A Review of International Medical Device Regulations: Contact Lenses and LensCare SolutionsMarina Zaki1,2; Jesús Pardo 3; Gonzalo Carracedo G3,4 PhD1School of Biomolecular & Biomedical Science, UCD Conway Institute, UniversityCollege Dublin, Ireland2School of Nursing, Midwifery & Health Systems, University College Dublin, Ireland3Ocupharm Diagnostic Group Research, Faculty of Optic and Optometry, UniversidadComplutense de Madrid, Madrid, Spain4Department of Optics II (Optometry and Vision), Faculty of Optic and Optometry,Universidad Complutense de Madrid, Madrid, SpainDisclosure: The authors do not have any financial interest on the materials andinstruments used in this studyCorresponding Author:Gonzalo Carracedo RodríguezFaculty of Optic and OptometryDepartment Optics II (Optometry and Vision)C/Arcos del Jalon 11828032 (Madrid)Spaine-mail: [email protected]

ABSTRACTMedical devices are under strict regulatory oversight worldwide and such regulationsprioritise patient safety and efficacy over anything else. Contact lenses fall under themedical device category - a result of direct contact with the eye. Equally regulated are thecontact lens care product solutions, which include cleaning and maintenance solutionsand lubricating and rewetting drops. In the USA, it is the FDA Centre for Devices andRadiological Health (CDRH) overseeing the regulations of medical devices, since 1976.In the European Union, it is the EU Commission responsible for regulating devices inMember States. The categorisation of contact lenses into medical devices is based on theirinherent risk to the wearer. Contact lenses are subject to crucial regulatory oversight fromconcept to clinical evaluation, clinical investigations through to the finished lens product,and finally, strict conditions associated with their marketing approval including postmarketing surveillance. The physiochemical and manufacturing testing, such asbiocompatibility testing alongside pre-clinical stability, sterility and microbiologicaltesting are just some of the essential testing lenses must endure. Only throughunderstanding the inherent risks and potential complications that can arise from contactlens wear, can one truly appreciate the need to adhere to strict regulations. The challengehowever, lies in the need for more standardised regulations and flexible approaches,ensuring innovative device technologies reach patients in a timely manner withoutcompromising public health and safety. This review highlights some key requirement,differences and similarities between the FDA and EU administrations in the approval ofcontact lenses.2

KEYWORDSClinical investigation; market approval; contact lenses; care solutions; Clinicalevaluation3

1. IntroductionWithin the European Union (EU), a medical device can be broadly defined as "anyinstrument, apparatus, appliance, material or other article, whether used alone or incombination, including the software necessary for its proper application intended by themanufacturer to be used for human beings"[1]. The commonality between the EUdefinition with other definitions, such as the United States of America, lies in the purposeof such medical devices: for the diagnosis, treatment, cure or mitigation of onset of certaindiseases or conditions and "intended to affect the structure or any function of the body"in man or animals. These can also include active implantable medical devices (or AIMD)or in vitro medical devices. The range of such devices vary significantly, and include:bandages, wheelchairs, endoscopes but also, contact lenses and contact lens caresolutions.For the purpose of this article, emphasis will be on key regulatory agencies including theFood and Drug Administration (USA) and the European Commission (EC) who haveregulatory oversight of medical devices in their respected regions. The EC 'harmonizes'both the requirements for and regulations of medical devices inside the European Union.The Medical Devices Directive (MDD) is a central component of legislation. The ECworks in close conjunction with each country's ('Member State') respected HealthAuthorities. The aim, therefore, is to integrate the various national requirements into asingle law that could be rolled out and applied across the EU. It is important to note thatthe new Medical Device Regulation (May, 2017) will replace the existing EU Directiveon AIMDS (90/385/EEC) and Medical Device Directive (93/42/EEC), both of which areamended by the Directive from 2007(47/EC) [1-3].4

Until the 1990s, each country within the EU adopted its own approach when it came tothe evaluation of medical devices. Plans to harmonize this diverse market led to theintroduction of EU directives with 'Essential Requirements' that must be met for a deviceto be marketed across EU member states, post-CE marking [4]. These directives in the1990s therefore saw the inclusion of contact lenses into the medical device family. Incontrast to the US FDA's PMA application process (see later), medical devices in the EUas mentioned are subject to conformity assessment procedures, usually carried out by anindependent third party ('notified body'), acting under the control of the nationalauthorities. Once cleared and 'certified', the device receives the CE marking, allowing forharmonization of its use within the EU/EFTA countries [5]. In 2012, the EuropeanCommission put forward two Regulations for medical devices (Medical DevicesRegulation (MDR)) and in vitro diagnostic devices, which will repeal the existing threemedical device Directives (93/42/EEC, 90/385/EEC, 98/79/EC)[1, 2, 6]. The aims ofthese new regulations are to emphasize the need for safe and effective medical deviceswhilst adopting a more innovative approach in the sector.The Food and Drug Administration (FDA) has the legal authority to regulate medicaldevices in United States (US), as per the Federal Food, Drug & Cosmetic Act (FD & CAct, 1938) in the USA [7]. Through this, the FDA has published and implemented theappropriate regulations, within which exists the CFR, Code of Federal Regulations. Morespecifically, for the purpose of medical device regulations, medical devices (along withradiation-emitting products) are located in Title 21 CFR, Parts 800-1299. These specificregulations that are codified in the CFR include content on the design, clinical evaluation,manufacturing, packaging, labelling and post marketing surveillance of medical devices5

[8]. In 1994, the US regulatory bodies released the Premarket Notification (510K))Guidance Document for Class II Daily Wear Contact Lenses.Contact lenses in the US have had regulatory oversight from the FDA since the 1960s.However, soft hydrogel lenses were regulated as per 'new drug product' FDA regulations[9]. It was the 1976 Medical Device Amendment to the Federal Food, Drug and CosmeticAct (FDCA) that paved the way for newfound medical device regulations in the USA andthese included contact lenses. This then led to the transition of extended-wear lenses intoClass III medical devices, requiring Pre-Market Authorization (PMA) due to their higherrisk of adverse events. Daily-wear soft and rigid gas-permeable (RGP) lenses becameClass II medical devices in 1994 [9]. Studies of daily wear contact lenses are deemed tobe of non-significant risk. Studies investigating extended-wear contact lenses howeverrequire an Investigational Device Exemption (IDE) application to the FDA prior tobeginning the study [10]. Both however, require Institutional Review Board (ethical)approval. Products of contact lenses were also categorized under Class II medical devicesin 1997 and will be discussed further later. FDA Guidance specific to contact lenses,including for example regulations in the region of toxicology, microbiology,manufacturing/chemistry properties, clinical, labelling, equivalence claims and care forsolutions is synthesized in the latter part of the article but will be discussed more broadlyfor medical devices in the following section.To delve further, it is important to comprehend that the regulation of contact lenses andaccompanying contact lens care solution, is crucial for patient safety. The EuropeanCommission Classification of Medical Devices discusses the "risk-based system"incurred, based on the "vulnerability of the human body" (MEDDEV 2.4/1 Rev 9, 2010)6

[11]. This emphasizes the importance of regulating all medical devices, including thosein a lower risk category. In the interest of harmonization, only products that fulfil the EU's'Essential Requirements' can be put through to market [12]. The acceptance of thesestandards, directives and regulations can only come from understanding the importanceof oversight prior to a medical device making contact with the human body. The FDA, inits Guidance for Contact Lens Care Products Labelling, discuss the importance ofemphasizing the risk of eye infections when it comes to the use of contact lens and itsrelevant care products. Mitigating the potential risks and complications associated withtheir use is therefore of utmost importance. This arises from ensuring accurateinformation in the accompanied label and correctly following these instructions for use(IFU). The literature discusses devastating toxic and microbiological complications thatcan arise from contact lens wear, due to their potential to alter the normal homeostasis ofcorneal surfaces [13, 14] but also the toxic and allergic effects of preservatives found insoft contact lens solutions, potentially causing ocular delayed hypersensitivity [15-17].These are just some of the many risks that can occur because of contact lens wear and useof solutions. Therefore, this is justification for why oversight, in the form of regulations,are crucial for patient safety.Firstly, however, one must understand the similarities and differences between the keyregulatory authorities. Table 2. Overarching the EU regulations when it comes to medicaldevices is the EU Commission. More specifically, contact lenses require a CE(Conformité Européene - European Conformity) Marking, discussed in the EU93/68/EEC Directive [18]. CE Marking and its accompanied directives have a set of"Essential Requirements" that need to be met. In the USA, it is the Food and DrugAdministration (FDA) overarching the regulation of such medical devices, namely but7

not always, through their 510(k) application process for its registration. Both have a coremission: ensuring the safety and effectiveness of drugs and medical devices for patientuse. Differences requirements between both regulations mean to have contact lenses orcare solutions approved in FDA or EU and not in both at the same time.A gap in the literature was noted with regards to explaining similarities and differencesbetween the FDA and EU Commission's regulations of contact lens and their caresolutions. A consequence of this gap, was therefore the lack of published scientificliterature for researchers, clinicians and scientists to fully comprehend the importance ofregulatory oversight for patient safety and highlight any differences between nations. Theobjective of this article therefore, is to review the current literature and internationalregulatory medical device guidelines, specifically of contact lenses and care solutions,and to compare and contrast the FDA and European Commission administrativeregulations in both pre-clinical and clinical studies prior to the registration and approvalof contact lenses and contact lens care solutions.2. Contact lens and care solutions classificationIt is important to note that in both the EU and USA, governing bodies classify medicaldevices according to their low, medium or high risk. This classification in turn allowsmanufacturers to determine the need for a regulated clinical study (commonly referred toas a 'trial' or 'clinical investigation, specific to medical devices) or a clinical evaluation ofprior clinical data and the scientific literature.Daily-wear contact lenses are deemed to pose a 'moderate risk' to patient safety and inaccordance with FDA classifications, are therefore labelled as Class II medical devices8

[19], along with contact lens care solutions. Class II devices necessitate additionalregulations to ensure adequate safety and effectiveness through for example, their postmarketing surveillance and also labelling of the device. Overnight lenses however (thosefor extended-wear use) and contact lenses indicated for myopia control, are perceived tohave a much higher risk, and so are labelled as Class III devices [20]. Class III medicaldevices are subject to pre-marketing approval (PMA), in order to achieve FDAacceptance. In the EU, however, the classification is slightly different. As brieflymentioned, in the EU, there is a conformity assessment that manufacturers of devicesmust demonstrate to comply with Directive 93/42/EEC [1] and their requirements. Theclassification of these medical devices will therefore play a role on the conformityassessment the manufacturer must adhere to, as a means of achieving CE marking [21].Short-term corrective contact lenses are Class IIa medical devices, while long-termcorrective contact lenses are in Class IIb. Equally labelled as a medical device, contactlens care solutions for the purpose of "disinfecting, cleaning, rinsing" the contact lens, arein Class IIb of the EU Medical Device Guidance on Classification.3. Pre-clinical studies for contact lens and care solutions approvalContact lenses and their care solutions must undergo rigorous testing, namely theaforementioned tests in table 2, to demonstrate: biocompatibility physical compatibility(between care solutions and contact lenses), stability and sterilization Figure 1.Biocompatibility testing refers to the biological safety evaluation of a product, in thiscontext, medical devices, as a means of mitigating the risk of biological incompatibilitywith the human body. The FDA has stated that in general, clinical studies are not deemedsufficiently sensitive to determine concerns of biocompatibility - leading to the need forpre-clinical animal testing. Data from in vivo animal studies of the final medical device9

may be used instead of certain biocompatibility tests (FDA Guideline, 2016) [22].Biocompatibility testing for medical devices regulated by the EU Commission also reliesheavily on the EN ISO 10993-1 standard [23].Fig 1. Summary of Approval Steps for Contact Lens and/or care solutionThe recent FDA Guideline, issued in 2016 entitled: "Use of International Standard ISO10993-1, "Biological evaluation of medical devices - Part 1: Evaluation and testing within10

a risk management process" aims to assist those preparing PMAs, 510(k)s and requestsfor medical devices that are either in direct or indirect contact with the human body. Theimportance of clear guidance here comes from understanding the possibility of an"unacceptable adverse biological response" that may come from device's materialsinteracting with the body [23].Emphasis here is on discussion of 'risk-based approaches' required to determine whetherbiocompatibility testing is necessary. This comes from the responsibility of sponsors tostate whether their device "does not have any direct or indirect tissue contact" andtherefore additional biocompatibility information would not be required. If, however, a'change' exists that could alter tissue-containing components of the device, either directlyor indirectly, a biocompatibility evaluation is required to evaluate this impact.In brief, cytotoxicity testing involves cultured cells being exposed to the lens solutionwhile sterility tests investigate the microbiological aspects of the lens (UNE EN ISO10993-5) [24]. Other similar tests, such as those to test for ocular irritation are performedon rabbits and labelled under the necessary 'pre-clinical studies' that regulators requestprior to registration and approval (UNE EN ISO 10993-10) [25].It is crucial to make reference to the ISO 11981: 2017 standard when discussing theprocedures and performance criteria to assess the physical compatibility of contact lensesand their associated care products. By definition, ISO standards are international andtherefore recognized by both FDA and EU regulatory oversight. The procedures aim todetect changes in the characteristics of contact lenses and investigate methods todifferentiate irreversible changes from reversible changes in lens characteristics [26]. A11

completed list of the key ISO standards relevant to contact lenses was created throughhandsearching the ISO website and can be found in Table 1.Although almost a quarter of a century old, an FDA guidance (1994) provides furtherinformation on the compatibility of lenses with its proposed care regimen, as per thelabelling (Amendment 1 to May 12, 1994, Premarket Notification (510(k)) GuidanceDocument for Daily Wear Contact Lenses) [19]. The guideline briefly discusses a 30-daycycle lens/solution compatibility test. Justification for not submitting a compatibility testwith a 510(k) application is if such cleaning, rinsing or disinfecting products have priorapproval with a lens of the same hydrophilic or hydrophobic lens group, respectively. TheFDA also requests the content of documents submitted by manufacturers, to includeaspects of chemical composition of lenses and purity of monomer components.Manufacturing methods, polymerization and annealing conditions, sterilization methodsand packaging methods and materials are just some of the manufacturing information alsorequested by the FDA. This is alongside criteria of investigating: leachability, physicaland optical parameters of finished lens and their tolerances, preservative uptakes andrelease (for new/modified lens materials), physiochemical properties and information onlens blanks.12

Table 1: Key ISO Standards specific to Contact LensesISO NameBrief Details/TitleEN ISO 11980:2012Ophthalmic optics - Contact lenses and contact lens care products Guidance for clinical investigationsEN ISO 14534:2011Ophthalmic optics - Contact lenses and contact lens care products Fundamental requirementsEN ISO 183691:2017Ophthalmic optics - Contact lenses Part 1: Vocabulary, classification system and recommendations for labellingspecificationsEN ISO 183692:2017Ophthalmic optics - Contact lenses Part 2: TolerancesEN ISO 183693:2017Ophthalmic optics - Contact lenses Part 3: Measurement methodsEN ISO 18369-4:2006Ophthalmic optics - Contact lenses Part 4: Physicochemical properties of contact lens materialsEN ISO 11978:2017Ophthalmic optics - Contact lenses and contact lens care products LabellingEN ISO 11986:2017Ophthalmic optics - Contact lenses and contact lens care products Determination of preservative uptake and releaseEN ISO 14729:2017Ophthalmic optics - Contact lenses and contact lens care products Microbiological requirements and test methods for products and regimens forhygienic management of contact lensesEN ISO 13212:2014Ophthalmic optics - Contact lenses care products Guidelines for determination of shelf-lifeEN ISO 11981:2017Ophthalmic optics - Contact lenses and contact lens care products Determination of physical compatibility of contact lens care products with contactlensesEN ISO 9394:2017Ophthalmic optics - Contact lenses and contact lens care products Determination of biocompatibility by ocular study with rabbit eyesEN ISO 18189:2016Ophthalmic optics - Contact lenses and contact lens care products Cytotoxicity testing of contact lenses in combination with lens care solution toevaluate lens/solution interactions13

Table 2: Comparison FDA and EU Commission in Regulations of Medical Devices,specially contact lenses and their care solutions.Market ApprovalviaFDAEU Commission510(k) or PMACE Mark assessment.Key Requirement Safety and EfficacyRegulatoryAcceptance byCategorisation ofContact LensesSafety and performanceCDRH/FDANotified Bodies, (non-governmental)Central GovernmentalAgency (Central RegulatoryAuthority) Daily-wear soft andrigid gas-permeablelenses –Class II (ModerateRisk)Contact lens careproducts – Class II(Moderate Risk)Extended-wearlenses –Class III (High Risk) Short-term corrective lenses–Class IIa (Medium Risk)Long-term corrective lenses–Class IIb (Higher Risk)Contact lens care products –Class IIb (Higher Risk)GuidanceFDA 21 Code of FederalRegulations 800-129921 CFR 886.591621 CFR 886.591821 CFR 886.592521 CFR 886.5928EU Directives –Conformity to EssentialRequirementsMDD 93/42/EEC as amended (now,MDR and IVDR)EU Regulation 2017/745ChecksPMA: preapprovalinspection andpostapproval inspections.Post 510(k) clearance FDA inspection.Design controlManufacturing controlCE marking requires at least 2preapproval audits: producttechnical file audit and qualitymanagement system auditContact outsideCountryOutside of USA, FDArequires 'US Agent' ifimporting medical devicesinto USOutside EU, contract 'Authorisedrepresentative'Quality21 CFR 820QMS compliant with ISO13485DocumentationSummary of safety andeffectivenessDevice identification andclassIndications andContraindicationsWarnings and precautionAlternative practices andproceduresTechnologicalcharacteristicsTechnical fileDevice descriptionDesign and manufacturinginformationGeneral safety and performancerequirementsBenefict risk analysis and riskmangementProduct verification and validation14

Non clinical testClinical testsBiocompatibilityPre-Clinical TestsClinical StudiesFDA Guideline, 2016:Device master file forbiocompatibilityevaluationsISO 10993-1, "Biologicalevaluation of medical devices Biological safety reportCytotoxicityOcular irritationAcute systemic bilityCompatibility with lens care testsPreservative interactionBioburdenShelf lifeSterilizationClinical Investigation and/or Clinical EvaluationStandardsEN ISO, ANSIEN ISO*FDA (Food and Drug Administration), federal agency of United States of America Departmentof Health and Human Services*EU (European Union) Commission - politically independent commission involved in Europeanlegislation*PMA (pre-market approval) in FDA to show safety and effectiveness of class III medicaldevices.*CE Mark (Conformité Européene): European Conformity mark indicating conformity withhealth and other key standards in the European Economic Area*CDRH (Center for Devices and Radiological Health) promote and protect health in the FDA*ANSI (American National Standards Institute) is the member body to ISO based in the USA.*CFR (Code of Federal Regulations) – codification of permanent rules by Federal Governmentof USA*MDD (Medical Device Directive) for the safety and performance of medical devices in the EU*ISO (International Organization for Standardization) – create and publish internationalstandards4. Clinical studies (trials and investigations) for contact lenses and care solutionsIt is important to differentiate between a clinical trial and a clinical investigation. Arandomized controlled clinical trial (RCT) can be defined as a prospective study onhumans to test the safety and/or effectiveness of an interventional treatment.Methodologically sound trials assess patient safety and efficacy of: medicinal15

compounds, surgical interventions, nutritional supplements, behavioural and exerciseinterventions. However, clinical studies involving medical devices are referred to as'clinical investigations' (CI). While clinical trials and clinical investigations do share somesimilar characteristics (table 3), table 4 shows some differences.One aspect, as per table 4, crucial to an RCT to minimize subjectivity bias but not alwayspossible in medical device clinical investigations, is that of blinding. Clinicalinvestigations may see blinding when it comes to the assessment of outcomes [27]. Thisinvolves data managers, independent data monitoring committee members andstatisticians being blinded to the patient data and not knowing whether it belongs totreatment or control group - similar to a clinical trial, with a key difference of the difficultyblinding the healthcare professional (e.g. clinician implanting the device) and the patientbeing aware of the intervention. Another key characteristic of RCTs not present in clinicalinvestigations includes that of randomization and control groups, as briefly noted in table3. It would be considered highly unethical to ‘randomize’ or leave up to chance theassigning of a sham device (in lieu of a placebo in drug trials) to a patient. This wouldinvolve exposing patients to unnecessary invasive procedures to insert the medical device.This point is covered in more detail elsewhere by other authors (Neugebauer et al., 2017).Contact lens clinical investigations are often designed as 'clinical outcome studies'. Interms of a comparator, control lenses are provided to be tested against the test lens.Certain observations and outcomes that are assessed in these investigations include: bestcorrected visual acuity, slit lamp analysis and, keratometry/topographic analysis, cornealthickness evaluation (pachymetry), wearing time and subjective symptoms [28].16

In the clinical investigation, defined as a study conducted on human subjects to assess thesafety and/or efficacy of a medical device, the aim is not only to establish the safety andperformance of the device being investigated, but also to assess whether it is suitable forits intended use and targeted population. The EC MEDDEV 2.7/4 (Guidelines on ClinicalInvestigation: A Guide for Manufacturers and Notified Bodies, 2010) emphasizes theimportance of properly conducted clinical investigations, their compliance to theirclinical investigation plan (CIP) and adherence to national laws and regulations, to protectsubjects and ensure the integrity of the data [29]. In line with EU regulations, the datathat is obtained is required to be acceptable to demonstrate conformity to the EssentialRequirements. Clinical investigations, must be conducted in adherence with GoodClinical Practice (GCP), where EN ISO 14155 is the standard for the GCP of medicaldevice clinical investigations (see ISO 11980:2012 below for more detailed guidance onCI of contact lenses) [30]. It also goes without saying that as with any clinical study, atrial or an investigation, "the rights, safety, and well-being of clinical investigationsubjects shall be protected, consistent with the ethical principles laid down in theDeclaration of Helsinki" [31].In its aim for 'global harmonization', ISO released standard 11980:2012 - a guidance forclinical investigations of the safety and performance of contact lenses and lens careproducts [30]. Despite its international recognition, uniformity proves challenging, wherenational regulations and legal requirements takes precedence over international guidance,such as the ISO standards. Elements central for the rigor of reporting CI includes: studydesign, duration and size, variables, statistical considerations for extended wearevaluations, adverse events/effects, evaluation of visual, refractive and lens performanceand subject acceptance, lens fitting characteristics and lens surface characteristics. ISO17

11980:2012 also discusses special indications for CI of contact lenses in paediatrics,inclusion/exclusion criteria of patients recruited to the CI, the need for a statisticalanalysis plan, monitoring procedures for the collecting and recording of data, details ofcontrols (e.g. historical)/comparator, information in the case of an uncontrolled study andthe contents of the clinical research plan [30].Table 3: Characteristics of Clinical Trials and Clinical InvestigationsClinical Trial Clinical InvestigationRequiring 'favourable opinion' from a relevant ethics committee Conducted under Declaration of Helsinkiethical guidanceAppropriate insurance and clinical indemnity schemes required at each study site Request for investigators to have relevanttraining, qualifications and experience toconduct study (ICH GCP E6 /ISO 14155/ISO11980) Protocol/Investigation Plan Informed Participant Consent Randomisation x*Blinding xComparator Group Sample Size Calculation ** Risk Analysis Inclusion/Exclusion Criteria *** Follow up schedule Clinical endpoints Reporting of Adverse Events (Vigilance) Adherence to Data Protection Acts and GDPR Register on Trial Registries Post-marketing Surveillance 18

*randomisation in medical device clinical investigations have proven to be a challenge butapproaches to randomising in these studies do exist**while clinical trials often see a placebo as a control, it would be unethical for medical devicestudies to use a 'sham' device and so often the comparator can be other approved devices***interventional clinical trials are required, under the revised ICH GCP E6 guidelines to take amore 'risk-based approach' to monitoring. Monitoring for contact lens clinical investigations onthe other hand, are part of the safety analysis and looks out for adverse events such as cornealulcers, inflammation of the iris, central and peripheral infiltrates, conjunctivitis and abrasions,amongst many others (Lippman, 2012).Table 4: Differences between Clinical Trials and Clinical InvestigationsClinical TrialClinical InvestigationParticipantsEarly phase trials often seehealthy volunteers beingrandomised. Late phase trialsare more likely to test theintervention on patientsDue to the invasive nature of someclinical investigations, they areonly carried out on patients of thecondition in question, where it willbe of some benefit investigating itin the targeted populationPrior ApprovalA study can be known as a trialif it is investigating a new drugcompound or an existing drugcompound for a new use/newdosage, different than thatalready with marketingauthorisationDevices that already have CEmarking should not undergoclinical investigation, unless theinvestigation is for a differentpurpose than that intendedSponsorsSponsors of a trial can vary,from academic institutions topriv

medical device Directives (93/42/EEC, 90/385/EEC, 98/79/EC)[1, 2, 6]. The aims of these new regulations are to emphasize the need for safe and effective medical devices whilst adopting a more innovative approach in the sector. The Food and Drug Administration (FDA) has