slow down the development of therapeutics that will be needed in all geographies.
COVID-19 calls on all nations around the globe to join together in recognizing a central regulatory mission (All for One), and to act for the good of patients everywhere (One for All), in the face of a fast-moving global pandemic.
Response and responsibility
In response to COVID-19, pharma and biotech companies have diverted enormous resources to the development of vaccines, neutralizing antibodies and repurposed drugs.
The magnitude of this response is astounding, especially considering many companies had long ago abandoned infectious diseases research.
Many pharmas have set aside competition, at least temporarily, in order to address the crisis together.
R&D heads from more than a dozen top pharma companies have gathered together to create COVID R&D, a pre-competitive consortium that is aiming to expedite the creation of therapies and vaccines by channeling ideas from across the biomedical community (see “Pharmas Align Behind Crowdsourcing Solution”).
A separate consortium, ACTIV, run by NIH and FNIH, contains pharma companies, non-profits and representatives from FDA and EMA, as well as CDC and NIH (see “Collaborating to Clobber COVID-19”).
But there has yet to be visible collaboration among the regulators - guidelines and timelines for regulatory review, and requirements for regulatory approval are still undefined and uncertain.
The WHO, which was created to address major global public health issues, has done a good job of coordinating clinical trials. But WHO has no clear role in harmonizing worldwide regulatory actions, nor has it any jurisdiction at any national level to encourage, let alone require, cooperation among countries. Meanwhile, regulatory actions taken by individual nations have conflicted with one another and offered no clear guidance to other countries.
“Regulatory entities around the world must recognize the new realities of global innovation, manufacturing and supply ecosystems by adopting a global regulatory framework.”
To take just a few examples: FDA allowed the RNA vaccine from Moderna Inc. (NASDAQ:MRNA) to progress from viral gene sequences to patient dosing in two months, but the regulatory discretion behind this extraordinary decision is unclear.
Similarly, FDA issued an Emergency Use Authorization (EUA) for chloroquine and hydroxychloroquine, but did not explain what criteria or standards were applied, while EMA warned about the use of those two drugs in Europe.
In China, CanSino Biologics Inc. (HKEX:6185) moved its COVID-19 vaccine into Phase I in March and subsequently Phase II testing on the basis of undefined safety data and evidence of benefit, in what seemed to be a rushed decision.
The lack of guidance from key regulatory authorities for COVID-19 products has created unnecessary competition, wasted resources, and divided patient populations between a large number of clinical trials that have poorly defined endpoints, controls and clinical objectives (see “Master Protocols Need to Replace the Deluge of Small, Inadequate Studies for COVID-19”).
The problem underlying this largely uncoordinated response is that FDA and other regulatory entities were established when the world was a different place and time: drug regulation occurred at the national level because most products were domestic in origin.
Today, about 80% of APIs are manufactured outside the U.S. and about 40% of finished drugs sold in the U.S. are imported.
The global pharma industry is increasingly driven by trade agreements that cross international boundaries. Distinctions between domestic and foreign drugs are vanishing.
Regulatory entities around the world must recognize the new realities of global innovation, manufacturing and supply ecosystems by adopting a global regulatory framework.
Progress and predicament
There has been some movement, albeit piecemeal, towards creating a global framework.
For example, WHO coordinates efforts and resources and organizes meetings and discussions about regulation under the auspices of the International Conference of Drug Regulatory Authorities (ICDRA). The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) provides guidance and standards to ensure efficient development and registration of drugs around the world.
Another global healthcare issue, antimicrobial resistance (AMR), has been the focus of international regulatory convergence under a UN Action Plan, resulting in the formation of various bi- and multilateral partnerships and initiatives between the U.S., EU, Japan, Canada and Norway.
Despite industry’s strong interest in having a single, concerted approach to tackling AMR, these collaborations have had little impact on the issue because they weren’t truly global, still had disparate guidelines, didn’t adequately define the roles of national regulatory entities, and didn’t mutually recognize decisions.
“Any national interest is inextricably linked to global interests, because no one country can solve this problem alone.”
Absent a central regulatory authority that reviews, approves and registers drug products, companies must gain regulatory approval one country or region at a time, imposing cost burdens and delaying delivery of innovative medicines to patients.
At the same time, individual regulatory entities often duplicate each other’s efforts by conducting overlapping data reviews or site inspections. This tangle of regulatory red tape discourages smaller companies - the primary drivers of innovation - from becoming global players, putting much needed medicines even farther beyond patients’ reach.
United we stand, divided we fall
Given that the mission of major regulatory entities, as well as ICH and WHO, is ultimately to promote public health, why isn’t global regulatory harmonization already happening?
National sovereignty is often cited as a major impediment to, and even an argument against, global harmonization. There is no question that every country has a sovereign right to protect its own national interests and citizens through established legislative processes and rigorous regulations.
But when the entire world is under attack from an indiscriminate pathogen, our borders dissolve before our eyes. Where COVID-19 is concerned, any national interest is inextricably linked to global interests, because no one country can solve this problem alone. COVID-19 calls upon us to strike a new balance of sovereignty and regulation to deal with global health threats.
COVID-19 forces us to take bold steps towards greater harmonization of regulatory decisions and actions for critical diseases, critical drug classes and critical populations.
As a starting point, regulatory entities around the world could sign on to a global regulatory working group - perhaps under the auspices of WHO and akin to its COVID-19 R&D Blueprint - designed to speed the development of COVID-19 treatments. In this spirit of “One for All”, key regulatory agencies would maintain open communications and transparency with each other, and work together to identify and resolve any pitfalls that could hamper our global response to COVID-19.
Whatever we choose to do, we are writing our own history with each passing day.
Whether or not we can work together to address the COVID-19 pandemic expeditiously will literally translate into massive numbers of lives, in both the most advanced and poorest countries.
COVID-19 is a warning of the shape of things to come: if we don’t stand united in the face of global health threats, then surely we will all fall.
Zhi Hong is co-founder, president and CEO of Brii Biosciences Ltd.
Signed commentaries do not necessarily reflect the views of BioCentury.