Regulatory Science: Europe is Flying Blind

johner-institute.com/articles/health-care/regulatory-science

Thursday 19th November 2020

Author:

Prof. Dr. Christian Johner

In German-speaking areas, regulatory science is rarely practiced systematically.

And this failure creates problems for medical device manufacturers and harms both the
health system and the region as a business location. It's high time the situation was
changed!

1. What is regulatory science?

a) Definition

“Regulatory science” is a science that develops the (technical) principles, processes,

methods and tools for:

Formulating regulatory requirements that ensure the safety, performance and

effectiveness of medical devices based on these principles, processes, methods and
tools
Understanding and anticipating the economic and other implications of these
regulatory requirements on the healthcare system and the economy

A short and slightly simplistic definition could be:

Definition: Regulatory science
“Regulatory science consists of the application of science to support regulatory activity,
particular the setting of regulatory objectives.”

Based on source

b) Difference between regulatory science and regulatory affairs

In contrast to regulatory affairs, regulatory science does not deal with:

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 Making sure the wording and publication of regulations (laws, ordinances,
guidelines) is legally watertight
How these regulations are monitored (e.g., audited) and enforced
Which documents manufacturers have to provide and in what form

Conversely, scientifically evaluating the logic and effectiveness of regulations is not part of
regulatory affairs.

 Additional information
Read more on regulatory affairs here.

2. Why we need regulatory science

a) Otherwise regulatory bodies are flying blind...

The bodies establishing regulations should know what the consequences of their actions
are. But a lot of regulators (legislators, regulatory authorities) fail to meet this basic
demand. They can’t know either since they don’t have the scientific basis.

Asking a few experts is not enough to build up this basis. A manufacturer who used a
similar method, i.e., based primarily on interviewing patients or experts, would be
reproached by the authorities and notified bodies for a lack of evidence. And rightly so.
Eminence does not replace evidence.

Every law, every ordinance, every guideline has side effects. Designing these regulations
in a way that optimizes the benefit-risk ratio requires an understanding of the
economic and technological interdependencies. Researching these interdependencies is a
key task of regulatory science.

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 Fig. 1: Example of interdependencies and effects of regulations. Investigating them is the job of
regulatory science.

Conclusion: If they do not have an understanding of these interrelationships, legislators

do not have an adequate basis for their decision-making. They are regulating completely
blindfolded.

b) … And the regulations harm markets and patients

Regulations are generally introduced with the best of intentions. It is true that laws and
other regulations in some countries are also used to close off their markets. Nevertheless,
(hopefully) their primary goal is to contribute to optimal healthcare through safe and
clinically effective devices.

But the legislators do not know the answers to key questions:

Will, for example, the MDR and IVDR achieve this goal better than the previous EU
directives (MDD, IVDD and AIMDD)?
How many deaths and seriously injured patients does the EU Commission hope to
prevent through the new regulations?
And how many deaths and seriously injured patients caused by devices that the
MDR and IVDR have prevented does the EU think there are?

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What database did Brussels base its decisions on? Decisions that directly affect the
European MedTech market worth over €120 bn per year and indirectly affect the
healthcare market as a whole, which generates €1 bn in added value in Germany – every
day! [Source]

The FDA goes so far as to claim:

In the U.S., FDA-regulated products account for about 25 cents of every dollar spent by
American consumers each year — products that touch the lives of every American every
day. 

Source

Fig. 2: Regulatory science should contribute to an optimal balance between the benefits and harms of
regulation

c) Otherwise we be dependent on, e.g., the FDA

The FDA is actively involved in the field of regulatory science. The “Advancing
Regulatory Science” website provides an overview of its activities.

The easiest European approach might be (and probably is) to use these results for its own
benefit without having to engage with the issue itself and without investing in regulatory
science itself. But there are arguments against taking this easy option:

1. Unnecessary dependence

being dependent. The FDA could refuse access to
Relying on these results means
this data at any time.

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 2. Limited transferability of data
The FDA's focus is justifiably on the USA. Its concern is the safety of US patients.
And not all the results can be transferred to Europe. We don’t have identical device
classes in Europe, nor do we have a population that is comparable in all aspects. The
contexts of use (e.g., user, working environments) cannot be unthinkingly
transferred to Europe.
3. Suboptimal evidence
Science does not stop at
national borders. On the contrary, science, like regulatory
science, is more successful when it has access to numerous resources, in particular a
lot of data and scientists, worldwide. So, it is not about Europe versus the USA or
versus the rest of the world. The aim is to create the broadest possible database and
to gain as much knowledge as possible.

d) Otherwise manufacturers miss opportunities and lose time and money

The job of regulatory science isn’t just to prevent unsafe devices. It is also to promoting
innovation and giving manufacturers new options for:

Demonstrating the effectiveness and safety of their devices to authorities and

notified bodies more easily, credibly and quickly (e.g., using computer models)
Reliably detecting risks posed by their devices during development as well as once
they have been placed on the market before they cause any harm to patients
Being able to track the state of the art
Finding out about new and alternative processes, methods, materials and tools to
quickly develop better devices and gain a market advantage

3. Regulatory science should answer these questions

In order to achieve the above goals, regulatory science should provide answers to all
relevant questions from all stakeholders.

a) Questions that regulators (should) ask themselves

Questions on the effects on the medical device market (incl. manufacturers)

What will it cost manufacturers to implement a new regulation?

How much damage to health will a new or amended regulatory requirement help to
prevent?
How manufacturers will be able to meet this requirement? And how long will it take
them to do so?
What percentage of manufacturers will fail to overcome this hurdle? Which medical
products will not be available as a result or have their availability delayed?
What are the consequences of these delays or of the device not being placed on the
market for the health system?
In what way do regulations harm small companies and/or innovation? How can
regulations actually promote innovation?

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 What disadvantages can new regulations lead to for a location? How can the
location be strengthened by regulations?

Questions on the effects on authorities and notified bodies

How long will it take for authorities and notified bodies to be able to monitor and
enforce these requirements?
What bottlenecks could they lead to for these stakeholders? (personnel, training,
availability)
Are they able to effectively enforce the requirements with manufacturers outside the
EU as well?
Which tools can/should authorities and notified bodies use to monitor compliance
with the requirements as efficiently and effectively as possible?
Which authorization procedures are available for which devices?

Questions on the effects on patients

To what extent can regulations act in the interest of patients? Where do they
interfere inappropriately with an individual patient’s freedom of choice and risk
acceptance?

Questions on future legislation

What trends do we have to be prepared for? Which devices, technologies, methods

and materials will new regulations be needed for in the future?
Which current regulatory requirements are no longer state of the art?
Where are regulations that would be necessary to improve healthcare, e.g., through
safer devices, missing? Where do regulations hinder and damage the location or
even the health system?
How can the regulatory framework be designed so that, on the one hand, the state of
the art is adopted quickly enough and, on the other, the legislation can keep up with
the speed of change?
How is it possible, on the one hand, to word the regulations so specifically that
manufacturers know exactly what is required and can adapt to them and, on the
other, to not restrict manufacturers unnecessarily in terms of their design options?
What do we have to require from manufacturers so that, on the one hand, safety and
effectiveness are actually demonstrated and, on the other, that this proof (e.g., from
clinical investigations) does not unnecessarily endanger patients?

Questions on support and design

How do we as legislators have to position ourselves in terms of personnel and

content?
What recommendations should we make to authorities and notified bodies to
increase their efficiency and effectiveness (e.g., through digitization)?

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 How can we divide the tasks in the context of regulatory science between
authorities, industry, professional bodies, science, patient (representatives) and
others?
What can we offer to manufacturers to help them? This could include guidelines as
well as validated computer models, e.g., of organs.
Which areas do not have a scientific basis? Where would support be particularly
worthwhile?

b) Questions asked by manufacturers

What is the state of the art (regarding an issue)? How can I identify it?
What options do I have for demonstrating the safety, performance and effectiveness
of my devices? Which of the options are particularly efficient?
Will the notified bodies and authorities accept these options?
How can I develop, verify and validate my medical devices quicker using computer
models?
What do I have to do to validate these computer models?
Which patient population do I have to conduct clinical investigations in? What part
of this can I replace with in-silico clinical trials?

 Additional information
Read more on computer-based modeling and simulation here and find out how the FDA is
using it to encourage quicker development and testing of medical devices.

c) Questions authorities and notified bodies (should) ask themselves

How do I assess the risks and performance of new

devices and device classes (e.g., robots)
technologies (e.g., machine learning)
methods (e.g., for manufacturing such as 3D printing) and
materials (e.g., nanoparticles)?
How do I give myself the biggest possible chance of detecting non-conformities in
devices and manufacturers with limited time and human resources?
In which areas (devices, manufacturers, markets, technologies) should we expect
problems in the future? How can we counteract this?
How can we digitize the authorization process and market surveillance so that we
detect black sheep faster and more effectively and
limit our own costs?
How can I assess how suitable the manufacturers' evidence is for the widest possible
range of situations (context of use, patient populations)? How can I spot any gaps?

4. Practicing regulatory science

a) The actors

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Regulatory science isn’t just for universities. It is a societal task that requires the
cooperation of:

National and international legislators, authorities

Notified bodies
Professional boards such as standards bodies, IMDRF etc.
Colleges, universities and other research institutions
Hospitals, clinics and other healthcare facilities
Patients
Manufacturers
Service providers, consulting companies, test laboratories, further education
institutes

The Johner Institut has also been actively working for years on:

Developing guidelines (e.g., on IT security, on artificial intelligence)

Contributing to the further development of standards
Developing concepts, data and thought models
Training young scientists
Digitizing, and thus increasing the efficiency of, processes such as
post-market surveillance and
continuous worldwide research of new and amended regulations

b) The method

The method for regulatory science is science.  

 Definition: Science

“Science is the totality of human knowledge, insights and experience that is

systematically expanded, collected, stored, taught and passed on.”

According to Wikipedia

Scientific work is characterized by the fact that it

is systematic
answers questions as completely as possible
is objective
is universality valid in the given context and therefore relevant and
is verifiable

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 Fig. 3: Criteria for scientific work that also apply to regulatory science

To satisfy these criteria scientists must work systematically and use appropriate methods.

Regulatory science methods include for example:

Calculations and modeling, e.g., with computer models

Experiments, including clinical investigations and usability tests
Analysis of available data, data mining, searching for interdependencies, comparing
health systems, devices, methods, materials
Surveys and observations
Prototype development

5. Conclusion, summary

a) The current approach to regulation is regularly too naive

The approach of a lot of regulators, with protecting patients from unsafe devices as the
only aim, is not good enough. You could just ban all medical devices and have absolute
safety.

But the aim should be to optimize the benefit-risk ratio. This, in turn, requires the
benefits and risks to be known and evaluated. And for this evaluation you need data.

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Without this data, even well-intentioned legislation degenerates into wild blindfolded
“governing”.

Conclusion: Legislators are not meeting the requirements for demonstrating the
positive benefit-risk ratio that they demand from manufacturers.

b) It is not just about preventing, it's also about shaping

Professional regulatory science helps

Encourage innovation
Support markets
Ensure that affordable, effective and safe devices are available to the health system

The FDA has long recognized this and is driving regulatory science forward. With over
15,000 employees and a budget of more than USD 3 billion, it has resources that
European regulators can only dream of.

c) The regulatory science needs us all, we all need regulatory science

In Germany and many other European countries, the field of regulatory science is largely
a desert. The fact that legislators can do better has been demonstrated in the fight against
the coronavirus pandemic: Politicians and authorities have involved science/scientists
and virologists.

If the approach to battling the pandemic had been the same as the approach to medical
device law, the legislator wouldn’t just ignore scientists such as virologists. They’d ignore
the entire field of virology.

In order to get from this level more befitting of a third world country to the level of the
FDA, e.g., with regard to computer-based modeling, a big effort is required. This can only
be achieved together. The Johner Institute is on board.

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