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EF: What does access mean to you?
HR: Speaking from a regulator’s point of view, even if we have the best medicines in the world, if they are not made available to the populations that need them, they will have no impact. The role of the regulator is to ensure that the medicines in the country are safe, efficacious, high quality, and in the public interest. This is what we must do, and if in executing this role we are not efficient, we become a barrier to access. If the regulatory authority is not registering important new medicines or vaccines, they are denying the population access to the latest technology, the latest therapeutics, and the latest preventive measures. If companies do not register generics quickly and in quantity, they are denying the government and the population the potential of a competitive market place. Generics are drugs that are no longer protected by intellectual property and might be very commonly needed for diabetes o hypotension which is common afflictions, the government buys those drugs but if there aren’t enough good generics available to compete in the market to push the price down, there won’t be competitive tendencies or competitive prices. This is why, if the regulator is not efficient in how it works, it will impact directly on access. Regulator’s priorities are safety, quality, efficacy, and public interest. When a regulator is efficient, the patient doesn’t have to worry about the quality or efficacy when they are prescribed medicine or when at the hospital they get an IV drip. The people must have confidence and trust in their country’s regulating authority, that it has ensured that all the available medicines are good in quality and volume, otherwise, it will become an obstacle to access.
From an African level, there is much more interest now in access to medicines to what we call neglected diseases and the scientific community wants to develop new vaccines for these neglected diseases like the Ebola, and in terms of investment, the biggest investment would be in the African population because, a) we are not accessing the population with everything we should and b) the population is going to grow.
EF: What is at the top of your priority list?
HR: SAHPRA was established in February 2018 taking over from the Medical Control Council which was established through legislation going back to 1965. It is now understood that the best practice for a drug regulatory authority is to have a level of autonomy and must be extremely aware and sensitive to the environment, the needs of the population, and of the industry, either local or global, but always with independence and autonomy. Decisions must be safe and not influenced, guaranteeing the quality in terms of manufacturing and how it fits in with the public health needs. When we took over from the Medicine Control Council, we found an institution that was outdated in terms of its work methods: it was paper-based, dossiers in boxes, storage, and very many boxes. In registrations, there were a lot of expert committees that would review different aspects of an application or registration. A clinical committee, a pharmaceutical analytical committee, a scheduling committee, and it was also involved in the manufacturing, so the spectrum was huge. There were insufficient skills and technical resources able to do those reviews, so the committees were staffed by external academics who were independent experts but had no service level agreements. As an example, committee A could have an excellent academic that would do the work very quickly and would present a report to the committee for review within a 6 month period. But when it was committee B’s turn, the report could take a year because there could be a very busy academic involved, and then committee C could take even longer. External evaluators with no service level agreements and day jobs are not in itself the best design for a problem like this one, especially if Committee A approves it, but Committee B or C send it back for revision in a later stage. All the relevant committees had to be in place for the registration, then it went to the council for approval, which may conclude to restart the whole process again. It was a paper-based, inefficient system with a structure that led to inefficiencies. Without the capacity and the skills within the regulatory authority, there was an uncertainty factor on when one could get the registration process done. This is why the actual process needed to be re-engineered for better performance. Also, as a result of this inefficient system, a huge number of applications stacked up, so it did the complexity. When SAHPRA took over, there was a backlog nobody had been quite able to quantify, nor understand what it entailed (new chemical entities, generics). We just knew it wasn’t working well. SAHPRA’s first priorities were to focus on the backlog and reengineer the outdated system while building the capacity of the staff within the system. We knew we would always need experts because medicines change rapidly and we would need state of the art skills for even the most routine things. We had to build up muscle, knowledge, and capacity. We started a backlog project with a big grant from the Bill & Melinda Gates Foundation, which was essential, and we established that there were 16.000 dossiers in the backlog. 50% of those were 5 years old or older, the oldest was from 1992. 90% of the backlog was generics and 10% new chemical entities. We then negotiated with the industry a way to deal with the situation. We reduced the backlog as quickly as we could and we wanted to make the commitment to deal with the whole backlog process within 2 years. There is so much that needs to be done to rebuild the systems for a state of the art regulatory authority that everybody sees it as a 5-year project. We also discovered there were around 500 new applications for registrations every year, and less than half were being dealt with. So without counting new registrations, we arrived at the conclusion it would take us 8 years to clear the backlog, and that would be without taking into consideration the new applications. Industry came to the table and we developed a totally new reengineered process. We took everything that was 5 years and older and asked the industry to resubmit it electronically, and if within a specified time period we didn’t hear from them, then we would assume the company either no longer exist or have lost interest in the registration of the product. With that, we lost 3000 registrations from that section, which was around 50% of that specific queue. Next, we looked at things that could be quickly responded to, like issuing certificates which were another 3500 registrations that we planned to finish by the end of November. Then, we started on the actual backlog. When we have asked everybody to resubmit electronically, we ensured that the format for submissions has been agreed on based on global standards for submission. Over the next 2 years, we have prioritized public health which we have negotiated with the health department having a strategic public health priority, focusing the first 2 months for HIV, TB, and vaccines, following oncology. Also, we provided the industry a commitment to get answers out in a specified time period.
Before we started all this, we had to know how we were reengineering the system and we needed external evaluators from South Africa, the region and global experts, ensuring that the external evaluators all had service level agreements with payment linked to the productivity. For the backlog, we are using external evaluators, but we are also building capacity for the future. To this end, we have hired a whole team to work on the backlog: before there was a staff of 200, about 50% of them were administrative. We have now employed another 120 people on top of that. We plan on doubling the staff in the near future and train them up. Because of the mandate of the MCC, we will need more staff, as SAHPRA is also looking at medical devices, in vitro diagnostics and radiation control. This is something the MCC did not do before. It did look at complementary medicine, but it is an area we really need to strengthen, as it is a massive industry and there is a lot of public interest on this subject.
EF: In Mexico, medical devices are 70% of the dossier applications, how do you predict which will be the areas of most interest in your case?
HR: When we started we only had one person in medical devices. We know there are hundreds of medical devices, so there are discussions in this area to understand the best way to solve this problem, as there is an enormous spectrum, also having radiation control. We have adopted a global approach as many of the world’s experienced regulators have done, which looks at the level of risk, so it is a risk-based approach according to global guidelines. Some of our new staff are going to medical devices and some to radiation control. In terms of training, we are still transitioning, and we haven’t taken away the expert committees, we want them involved, especially to participate in the training and to mentor junior evaluators; we are developing a training framework that would allow the juniors team to learn from the academics via a mentorship model.
EF: What do you think is SAHPRA’s role as a reference regulator for the region?
HR: The countries with better-developed economies are the ones that have more mature regulators with more resources. This is why we are looking at reliance mechanisms which are something all regulators are talking about and wanting to implement. If a dossier for a new vaccine has been approved by the EMA and the EU, and the same dossier is presented to us, we are willing to take into consideration those evaluations, especially if they had prior approval given by the EMA or Swiss Medic or the Australian TJ or the Canadian regulator. We would only look at some specific pieces that apply to South Africa, and so it becomes an abridged review due to the reliance and sharing of information. This is a way of exchanging skills between developing and developed countries, and it cuts the time down for the registration of products. The very nationalistic attitude of believing we need to do everything from A to Z is not really necessary if we work with countries that have really mature regulators. Another thing we want to work on is to work hand in hand with regional regulatory authorities. There is already a Southern East African group called ZAZIBONA, which started off with 4 countries Zambia, Zimbabwe, Botswana, and Namibia but now includes 12 or 14 countries. If, for example, there is a vaccine with regional impact, and there is interest in registering it in all the countries, it makes sense to have a collective review of that registration: one country can look at the clinical data, another at pharmaceutical and analytical data, another country at biological aspects and so on. All of these results could be shared with the association and they could provide a recommendation. This also is reliance on a sub-regional level of the regulators’ network. The same is happening in West and East Africa, where the networks in the region can share skills and knowledge. The African Union seems to me to be moving quite rapidly on having an African Union umbrella regulator for harmonization and reliance. This will set standards that can be adopted for the African region and would allow us to import and export easily within the continent, as the same standards are shared. ZAZIBONA has of course done this to a certain extent, and it should be replicated in other areas. Harmonization of standards in the region with the AU regulator umbrella body is very much under discussion. There is a third group called AVAREF, originally set up for vaccine evaluation and clinical trials coordinated by the WHO, which became very important with the EBOLA vaccine trials. This is a group of regional countries with WHO support, with the idea of doing things together which is really growing in acceptance.
EF: Do you see NHI as a challenge or an opportunity?
HR: As an opportunity, I think pretty much everybody agrees on several aspects of the analysis that have led to the NHI proposal. First, we have terrible disparities between the private and public sectors. Countries that have big economic disparities are not healthy countries, so we need to get the economic disparities down to be able to get to the health disparities. We are aware of the major challenges in the public health sector which we need to uplift and it is a matter of urgency.
Secondly, we also know the private health sector is being run inefficiently because it is done on a fee for service basis so if we could uplift the one and take the best of the private sector finding clever solutions with integrated packages. I don’t think base it on a fee for service basis is the best, because it makes it extremely expensive, the private sector consumes a lot of the budget and has an inefficient use of expert time. We need to ensure that our healthcare system will look after the rich and poor, with properly evaluated packages that will open up access. So I think NHI is very necessary, but we need to do a lot of work on this model, we don’t have the solution yet, but the principle behind it is the correct one. People are frightened of it but that in itself is normal because people are frightened of challenges especially in the public health sector. So we need to work very carefully on the model and build up confidence from there.
EF: How was your conversation with Melinda Gates yesterday?
HR: We spoke mostly about HIV and HIV prevention. We do a lot of work on new-age prevention technologies, not only clinical trials developing the technologies but also on the implementation of the technologies themselves. First through tighter studies, and then as roll out studies. We spoke a lot about the oral pre-exposure prophylaxis, which is an antiretroviral which with one tablet a day prevents HIV. That sounds great in theory, but to get people to take a tablet every day is a challenge. There are newer technologies that are more convenient, such as a monthly ring, but that is only partially effective so we are evaluating better options like long-acting antiretrovirals as an injection or an implant, new delivery systems, and new categories of drugs which would include what we broadly call neutralizing antibodies. We had 3 young women participate and asked them about their challenges, 2 of them are taking the oral tablet. Another thing we talked a lot was about our extraordinarily high rates of sexually transmitted diseases amongst young women in the country, as we have just completed a big study with Gates Foundation funding.
EF: Is there any final message on the role of SAHPRA as a regulator you would like to share with us?
HR: There is a complete understanding from the SAHPRA board and from the staff about the extraordinarily important role that the regulator has for public health, for the health of the individual patient, the community, and also for a healthy country. Another thing we need to do inside South Africa and in the region is developing our own competencies: we are going to have growing populations, and this means there will be opportunities if we start to manufacture our own drugs, whether they are generics, new chemical entities or vaccines, there are all opportunities that deserve a functioning regulatory authority. There is a total understanding of the importance of this, as well as a real commitment to fix the difficulties we found. Unfortunately, it is not a 6 months fix. We said right from the start that the backlog we found would take years to do. I think that after 3 years from when we started we will have a good functioning regulator. Our aim is to become world-class, be part of this seamless network of regulators that are in communication, sharing information. The regulatory authority we are aiming to be is one completely attuned to the needs of patients and communities and which will support the evolution of the industry in South Africa and beyond. As regulators, we cannot and sacrifice safety, efficacy, and quality. If we do that, we are doing patients, the communities, and the industry a disservice.
