023 celebrates the tenth anniversary of the Caribbean Public Health Agency (CARPHA), formed to strengthen and equip health systems in the regional Member States to address existing and emerging public health challenges and as a public health umbrella to address issues requiring a broad regional response. In this interview, Caribbean Regulatory System Programme Manager Rian Extavour shares the agency’s past, current state, and what it needs to continue to do to ensure the safety of healthcare products and the patients who use them in its jurisdiction.

Rian Extavour: CARPHA was established in 2013 and is headquartered in Port of Spain, Trinidad and Tobago. It came about because there were different regional health institutions operating with different areas of focus in CARICOM, the Caribbean community. Five institutions came under one umbrella to form the Caribbean Public Health Agency: the Caribbean Environmental Health Institute, the Caribbean Epidemiology Centre, the Caribbean Food and Nutrition Institute, the Caribbean Health Research Council, and the Caribbean Regional Drug Testing Laboratory.

CARPHA brings together the public health functions we need: disease surveillance, quality testing of medicines, things related to environmental health and noncommunicable diseases, and disease management for public health. Its vision is healthy people, healthy spaces, and a healthy Caribbean. The idea is a unified approach to help the Member States of CARPHA manage their public health issues and to improve and strengthen their health systems more closely and more collaboratively.

DIA: Is it too simplistic to think of CARPHA as the same type of organization as the Pan American Health Organization (PAHO)?

RE: There is a unique relationship between PAHO and CARPHA. What used to be the Caribbean Epidemiology Center (CAREC) was administered via PAHO and there’s still a sibling-type relationship between the two agencies. In a simple sense, PAHO supports certain large policy areas for health system strengthening. Because PAHO has all of the Americas as its remit, CARPHA presents the opportunity for more focused support for countries of the Caribbean community, which are usually English-speaking, small island developing states. Some Dutch territories are also beneficiaries of what CARPHA does.

Sometimes we find (I guess because of how close we tend to be) that CARPHA can help operationalize certain things in a lot of these smaller states that PAHO may do on a policy level.

DIA: Would you explain the relationship, and the respective roles and responsibilities, between CARPHA and the Caribbean Regulatory System?

RE: In 2016, CARPHA and PAHO agreed to establish the Caribbean Regulatory System (CRS) under CARPHA’s umbrella, where we became an additional unit. It was funded and is still funded through the Bill and Melinda Gates Foundation and through PAHO. So, we began to become more integrated within CARPHA than before. All our offices are at CARPHA’s headquarters in Port of Spain, and all our operations are through there. The administration of CRS is within CARPHA.

DIA: What products are eligible for CRS evaluation and recommendation?

RE: Medicines, primarily. Essential medicines are given priority because of the need for rational use and helping countries select the most important ones. Essential medicines as well as vaccines, if that’s outside of the PAHO relationship with each country for vaccine access. If there are vaccines outside of that, or an applicant or sponsor has an interest in marketing their vaccine in the country, then we accept vaccines that have been pre-qualified by the World Health Organization (WHO) for review.

In the pandemic, we included vaccines and medicines under the emergency use listing by WHO or those that were reviewed by a stringent regulatory authority that we recognize. We ventured into verification as well with in vitro diagnostics or test kits for COVID-19, but we have not expanded fully to all types of in vitro diagnostics just yet. We are looking to expand the types of products we evaluate and to accelerate our evaluation, but we’ll have to develop the process and criteria for it and ensure that we have the capacity to handle different types of products.

DIA: Thank you for pre-empting our question about diagnostics. What lessons did CRS learn during the pandemic and how have you applied those lessons as we’ve moved out of the shadow of COVID?

RE: During the pandemic, CRS was able to adjust its reviews. We do a verification review of medicines or vaccines based on regulatory reliance, so we applied that approach to medicines and vaccines that were evaluated and approved for emergency use authorization (EUA) or WHO’s emergency listing. It’s one thing for Member States to be able to say “This has been approved by a regulatory authority or by WHO.” But many countries do not have the capacity for the steps involved to register it with the required information that comes with dossiers, so we took on that role: We did it voluntarily for the COVID-19 vaccines under the EUA, so the sponsor did not have to approach us directly. We worked with WHO, which would confirm with the sponsor that it’s okay to allow us regulators to have access to the dossier. In regular practice, we access the WHO dossier and provide a summary and a recommendation for emergency use approval or temporary marketing authorization that allows all Member States to accept and register vaccines through COVAX or any other mechanism. We can access COVID-19 vaccines under emergency use listing much faster and have that technical information all in place. The role was to create a regulatory efficiency mechanism. Our efficiencies and that summary meant that our Member States could make approvals faster.

When things would change, for example post-approval changes, we would also go back and look at any updates changed or approved by WHO. When a sponsor change was approved by WHO, we would give our Member States updates. We created and shared an appendix as changes occurred, so we could share that change information. When stability data continue to emerge and shelf lives change, we provide those kinds of updates: We can use this batch for much longer. We don’t have to dump it. That really was important to know: you don’t want to dump vaccines that you could have kept much longer.

Once we recommended a vaccine under COVID-19, we conducted a webinar with our regulators to walk through the key source technical information, to distill the safety and efficacy data as well as information on stability and storage. They not only got the written report, but they were also brought into these technical webinars to see what critical points we looked at in the dossier. We like to think these are building capacity and we want to continue doing that.

It didn’t translate as easily for medicines, but that’s still an option: If there are pre-qualified medicines for COVID-19 that all Member States are interested in, the sponsor will have to grant permission for sharing the dossier and providing the summary. That’s still an opportunity because we recognize that management of COVID-19 remains important at this stage.

Key lessons learned? Understanding the reference authority’s process and requirements is important for our own interpretation or follow-up request. For instance, if something has been adjusted and approved, the nature of that approval can vary depending on the nature of that post-approval change. We’ve learned about differences among some of the reference authorities we rely on. We’ve also noted the challenges that some of our Member States continue to face. They have mostly been very appreciative of how we share that information in a timely manner, but sometimes details as to how that information helps do not come back as quickly as we would like.

In our region, there are Member States that have yet to develop or strengthen their legislation to provide for assessment of vaccines and medicines. Even if you’re procuring through a trusted mechanism, having information from the dossier is important. So, we encourage our Member States procuring through the revolving fund or through PAHO’s strategic fund to reach out and get that dossier, because they may have a question about that product and that’s where you would find key information that led to the product approval. We do have some systems that need to be strengthened in medicines and vaccine assessment. Where we can provide opportunities to share our experiences on the use of regulatory reliance, we want to continue to do that. We’re looking at planning workshops that we can walk through with our Member States.

DIA: May we ask you to share another CARPHA success story or accomplishment outside of the pandemic?

RE: Sometimes we think that the process ends with the approval of a medicine or a vaccine. One of the things we’re proud of is our network for pharmacovigilance and what we do with what we call the VigiCarib. We created reporting forms for pharmacovigilance of medicines and vaccines and made them available on our webpage. We refer to them to look at suspected adverse reactions as well as adverse events following immunization with a vaccine. That was a new iteration of the adverse event form because of COVID-19 vaccines. We were able to get funding for a social media campaign to sensitize the public about what to report and how to report it. We paired that with training and workshops for health professionals, so they know what’s key to report for suspected adverse drug reactions and adverse events following immunization. It’s not just public awareness but giving health professionals more information about what to do. Our forms were able to collect data from reporters whose local reporting system may not have been easily identifiable or may have required a manual process or their return to the health facility to report. Many times, it’s not very feasible.

We also know that doctors in private practice will see patients after they’ve received a vaccine at a public health institution. They will tell the doctor about it but that report stays within the patient’s file and does not get back to the responsible government or ministry. Information as to the safety and efficacy of these products may be lost. Even though the form is not country-specific, we would divert that case report to the country’s focal point. That allowed market authorization holders as well as physicians in private practice to send us reports. That interface is something we’re very proud of. Of course, we continually need to remind people that it exists!

I think all regulatory institutions face that challenge: You always have to remind people that this happens, that this exists, and what it means. Just because something is reported doesn’t mean it’s attributable to that medicine or vaccine. It’s a process, but at least we have taken the first step in the process and the Member States could take it forward from there. There was a report from a market authorization holder who posted a falsified version of a COVID-19 medicine to our system in one of our Member States. We were able to connect the regulator with that sponsor, the sponsor confirmed it had been tested and was found falsified, and regulators were able to start clamping down more stringently on unauthorized imports or unregistered versions of the product. It’s really a small step, but it’s an important step.

DIA: What are the biggest needs for educational or human resources in your organization and are there plans and funding to meet these needs?

RE: We support two functions at this time: market authorization decisions through dossier reviews and pharmacovigilance through spontaneous reporting and case transfer. We need to be able to source qualified persons who are willing to be trained in this work. There are multiple aspects to regulating pharmaceuticals, as you can imagine. We would like to expand to support licensing and inspections of establishments. That will require personnel, training, and standardization of processes. We need to strengthen continuing education for our current staff and have entry-level professionals with at least baseline knowledge or access to education. Most regulators learn on the job and through conferences after we’ve been employed. It’s not a negative, it’s not a criticism, it’s just how it is, but it takes a little longer for people to get to a point where they can create new processes or apply those skills in full.

Capacity strengthening is necessary, particularly in pharmacovigilance, signal generation and detection, handling, and causality assessment. One of our challenges is that we depend on information from the countries; we’re not on the ground to do investigations ourselves. The ideal would be to have a PV officer on each island or each state that can support and do that kind of work with the Member States and then feed it into some regional or subregional mechanism. That’s a challenge to the capacity we have in-house. We want to expand to other functions, but it will take some adjustment. It will take more staff and staff training in these areas, particularly inspections and even good manufacturing practices, because we do have some manufacturing facilities in the Caribbean. Many are finished product manufacturers, where they have sourced the active ingredient elsewhere and just finalize the product, simple manufacturers who just combine ingredients to make a finished syrup or something.

There’s so much work. I see a lot of opportunities around inspections. I would really like to know how we are doing with the most recent issues of contamination and falsification in the Caribbean. There are considerations for inspecting existing manufacturing facilities, but there’s also interest in expanding manufacturing in the Caribbean so that we can be less reliant on imports. That may be long-term, but definitely inspections and ensuring supply chain management are envisioned to support that.

DIA: Is there anything we didn’t ask that you wish to share?

RE: I’m happy to see DIA give us a forum and ask about what we do. I know it is a challenge when country-level systems may not turn decisions around quickly or may vary in all these decisions. But I always encourage applicants to remember that this is a very new system and we’re working with countries that have different challenges in capacity and legislative frameworks. I am seeing changes. I’m seeing countries trying to work with what we do, to integrate it into their decision making, even informally.

I want to let them know there is hope. We are continuing to work towards making sure we use reliance approaches efficiently and to the best of our ability to implement market access to quality medicines and vaccines. We are fortunate to be able to introduce better electronic systems. For instance, our application system is going to be through a registration portal and we’re looking forward to strengthening that so when applicants submit, they know that their dossier information is not being sent by email, which could possibly have vulnerabilities. We encourage applicants to not feel daunted. Change does take a little time. We can help Member States make the best use of what we’re doing.

Read Part 1 of Global Forum‘s Special Section on Research and Regulation in Latin America in our previous issue.