Emerging Device Topics for Regulatory Consideration .

Janine Jamieson May 2015

Disclaimer

• These are my personal views and not necessarily those of

MHRA as an organisation.

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European regulation of combination products • No legal definition as per FDA

• Medical Device Directives: – safety and performance – manufacturer responsible for affixing CE mark – involvement of notified bodies depending on risk classification – European wide market access

• Medicinal Products Directives – quality, safety and efficacy – authorisation required for each member state

• 28 member states; 60 + notified bodies

Medical device and medicinal product presentations – intended for use in combination

• Drug products presented as an integral combination with a medicinal product are regulated in its entirety as medicinal products.

• Drug products presented to include a drug-delivery device which is separate from the medicinal product (non-integral).

• Drug products recommended for use with specific CE marked devices • Drug products recommended for use with non-specified CE marked devices • CE marked devices for non-specific medicinal products • CE marked devices recommending use with non-specified medicinal products to

enhance targeting/ reduce systemic side-effects

• Medical devices incorporating a medicinal substance (for an ancillary role) – regulated as medical devices

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Background

Medical devices incorporating ancillary medicinal substances Medical Device Directive 93/42/EC as amended:

The quality, safety and usefulness of the substance must be verified by analogy with Annex I to Directive 2001/83/EC.

Drug-eluting stent Heparin coated catheter Wound dressings containing silver

- Class III high risk devices under rule 13 of MDD

- Notified Body must consult with Medicines CA or EMA

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Drug-delivery devices MPD

Medicinal products with medical device component Currently minimal requirements: Medicinal Products Directive 2001/83/EEC as amended , Annex I (3.2)

• 12. Where applicable and if needed, a CE marking which is required by Community legislation on medical devices shall be provided.

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Drug-delivery devices MDD

Currently more extensive requirements stated here: Article 1 (3) Medical Devices Directive 93/42/EEC as amended

• Where a device is intended to administer a medicinal product ……. that device shall be governed by this Directive………...

• If, however, such a device is placed on the market in such a way that the device and the medicinal product form a single integral product which is intended exclusively for use in the given combination and which is not reusable, that single product shall be governed by Directive 2001/83/EC.

• The relevant essential requirements of Annex I to this Directive [93/42/EEC] shall apply as far as safety and performance-related device features are concerned.

• Are these requirements being applied consistently?

Annex I of MDD

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Usability / Human factors

Introduced by Directive 2007/47/EC

Other ERs relevant to combination products e.g 12.9, 13.1

Proposed new Medical Device regulation

Article 91 Amendments to Directive 2001/83/EC

In Annex I of Directive 2001/83/EC, point 12 of Section 3.2. is replaced by the following: ‘(12) Where a product is governed by this Directive in accordance with the second subparagraph of Article 1(4) or the second subparagraph of Article 1(5) of Regulation (EU) […/…] on medical devices[1], the marketing authorisation dossier shall include, where available, the results of the assessment of the conformity of the device part with the relevant general safety and performance requirements of Annex I of that Regulation contained in the manufacturer’s EU declaration of conformity or the relevant certificate issued by a notified body allowing the manufacturer to affix a CE marking to the medical device. If the dossier does not include the results of the conformity assessment referred to in the first subparagraph and where for the conformity assessment of the device, if used separately, the involvement of a notified body is required in accordance with Regulation (EU) […/…], the authority shall require the applicant to provide an opinion on the conformity of the device part with the relevant general safety and performance requirements of Annex I of that Regulation issued by a notified body designated in accordance with that Regulation for the type of device in question, unless the authority is advised by its experts for medical devices that involvement of a notified body is not required.

- Conformity assessment by manufacturer or, where applicable a notified body - Results to be provided in dossier - What exactly should be provided?

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Usability/ Human Factors testing

• IEC 62366-1:2015 • Medical devices -- Part 1: Application of usability

engineering to medical devices • IEC 62366-1:2015 specifies a PROCESS for a MANUFACTURER to analyse, specify, develop and evaluate the

USABILITY of a MEDICAL DEVICE as it relates to SAFETY. This USABILITY ENGINEERING (HUMAN FACTORS ENGINEERING) PROCESS permits the MANUFACTURER to assess and mitigate RISKS associated with CORRECT USE and USE ERRORS, i.e., NORMAL USE. …….

• Part 1 has been updated to include contemporary concepts of usability engineering, while also streamlining the process. It strengthens links to ISO 14971:2007 and the related methods of risk management as applied to safety related aspects of medical device user interfaces.

• Part 2 contains tutorial information to assist manufactures in complying with Part 1, as well as offering more detailed descriptions of usability engineering methods that can be applied more generally to medical devices that go beyond safety-related aspects of medical device user interfaces.

• FDA Human Factors guidance for medical devices • Draft guidance for combination products soon….

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Current activity • MHRA Human Factors stakeholders meeting Feb 2015

– Devices and drug-device combination products – Ongoing activity to contribute in best way to other work in this area

• Discussions with other EU regulators – Raising in different forums with notified bodies, medicines CAs, EMA – TOPRA Drug-device combination product joint Pharma / MedTech session

October 2015

• EMA Pharmacovigilance Risk Assessment Committee (PRAC) • Draft for comment until June 14

– Good practice guide on risk minimisation and prevention of medication errors

• Medical Devices revision – to be agreed by European Parliament

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General comments from industry and EU regulators

• Need for clarity on the CE mark requirements for device component • What does the CE assessment actually cover? • Clarity of role of manufacturers, notified bodies, competent authorities? • Requirements for GMP / ISO 13485 • Scope of the usability studies and HF testing requirements • Where should device data be presented? Relevant sections and 3.2.R ? • Bridging of clinical trial device to marketed product • Device – Product Life Cycle management / variation applications? • User instructions - self standing document or provided as part of the user

instruction of the medicinal product? • Information to be provided in SPC regarding separately CE marked devices?

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General comments from industry and EU regulators ctd

• Good to have common approach to assessment of medical device components

• Caution over regulatory burden – duplication of work • EU guidance would be useful

– form of Q&A, reflection paper or a guideline? • The combination of IVD, Software and Medicinal Products will grow, a

strategy is need for such SYSTEMS

• Improved understanding, clarification of roles and

collaboration between medicines CAs, devices CAs and notified bodies beneficial

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Thank you

Dr Janine Jamieson Pharmaceutical Assessor PLAT 1, Notified Body Consultations, Drug-Device Borderline and Combination Products Medicines and Healthcare Products Regulatory Agency 151, Buckingham Palace Road London SW1W 9SZ

• Email: Janine.Jamieson@mhra.gsi.gov.uk • Linked In • Tel: +44 (0)203 080 7067 • Usual working hours Mon, Tue, Thur, Fri 8.00 am – 2. 30 pm

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What does the CE mark mean?

Class I medical device Class IIb medical device

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