A
Regulatory Primer (Part 6):
CEO Confidential: 14 Medical
Device Myths and Realities
In the first part of this series, it was explained how device classification can play an important role in determining not only the quickest route to market, but also, potentially, in which of the major markets, United States (US) or Europe (EU), the product is likely to achieve first clearance for sale. The second article looked in more detail at classification issues in the US, and the third provided detail on the European classification system. The fourth and fifth focused on quality system and post-market requirements.
In this final article, a number of popular regulatory misconceptions are considered.
Whether they lead early-phase or extremely
mature companies, CEOs of medical device enterprises
need to have sufficient knowledge to make informed regulatory,
clinical study, and quality system decisions related
to their companies and products. Unfortunately, many
do not. As a result, either poor decisions are made
or there is an unhealthy reliance on external support
without any internal knowledge. CEOs do not need to
be expert in regulatory affairs, clinical affairs
or quality systems; however, they should have a basic
understanding of these areas.
In particular, CEOs of
early-phase medical device companies need to grasp
the basic concepts of design controls that apply to
the products they are developing. If they lack this
understanding, the wrong design decisions can have
significant adverse affects on the success of the
project, and therefore on the future of the company.
CEOs of more mature companies, operating
under a certified quality system, have very
specific responsibilities, which are not always
clearly understood. These responsibilities
are specified in the U.S. Quality System Regulation
(QSR) (21 CFR 820) for “management
with executive responsibility,” defined as “those
senior employees of a manufacturer who have the authority
to establish or make changes to the manufacturer’s
quality policy and quality system.” Similar
responsibilities are found in the European harmonized
standard for medical device quality systems, EN ISO
13485:2003, where “top management” is
defined as a “person or group of people who
controls an organization at the highest level”.
Sufficient
regulatory, clinical study, and quality system-related
knowledge, will also help CEOs avoid believing
and acting on incorrect assumptions which
may have disastrous consequences for their
companies and products. We’ll
now take a look at some of these 14 myths
and their corresponding realities.
Myths and Realities
Myth: “I
can meet with FDA for a brainstorming session to
identify our U.S. regulatory strategy.” Reality: FDA is not a regulatory consultancy.
FDA is a regulatory agency that publishes regulations
and guidelines, and manufacturers should read and
understand these before engaging with FDA. FDA is
willing to offer advice when a manufacturer has a
strategy based on the regulations and guidance, or
to clarify any unclear points. However, meeting with
FDA to discuss aspects that are fully detailed in
freely available publications is not a prudent use
of FDA time.
Myth: “It’s easier
to get approval in Europe than in the United States.” Reality: Although both U.S. and European
regulatory systems provide risk-based market clearance
routes, there are differences, and these work both
ways – some
devices attract a higher risk classification in the
United States, and others have a higher classification
in Europe. It is therefore important for manufacturers
to establish the classification of their device in
both of these major markets before deciding which
to target first, as it may be that the United States
offers a quicker route than Europe.
Myth: “My marketing strategy
will drive my regulatory strategy.” Reality: As a continuation of the
previous "reality,"
there may be significant differences in the timescales
necessary to achieve market clearance in the United
States and Europe, because of, for
instance, device classification or the acceptability
of existing clinical data. It is therefore important
to understand the full regulatory picture before making
detailed marketing plans. Otherwise it is possible
that the wrong target has been selected.
Myth: “I’ve
made a prototype, so now I can give it to a clinician
to try it out.” Reality: The days when clinicians
could decide on the suitability of prototypes for
human use are long gone. Regulations in just about
every country now require the use of new devices on
patients to be subject to strict controls and approvals.
Voluntary standard ISO 14155 describes the minimum
procedural checks and safety requirements that have
to be achieved before patient use of pre-production
devices.
Myth: “We don’t
need design controls yet.” Reality: There are significant benefits
when manufacturers control device design from the
point when it moves from "concept" to "specification"
(or "design
input"), whether design controls are required
or not. Useful
guidance on the subject has been published
by FDA.
Myth: “Software
designed to European standards will be OK for FDA.” Reality: Although the requirements
for the control of software design and validation
are similar between the United States and Europe,
the depth of review of software documentation during
market clearance can be significantly different.
Software developers who do not follow
these guidelines during the design phase will probably
find that a significant part of the software risk
analysis, development, validation, and verification
testing will have to be redone to satisfy FDA, even
if the device is already CE marked for sale in Europe.
Myth: “Class I devices don’t
need clinical data.” Reality: While this may
often be true for the United States because class
I devices are exempt from premarket notification,
the 2007 European directive revising the Active Implantable
Device Directive (90/385/EEC) and the Medical Device
Directive (93/42/EEC), which takes effect from March
2010, clarifies that clinical data are expected for
all classes of device.
Myth: “You can’t
use clinical data gathered outside of the US for FDA.” Reality: Non-U.S. clinical data
can be used for U.S. submissions as long as certain
criteria are met, which are defined in the Premarket
Approval (PMA) regulations (21 CFR 814.15), but is
also applicable to clinical data in support of a 510(k),
when needed. For example, the non-U.S. clinical study
data must be applicable to the US population and U.S.
medical practice. The studies must be performed by
clinical investigators of recognized competence and
other criteria. However, having FDA review the study
protocol before it is final to ensure FDA acceptance
is highly recommended. Not to do so is extremely risky
with regard to FDA acceptance of clinical study data.
Myth: “Only the first part
of the clinical study needs to be monitored.” Reality: Whenever clinical studies are conducted, whether during
the pre-market stage to determine safety and effectiveness
or performance, or for post-market purposes, monitoring
of the study must take place, otherwise the results
may be considered invalid.
Myth: “510(k)s
and PMAs must be filed by a US organization.” Reality: 510(k)s and PMAs can be
submitted by anyone, from any country. All that FDA
requires of non-U.S. manufacturers is that at the
time of first making devices available for sale in
the United States, a "U.S.
Agent" is designated. The "U.S. Agent" is
someone, locally based, who is responsible for assisting
FDA in communications with the non-U.S. manufacturer,
responding to questions concerning the company’s
products that are exported or offered for export to
the United States, and assisting FDA in scheduling
inspections of the company. FDA does not require the
U.S. Agent to report adverse events under the Medical
Device Reporting regulation (21 CFR Par 803) or submit
510(k)s or PMAs.
Myth: “I’m just a one-person start-up – I
don’t need regulatory support yet.” Reality: Even at the earliest stage
in the life of a device company, good regulatory advice
can be critical to its future success. Making the
wrong strategic decisions early on, based on bad regulatory
understanding or advice, can lead companies into "blind
alleys,"
hindering their ability to meet investor milestones
and raise additional funds.
Myth: “I’ve
read the regulations. I
don’t need to do all that, do I?” Reality: Yes, you do! Companies should
approach regulatory compliance in a pragmatic manner,
but some companies seem to think that the regulations
don’t apply
to them when in fact, they do. In some cases, a tremendous
amount of energy is spent on trying to avoid compliance
with a regulation when the same energy could be used
in achieving compliance. Companies should certainly
avoid doing what is unnecessary, but should not try
and "get round" the regulations. Investing
in the infrastructure to ‘do it right’ will
pay dividends in the long run.
Myth: “I don’t
need to understand about QA/RA. I’ve
got a QA/RA manager to do that.” Reality: As mentioned in the introduction to this
article, CEOs, when their companies operate under
a certified quality system, have very specific responsibilities,
which are not always clearly understood. Even if the
company has an experienced QA/RA manager, the CEO
needs to understand the ‘basics’, especially
with regard to those aspects of US and European quality
system requirements that refer to ‘management
responsibility’.
Myth: “We don’t
need to audit the CEO during our internal audits.” Reality: As covered in the previous
"reality,"
the CEO has specific responsibilities within certificed
quality systems. A further requirement of these quality
systems is that all aspects of compliance with the quality
system must be regularly audited, to ensure continued
compliance. It therefore follows that internal audits
of responsibilities allocated to the CEO must be included.
About the authors:Maria
E. Donawa, M.D. is
President of Donawa
Consulting (Rome, Italy), and has
over 25 years of medical device regulatory experience.
From 1980 to 1986, she worked with the U.S. FDA in the
area of medical device regulation, founding Donawa Consulting
when she moved to Rome in 1986. Dr. Donawa holds U.S.
degrees in pharmacy and medicine, with a post-doctoral
specialty in clinical and anatomical pathology, and is
licensed to practice medicine in the United States.
Roger
Gray holds a B.Sc. in mechanical engineering and
is Director, Global Regulatory Affairs at Donawa
Consulting (Rome, Italy), where he is responsible
for assisting medical technology clients obtain marketing
clearance for both Europe and the USA, in addition
to managing the company’s
European Authorized Representative portfolio. He has
over 25 years' experience in the device industry and
was involved with the development of the Medical Devices
Directive during its formative stages.
