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

Transcription

1 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 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 2

3 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/ edical-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 reference=2012/0266 COD Council Consolidated draft for EPSCO 19 June pages with many alterations and additions Sept Council s full General Approach ocument/st rev-1/en/pdf ocument/st add- 1/en/pdf 3

4 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 Q Q1 EU Medical Device Regulation enter into force Expected 3 year transition for Medical Device Regulation 4

5 Manufacturers Route to CE Marking MDD/MDR 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 5

6 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 6

7 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 7

8 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 8

9 EU Classification Device or Drug Guidances: Device Drug MEDDEV 2.1/3 Rev 3 o Definitions o Classification examples o Consultation process overview o Documents required o NB actions o Adverse event reporting 9

10 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 10

11 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 11

12 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 12

13 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. 13

14 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 14

15 US Medical Device Regulatory System EU Medical Device Regulatory System (MDD or MDR) QSR - 21 CFR Part 820 Inspection by FDA ISO Assessment by Notified Body (depending on classification) PMA or 510(k) Reviewed by FDA FDA US Market Clearance Technical Documentation Sampled by Notified Body (depending on classification) Essential Requirements Risk Assessment Clinical Evaluation (taking account of equivalent devices) Manufacturers Declaration of Conformity 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 15

16 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) NB MED Technical Documentation Guidance MED-R2_5_1-5_rev4_Technical_Documentation.pdf NB/BSI The future: International Medical Device Regulatory Forum (IMDRF) - IMDRF/RPS WG/N9 FINAL:

17 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 17

18 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 18

19 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 19

20 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). 20

21 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. 21

22 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 22

23 EN :2015 Created to be more usable, easier to understand than original Original 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 Closer ties to risk management, EN ISO 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 23

24 Major activities (shalls*) in EN :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/

25 What s in the new EN :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 25

26 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 26

27 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

28 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 08/12/

29 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) 29

30 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 30

31 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 31

32 Name: Title: Paul Brooks Senior Vice President HealthCare Solutions Address: BSI Group Americas Inc, Worldgate Drive, 8 th Floor Monument II Herndon, VA USA. Phone: Paul.Brooks@bsigroup.com Links: 32

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