EU Joint Regulatory Assessment Project Bears Fruit In COVID-19
Four more agencies are seeking to join ICMRA
Executive Summary
The European Medicines Agency has reported progress with a collaborative project that involves other regulators in its assessments of COVID-19 products, and with the EU Medicines for All initiative for evaluating products for non-EU markets.
The EU’s OPEN pilot project, which allows a group of national regulatory bodies to take part in the European Medicines Agency’s evaluation of COVID-19 vaccines and therapeutics, is producing results, with four vaccines and five therapeutics collaboratively assessed between 1 January and 26 July this year, according to the EMA.
The pilot OPEN initiative was launched in December 2020, initially for COVID-19 products and involving the EMA and regulators from Australia, Canada, Japan and Switzerland, as well as the World Health Organization. (Also see "Coronavirus Notebook: Regulators To Work Together On Vaccine Evaluation, AstraZeneca In Russia Link-Up" - Pink Sheet, 18 Dec, 2020.) Representatives of these bodies participate in the COVID-19-related work of the EMA’s human drugs committee, the CHMP, as well as the EMA COVID-19 pandemic task force (EFT).
The WHO’s representatives include three experts and observers from Brazil, China, Ethiopia, Ghana, South Korea, Mexico, South Africa and Tanzania.
The aim is to allow the partners to work together and “understand the process by which we reached a decision so they better understand the science and the regulatory decisions and are better equipped to then rely on the decision and take their own national decisions,” according to Martin Harvey, head of international affairs at the EMA.
“This is a global pandemic, and we are all regulators, regardless of whether we are well resourced or not. We are all facing common challenges, and sharing the burden is particularly important,” Harvey told delegates at the TOPRA (The Organization for Professionals in Regulatory Affairs) Annual Symposium 2021, which took place virtually from 22-24 September.
Explaining how OPEN operates at a 22 September session on regulatory reliance, Harvey said that all the partners participate under confidentiality arrangements “so we know that the information is kept confidential.”
He said they were “full partners, they engage, they receive the information, they receive the documents and they have access to the discussions. But their role stops when the CHMP takes the final decision on benefit risk, and they are not part of that particular discussion.”
“The OPEN pilot has provided the basis for reliance for about 40% of all the regulatory decisions taken by regulators in Africa” – Martin Harvey, EMA
He also noted a presentation by Murray Lumpkin earlier in the same session in which the Bill and Melinda Gates Foundation official said that to date there had been a total of 248 approvals of COVID-19 vaccines in Africa. (Also see "Regulatory Reliance Behind The Success Of African COVID-19 Vaccine Approvals" - Pink Sheet, 23 Sep, 2021.)
“I did a quick calculation, on the basis of which 108 of those regulatory actions in Africa are based on vaccines that the WHO has given an EUL (emergency use) listing for, Harvey said. “And so you can get a size of the impact of the OPEN pilot, the fact that it has provided the basis for reliance for about 40% of all the regulatory decisions taken by regulators in Africa. I think if you're looking for a metric, that's quite a strong metric to focus on.”
EU Medicines for All
The EMA official next looked at progress with another EU regulatory project intended to facilitate the approval of medicines in non-EU countries: the EU Medicines for All initiative (EU-M4all).
EU-M4all, launched in 2004, allows the CHMP to issue a scientific opinion on the benefit-risk of high-priority medicines, including vaccines, that are intended for markets outside the EU. Based on Article 58 of Regulation EC (No) 726/2004, it aims to speed access to medicines in low and middle-income countries by facilitating prequalification of products by the WHO and their registration in the target countries.
Harvey told the TOPRA session that a total of 142 decisions on regulatory approval of medicines had so far been taken across 91 non-EU countries based on positive opinions delivered by the CHMP under EU-M4all. The approvals were chiefly in countries in Latin America, Africa and Asia.
Last year, the initiative was extended to allow EUM4all to be used for parallel Article 58 and standard EU centralized marketing authorization applications, in a drive to optimize the use of regulators’ resources, prevent discrepancies between the two submissions, and reduce the time to secure a CHMP opinion if the medicine is also for use in the EU. (Also see "EMA Offers Simultaneous Review Of Products For EU And Non-EU Markets" - Pink Sheet, 28 May, 2020.)
The first product undergoing the parallel procedure is Takeda’s tetravalent dengue vaccine, TAK-003, which the company wants to market “as broadly and as quickly as we can.” (Also see "Takeda Test Drives EMA’s Parallel Review Route For EU And Non-EU Markets" - Pink Sheet, 18 Jun, 2021.) Harvey said the EMA was “very much hoping this will lead to the first successful outcome” of the parallel procedures.
“And what's important is… we have experts from not just WHO but also from countries where Takeda either intends to market, or countries where clinical trials have taken place as part of the CHMP assessment,” he declared.
ICMRA
Harvey also gave an update on the work of the International Coalition of Medicines Regulatory Authorities, an informal group of heads of medicines agencies who discuss strategies on collaboration, communication and addressing common regulatory challenges.
He described ICMRA as a “coalition of the willing” where participating regulators looked at ways of pushing for more alignment in various areas. “We are trying to set some strategic direction for the involvement of agencies in ICH (the International Council on Harmonisation), for example, in PIC/S [Pharmaceutical Inspection Cooperation Scheme) and the IPRP [International Pharmaceutical Regulators Programme], and in different international forums, so that we begin to create a common strategic direction about where we want to go.”
“We are looking actively to increase the regulatory footprint to make sure that we have high-income, low-income, middle-income” countries” – Martin Harvey, EMA
ICMRA now has 34 participating agencies as well as the WHO as an observer, Harvey said, adding: “I think we currently have another four countries that are lining up to join in the coming months.”
He declined to identify the candidate agencies, saying there was a process by which they had to be assessed. What was important, he said, was that there was “continued interest” in the collaboration. “We are looking actively to increase the regulatory footprint to make sure that we have high-income, low-income, middle-income” countries so that “all the different regions of the world are represented.”
The focus now is “very much on convergence and alignment between the regulators,” Harvey said. As an example, he noted that over the summer ICMRA published a set of recommendations and common themes for regulators looking to establish track-and-trace systems for medicines on the market.
“We're doing a lot of work together at the moment on antimicrobial resistance, looking ahead to the World Antibiotic Day coming up in December,” he continued. “We just published a report about the regulatory impact of artificial intelligence for regulators and some of the issues that we believe they will be facing. And there's a great deal of work ongoing in the area of big data and real-world evidence.”
ICMRA also hosts “a very active exchange” at the level of pharmacovigilance, Harvey said, to make sure that agencies, while not necessarily taking the same decisions, are “discussing the common evidence and science base from which to take our own decisions, including aiming for some sort of convergence.”
'Flexibilities And Agilities'
The coalition is also engaged in “quite an important piece of work” relating to regulatory agilities and flexibilities introduced during the pandemic, and hopefully industry will have recognized that regulators are being more flexible,” he said. “We're looking at which of those agilities can we keep for the future when we go back to normal business.”
Other areas of focus include looking at hybrid and collaborative inspections, and clinical trial designs for use in future health emergencies.
All this requires a great deal of information sharing, so the agencies are holding regular teleconferences “at least every two weeks,” Harvey said. He also stressed that collaboration and regulatory reliance were not just aimed at agencies in lower-income countries.
“Whether you are well resourced, or a poorly resourced agency, we need to collaborate in order to do our businesses as regulators,” he told the conference. “We've been using different terms like reliance in work sharing and reliance in collaboration, so there's a spectrum across which regulators can cooperate depending on their level of confidence, the level of resource, etc. So it is a continuum. I think we all need to work out where we want to be along that continuum.”
He also highlighted the importance of transparency. “Unless there is transparency in the work of regulators, this reliance and worksharing cannot happen.”