Regulation of Medical Devices Essay
In the field of Medicine and health sciences there are thousands upon thousands of devices that are utilized on a day to day basis. There has been a heightened rate of innovation over the past several decades. As a result of the necessity to place this universe of devices in categories, there was introduced a taxonomy methodology which accommodates all the devices within broad categories namely Class I, Class II, Class III up to Class VIII. However during conformity procedures, the medical devices are divided into four categories; Class I, Class IIa, Class IIb and Class III (Cornelia Henschke et al., 2015). This is the classification criteria according to the EU directives. It is based on the risks that are attached to each of the devices. Regulation of Medical Devices Essay.
The Global Medical Device Nomenclature (GMDN) is an international coding system that was started having regard to the different existing nomenclatures (Cornelia Henschke et al., 2015). Class I devices are also known as the low risk devices. They undergo the least regulatory procedures, since their utilization does not expose the consumers to much jeopardy, physical or otherwise. Class I devices include dental floss, conventional wheelchair and spatula. Class II devices are of a higher risk than the latter and as such they require a more stringent regulatory procedure as an assurance that the consumers will not be exposed to the risks therein. They are divided into two; a and b. Class IIa are non-active and they include clinical thermometers, contact lenses and dental crown while Class IIb are active and they include x-ray machines, insulin pens, long-term corrective contact lenses and dental implant (Cornelia Henschke et al., 2015). Class III devices are the high-risk devices. Examples include cardiac stent and breast implant. Class IV devices are the active implantable devices. It lies under directive 90/385/EEC thus the risks associated are a bit higher than the latter while V to VIII are devices that require the assessment of the risk alongside the benefit accrued by the patient e.g. Ebola virus antigen IVD (Cornelia Henschke et al., 2015).
Class I devices require general controls. Class II devices require both general and special controls. In most instances Class I and II devices undergo premarket notification.Regulation of Medical Devices Essay. Class III devices play a critical role in supporting or sustaining human life thus they must as a requirement undergo both need general and pre-market Approval (PMA). This is a scientific process of evaluation so as to ensure the devices are safe and effective (FDA, 2011). Class II and III devices may also undergo investigational device exemption (IDE).
Premarket Notification is done on devices that do not require a Premarket Approval. According to the U.S Food and Drug Administration, such devices go through a 510(k) procedure to show that they are on the minimum as safe and effective and an equivalent of a legally marketed device (21 CFR 807.92(a)(3) thus does not need to undergo a PMA. The submitters must as such compare their devices to one or more previous legally marketed devices as a way of backing their present equivalency claims. Premarket Approval on the other hand is the scientific process of evaluating the safety and effectiveness of Class III devices. These are devices that not only support and sustain human life but also pose a potential risk of illness or injury (FDA, 2011). They therefore go through a PMA application under Section 515 FD&C Act. The approval is based on scientific proof that the device is safe and effective for its intended utilization. The PMA applicant who would potentially become the PMA owner is a person who exercises ownership rights over the said patent and after approval he acquires private license to distribute the product which he can extent to another (FDA, 2011). According to the FDA regulations, the FDA advisory committee may review the PMA at a public meeting and provide recommendations on whether FDA should approve the submission, thereafter the FDA will notify the applicant whether his product has been approved or denied. An investigational device exemption (IDE) is usually done to support the findings of a PMA and a small number of 510ks. It involves a clinical study on the said device so as to gather data on its safety and effectiveness. Regulation of Medical Devices Essay.
Unlike the 510k and PMA, an IDE is not a mandatory procedure but is useful for learning and cultivation/ improvement of ideas on innovation. It may be used after a 510k and PMA has been conducted as a way of backing/ explaining the findings therein. A PMA procedure is more stringent than a 510k procedure because of the level or risks attached to the devices that are being investigated on.
Indeed it is accurate to infer that regulation of medical devices is ten years behind regulation of drugs. The first legislation that was introduced in the U.S to cater for the regulation of medical devices was the enactment of the 1938 Food Drug & Cosmetics Act while with regard to regulation of drugs as far back as 1848 there was already legislation thereto. This is highly attributed to the wake of advancement in technology during the 21st century. As far back as during the pre-historic era man had already started identifying plants and roots that would heal him during times of physical turmoil. With the emergence of modern society and governance, the medical fraternity also started regulating the drugs that would be submitted by manufacturers so as to be sure of their safety and effectiveness. However, the pace in technological advancement was slower thus causing the regulation of medical devices to be behind schedule.
Cornelia, H., et al., (2015). Taxonomy of Medical Devices in the Logic of Health Technology Assessment. International Journal of Technology Assessment in Health Care, 324–330. Cambridge University Press 2015.
U.S Food and Drug Administration, FDA. Overview of Regulatory Requirements: Medical Devices. Medical Devices. Retrieved from;
<http://www.fda.gov/Training/CDRHLearn/ucm281656.htm> at 19 November 2016.
U.S Food and Drug Administration, FDA. Device Advice: Investigational Device Exemption, IDE. Medical Devices.Retrieved from;
<http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/HowtoMarketYourDevice/InvestigationalDeviceExemptionIDE/> at 19 November 2016.
INTRODUCTION TO MEDICAL DEVICE REGULATIONS IN THE EUROPEAN UNION:
A Medical Device under the jurisdiction of the European Union is defined as “an instrument, apparatus, appliance, material or other article, whether used alone or in combination, together with any software necessary for its proper application, which –
a) is intended by the manufacturer to be used for human beings for the purpose of
i. diagnosis, prevention, monitoring, treatment or alleviation of disease,
ii. diagnosis, monitoring, treatment, alleviation of or compensation for an injury or handicap,
iii. investigation, replacement or modification of the anatomy or of a physiological process, or
iv. control of conception; and
b) does not achieve its principal intended action in or on the human
body by pharmacological, immunological or metabolic means”.1
The clinical investigation and the subsequent introduction of a medical device in the European market is primarily regulated and governed by the MHRA (Medicines and Healthcare products Regulatory Agency) with the assistance of competent regulatory institutions called the Notified Bodies.Regulation of Medical Devices Essay. “A Notified Body is a certification organization which the national authority (the Competent Authority) of a Member State designates to carry out one or more of the conformity assessment procedures described in the annexes of the Directives.”3
The MHRA regulates with the help of two sets of medical device regulations viz. the Statutory Instruments 2002 No.618 (Consolidated legislation) and 2003 No.1697. These legislations employ the three device directives issued by the competent authority into the european law. The directives help the manufacture in better understanding of the manufacturing and the requirments for inroduction into the market of the devices. These directives are:
Directive 90/385/EEC: Active Implantable Medical Devices directive:
This directive encompasses medical devices that are active(i.e powered) and implanted(i.e left in the human body). These include pacemakers, implantable defibrillators, implantable infusion pumps, cochlear implants and implantable neuromuscular stimulators etc. Regulations realizing the Directive came entirely into force in the United Kingdom on January 01 1995.
Directive 93/42/EEC: Medical Devices directive:
This directive covers an extensive array of devices from uncomplicated bandages to orthopaedic implants and high-end radiology apparatus. Regulations realizing the Directive came entirely into force in the United Kingdom on June 13 1998.
Directive 98/79/EC: In vitro Diagnostic Medical Device directive:
“This Directive covers any medical device, reagent, reagent product, kit, instrument, apparatus or system which is intended to be used for the invitro examination of substances derived from the human body, such as blood grouping reagents, pregnancy testing and Hepatitis B test kits. Regulations implementing the Directive came into force in the UK on 7th June 2000 with a transitional period until 7th December 2003. There is no clinical investigation system for in-vitro diagnostic medical devices. Performance evaluations of in vitro diagnostic devices that are performed outside the manufacturer’s premises should be notified to the UK Competent Authority in accordance with the Medical Devices Regulations 2002: Section 44.”2
The rationale backing these directives is to permit easy movement of the medical devices throughout the European Union whilst upholding high standards of device safety and up-to-the-mark quality. Regulation of Medical Devices Essay.
Classification of medical devices:
Devices are classified purely based on risk associated with their use. Ranging from low risk to high risk, they are Class I, IIa, IIb and III. A classic example of a class III medical device is a cochlear implant, which is both active and implantable and thus comes under the purview of Directive 90/385/EEC: Active Implantable Medical Devices directive. Let us discuss in detail the regulatory requirments specified as per the MHRA to bring an active implantable cochlear implant into the market designated bt the European Union as the EFTA(European Free Trade Area). “Examples of AIMDs include:
“Cochlear implants are electronic hearing prostheses that bypass the damaged hearing components by providing electrical stimulation directly to the auditory nerve fibres in the cochlea. The electrical stimulation is interpreted by the brain as sound. Cochlear implants consist of an external microphone, speech processor and transmitter coil, and an internal stimulator (implanted under the skin just behind the ear) attached to a stimulation electrode which passes into the cochlea. A variation of the cochlear implant is the auditory brainstem implant where electrodes are implanted directly into the auditory area of the brainstem. This can be used in patients who do not have a functional auditory nerve.”5
The regulatory process of bringing a cochlear implant in the European market:
It is mandated by law that the manufacturer who intends to bring the device into the EFTA abides by the Essential Requirments stated in the Directive 90/385/EEC: Active Implantable Medical Devices directive and demonstrate the compliance of the device with the safety and efficacy standards set forth in the directive. There are essentially two ways to do it viz.
Product launch on the basis of evaluation and review of scientific literature can be considered as acceptable if equivalence can be scientifically demonstrated with a device existant in the market and routinely used in clinical practice. Regulation of Medical Devices Essay. Equivalence has to be demonstrated w.r.t technology, critical performance, design, principles of operation, biological safety, population involved, conditions of use and clinical purpose. However, unless satisfactory evidence can be collected by means of scientific literature review, the use of a well-planned clinical trial/investigation should be considered as the best way to attest permissible levels of safety and efficacy.
In case of scientific review or pre-clinical assessment, the following fees apply: Class I, IIa, or IIb other than implantable or long-term invasive: £3,000 (Re-notification incase of objection by MHRA £2,100). Class IIb implantable or long-term invasive, Class III, and active implantable: £4,100 (Re-notification incase of objection by MHRA £2,700).
Applications for a proposed clinical investigation of the medical device should be made by filling the forms PCA1 and PCA2 along with the necessary information required by the clauses in the forms. Applications should be labeled clearly as “documentation only”. The use of English language is mandatory. Documentation should be clear and legible and remain so after reproduction. Electronic applications should be discussed with the MHRA. The manufacturer, for scrutiny by the MHRA should make a total of eight full submission copies available. The charges for the scrutiny of applications are laid out in the Medical Devices Regulations 2002: section 56. They are as follows: “Fees for Group A (low risk) devices are £2,700 (initial application) or £1,800 (resubmission). Increasing to £3,000 and £2,100 on 1st April 2008. Fees for Group B (high-risk) devices are £3,800 (initial application) or £2,400 (resubmission). Increasing to £4,100 and £2,700 on 1st April 2008.”2 Applications should be forwarded to:
Mrs Daniella Smolenska, Medicines & Healthcare products Regulatory Agency (MHRA), European and Regulatory Affairs, Market Towers, 1 Nine Elms Lane, London, SW8 5NQ, Tel: 020 7084 3363, Email [email protected].
Approval from the MREC (Multi-centre Research Ethics Committee)/LREC (Local Research Ethics Committee) can be obtained along with the notification to the Competent Authority. However, a clinical investigation can begin only after approval has been obtained from the MREC/LREC and the Competent Authority has not raised an objection to the investigation within the 60 days time constraint period; or approval has been obtained from both the authoritative bodies. Regulation of Medical Devices Essay.
A well-defined clinical plan whose methodology and ethical considerations conforms to the standards set forth in the Medical Devices Regulations 2002: section 16 and section 29, the Active Implantable Medical Devices Directive, Annexes 6 and 7, and the Medical Devices Directive, Annexes VIII and X.
Supplementary standards are set forth in Standard BS EN ISO 14155-1; 2002, “Clinical Investigation of Medical Devices for Human Subjects-part 1: General Requirements”, and BS EN ISO 14155-2:2002, “Clinical Investigation of Medical Devices for Human Subjects-part 2: Clinical Plan”.
The CA should be notified incase of differences in the EU and non-EU protocols and the reasons for the same.
“All applications must contain a statement (Active Implantable Medical Devices Directive: Annex 6,2.2; Medical Devices Directive: Annex VIII, 2.2): that the device in question conforms to the Essential Requirements except with regard to those aspects of the device that are to be investigated and that in respect of those aspects, every precaution has been taken to protect the health and safety of the patient. By signing this statement, the manufacturer is declaring that the device meets all of the relevant Essential Requirements, other than those subject to the investigation. Manufacturers must therefore ensure that at the time a notification is made to the Competent Authority, they have all documentation required to demonstrate conformity with the relevant Essential Requirements available for submission to the Competent Authority when requested.”2
Device information like name, model, materials used and sterilization standards etc must be provided as set forth in the directive.
Pertinent information about the clinical investigation plan, investigation parameters and design, data collection and analysis methods etc. should be made available to the CA.
It is strongly advised that Class III devices follow a well-designed post-marketing plan under the Medical Devices Vigilance.
Extra care should be taken when labeling devices meant for clinical investigations. “All devices intended for clinical investigation must bear the wording “exclusively for clinical investigation” (Medical Devices Directive: annex 1, para 13.3(H) and the Active Implantable Medical Devices Directive: annex 1, 14.1).”2
Reporting of adverse incidents: “A serious adverse incident is one which:
All such incidents should be recorded and reported to the CA as set forth in the Regulation 16(10)(a) of the Medical Devices Regulations 2002 (SI 618) and Annex X of the Medical Devices Directive 93/42.
Final written report: A report in conjunction with the Medical Devices Directive (Medical Devices Regulations 2002: Section 16(10) and Section 29(9)) should be submitted to the CA for devices undergoing investigation for a CE marking.
However, Class III devices need to be highly regulated, before, after and during the clinical investigation. Owing to the high risks associated with their use, some say the risk can be quantified only as social and not scientific. “Risks, rather than being inherent within these implant devices, may be seen as socially derived, in processes of negotiation and conflict such as those in the case of hip and breast implants….most recently, in the wake of the controversies surrounding breast implants and the 3M Capital hip, attention has been drawn to the uneven performance of notified bodies in the EU, which approve new products. Regulation of Medical Devices Essay. This has led to the setting up of a new European Notified Bodies Operations Group (NEBOG) and calls by the MDA for all implants to be reclassified as high risk, Class III. A review of the operation of EU EMDD is also about to begin (MDA, 2001b). It thus appears that increased political scrutiny is being focused on this sector.”6