Compliance Navigator Blog

The FDA has defined stand-alone medical software in the Preamble Section AA Special Requirements for Stand-Alone Software—Final § 801.50 of the Unique Device Identification (UDI) System Regulations as ‘medical software that is itself a medical device and is not a component, part, or accessory of a medical device’.

The IVDR (EU 2017/746) brings new requirements for manufacturers with regard to Performance Evaluation and Clinical Performance Studies and one of those is the need for a Performance Evaluation Plan (PEP) and Performance Evaluation Report (PER).

A new technical specification has been issued as Part 4 to the ISO 11137 series of standards for radiation sterilization using gamma, electron beam or x-ray irradiation.

The IMDRF defines ‘SaMD’ as ‘software intended to be used for one or more medical purposes that perform these purposes without being part of a hardware medical device’.

Medical Device Coordination Group (MDCG) endorses guidance for notified bodies.

Manufacturers should be careful to distinguish a PMCF investigation from other types of PMCF.

European request for standards to support the regulations of medical devices rejected by the European Standards Organizations.

The need to report only SAEs with a causal relationship with the investigational device, comparator or investigation procedure is an important difference from the AIMDD and MDD.

The UK Medicines and Healthcare products Regulatory Agency (MHRA) has issued updated guidance to help identify the health apps which are medical devices.

The MDR introduces new requirements, which need to be carefully reviewed and addressed in applicable procedures for the conduct of clinical investigations under the MDR.

The delivery of a validated and accurately controlled sterilization process is enabled by the use of sterilizing equipment that is designed, constructed and installed to deliver the sterilization process safely and reproducibly. There are currently no international standards for sterilizing equipment.

Modifications to regulatory approaches for AI–based medical device software will depend on the type and nature of the algorithm, and the associated risks.

The MDR sets out very detailed requirements regarding clinical investigations in comparison with the Directives.

As further advancements are made with AI technology, regulators may consider multiple approaches for addressing the safety and effectiveness of AI in healthcare.

Under the European MDR, there are important new requirements for pre-market and post-market clinical investigations.

The International Medical Device Regulators Forum (IMDRF) is a voluntary group of medical device regulators from around the world. They have recently issued a final guidance document - Personalized Medical Devices – Regulatory Pathways.

Data quality is a key factor in the success or failure of a machine learning system; in fact, data quality is as or more important than the machine learning algorithm.

Guidance on the application of the BS EN ISO 11607 series of standards, which specifies requirements for sterile barrier systems, is being balloted.

There are several microbiological methods that are used in developing, validating and routinely controlling sterilization processes.

The Medical Device Coordination Group (MDCG), which is composed of representatives of Member States and chaired by the EU Commission, has issued four further guidance documents on clinical investigation and evaluation.

If medical device regulators, clinicians, and patients are going to reap the benefits of machine learning AI, it is critical that an appropriate level of trust in these systems be established by a collaborative regulatory system.

PMS requirements under the MDR must be met from 26 May 2021; however, some companies have questioned whether this also applies to the development of PMCF plans.

Even with the postponement of the date of application for the MDR to 26 May 2021, manufacturers still need to pay attention to devices for which there are no transitional provisions.

Postponement of the date of application of the MDR provides some respite to all those manufacturers, notified bodies and competent authorities trying to deal with the demands of the COVID-19 pandemic.

Standards for validation and routine control have a common format and use a common set of definitions.

Machine learning AI systems, unlike simple rules-based systems, are cognitive in some sense and can modify their outputs accordingly.

On 25 March 2020, three Commission Implementing Decisions on harmonized standards were issued to support the MDD, AIMDD and IVDD. This is a new format for updating the list of harmonized standards.

ISO 20417 sets out requirements for the identification, marking and labels on a medical device or accessory, and the information necessary to accompany the device or accessory.

Ballots on amendment to European adoption and new international edition of ISO 15223-1.

The MDR presents requirements for sterile devices but does not provide a definition of the term ‘sterile’. The EN 556 series of standards defines requirements for designating devices as sterile.

Work is in progress to include Annex Zs into new editions or amendments to the applicable sterilization and aseptic processing standards.

Arguably the biggest change in the IVDR is the introduction of a risk-based approach to classification in combination with increased Notified Body oversight.

The new system of risk classification of IVD medical devices is one of the few radical changes brought about by the new medical device regulations. It aligns the classification of IVD medical devices with other medical devices and international practice as advocated by the GHTF.

It’s widely accepted that healthcare has lagged behind other industries when it comes to cybersecurity, and that the industry needs to close the gap. Thankfully, healthcare managers can use standards to build resilience across diverse cybersecurity fronts simultaneously.

With significant data breaches hitting the headlines each year, healthcare cybersecurity is a major and expanding area for investment. Some experts predict the market will grow by almost 20% over the next five years, and it’s not difficult to see why.

The final draft of EN ISO 14971 circulated for ballot included drafts for five European Annexes Z. However, these Annexes Z were not included in the published text. This was because comments received from the independent review of the Annex Zs were taking time to resolve.

UK notified bodies are still able to issue, maintain and support CE marking certificates until the end of 2020. This post is an article published by Medtech Insight.

BSI’s Bill Enos (Americas Senior Commercial Director, Medical Devices) and John Bis (VP of Medical Device Solutions Sales) offer three key pieces of advice for medical device companies trying to compete in the new EU MDR environment.

Standards writers for medical devices, in particular anaesthetic and respiratory devices, are concerned about the EU Commission’s timelines for harmonized standards.

Widely viewed as the de facto risk management standard in medical devices, BS EN ISO 14971 has just been revised. This blog post looks at risk in respect of medical devices and asks what’s new.

Medical device manufacturers have several risk control options for eliminating or reducing risks to an acceptable level.

The risk management process described in the new ISO 14971 consists of several steps. The first of these steps is the risk management plan. All risk management activities must be planned. The plan provides a roadmap for the risk management activities to be conducted during the life cycle of the medical device.

Under the IVDR the manufacturer is responsible for identifying the risk class applicable to its IVD device.

The key issue in the second corrigendum is the introduction of a transitional period for class I devices that are classified higher under the MDR than they were under the MDD and therefore require the involvement of a notified body.

Read this blog post for insight into challenges that both manufacturers and notified bodies face with regards to the IVDR classification rules. The post will also give an overview of the immediate actions to be taken by manufacturers in response to these requirements.

New requirements always raise issues of interpretation and the IVDR classification requirements are no exception. Read this blog post for a discussion of several key interpretative issues from the risk classification rules of the Regulation.

The risk classification system of the IVDR is rule based, although it retains a residue of the old system of the Directive by resorting to a certain degree of listing. The Regulation establishes four risk classes D, C, B, and A, with D being the highest risk class and A the lowest.

A resolution to release ISO 80369-2 has been unanimously approved.

The new IVDR aligns the regulatory approach for IVD medical devices with that of the medical devices in general by establishing a set of risk-based classification rules. The new rules are largely based on original work done by the Global Harmonization Task Force.

In many cases, 3D printed devices are designed around the needs of a specific patient, and these are considered ‘custom-made’. The MDR, however, changes the definition of custom-made devices.

Article 15 of both the Medical Device Regulations and the In Vitro Medical Device (IVD) Regulations have requirements for appointing a ‘person responsible for regulatory compliance’ (PRRC). Manufacturers and Authorised Representatives (AR) for both medical devices and IVDs have to identify at least one PRRC.

Bioprinting techniques first emerged in 2003 with the first demonstrations of cell printing. Bioprinting offers a potentially attractive route to biological enhancement of medical devices.

ISO 20916 - In vitro diagnostic medical devices — Clinical performance studies using specimens from human subjects — Good study practice - was published in May 2019. It is the first edition of a standard on this subject.

This week's blog post is the second part in a two part series on the biomedical applications of 3D printing. The post briefly outlines the use of 3D printing in the manufacture of dental devices, hearing aids, orthotics and prosthetics.

3D printing has a number of major commercial application areas within the biomedical sphere, including surgical guides, musculoskeletal implants, hearing aids and orthotics. This week's blog post explores the use of 3D printing in the production of surgical guides.

Medical device risk management requirements have undergone significant change since the publication of the European Directives. Read this blog post for a recent history of medical device risk management.

AI and machine learning technologies are being adopted across a broad range of sectors, including the medical devices sector. A key attraction of machine learning is continual improvement: as more data becomes available to train a modern machine learning system, the performance of the system – in terms of accuracy – gets better.

The clause on production and post-production information has undergone considerable modification in the third edition of ISO 14971. The principles of collecting and reviewing information have not changed, but the requirements and the activities are described more elaborately and more precisely.

The draft Implementing Regulation containing the Common Specification – Single-use medical devices – safety and performance requirements for reprocessing – was made available for comment on 23 July 2019. This period ended on 20 August 2019. The draft indicates that the regulation enters into force 20 days after publication of the final text and that it applies from 26 May 2020.

Once all individual risks have been controlled and judged acceptable in the risk management process described in ISO 14971, it is important to also consider the contributions of all risks together. Read this blog post for a discussion of key changes to overall residual risk evaluation in the third edition of ISO 14971.

The European MDR and IVDR have specific roles for harmonized standards in demonstrating conformity. In order for a standard to be harmonized under the regulations, a standardization request has to be agreed between the European Commission and the European Standards organizations. The draft of this standardization request has now been published by the European Commission.

The second edition of ISO 14971 was published in 2007 and the third edition is expected in 2019. ISO 14971 provides a generic process for risk management of all kinds of medical devices. Due to its generic character, this standard needs to be applied in combination with other process standards and device-specific standards in order to ensure the safety of the medical device and to demonstrate compliance with all regulatory requirements.

If you are a non-European manufacturer with medical devices on the European market, you will have already an authorized representative (AR) in the European Union (EU). The moment you claim compliance with the new European regulation on medical devices (2017/745 - MDR), your existing AR may become instantly obsolete. It would then be illegal to place your devices on the EU market.

The third edition of medical devices risk management standard ISO 14971 will be published in 2019. There will be a transitional period of three years following publication to allow all stakeholders to adapt to the requirements in the new edition. The commitment of top management is indispensable for proper risk management. Large corporations can consist of separate entities (such as divisions or business units), where each entity can have its own risk management process and its own quality management system. In such cases, top management refers to those individuals who direct and control that entity.

ISO 14971:2007 - Medical devices - Application of risk management to medical devices - is a critical horizontal standard supporting the regulation of medical devices. It was decided in late 2016 that the international standard ISO 14971:2007 would be revised. The revision process has now completed all its comment and ballot stages.

This week’s Compliance Navigator blog post is the final video excerpt from a presentation delivered by BSI’s Peter Bowness at the 2019 Med-Tech Innovation Expo. The excerpt touches on Medical Device Coordination Group (MDCG) documents on MDR Article 54 and the registration of legacy devices in EUDAMED, amongst other things.

One new element in the IVDR is the implementation of Unique Device Identification (UDI) for the EU. The UDI rule implemented by the IVDR is substantially similar to the US rule, but there are several differences which will require manufacturers who already have a system in place to make some modifications to their rules.

See BSI’s Peter Bowness, Technical Team Manager from the Medicinal and Biologics Team, discuss the new EU regulatory regime for medical devices.

The International Medical Device Regulators Forum (IMDRF) is a voluntary group of worldwide medical device regulators working with the aim of accelerating international medical device regulatory harmonization. IMDRF was formed in 2011, replacing the Global Harmonization Task Force (GHTF), which had its first meeting in 1993, formed to foster the global harmonization of medical device regulation. During its years of operation, GHTF issued numerous guidance documents covering medical device premarket evaluation, post-market surveillance and vigilance, quality systems, auditing and clinical studies.

There are several drivers for the incorporation of AI into medical devices. In areas where the quantity or complexity of data is high assistance to a human interpreter can be provided by systems that can suggest diagnoses, or can retrieve cases which are in some sense, similar. This can support differential diagnosis, particularly for rare forms of some disorder; it is more than simply a retrieval system, as the criteria for matching is likely to be quite difficult to construct.

Virtually all active diagnostic devices that use software to interpret sensor data could be expected to benefit from incorporating AI into their controlling software. Devices that are deemed to be “good enough” might, of course, not need to be improved. But in principle, devices that can capture and make use of more information about a patient’s immediate physiological state, or emerging response to treatment, might be expected to yield better patient outcomes.

The answer to this question needs to consider the types of algorithm that are used in the AI system. Devices that make use of sensor data that is captured from patients might be expected to have input/output mappings that are very well defined. However, as the number of sensor measurements increases, or the history over which a signal is analysed (i.e. time-scale), there is arguably an increased possibility of unexpected device behaviour.

Performance evaluation, in accordance with Article 56 and Annex XIII, including the new post-market performance follow-up (PMPF) plan must be defined within the QMS. This is an area that will have variation based on the classification of the device and should be adapted accordingly.

Updates on the use of ISO 13485 in the US regulatory scheme, the systematic review of the standard and its harmonization in Europe under the regulations for medical devices and IVDs.

Clearly, a system whose behaviour is impossible to guarantee seems unsatisfactory from a safety or regulatory perspective. Why should we opt for an approach that uses machine learning (ML) — an important form of artificial intelligence (AI) — in which an artificial neural network learns its own rules for diagnosis or control, rather than one that is carefully engineered to specification?

In mid-March of this year, the European Commission issued a public consultation on phthalates in medical devices. If your company markets or intends to market in Europe a medical device containing phthalates, you may already be aware of this consultation; if not, you need to be aware of it.

ISO 35001, which is under development, focuses on management of biorisks, namely the management of risks that organizations confront when handling biological agents and toxins.

The EN 868 series of European standards on packaging for terminally-sterilized medical devices has been revised. One of the intentions of the revisions of these standards was to increase the link with EN ISO 11607-1. In particular removing duplication and overlap and aligning with EN ISO 11607 in regards to general principles; terms and definitions; and information on precision and bias, repeatability and reproducibility for test methods.

The credibility of medical laboratories is paramount to the health and safety of the patients relying on the testing services provided by these labs. ISO 22367 (in development) deals with the reduction of error in medical laboratories through risk management and continual improvement.

AAMI, the US FDA and BSI are hosting an international conference on medical devices standards and regulation. The conference is a unique opportunity to get the latest information on important regulatory developments. It links these developments to the international standards that are being prepared to support regulatory requirements.

In an attempt to reduce the risks of injury and disease transmission, the WHO launched in 2015 a new policy on injection safety, calling on the international community to switch to safety-engineered syringes, whenever appropriate, by 2020. Standards are continuing to play a key role in improving injection safety as this deadline approaches.

The portfolio of standards for validation and routine control of sterilization are key horizontal standards. It is important that the content of these standards are regularly reviewed and kept current. Within this portfolio, the series of standards on microbiological methods are at various stages of being updated.

The European Commission’s website provides background to the MDR and IVDR as well as guidance on the Directives for medical devices. The site has recently been restructured and further guidance and information added.

Whilst AI technologies offer substantial potential benefits to the healthcare sector, their governance and regulation have been identified as significant challenges. Studies have been initiated to consider how to address these, and BSI and AAMI have been exploring the role of standards to support the deployment of novel technologies across this highly regulated sector.

Block chain has been successful in attracting investment. But, can the success of this digital technology be reproduced in the healthcare sector? Excitement around new technologies like block chain may be excellent for stimulating investment. But, is excitement equally conducive to healthcare's primary aim: patient benefit?

New editions of the ISO 11607 series of standards on packaging for terminally-sterilized medical devices have been completed. The new editions of these standards include changes to incorporate the increased emphasis on the sterile barrier system for sterile medical devices that have been included in the European Medical Devices Regulation.

Digital maturity is needed in healthcare as the sector faces the challenge of balancing digital technology's potential for impact and profit against its various risks.

Health Canada provided an update on progress with the transition at the MDSAP Forum Stakeholder Day held on 5 December 2018.

Nanoparticles can be designed to produce a therapeutic effect without direct application of drugs. Most of these effects are brought about by having the particle designed to create locally, free radicals or energetic electrons to kill specific cell types. There is a further possible way to treat diseased tissue by destroying it with local heat produced by nanoparticles that are designed to get warm in radiofrequency fields or infra-red light.

Learn about persons responsible for regulatory compliance, economic operators and management responsibilities under the IVDR with this excerpt of the BSI medical devices white paper Developing and maintaining a quality management system for IVDs.