Device regulationsYaba, why do you want clinical trials? the guidelines for device regulations are clear.
Like, why go to the sixth floor of building when everything you need is on the third floor. Why put R 90 insulation in your roof when all you need is r45?
Classification Of Medical Devices
It is not feasible economically nor justifiable in practice to subjectall medical devices to the most rigorous conformity assessmentprocedures available. A graduated system of control is more appropriate.In such a system, the level of control corresponds to the level ofpotential hazard inherent in the type of device concerned. A medicaldevice classification system is therefore needed, in order to channelmedical devices into the proper conformity assessment route.
Medical devices are divided into different categories. Theclassification identifies the level of regulatory control that isnecessary to assure the safety and effectiveness of a medical device.
In US, according to 1976 Medical device amendment Act, medical devices are classified mainly into three classes, on basis of risk-based system. The main classes are – class I, class II, class III and In Vitro Diagnostic Devices (IVD), the classification for these devices found under 21 CFR 862, 21 CFR 864 and 21 CFR 866.5,8 The different classes of Medical Device with example are tabulated in Table 1.
In European Union, medical devices are classified according to theirintended use. In European Union, there are 18 rules for classificationof medical devices. These rules are applied to help a manufacturerdetermine whether the device is Class I (low risk), Class II (mediumrisk), or Class IIb or III (high risk).
The 18 rules are combination of following criteria:6
- Duration that the device is in contact with patient
- Whether it is invasive or non-invasive
- Degree of invasiveness
- Anatomy affected by the device
- Active and non-active
- Special situations (e.g. devices incorporating a medicinal substance, contact lens solution).
Classification of medical devices in EU is tabulated in Table 2.
InJapan medical devices according to Pharmaceutical affair Law (PAL) areclassified into four categories. A new system of classification,separate the medical devices into three classes, which based on thedevice classification of the global harmonization task force andbasically depend on risk based system.6,10 The new classification system has been tabulated in Table 3.
Regulation Aspects Of Medical Devices
Medical devices are regulated by different regulatory structures anddifferent guidelines are followed in different countries to determinethe safety and efficacy of medical devices.
The Food and Drug Administration (FDA)is responsible for protecting the public health by assuring the safetyand effectiveness of a variety of medical products, including medicaldevices. CDRH of the FDA is responsible for premarket and postmarketregulation of medical devices.11 The FDA/CDRH mandate is topromote and protect the public health by making safe and effectivemedical devices available in a timely manner.5 There are several types of marketing applications that a medical device manufacturer may submit to CDRH.12
Medical device manufacturers must submit PMAs for novel devices, alsoreferred to as Class III devices. These devices tend to be higher riskor raise new types of safety and effectiveness questions that must beanswered before approval for marketing. Data in a PMA application mustdemonstrate a “reasonable assurance” of safety and effectiveness.Manufacturers submit 510(k)s for devices similar to those already on themarket. Data in a 510(k) submission must demonstrate that the newdevice is substantially equivalent in safety and effectiveness to aClass II device already on the market. Based on the incremental natureof device development, the majority of device applications cleared underthe 510(k) program are based on non-clinical testing with no clinicaldata. Although the majority of PMA applications do contain clinicaldata, study designs are not prescribed by regulations.10 The types of marketing application are compiled in Table 4.
In EU, the marketing of medical devices regulated by directives,describing the essential (safety) requirements that products have tofulfill to obtain marketing clearance. In the EU, the need to tighten upthe regulations covering the sale of medical devices was addressed bythree medical device directives, which were intended to ensure thesafety and performance of medical devices in the EU.
1. Active Implantable Medical Devices Directive – 90/385/EEC 4
The first directive to be implemented which covers all powered implantable medical devices.
2. Medical Device Directive – 93/42/EEC 5
This directive enforced from June 1998 regulates most medical devices,for example bandages, condoms and diagnostic X-ray Machines.
3. The In-Vitro Diagnostic Medical Devices Directive – 98/79/EC
This directive regulates products used to examine substances derived from the human body.7
Though there are many similarities in the regulatory process in the United States and countries within the European Union, there are important differences that impact the time and cost associated with the introduction of a new medical device. This is exemplified on basis of: Use of notified bodies, criteria for approval, and local site.13
The European Union system relies heavily on NBs, which are independent commercial organizations to implement regulatory control over medical devices. NBs have the ability to issue the [Confirmatory European (CE) mark], the official marking required for certain medical devices. NBs are designated, monitored, and audited by the relevant member states via the national competent authorities. Many functions performed by the FDA/CDRH within the United States are performed by NBs, including medical device certification, device type designation, assessment and verification of quality systems, and review of design dossiers for high-risk devices. Currently, there are more than 50 active NBs within Europe. A company is free to choose any NBs designated to cover the particular class of device under review. After approval, post-market surveillance functions are the responsibility of the member state via the competent authority. NBs typically function in a closed manner, providing little visibility on criteria required for approval. This dynamic allows for a high degree of variation as well as competition among NBs. As a result, NBs are perceived by industry to be less bureaucratic organizations that can respond more quickly and efficiently than the FDA. These potential benefits may be offset by a system that is intrinsically more fragmented and highly variable and has resulted in the approval and continued marketing of devices, e.g., abdominal aorta stent grafts in Europe that failed efficacy trials in the United States.
Criteria for approval of high-risk devices are different in the EU. To receive approval to market a class III high-risk (and some class II) device in theUnited States, the manufacturer must demonstrate the device to be reasonably safe and effective, which typically requires a prospective, randomized controlled clinical trial. To receive approval to market a device in the EU, the manufacturer must demonstrate that the device is safe and that it performs in a manner consistent with the manufacturer’s intended use this difference has a profound impact on the size and scope of the clinical studies for regulatory approval. This significant difference is illustrated by examining the introduction of distal protection systems.7,13
In Japan the evaluation of the safety and effectiveness of medicaldevices is performed by two centers under the control of Ministry ofhealth and labor welfare (MHLW): Pharmaceuticals and Medical DevicesEvaluation Center (PMDEC) and Japan Association for the Advancement ofMedical Equipment (JAAME). PMDEC reviews manufacturing and importapproval applications for drugs, cosmetics and medical devices and isresponsible for evaluating all approval applications and clinical trialapplications for new and improved medical devices. JAAME performsequivalence reviews of all generic, or me-too, medical device TheJapanese regulatory environment for medical devices has changedsignificantly since the enactment of the Pharmaceutical Affairs Law(PAL). In Japan, a consolidated organization, the Pharmaceutical andMedical Devices Agency (PMDA), will be the cornerstone ofJapan’s medicalproduct regulation.12
Currently, the medical device approval process depends on the type of medical device being submitted. There are different standard with regard to different classes, which are as follows-
CLASS-I – devices are renamed as general medical device and requiremarketing license from the prefecture government. They do not needmarketing approval and their sale is not regulated.
CLASS-II- devices are renamed as controlled medical device and requirethird party certification. MHLW is establishing standard for accreditingthird parties. MHLW will also regularly audit all third partyorganization. These marketing approval holders apply directly to thirdparty certification body for marketing authorization. The third partydetermines whether the medical device confirms to the standardspublished by MHLW.
CLASS-III & IV – devices are designated highly controlled medicaldevices. These products are highly regulated and require marketingapproval by MHLW.6,10 Approval requirement for different classes are described in Table 5.
Medical devices firms have faced strict regulatory measures in theUnited States, the EU andJapan for several decades for ensuring safetyand efficacy of medical devices. These three regions share somewhat ofsimilarities beside of difference regarding classification andregulation of medical devices. The Comparison of theU.S., EU, andJapanese regulatory systems are shown in Table 6.
Conclusion
The demonstration of safety and efficacy for a new medical device is along, arduous, and expensive developmental process. The regulationregarding confirmation of safety and efficacy of medical devices isdiffering from country to country. There is a need to establish auniform format for different countries to certify that the medicaldevice being exported complies with their domestic regulatoryrequirements. This certification process will greatly help importingcountries to control medical devices, enhancing patient safety andincreasing access to safe, effective and clinically beneficial medicaltechnologies around the world. The Global Harmonization Task Force isone of initiative towards this path. However, there is further need ofenhancing this global harmonisation.