the technicalities of a quality management system under ... · pdf fileand a post-market...

The Technicalities of a Quality Management System

under MDR / IVDRDecember 5, 2017

Jonathan Bretz, OT/L, MBA, RACRSQM Associates, LLC

Introduction

Jonathan Bretz, OT/L, MBA, PresidentRSQM Associates, LLC

• Over 40 years experience in the medical device field - private and provider sectors. Has held various senior executive positions – in marketing/sales, operations, and then coordinating, managing and staffing a regulatory and quality departments.

• Responsible for regulatory submission to the FDA, EU and Health Canada and managing Quality systems.

• Guided over 40 companies to implement UDI programs, update and create quality systems, regulatory submissions (FDA and EU), project management, software/equipment validation and quality system, UDI program and HIPAA assessment/auditing.

“To ensure that devices manufactured in series production continue to be in conformity with the requirements of this Regulation and that experience from the use of the devices they manufacture is taken into account for the production process, all manufacturers should have a quality management system and a post-market surveillance system in place which should be proportionate to the risk class and the type of the device in question. In addition, in order to minimize risks or prevent incidents related to devices, manufacturers should establish a system for risk management and a system for reporting of incidents and field safety corrective actions.” (32[31])

MDR[IVDR] Introduction…

Technicalities of a QualityManagement System

Quality Management

System

1. Transition Timeline

2. Major Quality Management

System Requirements

3. Bringing it all Together

4. MDR / IVDR Quality System Requirements

5. General Obligations of Manufacturers

• Overview• Recommended Procedures

Major Quality Management System Requirements…

Overview of the changes…

Classification… (Article 51 [47])

• Check to see if your devices have been re-classified• Update classification processes to reflect changes• Revise Technical File process to include new

classification rules and classification justification• Change in classification may impact your quality

system procedures

Responsible Person [Article 15]

• At least one responsible person with requisite expertise in medical devices [in vitro diagnostic medical devices] and shall have… (34[33] / Article 15 [Article 15])

- a diploma, certificate or other evidence of formal qualification, awarded on completion of a university degree or of a course of study…, and at least one year of professional experience in regulatory affairs or in quality management systems relating to medical devices [in vitro diagnostic medical devices]; OR

- four years of professional experience in regulatory affairs or in quality management systems relating to medical devices [in vitro diagnostic medical devices].

Organizations Must…• Responsibilities and authority defined in job description• Not disadvantage person within the organization in relation to proper fulfillment of

responsibilities, whether employee or not• Register persons name and address and contact

information in Eudamed database

Post-Market Surveillance System…• Establish a comprehensive post-market surveillance system… (74[75])

- Implement process in accordance with Chapter VII and Annex III- Set up PMS and PMCF plan and reporting system; updates and summaries are

mandatory- Update CER with PMS data (bi) annually- Periodic Safety Update Reports (86[81])

- Summary of Safety & Clinical Performance[Summary of Safety & Performance]

- Communication with Competent Authorities, NB, other economic operators, users

Post-Market Reports…MDR IVDR PSUR SSCP [SSP]

Class I Class A, BStrictly N/A, however Article

85 [80] – Class I [A/B]PMS Report updated

“when necessary”

-

Class Im, Ir, Is - -

Class IIa - As necessary and at least every 2 years -

Class IIb Class C, D Annual -

Class IIb Implantables - Annual to NB(Eudamed)

Annual to NB(Eudamed)

Class III - Annual to NB(Eudamed)

Annual to NB(Eudamed)

Im = Class I measurable; Ir = Class I reusable instruments; Is = Class I sterile

Manufacturers Shall…• … establish, document, implement and maintain a

system for risk management… (Article 10, Paragraph 2)

• … establish, document, implement, maintain, keep up-to-date and continually improve a quality management system… (Article 10, Paragraph 9[8])

Notified Bodies Involved with Following Manufacturers…

Class I measuring

Class I sterile

Class I reusable instruments

Class IIa/IIb, III, implantables

Supply Chain Control• Contracts with economic operators• Critical suppliers must be part of technical

documentation and QMS• Complaint reporting timelines, vigilance and FSCA

require your economic operators promptly provide information• Private label companies must have complete technical files;

update OEM / PL agreements• Manufacturer is responsible for organizing and training supply chain stakeholders

General Safety & Performance Requirements• Process to ensure sufficient effectiveness & performance data is available• Risk management process to be continuous procedure throughout entire life

cycle of product• ISO 14791:2012 risk benefit ratio needs to be incorporated into procedures

Clinical Evaluation (MDR Annex XIV)• Procedures to accommodate new requirements• CER needs to take the entire life cycle of device into consideration• PMCF process including plan and report• Clinical study requirements are much more strict – studies must be performed in line with

legal requirements

Traceability & Registration• UDI is mandatory under MDR / IVDR

• EUDAMED registration is mandatory under MDR / IVDR

Liability Insurance• Mandatory for manufacturers• Agreements with Authorized Representatives need

to include their liability for defective products

Authorized Representatives• Shall ensure AR’s have…

- necessary documentation permanently available- 1 responsible person for regulatory requirements

“Shall” appears….1,697 times in the MDR1,517 times in the IVDR

Compared to….1033 times Subchapter H Medical Devices(including UDI 830 – 27 & PMS 809 – 44)

Bringing it all together….

Understanding the details…

The Manufacturer Shall…• Establish, document and implement a quality management system, as

described in Article 10(9)[10(8)], and maintain its effectiveness throughout the life cycle of the devices concerned

• Ensure the application of the quality management system as specified in Section 2, and shall be subject to audit as laid down in Sections 2.3 and 2.4 and to surveillance as specified in Section 3

Quality Management System – Annex IX, Chapter 1

The Manufacturer Shall…• Submit “an application for assessment of its quality system with a notified

body” (does not apply to standard Class I devices)

• The application shall include documentation of:- Manufacturer’s QMS - Procedures to ensure QMS will remain adequate and effective- Manufacturer’s post-market surveillance system*- Clinical evaluation plan*- Documented description of the current procedures that meet the obligations

of both the QMS and MDR / IVDR regulations

*Including descriptions of procedures that will keep these up to dateQuality Management System – Annex IX, Chapter 1

Quality Management System Implementation :• Shall ensure compliance with this Regulation• Shall be documented in a systematic and orderly manner in the form of a

quality manual and written policies and procedures• Should include these elements:

a) quality objectivesb) organization of the businessc) procedures and techniques for monitoring, verifying, validating

and controlling the design of the devicesd) verification and quality assurance techniques at the

manufacturing stagee) appropriate tests and trials


Audits by Notified Bodies

• Audits will be used by NBs to determine if QMS meets the requirements…- NB will assess conformity with harmonized standard

or CS related a QMS- Conducted on premises of manufacturer, suppliers,

subcontractors


Planned Changes to QMS• Manufacturers must inform NB if there are substantial planned changes to

QMS, or device-range covered…- NB will assess changes to determine conformity


Surveillance Applicable to…• Class IIa, IIb, III devices• Must provide access to documentation• NB will periodically (at least once every 12 months)

conduct audits and assessments


Quality Management requirements also included in:MDR / IVDRAnnex IX – Conformity Assessment Based on a Quality Management System and on Assessment of Technical Documentation

Chapter I - Quality Management SystemMDRAnnex XI – Conformity Assessment Based on Product Conformity Verification

Part A. 6. - Quality Management System

IVDRAnnex XI – Conformity Assessment Based on Production Quality Assurance

Part 3. - Quality Management System

MDR / IVDR Quality System Requirements

QMS Procedures and Economic Operators*

*Quality Management Systems requirements of the MDR and IVDR, Eamonn Hoxey & Michael Murphy, ABHI Regulatory Conference, 5-October-2017

Manufacturer (Article 10)

Authorized Rep (Article 11&12)

Importer (Article 13)

Distributor(Article 14)

Assembler (Article 22)

Eudamed Registration

Technical Documentation

Handling, storage, and distribution

Nonconformities

Field safety correction action

UDI/Labeling

Complaints

Post-Market Surveillance (PSUR, SSCP)

Persons responsible for regulatory compliance

Design and development, manufacture or assembly

Quality Management System (Annex IX)Class I Class Im*, Ir*, Is*, IIa, IIb,

III, Implantables Class A Class B, C, D

ISO 13485:2016 Certificate Optional; Must have a Quality System in place that meets requirements of MDR / IVDR based on device risk (classification)

*Im = Class I measurable; Ir = Class I reusable instruments; Is = Class I sterile

Declaration of Conformity (Article 56 [Article 17])Class I Class Im*, Ir*, Is*, IIa, IIb,


Notified Body not required. Manufacturer self-declares conformity with MDR including QMS

Notified Body required to assess conformity with MDR *Microbiology & Sterilization Procedures

Notified Body not required. Manufacturer self-declares conformity with IVDR including QMS (other than devices for Performance Study)

Notified Body required to assess conformity with IVDR


Quality System Audits (Annex IX, Clause 2.3)Class I Class Im*, Ir*, Is*, IIa, IIb,


N/A

Audits performed by Notified Body *Surveillance audits

N/A

Audits performed by Notified Body


Clinical Evidence (Article 61 [Article 56])


Class I Class Im*, Ir*, Is*, IIa, IIb, III, Implantables

Class A Class B, C, D

Clinical Evaluation Report Process and Procedures – Class I, IIa

Clinical Evaluation Consultation Procedure (Class III Implants), Clinical Investigational Studies and Report Process and Procedures – Class IIb, III

Performance Evaluation Report • Update throughout life of

device

Performance Evaluation Report • Update at least

annually

Post-Market Surveillance (Article 86 [Article 78])Class I Class Im*, Ir*, Is*, IIa, IIb,


SOP’s and Infrastructure Procedures • PMS Trend Report • Periodic Safety Update

Report (PSUR) – “when necessary” – need to tell when will be done

SOP’s and Infrastructure Procedures • PMS Trend Report • Periodic Safety Update

Report (PSUR) – Class Ir, Is, Im, IIa, IIb, III (Class Ir, Is, Im – update as necessary) (Class IIa – as necessary; at least every 2 years) (Class IIb – Annual) (Class II Implant, Class III – Annually submits via EUDAMED to NB)

• Summary of Safety & Clinical Performance (SSCP) – Class III, Implantables

SOP’s and Infrastructure Procedures • Post-market Surveillance

Report (PSUR) – (Class A, B - update when necessary)

• Make available to NB and CA when requested

• Post-market Performance Follow-up (PMPF)

SOP’s and Infrastructure Procedures • Periodic Safety Update

Reports (PSUR) – (Class C, D – at least annually) (Class D - Annually submits via EUDAMED to NB) (Class C – make available to NB and CA when requested)

• Post-market Performance Follow-up (PMPF)

Registration (Article 29/30/31 [Article 26/27/28])Class I Class Im*, Ir*, Is*, IIa, IIb,


Procedures for registering devices, economic operators and manufacturers


Unique Device Identification (Article 27 [Art8cle 24])Class I Class Im*, Ir*, Is*, IIa, IIb,


Procedures for managing UDI process – registration, assigning Basic UDI-DI, assigning Device Identifiers, collecting and submitting device data to EUDAMED, change control process for managing device data changes/updating EUDAMED


Implant Card (Article 18)Class I Class Im*, Ir*, Is*, IIa, IIb,


N/A SOP(s) to manage process for all Implantables N/A N/A


Translation of labeling content (Annex I)Class I Class Im*, Ir*, Is*, IIa, IIb,


Procedures for complying with requirement to ensure device is accompanied by the information set out in Section 23 of Annex I in an official Union language(s) determined by the Member State in which the device is made available to the user or patient.

Procedures for complying with requirement to ensure device is accompanied by the information set out in Section 20 of Annex I in an official Union language(s) determined by the Member State in which the device is made available to the user or patient.


Technical Documentation (Annex I & II) Procedures for creating and maintaining Technical Files, including documentation for these Safety and Performance Requirements (SPR Number):



• Risk Analysis - Comparison to EN ISO 14791:2012 (2, 3, 4, 5, 8)

• Substances that are carcinogenic, mutagenic toxic to reproduction, or endocrine disrupting (10.4)

• Nanomaterials (10.6) • Infection and microbial contamination (11) • Substances that are absorbed and locally dispersed (12.2) • Tissues, cells, or derivatives of human origin (13.1) • Using non-viable biological substances (13.3)

• Risk Analysis - Comparison to EN ISO 14791:2012 (2, 3, 4, 5, 8)

• Performance characteristics shall be maintained during the lifetime of the device as indicated by the manufacturer (9.2)

• Metrological traceability of values assigned to calibrators and/or control materials (9.3)

• Substances that are carcinogenic, mutagenic toxic to reproduction, or endocrine disrupting (10.3)


Technical Documentation (Annex I & II) (con’t)



• Adjustment, calibration and maintenance: safety and effectiveness (14.4)

• Interoperability and compatibility reliable and safe (14.5) • Safe deposal after use (14.7) • Information security (17.2) • Specific features of mobile platforms (17.3) • Protection against unauthorized access (17.4) • Errors likely to be made when refitting (20.5) • Devices intended for use by lay persons (22) • New requirements for labels and instructions for use (23)

• Infection and microbial contamination (11) • Tissues, cells, or derivatives of human origin (12) • Safe deposal after use (13.6) • Information security (16.2) • Specific features of mobile platforms (16.3) • Protection against unauthorized access (16.4) • Errors likely to be made when refitting (18.7) • Devices intended for self-testing or near-patient testing

(19) • New requirements for labels and instructions for use (20)

*Im = Class I measurable; Ir = Class I reusable; Is = Class I sterile

General obligations of manufacturers (Article 10)

Manufacturers shall ensure that procedures:• are in place to keep series production in conformity with the requirements of this

Regulation• changes in device design or characteristics and changes in the harmonized

standards or CS by reference … shall be adequately taken into account in a timely manner

• Manufacturers of devices, other than investigational devices [other than devices for performance study], shall establish, document, implement, maintain, keep up to date and continually improve a quality management system that shall ensure compliance with this Regulation in the most effective manner and in a manner that is proportionate to the risk class and the type of device. Paragraph 9[8]

General obligations of manufacturers (Article 10)

The quality management system shall:• cover all parts and elements of a manufacturer's organization dealing with the quality

of processes, procedures and devices. • govern the structure, responsibilities, procedures, processes and

management resources required to implement the principles and actions necessary to achieve compliance with the provisions of this Regulation. (Article 10, Paragraph 9[8])

QMS Procedures and Economic Operators*

*Quality Management Systems requirements of the MDR and IVDR, Eamonn Hoxey & Michael Murphy, ABHI Regulatory Conference, 5-October-2017

Manufacturer (Article 10)

Authorized Rep (Article 11&12)

Importer (Article 13)

Distributor(Article 14)

Assembler (Article 22)

Eudamed Registration

Technical Documentation

Handling, storage, and distribution

Nonconformities

Field safety correction action

UDI/Labeling

Complaints

Post-Market Surveillance (PSUR, SSCP)

Persons responsible for regulatory compliance

Design and development, manufacture or assembly

General obligations of Manufacturers (Article 10)

Recommended Procedures and ProcessesMDR /IVDR General Obligations Comparison to FDA

QSR Regulation (§ 820) Comparison to FDA

IVD Regulation (§ 809) Conform with Common Specifications, as required (Article 9) N/A N/A Procedures to monitor for publications of and/or changes in Common Specifications, Implementing Acts and Delegated Acts (Article 1, Annex XVI)

N/A N/A

Procedures to monitor for or identify Member States where reprocessing is permitted, if applicable (Article 2)

N/A N/A

Device are designed and manufactured per MDR requirements. N/A N/A Manufacturer’s shall draw up and keep up-to-date technical documentation (non-custom-made devices) (Article 83)

N/A N/A




IVD Regulation (§ 809) Manufacturers of custom devices shall draw up and keep up-to-date documentation available for competent authorities (Annex XIII)

N/A N/A

Processes to manage agreements between manufacturers to allow one to use the others clinical evaluation when devices are “equivalent.” (Article 61)

N/A N/A

Person responsible for regulatory compliance (Article 15) § 820.25 § 820.25 Strategy for regulatory compliance (Article 10. Clause 9(a)) § 820.5 § 820.5 Identification of applicable general safety and performance requirements (Article 10. Clause 9(b))

§ 820.30 § 820.30

Responsibility of management (Article 10. Clause 9(e)) § 820.20 § 820.20




IVD Regulation (§ 809) Resource Management, including selection and control of suppliers and sub-contractors (Article 10. Clause 9(d))

§ 820.50 § 820.50

Risk Analysis and management (Article 10. Clause 9(e)) Guidance Guidance Product realization, including planning, design, development, production and service provision (Article 10. Clause 9(g))

§ 820.30, 820.70, 820.200

§ 820.30, 820.70, 820.200

Verification of UDI assignments (Article 10. Clause 9(h)) § 830 N/A Handling communications with competent authorities, notified bodies, other economic operators, customers and/or other stakeholders (Article 10. Clause 9(j))

Various Various

Processes for reporting serious incidents, field safety corrective actions (Article 10. Clause 9(k))

§ 803 § 803




IVD Regulation (§ 809) Management of corrective and preventive actions (Article 10. Clause 9(l))

§ 820.100 § 820.100

Process for monitoring and measurement of output, data analysis and product improvement (Article 10. Clause 9(m))

§ 820.30 § 820.30

Label requirements (Article 10. Clause 11) § 801 § 809.10 / § 809.11 Vigilance – Recall and reporting of incidents and field safety corrective actions requirements (Article 10. Clause 12)

§ 806 § 806

Record retention (Article 10. Clause 8) § 820.180 § 820.180 Procedure for communication with Commission/Member States to obtain Single Registration Number (Article 31)

§ 807 § 807

Procedures on requirements for Distributors (Article 14) and Importers (Articles 31 & 13)

N/A N/A

The future is fast approaching…

What you need to do…starting now…• Review Manufacturer requirements and make gap

assessment against your existing QMS • Amend and implement QMS• Apply amended QMS to products

Turning back time is not an option…

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