Q&A with Robyn Meurant, IVD Regulations Expert, NSF International
07 Aug 2020
Med-tech product developers are navigating many uncertainties, especially during the technology development and validation stages of product development. Bringing a medical device like a rapid point-of-care diagnostic to market from early concept to full commercialisation is a complex task and key amongst these challenges is the need to meet regulatory standards.
To coincide with the first Longitude Prize Sprint workshop focused on regulation, we spoke to regulatory expert Robyn Meurant, Executive Director, of the Health Sciences Division of NSF International to capture her advice to innovators working in this space.
1. At what stage of the product development roadmap is the best to address regulatory issues?
Although regulation does not normally govern the earliest stages of product design (from the start), consideration of regulatory requirements is actually an asset to an assay developer.
Knowledge of ISO 14971, the risk management standard for medical devices, will help you consider not only what is a design that works and will be useful, but it also brings into the picture manufacturing risks, which will help you consider how and/or if you can achieve all these features within your budget.
”Regulation is in place to ensure something works as intended, is safe and has clinical benefit to the patient. these are great principles to incorporate into the early design stages.”
2. What are the common pitfalls that you see product developers and manufacturers falling into?
A lot of product developers, and here I speak of those with minimal experience with manufacturing diagnostic tests and medical devices in general, do not realise the gap that lies between the great idea and the point when you can start clinical trials. We often hear of the four stages of clinical trials for medicines and vaccines, and it is assumed this is the smooth pathway that exists from discovery/design idea to bringing an IVD to market. The part of the journey that must happen before you can even think of serious clinical trials for all health products is often much longer than we think. Companies that are successful in shortening the transition usually have knowledge of this and the resources to make a lot of complex steps happen sequentially – but that is not the norm.
3. Are there aspects of regulatory compliance, product assessment and validation that are regularly under or overestimated by developers and manufacturers?
This gap between idea and finally reaching clinical trial stage is the first underestimated step. Product optimisation can in itself, be much harder than anticipated.
For example, here’s a scenario: “I have a great marker, but can’t make it stable or specific.” But let’s say we’ve managed that OK. We have even managed to meet some tough regulatory requirements and have been granted market access, and the product is a success. BUT, we now have to scale-up and we do not realise how difficult that is.
It takes knowledge and preparation.
In my experience, these are the two most underestimated steps: the journey before clinical trial stage and the journey of manufacturing a suddenly-wanted assay.
4. What are the key regulatory concerns for producing medical devices and products like diagnostics that will be in use in Africa?
Very few manufacturers really undertake a serious risk assessment of use of the devices in the challenging conditions that can be faced on the continent. Product stability claims are frequently based on European conditions, interfering substances may be those encountered in the USA. Even the impact of dust or mould, or both, on optics is not considered with sufficient veracity. The diversity of languages, customs and other unique variabilities seem too hard to even contemplate.
5. Drawing on your experience with the WHO, what advice would you give to developers focused on creating products for East and South African countries?
Definitely seek advice sooner rather than later.
Ensure you understand the role of the different actors such as WHO, Global Fund, etc. If you chose to use a consultant, ensure they know the lay of the land.
”Words of wisdom early in the development process can save you years of time, money and disappointment.”
6. Do you have a success story and lessons learnt you can share on a company’s market entry into East Africa/South Africa with a MedTech product?
The introduction of HIV self-testing on the continent has proven a success story. The need for self-testing was driven by the fact that routine testing services were not identifying scores of infected individuals who, for many reasons, were not tested. Self-testing was firstly an empowering experience for an individual, with stigma associated with appearing at a clinic for testing no longer the first barrier. WHO led the feasibility studies. Working with manufacturers of the diagnostic tests was an essential activity as instructions and sometimes design had to be adapted to ensure the tests were fit for the intended user population – often diverse. In addition, local partners provided the support needed. Wits University in Johannesburg undertook usability studies for all the interested manufacturers to really ensure design was optimised and instructions were appropriate. My “old” department, Prequalification, provided the regulatory advice, to ensure that standards were upheld. A solid body of evidence was developed. So: we started with a real need, and no clear solution. The solution came with empowering the patient and ensuring the test design really was optimised for the end user and this market by rigorous and disciplined studies of usability. Vision and hard work, local engagement and evidence-building were the essential stepping stones. HIV self-testing as we know, is being rolled out in many places and its success in Africa is a credit to all involved, from WHO to each manufacturer who decided that this was a worthwhile project.
7. How has the experience of Ebola, and now COVID-19, impacted the demand for — and the delivery of — diagnostics and medical devices in Africa?
For me, it was sad to see that the world (including manufacturers) only reacted to the 2014 outbreak of Ebola when westerners were affected. We are a global village now. A virus is in one region now, and in less than 24 hours can be anywhere. I do think that Ebola started to bring some realisation to these facts.
”But for whatever the reason, the world was caught off-guard at the start of covid-19, with little understanding of how quickly it would become an international concern. from all this, the importance of diagnostic tests is finally becoming an established fact. the need for fit for purpose diagnostics and medical devices is greater than ever.”
We are still some way from really understanding that, and the situation is still not as it should be for Africa. Many of the continent’s member countries cannot afford the molecular tests that are needed for diagnosis, and there is no clear policy to support other diagnostic alternatives. This remains a great problem and one I am still trying to raise as a critical issue. There is no single solution that fits all. Also, it has been shocking to hear that some critical health products have been sold in advance to certain high-income countries and none are available for distribution to the African continent. Counter to this are the good news stories that we are beginning to see local production of certain health products.
8. More generally, how do you think COVID-19 has changed our understanding and awareness of the need for rapid diagnostics in public health?
The demand on hospital services has made every one of us realise that a functioning health system relies on functioning hospitals and that includes laboratory capacity. Centralised testing will always have a role, but with a disease with so many clinical spectrums, we have needed multiple diagnostic solutions, including roll-out of rapid tests that do not require highly-skilled laboratory staff. An aspect that has been raised multiple times during this pandemic is the need by policy makers for accurate test result data. Rapid tests are great for an individual, but the results optimally should be transmitted to those defining the response policies so that they too can provide agile advice that is timely and pertinent.
There have been a few important failures with rapid tests during COVID-19 that we should keep in mind when discussing this topic. A number of countries wanted to roll out rapid antibody tests to be able to give immunity certificates. The problem here as we know, is that firstly, there was no evidence in the early stages that the antibodies conferred immunity. This means that there can be no claims made regarding this as a function of the tests. This should be noted as a test limitation. Secondly, many of the rapid tests first on the market were found not to meet performance claims when tested independently. The lesson here is, comprehensive verification and validation by the manufacturer will save not only the manufacturer’s reputation, but also save health programmes money and time. We often use the term “simple rapid test” but whether it be a lateral flow test or a LAMP assay, simple is rarely the term we should use to consider the work needed to ensure claims can consistently be met, and that the claims are founded on science.
9. How do you think this impacts or shapes the AMR agenda?
With respect to COVID-19, hopefully it will put the foot on the accelerator. In nearly every country I know, normal diagnostic pathways have been altered to accommodate COVID-19 patients. Because we don’t have the affordable, rapid, specific tests we need to identify whether a patient needs an antibiotic or not and if so, which one, we are going to be overusing antibiotics during this pandemic. It has the potential to be just another of the great disasters that may result from this unbelievable viral infection (along with disruption to the normal disease programs).
10. And, related to the above, what should the diagnostics manufacturers and medical device manufacturers, who are working to develop products that could help tackle AMR, be doing differently today?
I think this is the moment to focus on what is needed. Really think of the end game and work backwards, at least for deciding the best solution. Then work smartly, seeking the best experts to help with design, development, production, quality systems, and regulation from as soon as possible to fast track these solutions.
11. Lastly, what are the key emerging trends in medical device regulation and commercialisation that developers should keep a close eye on?
The new EU regulations have raised the bar enormously and are a challenge to mature manufacturers let alone those new to the game, . First you must realise that CE marking is recognised in so many countries worldwide as a mark of quality. And with the new regulations it feels like we have gone from light touch regulation to something at the other end of the spectrum. But it is hard to argue with the sentiment of the regulations. Evidence of the science behind a device is demanded and the focus is more greatly on the patient. But it is a bit like comparing high jump to pole vaulting – neither is for the faint-hearted.