DEPARTMENT OF BIOMEDICAL ENGINEERING

FACULTY OF ENGINEERING
UNIVERSITY MALAYA

KIB2005 – SAFETY, STANDARDS AND ETHICS

Supplying New Medical Device into Malaysia

PREPARED BY
Farhah Adlina binti Zameri

(17085099/2)

PREPARED FOR
Dr. Nasrul Anuar Bin Abd Razak
Bried description about the product, its origin and use in Biomedical Industry
Reactiv8 Implantable Neurosimulation system

Figure 1: Picture of Reactiv8 and where it is applied

Lower back pain is the most prevalent musculoskeletal complaint among adults, with an estimated
lifetime incidence of 60 to 70% in developed countries. There are many reasons for this, but the
most common are those related to style in life. With a lot of people in this world suffering from
intractable chronic lower back pain with no single treatment option available, ReActiv8 may
provide some relief for those whose symptoms haven't responded to other, more traditional
treatments.
The ReActiv8 Implantable Neurostimulation System is designed to aid in the control of chronic
low back pain caused by lumbar multifidus muscle muscular weakness in patients who have failed
to respond to other treatments such as pain killers and physical therapy and are also not a candidate
for spine surgery. This device is manufactured and developed by Mainstay Medical Limited,
originate from Brooklyn Center, Minnesota. Mainstay Medical Holdings received premarket
approval for its ReActiv8 product from the FDA in June 2020. The ReActiv8 System has become
available for purchase only in European Union.
ReActiv8 Implantable Neurostimulation System consist of several components includes an
implantable pulse generator (IPG), two stimulation leads, a magnet, and a wireless remote. The
IPG sends electrical stimulus pulses to specific nerves that activate the lumbar multifudus muscle
which is one of the most important muscles for stabilising the lower back. Rather than relying on
a sensory target to reduce pain caused by a physical structure, it aims to reduce pain by passively
stimulating muscles to facilitate spine strengthening and increase stabilisation.
 Figure 1.2: Components of Reactiv8
As shown in figure 1.2, the ReActiv8 treatment involves implanting two electrodes into the deepest
layer of muscles in the lumbar region in order to stimulate the L2 medial branch of the dorsal
ramus nerve as it passes the transverse process at L3. Similar to a pacemaker, these electrodes are
attached to a battery-operated electrical pulse generator inserted under the patient's skin.
According to a clinical review, the majority of patients that had the ReActiv8 device implanted,
showed significant improvements in pain symptoms after 120 days compared to the majority of
patients that had the ReActiv8. However, just like any other major surgery, there are some adverse
effects that could occur to patients including those associated with any surgical procedure and
those specifically associated with having an implanted ReActiv8 System. Example of the effects
are excessive fibrotic tissue, wound necrosis, lead and IPG migration, allergic response, skin
erosion at the implant site, hematoma and other common effects.
Explanation of each and every step to get the approval of Medical Device Act

Figure 2: Steps involved to supply medical device in Malaysia

First and foremost we need to classify the medical device into which category. In Malaysia,
medical devices are classified as Class A (low risk), Class B (low to moderate risk), Class C
(moderate to high risk) and Class D (highest risk), similar to the classification scheme used in the
European Union. These classification are made based on the duration of the device use,
invasiveness and risk to the user. ReActiv8 Implantable Neurostimulation System involve
implanting components in human’s body so it is classified in Class D (highest risk).
Based on figure 2, we need to register the device from the Medical Devices Authority (MDA),
which is a branch under Ministry of Health. According to Medical Device Authority (ACT 738)
and Medial Device ACT 2012 (ACT 737), those two regulatory bodies will be in charged to assess
and give license to new medical devices. Under MDA, there will be chief executive, officers or
servants that will work to regulate and monitor all activities to register the product from start until
end.
In order to supply this Reactiv8 system into Malaysia, we need to have three parties which called
establishments that are responsible for some tasks. The first one is manufacturers which
responsible to ensure products meet essential principles of safety & performance (EPSP) and are
manufactured in accordance with good manufacturing practice (GMP). They are also responsible
in applying for a registration of device. Next, importers and distributors responsible in ensuring
compliance with requirements of good distribution practice (GDP). Due to Reactiv8 comes from
foreign country, we need to appoint an Authorized Representative (AR) in Malaysia, who will
register the device.
Before registering for a license, we need to apply for standard certificate. Standards is a technical
document that specifies the minimum requirement of quality and safety for voluntary use by
public. Regulators, including the Medical Devices Authority (MDA), Ministry of Health
have adopted the ISO 13485 standard with the aim of harmonising the quality of system
requirements, reduce conflicts of different standards and facilitate licence application for
medical devices manufacturers.

The ISO 13485 specification is a good solution to meet all of the standards for a quality
management system. Adherence to ISO 13485 establishes a practical basis for manufacturers to
meet Medical Device Directives and obligations while also showing a dedication to medical device
safety and efficiency. In addition, IEC 60601 also need to be applied and obeyed by manufacturer
as Reactiv8 is an electrical device. IEC 60601 is related to safety and essential performance of
medical electrical equipment.

We know that Reactiv8 is from USA, however, if we submit the audit report like ISO 13485 from
SGS (UK), this will not be accepted by MDA. As a manufacturer or authorized representative, we
need to undergo simplified conformity assessments, or verifications, carried out by conformity
assessment bodies (CABs) registered under Section 10 of the Malaysian Medical Device Act for
recognition.

CAB is a body appointed by the MAD to perform specified CA activities to determine whether
the relevant requirements in technical regulations or standards are fulfilled. Elements of
conformity assessment includes quality management system (QMS), post-market surveillance
(PMS) system, summary technical documentation (CSDT) and lastly declaration of the
conformity (DoC).

After satisfactory audit by CAB, the verification Certificate is issued. AR can now prepare the
registration application Common Submission Dossier Template (CSDT) based on the technical
information from foreign manufacturer and submits it to the Malaysian Medical Device
Authority (MDA) through an online system. The registration process for new devices could take
up to a few years. It is highly recommended that foreign manufacturers interested in selling
devices in Malaysia begin the registration process as soon as possible.

After getting the license, distributor can now start to sell the device to the user in market.
However, distributor that is appointed need to have the establishment license. To comply with
the requirement, you have to get the GDPMD certificate as a distributor to sell the device. Lastly,
establishments shall monitor safety & performance of their products and also carry out post-
market obligations such as user training and complaint handling. As for users, they need to use,
maintain and dispose off medical devices appropriately. They also need to apply permit to
use/operate designated medical device.

Involvement of society in supplying the new product

Chronic low back pain is very common and are able to give rise to frustrations and obstacles to
both patients and health care practitioners. In Malaysia, low back pain was found to be prevalent
in a semi-rural neighborhood with percentage around 12%, while it was found to be much more
prevalent (60%) in a population at risk. Dr Neelakanta Reddy said in an interview with reporter
that four out of every five adults will have lower back pain It strikes more people in their middle
age, and it affects more women than men. They can occur due to some factors including improper
lifting of objects, overuse of muscles, bad posture, lifting heavy object and many more.
To make matters worse, low back pain is so difficult to treat. They are only resolved with non-
surgical therapies like traditional treatments and medical education to patients about how to
manage and keep the pain under control. Majority patients with lower back pain has been “treating”
themselves with painkillers and anti-inflammatory medications. However, these medications have
little effect on the root causes of back pain. Since the joint and muscle issues are not being treated,
reducing pain with medications can help the individual to be active, but they appear to intensify
and worsen over time. Moreover, these painkillers also could give harmful side effects if taken too
much.
Therefore, supplying Reactiv8 Implantable Neurostimulation system into Malaysia will benefit
not only patients but also doctors to provide treatment for them. ReActiv8 are able to treat chronic
lower back pain by restoring muscle activation to stabilize the lower back. The induced stimulation
can aid your brain and body in learning how to better control the muscles and allow the body to
recover day by day.

Endorsing the product to society

To implement this product in Malaysia society, we can held a campaign and take one Malaysian
volunteer to do a clinical study in order to show them how the device is giving benefits. The
volunteer must have 7-day recall of average Low Back Pain, age between 22 and 75 years old,
willing to give consent, able to comply with the instructions for use and to operate ReActiv8 and
also suitable for ReActiv8 surgery as determined by the implanting physician prior to inclusion.
The aim of this clinical study is to prove the effectiveness of Reactiv8 in treating lower back pain.
Next, the device could also be endorsed in social media which is becoming a very powerful and
popular marketing tool that can reach a large population. This is also applied to other media like
television ads. It's essential that you make your endorsement disclosure transparent and
conspicuous. Make it in a large, easy-to-read with a simple word choice. With this method, we can
easily introduce about the existence of Reactiv8 to the society especially those having discomfort
in their lower back.

Ethical aspect before the product has been supplied

First and foremost, we do need an approval letter from the real manufacturer or developer of
Reactiv8 before supplying it into Malaysia. This is because we want to credit the hard work that
they put off while inventing this device and avoid any crime such as plagiarism to occur.
Furthermore, the most important things to be prioritized in order to supply any new product into a
country are beneficience and non-maleficience. Beneficience is the obligation of any biomedical
engineer to act for the benefit of the patient while non-maleficience holds the obligation not to
harm patient by supplying a safe device.
The new medical devices that are used within healthcare system in Malaysia must be guided by
ethics and economics as well as by clinical studies to create evidence about the effectiveness of
this device. As ethics are being applied, it could give assurance and guarantees that the system can
help patients while not causing them disproportionate damage, and that people are properly
consulted when making decisions on implementing a new device. The manufacturer need to
provide a clear instruction or training to healthcare workers so that there will be no mistakes during
the procedure of implementing this device to the patient.

Ethical aspect after the product has been supplied

After this device is placed on the market, the manufacturers are responsible to do post-market
surveillance. As a biomedical engineer, our constant mission is to develop devices that are both
secure and useful for the end user. However, despite our best efforts, cases do arise in which the
device we supplied or developed is linked to a serious adverse effect. That is why it is important
for us to refer back to patients after a few months to ask if there are any side effects. This action
can avoid us to do the same mistakes on the next device that we want to supply or develop in the
future. We can create an appointment with the patients occasionally in order to monitor their
condition.

References
Brown, T. (2020). Understanding Post-market Surveillance for Medical Devices (US & EU
Markets). Retrieved from https://www.greenlight.guru/blog/post-market-surveillance-
requirements-medical-devices

D.ellis, L. (2020). FDA Approves Neurostimulation System to Treat Chronic Low Back Pain.
Practical Pain Management. Retrieved from
https://www.practicalpainmanagement.com/resources/news-and-research/fda-approves-
neurostimulation-system-treat-chronic-low-back-pain

Guidance for post-market surveillance and market surveillance of medical devices, including in
vitro diagnostics. (2020). Retrieved from
https://www.who.int/publications/i/item/guidance-for-post-market-surveillance-and-
market-surveillance-of-medical-devices-including-in-vitro-diagnostics

Medical Device Registration in Malaysia. Retrieved from

https://www.emergobyul.com/services/malaysia/malaysia-registration