Building Quality into Medical Device Documentation and ... · PDF fileenergy source) medical device in Class IIa or a higher class, in all other cases they are in Class I

Copyright © 2014 BSI. All rights reserved.

Building Quality into Medical Device Documentation and Impact of New Device Regulation (Context: Inhaled Drug Devices) v4

Paul Brooks SVP Healthcare Solutions Representing BSI Notified Body

2 Copyright © 2014 BSI. All rights reserved.

EU Medical Device Regulation Update • Medical devices are currently regulated under Medical Device Directive

93/42/EEC (MDD) • European legislation on medical devices is over 20 years old • The number of Member States in the EU has more than doubled • Substantial advances in device technology • Time to review the current Regulatory Framework and the next 20 years

• On 26 September 2012, the European Commission published proposals for two new regulations on medical devices and in vitro diagnostic devices (IVDs), which will replace the existing three directive


Sources for EU Medical Device Regulation Update

Commission

• Proposal for a Regulation of the European parliament and of the Council on medical devices, and amending Directive 2001/83/EC, Regulation (EC) No 178/2002 and Regulation (EC) No 1223/2009

• http://ec.europa.eu/growth/sectors/medical-devices

Parliament

• 2012/0266(COD) - 02/04/2014 Text adopted by Parliament, 1st reading/single reading

• EP adopted by 547 votes to 19, 63 abstentions

• http://www.europarl.europa.eu reference=2012/0266 COD

Council

• Consolidated draft for EPSCO 19 June 2015 - 400 pages with many alterations and additions

• Sept 2015 - Council’s full ‘General Approach’

• http://data.consilium.europa.eu/doc/document/ST-12040-2015-REV-1/en/pdf

• http://data.consilium.europa.eu/doc/document/ST-12040-2015-ADD-1/en/pdf

http://ec.europa.eu/growth/sectors/medical-devices




http://www.europarl.europa.eu/

http://data.consilium.europa.eu/doc/document/ST-12040-2015-REV-1/en/pdf











http://data.consilium.europa.eu/doc/document/ST-12040-2015-ADD-1/en/pdf












Medical Device Regulation Timeline – Realistic Expectations:

2016 Q1/Q2

• Trialogue concludes • Agreement on Medical Device Regulation

2016 Q3/Q4

• EC Administration • Translation into all EU languages

2016 Q4 2017 Q1

• EU Medical Device Regulation enter into force • Expected 3 year transition for Medical Device Regulation


Check Definition of Medical Device

Determine “Device Class” Select “Conformity Assessment Procedure” Identify Applicable “Essential Requirements”

Assemble “Technical Documentation” Apply Conformity Assessment Procedure with Notified Body as

appropriate Complete “Declaration of Conformity”

Affix “CE Marking”

Manufacturers Route to CE Marking MDD/MDR


EU MDD Definitions Medical device: Defined in Article 1, Directive 93/42/EEC as amended in 2007/47/EC Any instrument, apparatus, appliance, software, material or other article……….. for the purpose of: • diagnosis, prevention, monitoring, treatment or alleviation of disease, • diagnosis, monitoring, treatment, alleviation of or compensation for an injury or

handicap, • investigation, replacement or modification of the anatomy or of a physiological process, • control of conception,

and which does not achieve its principal intended action in or on the human body by pharmacological, Immunological or metabolic means, but which may be assisted in its function by such means; → Primary intended purpose achieved by physical or simple chemical means


EU Definitions

Medicinal substance: Defined in Article 1 Directive 2001/83/EC as amended by Directive 2004/27/EC as Any substance or combination of substances presented as having properties for treating or

preventing disease in human beings; Or Any substance or combination of substances which may be used in or administered to

human beings either with a view to restoring, correcting or modifying physiological functions by exerting a pharmacological, immunological or metabolic action, or to making a medical diagnosis


EU Regulatory Options for Medical Devices which combine with a Medicinal Substance

Under the terms of the MDD, products which combine a medicinal substance with a medical device are regulated in one of the following ways: • Drug-delivery products presented separately from the medicinal product are regulated

as medical devices e.g. drug delivery pump, nebulizer • Drug-delivery products presented as an integral combination with a medicinal product

are regulated as medicinal products e.g. pre-filled syringe, pre-filled inhalation device • Medical devices incorporating, as an integral part, an ancillary medicinal substance are

regulated as medical devices e.g. catheters coated with heparin or an antibiotic, drug eluting stents


EU Classification Device or Drug Guidances:

• Device Drug MEDDEV 2.1/3 Rev 3 oDefinitions o Classification examples o Consultation process overview oDocuments required o NB actions o Adverse event reporting

http://ec.europa.eu/growth/sectors/medical-devices/guidance/index_en.htm









MEDDEV 2.1/3 Rev 3 Section B2 Drug-delivery Products Regulated as Medicinal Products

• This category involves a device that is intended to administer a medicinal product in the

case where 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. According to the Medical Device Directive, this single product is governed by the Medicinal Products Directive, but, the relevant essential requirements of Annex I to the Medical Device Directive shall apply as far as the safety and performance-related device features are concerned.

• Inhalation examples: • Aerosols containing a medicinal product • Nebulizers pre-charged with a specific medicinal product

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MEDDEV 2.1/3 Rev 3 Section B3 Drug-delivery Products Regulated as Medical Devices

• This category concerns a device that is intended to administer a medicinal product within

the meaning of the MPD. In this case, that device is governed by the Medical Devices Directive (or AIMD) without prejudice to the provisions of Directive 2001/83/EC with regard to the medicinal product.

• Inhalation examples include: • Nebulizer • Spacer devices for use with metered dose inhalers

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Current EU MDD Classification Rules – Inhalation Devices

• Rule 2 - All non-invasive devices intended for channeling or storing blood, body liquids or tissues, liquids or gases for the purpose of eventual infusion, administration or introduction into the body are in Class IIa: - if they may be connected to an active (with energy source) medical device in Class IIa or a higher class, in all other cases they are in Class I

• Rule 11 – Active (with energy source) devices intended to administer and/or remove medicines, body liquids or other substances to or from the body • All active devices intended to administer and/or remove medicines, body liquids or other substances

to or from the body are in Class IIa – e.g. Nebulizers to be used on conscious and spontaneously breathing patients where failure to deliver the appropriate dosage characteristics is not potentially hazardous

• unless this is done in a manner: - that is potentially hazardous, taking account of the nature of the substances involved, of the part of the body concerned and of the mode of application, in which case they are in Class IIb – e.g. Nebulizers where the failure to deliver the appropriate dosage characteristics could be hazardous

03/05/2016


Proposed EU MDR Classification Rules – Drug Inhalation Devices

• Rule 2 – Unchanged for drug inhalation devices • Rule 11 – Unchanged for drug inhalation devices • New proposed Rule 22 - All invasive devices with respect to body orifices, other than

surgically invasive devices, which are intended to administer medicinal products by inhalation are in class IIa, unless their mode of action has an essential impact on the efficacy and safety of the administered medicinal product and those that are intended to treat life threatening conditions, in which case they are in class IIb.

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Routes to CE Marking

• Class I (non-sterile / non-measuring) – Manufacturer Declaration of Conformity – No Notified Body involvement

• Class IIa – Typically QMS conformity assessment by Notified Body including sampling of technical documentation and Manufacturer Declaration of Conformity

• Class IIb – Typically QMS conformity assessment by Notified Body including sampling of technical documentation and Manufacturer Declaration of Conformity

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US Medical Device Regulatory System

EU Medical Device Regulatory System (MDD or MDR)

QSR - 21 CFR Part 820 Inspection by FDA

ISO 13485 Assessment by Notified Body (depending on classification)

PMA or 510(k) Reviewed by FDA

Technical Documentation Sampled by Notified Body (depending on classification) •Essential Requirements •Risk Assessment •Clinical Evaluation (taking account of equivalent devices)

Manufacturers Declaration of Conformity

FDA US Market Clearance CE Marking

MDR Manufacturers Post Market Surveillance (complaints and vigilance)

FDA Inspections (24 months)

Notified Body QMS Audits (Annually)

Notified Body QMS / Device Recertification Every Five Years


CE Marking MDD Technical Documentation

• Medical Device Directive is not prescriptive on technical documentation format • Recommended formats:

• Global Harmonization Task Force (GHTF) Summary Technical Documentation (STED) • http://www.imdrf.org/docs/ghtf/final/sg1/technical-docs/ghtf-sg1-n011-2008-principles-safety-

performance-medical-devices-080221.pdf • NB MED Technical Documentation Guidance

• http://www.team-nb.org//wp-content/uploads/2015/05/nbmeddocuments/Recommendation-NB-MED-R2_5_1-5_rev4_Technical_Documentation.pdf

• NB/BSI • The future: International Medical Device Regulatory Forum (IMDRF) - IMDRF/RPS WG/N9

FINAL:2014 • http://www.imdrf.org/docs/imdrf/final/technical/imdrf-tech-140630-rps-nivd-toc.pdf

03/05/2016

http://www.imdrf.org/docs/ghtf/final/sg1/technical-docs/ghtf-sg1-n011-2008-principles-safety-performance-medical-devices-080221.pdf

http://www.imdrf.org/docs/ghtf/final/sg1/technical-docs/ghtf-sg1-n011-2008-principles-safety-performance-medical-devices-080221.pdf

http://www.team-nb.org/wp-content/uploads/2015/05/nbmeddocuments/Recommendation-NB-MED-R2_5_1-5_rev4_Technical_Documentation.pdf

http://www.team-nb.org/wp-content/uploads/2015/05/nbmeddocuments/Recommendation-NB-MED-R2_5_1-5_rev4_Technical_Documentation.pdf

http://www.imdrf.org/docs/imdrf/final/technical/imdrf-tech-140630-rps-nivd-toc.pdf


CE Marking MDR Technical Documentation

• Technical Documentation – MDR Annex II – More prescriptive than MDD • The technical documentation and, if applicable, the (STED) to be drawn up by the

manufacturer shall include: 1. DEVICE DESCRIPTION, SPECIFICATION, VARIANTS & ACCESSORIES

• Device description and specification • Reference to previous / similar generations of the device

2. INFORMATION SUPPLIED BY THE MANUFACTURER 3. DESIGN AND MANUFACTURING INFORMATION 4. GENERAL SAFETY AND PERFORMANCE REQUIREMENTS 5. RISK/BENEFIT ANALYSIS AND RISK MANAGEMENT 6. PRODUCT VERIFICATION AND VALIDATION

• Pre-clinical and clinical data • Additional information in specific cases


MDD Annex I Essential Requirements MDR Annex I General Safety & Performance Requirements

• All medical devices must address Annex I • Identify and address applicable requirements – justify when not applicable (typically

checklist and identification of appropriate standards) Annex I - General Requirements:

Safe, Perform as Intended, State of the Art, Risk Reduction, Risk Management, Risk Control, Lifetime, Packaging, Benefits, Usability, Known and Foreseeable Risks & Undesirable Side Effects

Annex I - Other Requirements Including: Chemical, Physical & Biological Properties, Infection & Microbial Contamination, Devices incorporating medicinal substances or materials of biological origin, Construction and environmental properties, Devices with a diagnostic or measuring function, Protection against radiation, Active devices and devices connected to them, Protection against mechanical and thermal risks, Protection against the risks posed to the patient or user by supplied energy or substances, Devices intended by the manufacturer for use by lay persons

Annex I - Information Supplied by the Manufacturer

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EU MDD Usability / Human Factors

EU MDD 93/42/EEC • ER1: reducing risk of use error • This shall include:

• reducing, as far as possible, the risk of use error due to the ergonomic features of the device and the environment in which the device is intended to be used (design for patient safety), and

• consideration of the technical knowledge, experience, education and training and where applicable the medical and physical conditions of intended users (design for lay, professional, disabled or other users).

• ER13: Instructions for use

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EU MDR Usability / Human Factors

Proposed EU MDR • In eliminating or reducing risks related to use error the manufacturer shall apply the following

principles: • reducing as far as possible the risks related to the ergonomic features of the device and the

environment in which the device is intended to be used (design for patient safety), and • consideration of the technical knowledge, experience, education, training and use environment,

where applicable, and the medical and physical conditions of intended users (design for lay, professional, disabled or other users).

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MDR - Devices intended for use by Lay Persons

• Devices for use by lay persons shall be designed and manufactured in such a way as to • ensure that the device is easy to use can be used safely and accurately by the intended user

at all stages of the procedure if necessary after appropriate training and/ or information, and

• reduce as far as possible the risk of error by the intended user in the handling of the device and, if applicable, in the interpretation of the results.

• Devices for use by lay persons shall, where reasonably possible appropriate, include a

procedure by which the lay person • can verify that, at the time of use, the device will perform as intended by the manufacturer, and • if applicable, is warned if the device has failed to provide a valid result.

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MDR - Devices intended for use by Lay Persons

• Devices for use by lay persons shall be designed and manufactured in such a way that they perform appropriately for their intended purpose taking into account the skills and the means available to lay persons and the influence resulting from variation that can reasonably be anticipated in the lay person’s technique and environment. The information and instructions provided by the manufacturer shall be easy for the lay person to understand and apply

03/05/2016


EN 62366-1:2015

• Created to be more “usable”, easier to understand than original 62366 • Original 62366 took to much of an expert to understand • Implements practices by developers • Attempts to harmonizes methods to meet FDA and international regulators • Contains the “what” requirements, the “how” is in 62366-2 • Closer ties to risk management, EN ISO 14971 • Hazard related use scenarios • No reference to usability goals, however goals may still have a need • Errors and/or shortcomings in the design to be addressed through risk • Evaluation • Reduced emphasis on functional analysis • Closer to FDA guidance • Legacy still addressed in annex* *Annexes are very helpful in implementation

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Major activities (shalls*) in EN 62366-1:2015 • Usability Engineering activities shall be planned • To reduce risk do: safe design, protective measures, and/or information on safety

• Establish a usability engineering process • Document usability activities to a usability file • Use specification • ID user interface** characteristics • ID hazards & situations (foreseeable, the unforeseeable is gone) • ID hazard use scenarios for summative evaluation • User interface spec • Prepare user interface evaluation plan (summative & formative)

• Perform the design & summative evaluations • Reduce risks * Most of the requirements **what the user looks at, uses

08/12/2015


What’s in the new EN 62366-2:2016?

This is he “how” document or “tutorial” • How safety relates to usability • Reasons to invest in usability • How to implement a usability program • Overall usability process • Prepare the use specification • Identify characteristics related to safety and potential use errors • Identify hazards • Identify hazard-related use scenarios • Select hazard-related use scenarios for summative evaluation • Establish user interface specification • Establish user interface evaluation plan • Design/implement user interface • Perform formative evaluations • Perform summative evaluations *note: the above is paraphrased by the author and the final version is not yet released

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Usability / Human Factors – Inhalation Drug Devices

• Explicitly consider intended users , address “lay persons”, and use environment to include a range from “home, clinic, mobile use, etc.”

• IFUs need understand-ability • Technical documentation should address risk assessment, mitigations, requirements,

validations, user information

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Current MDD NB Usability Expectations

• ER 1 and 13.1 addressed usability considerations • Follow a process, ideally the harmonised standard or rationale to meet ERs • Asking a couple of clinicians if they like the product is not enough……be careful of KOLs • Specification for the intended user and environment • Including usability in Risk Management • How verified that the device meets the usability requirements • Usability risks have been reduced as far as possible

Expectations are rising in Europe. For example: MHRA has task force on HF that is starting to look deeper into this topic and how it can be improved to reduce use errors – document for public comment expected June 2016.

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Conclusion

• Usability has become a vital part of the medical device development process • Usability activities should be conducted throughout all phases of the development

process, include it, not a separate process • Usability should be part of the overall risk management process

• BSI White Paper - The growing role of human factors and usability engineering for

medical devices http://www.bsigroup.com/en-US/medical-devices/Resources/Whitepapers-and-articles/

08/12/2015

http://www.bsigroup.com/en-US/medical-devices/Resources/Whitepapers-and-articles/












Changes to Own Brand Label / Private Label

• New clarity on requirements on own brand label / private label devices • Previously OBL’s were allowed to piggy back on CE Marking of OEM • New clarification: • Manufacturer identified on device label must • Take full responsibility for CE Marking the device • Hold the technical documentation • Demonstrate competence to be the manufacturer and control the supplier (OEM) • Subject of direct conformity assessment by Notified Body (appropriate to device

class)

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EU MDR Considerations

• No grandfathering of CE Marking under MDD to MDR • Conformity assessment required under MDR - CE Marking certificates under MDR

• Expanded scope – economic operators, clinical, post market • Essential Requirements replaced by Safety and Performance Requirements • Including new labeling requirements

• Unique Device Identification (UDI) requirements • EUDAMED database – Single Registration Number (SRN) • Person responsible for regulatory compliance • More prescriptive requirements for QMS, RM, PMS • More prescriptive clinical data, evaluation, PMCF expectations

03/05/2016


EU MDR Considerations

Manufacturers update technical documentation, systems and processes • General Safety and Performance Requirements • Including labelling requirements e.g. SRN, UDI etc. • Technical Documentation and Technical Documentation on PMS

Notified Bodies conduct conformity assessment & assessment of technical documentation • Assessing legacy devices – gaps to be addressed – new requirements and PMS • CE Certificates issued against MDR

Aligning expectations with new realities • Pre-market scrutiny / clinical expectations • Resources to achieve and maintain compliance


Name: Paul Brooks

Title: Senior Vice President HealthCare Solutions

Address: BSI Group Americas Inc, 12950 Worldgate Drive, 8th Floor Monument II Herndon, VA 20170. USA.

Phone: +1 703 464 1923 Email: [email protected] Links: www.bsigroup.com

mailto:[email protected]

http://www.bsigroup.com/