Medical Device and IVD Regulatory Conference Device and IVD Regulatory Conference 2015 Licencing...

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Medical Device and IVD

Regulatory Conference 2015

Licencing Requirements for

manufacturers, distributors and

wholesalers: Certification of

Quality Management Systems

Dr Mark D. Bodley MSc, PhD, EOQ, IRCA, FSASQ


DOH

SAHPRA

FoodMedicines

(Act 72)

Medical

Devices

Act 101

MEDICAL DEVICE MANUFACTURER, DISTRIBUTOR & WHOLESALER

SAMED


The South African Health Products

Regulatory Authority - SAHPRA

SAHPRA was formed to ensure that all medicines, complementary and alternative medicines (CAM) such as vitamins, herbs, homeopathic, ayurvedic and Chinese medicines and traditional African medicines, manufactured for sale to the public, could be checked for safety, quality and in some cases efficacy.

SAHPRA - are to evaluate medicines, medical devices (MEDDEVs) and products purporting to be medicines, for safety, quality and efficacy.

-will monitor advertising and work together with the Director General for health, to ensure that facilities producing these products employ GMPs.

Health Minister (Dr Aaron Motsoaledi) said they are fast-tracking efforts to abolish the MCC and replace it with a more effective SAHPRA (SABC News April 2012).


SAHPRA• DRAFT legislation paving the way for this new regulatory

body for medicines was tabled in Parliament early 2014;

hopefully this will lead to a more efficient authority than the

slow, and under-resourced MCC.

• In addition to ensuring safe, effective and high quality

medicines on the market, the council licences drug

manufacturers, scrutinises applications to launch new

products and oversee clinical trials. But the long approval

times (>3 years), is a problem to the drug industry. Thus

the DOH Department of Health intends to replace the

council with SAHPRA, an authority with far wider scope.


SAHPRA

• A new governance structure is one of the key

changes in the bill, in which SAHPRA’s CEO will have

the authority to appoint technical committees, and will

report to a board of between 10 and 15 experts

appointed by the Minister of Health.

• In the previous version, a CEO appointed by the

Minister of Health, with the minister given final

authority for the approval of new products, an agency

structure criticised for being vulnerable to political

interference.


SAHPRA

• SAHPRA will scrutinise sectors of the market that

have until now been unregulated, including medical

devices and diagnostics, foodstuffs, and cosmetics.

• This is the government’s second attempt at enabling

legislation for SAHPRA, since the first attempt to

enact amendments to the Medicines and Related

Substances Act in 2008.


MEDICINES AND RELATED SUBSTANCES CONTROL

ACT 101 OF 1965

To provide for the registration of medicines intended for human and

for animal use; for the registration of medical devices; for the

establishment of a Medicines Control Council; for the control of

medicines, Scheduled substances and medical devices; for the

control of manufacturers, wholesalers and distributors of

medicines and medical devices; and for the control of persons who

may compound and dispense medicines; and for matters incidental

thereto.


(g) by the substitution for the definition of ‘‘medical device’’ of the following

definition: ‘‘ ‘medical device’ means any instrument, apparatus, implement,

machine, appliance, implant, in vitro reagent or calibrator, software,

material or other similar or related article —

(a) intended by the manufacturer to be used, alone or in combination,

for human beings for —

(i) diagnosis, prevention, monitoring, treatment or alleviation of disease;

(ii) diagnosis, monitoring, treatment, alleviation of or compensation for an

injury;

(iii) investigation, replacement, modification or support of the anatomy or of aphysiological process;

(iv) supporting or sustaining life;

(v) control of conception;

(vi) disinfection of medical devices; or

(vii) providing information for medical or diagnostic purposes by means of in vitro examination of specimens derived from the human body; and

(b) which does not achieve its primary intended action in or on the human body by pharmacological, immunological or metabolic means, but which may be assisted in its intended function by such means’’


Medicines and Related Substances

Amendment Act, No. 72 of 2008


REGISTRATION of MEDDEVsProhibition of Sale: – if not registered, but subject to “registration list” to meet the “Prescribed Requirements”

-To be determined by the Council / Authority / Minister

- Marketing Code of Practice – for relevant industries to be determined by the Minister;

-No “bonusing” = rebates / other incentive schemes allowed

MEDDEV Registration Applications � Council CEO- Prove - safety, efficacy, suitability, Quality complies with “Prescribed

Requirements” – if available.

-Certification of Registration & No. issued (validity time frame to be determined)

-Registration fee (annual) required

Labelling & Advertisements: – to be approved by the “Authority” (“Prescribed Requirements”) & the Minister - To be determined by the Council / Authority / Minister.


REGISTRATION of MEDDEVs

New / Novel Devices: for appraisal / exhibition; shall be

as prescribed (e.g. Ethics Committee approval)

- No sampling (free supply) allowed

-Unregistered MEDDEVs may be sold – with “Authority”

approval (specific purposes and time scale)

Licence to Manufacture, Distribute, Wholesale:

issued by Director General / “Authority”; Licence

duration – to be determined.


LICENSING

Persons in South Africa required to make application for a licence

for MEDDEVs or IVDs are as follows:

1. MANUFACTURER LICENCE: to manufacture, import, export;

i.e. a person who designs, manufactures, packs, labels,

assembles, reprocesses, refurbishes the goods, or arranges for

another person to “manufacture” the goods, for supply (whether

in South Africa or elsewhere); or

2. DISTRIBUTOR LICENCE: to import, export or distribute; a

person who imports / exports, or arranges the importation /

exportation of, the goods into / from South Africa or who acts as

a distributor; or

3. WHOLESALER LICENCE: to act as wholesaler of MEDDEVs

or IVDs in South Africa.


Prescribed Regulatory Requirements

Electromedical: DOH – Hazardous Substance Act:

CE Mark currently adopted.

Other MEDDEVs: - determined by

- the Market; Private and Government (CE, FDA)

- CEO, Council / Authority / DG / The Minister of

Health


Acknowledgement: Jane Rogers SHS: SAMED July 2015


Council Requirements• Classification of MEDDEVs and IVDs; Class A – D (low to high);

Risk relating to patient or to public health.

• The classification of MEDDEVs and IVDs shall be as determined

by Council in accordance with the classification rules.

• All medical devices, except custom MEDDEVs, and all IVDs shall

be registered with the Council in terms of such call up notices

before they may be sold or used in the Republic.

• Where the classification of a MEDDEV or IVD is inconclusive and

places it in more than one class or between classes after following

the classification rules the Council will place it in the higher of the

risk classes.

• The Council shall consider the classification of a MEDDEV or IVD

individually taking into account its design and intended use.


Essential Principles:

set out the requirements relating to the safety and

performance characteristics of MEDDEV and IVDs as

approved by Council.

Authorised Representative:

is responsible for all aspects of the MEDDEV or IVD,

including performance, quality, safety and compliance with

conditions of registration.

Council Requirements


Acknowledgement: Jane Rogers SHS: SAMED July 2015


PMS – Market SurveillanceAuthorized Rep

Act 101MEDICINES AND RELATED SUBSTANCES

CONTROL ACT 101 OF 1965

MHRA

FDA / MCC - SAHPRA

CMDCAS (Canadian Medical Devices Conformity Assessment

System) / Health Canada

TGA

ANVISA (Brazilian National Health Surveillance Agency

registration) & INMETRO (National Institute of Metrology,

Standardization and Industrial Quality)

Adverse Incidents / Events; - Quackwatch (affiliated with

National Council Against Health Fraud),

- Maude, Iris, Gov. Gazette etc.

Competent Authority

Notified Body

Act 72MEDICINES AND RELATED SUBSTANCES

AMMENDMENT ACT 72 OF 2008 (2009)


Global Harmonisation:

International Bodies - MEDDEVsGMDN (Global Medical Device Nomenclature)

NBOG (Notified Body Operations Group)

GHTF (Global Harmonization Task Force); requires suppliers of critical items

– be ISO 13485 Certfied; else NB would have to audit these suppliers at

least once in the 3 year cycle. �

IMDRF (International Medical Device Regulators Forum); - voluntary group of

medical device regulators from around the world, building on the foundational work of the

GHTF on Medical Devices. This Forum will accelerate international medical device

regulatory harmonization and convergence.


Global Medical Device Nomenclature – GMDN

is a system of internationally agreed generic descriptors used to

identify all medical device products. Such products include those

used in the diagnosis, prevention, monitoring, treatment or

alleviation of disease or injury in humans.

The main purpose of the GMDN is to provide health authorities /

regulators, health care providers, medical device manufactures and

suppliers, conformity assessment bodies and others with a single

generic naming system that will support patient safety.


Notified Body Operations Group – NBOG

In July 2000, Member States and the European Commission agreed to

set up the Notified Body Operations Group (NBOG). This was in

response to widespread concern that the performance of Notified

Bodies in the medical device sector, and that of the Designating

Authorities responsible for them, was variable and inconsistent.

Accordingly NBOG’s terms of reference were agreed to be:

To improve the overall performance of Notified Bodies in the medical

devices sector by primarily identifying and promulgating examples

of best practice to be adopted by both Notified Bodies and those

organisations responsible for their designation and control.


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MANAGEMENT

RESPONSIBILITY

PRODUCTPRODUCT

REALIZATION

MEASUREMENT,

ANALYSIS &

IMPROVEMENT

RESOURCE

MANAGEMENT

INPUT OUTPUT

MODEL OF THE PROCESS APPROACH

QMS;

DOCUMENTATION,

DATA & RECORDS

CONTROL

4

5

6

7

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ISO/TR 14969Continual Improvement of the

Quality Management System?


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COMMITMENT,

PROCESS

INTERACTION,

SCOPE & FOCUS INTEGRATED

MANAGEMENT

SYSTEM

MANUAL

STRATEGIC

POLICY

DOCUMENT

PROCESSES

SUB- PROCESSES /

Work Instructions /

SOPs

STANDARD FORMS &

RECORDS

SEQUENCE &

INTERACTIVE

NATURE OF

PROCESSES

WORK PRACTICES,

VALIDATION AND

CONTROL OF

PROCESS

ACTIVITIES

DAILY RECORDING

DOCUMENTATION &

RECORDS (INCL.

ELECTRONIC MEDIA)


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Constructing the Key Processes Puzzle


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KP1

MGT SYS ADMIN &

PERFORMANCE

MEASUREMENT

KP5

PRODUCTION

KP6

HUMAN

RESOURCES

KP4

FINANCIAL

MANAGEMENT

KP2

CUSTOMER

MANAGEMENT

P1.1

MANAGEMENT

RESPONSIBILITY

P1.2

DOCUMENT,

DATA & RECORDS

CONTROL

P1.3

DATA ANALYSIS

for CONTINUAL

IMPROVEMENT

P1.4

INTERNAL

AUDITS

P1.5

CORRECTIVE

ACTION &

VIGILANCE

P1.6

PREVENTIVE

ACTION

P1.7CONTROL OF

NON-CONFORMING

PRODUCT&SERVICE

PRODUCT RECALL

P2.1

MARKETING &

SALES

P2.2

CONTRACT

REVIEW

P2.3

CUSTOMER

SATISFACTION &

POST MARKET

SURVEILLANCE

P4.1

ACCOUNTING

INVOICING

PAYMENTS

P4.2

SUPPLIER

ASSESSMENTS,

PURCHASING

P6.1

RECRUITMENT &

JOB PROFILES

P6.2

PERFORMANCE

APPRAISALS,

SKILLS

DEVELOPMENT &

TRAINING

6.2.1

Needs Assessment

6.2..2

Skills

Development

P6.3

EMPLOYEE

WELLBEING

Management System Overview

KP3

RESEARCH &

DEVELOPMENT

P3.1

DESIGN

CONTROL

P3.2

DESIGN INPUT

P3.3

DESIGN REVIEW

P3.4

DESIGN OUTPUT

P3.5

VERIFICATION &

VALIDATION

P3.6

DESIGN CHANGES

MD / GM, Mgt Rep FM PM HRMPDMMM

Process Owners /

Co-owners

P5.1

PLANNING

P5.2

IDENTIFICATION

&

TRACEABILITY

P5.3

GMP

P5.4

QUALITY

CONTROL &

PRODUCTION

CONTROL

P5.5

STERILISATION

(if appropriate)

P5.6

MAINTENANCE &

CALIBRATION

P5.7

PACKAGING,

WAREHOUSING &

DISTRIBUTION

KEY:

KP = Key Process

P = Process

WI = Work Instruction

SF = Standard Form / Format (electronic)


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Pathway to CE Marking / FDA Approval

Business / Quality Management System

Processes must be:

• Identified (logically and sensibly)

• Measurable - according to agreed Objectives & Measurement Criteria

/ Outputs � Vision, Mission, Quality Policy

• Managed – by Identified Process Owners

• Interrelated – demonstrable with Inputs and Outputs

• Results Focussed for Continual Improvement!


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CE Mark Specific Requirements

• Meet MDD 93/42/EEC requirements of the Appropriate Annex I - VII

• Application of the correct Annex of the MDD is determined by the Risk

Class of the Device concerned; i.e. Class I (low) – III (high risk).

• QMS System in place: ISO 13485

• The CE path diagram below indicates a combination of all possible

routes


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MDD 93/42/EEC

Annex VII / EC-Declaration of Conformity

Technical data, Essential Requirement, Clinical

Evaluation, Risk analyses, Vigilance, Post Market

Surveillance

Annex III / EC Type-Examination

Annex VI

Product

quality

assurance

~ISO 9001,

ISO13485

(excl. Design

&

Manufacture)

Annex II

Full quality

assurance

~ISO 13485 &

/ ISO 9001

Harmonised

STDs

Annex VIII

Statements

Design,

Manuf,

Performance

of Custom

Devices

#4

Examination of

the Design

Design

Dossier /

PMF's

incl. Clinical

Investigation

CE Mark

Annex I

Annex IV

EC

Verification

~Statistical

and/or single

unit

ISO 13485

applicable

elements

Annex V

Production

quality

assurance

~ISO 9001 /

ISO 13485

(excl. Design)

Harmonised

STDs

Class Im,

IIa, IIb, III

Class Im,

IIa, IIb (non

sterile)

Class I, Is, Im,

IIa, IIb, III

Class I, Is, Im,

IIa, IIb, III


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Latest version of ISO 13485

The latest version of the BS EN ISO 13485 Standard was published on 24/01/2012

replacing the previous version ISO 13485:2003.

The Standard was revised as a number of countries within the EU objected to the inference

that if you were certified to ISO 13485, it was almost assumed you were in compliance

with one of the three Directives (90/385/EEC AIMD, 93/42/EEC MDD and 98/79/EC

IVDD).

In response the main changes to the 2012 revision has been to extend the Annexes at the

beginning of the Standard to link each clause of the Standard against the requirements

of the Directives.

There have been no actual changes in the text of the Standard so no significant changes

are required. This means as long as you conform to existing requirements you should

receive an updated certificate from your Notified Body (expect them to request

references to the standard to be amended from 2003 to 2012).


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Certifications / Accreditations Required

ISO 13485: Standard for Medical Devices

ISO 9001: Business / Quality Management System Standard –Manufacturing & Service industries

ISO 14001: Environmental Management Standard

OHSAS 18001 / ISO 45001: Occupation Health and SafetyAssessment Series Standard

MDD 93/42/EEC – 2007/47/EEC: Medical Devices Directive of the EEC

CE Marking: Application of CE to products for export to the EU

ISO 17025 / GLP: Standard for Testing / Metrology Laboratories & Good Lab. Practice for Research Labs (OECD Guidelines)


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Supplementary Standards to be applied.

Sterilisation: ETO (EN 550 �ISO 11135); γ Irradiation (EN 552 �ISO 11137-1,2,3); Moist Heat (EN 554 & EN 285)

Clean Rooms: ISO 14644 Parts 1-4

EUCOMED Guidance: Technical Documentation Requirements & Design Dossier

Pharmacopoeias: British, US & European

GMP / GWP / GDP / GLP: Good Manufacturing /Warehousing / Distribution / Laboratory Practice

ISO 14971: Medical Devices Risk Analysis

ISO 14155 & MEDDEV 2.7.1: Clinical Investigation & Evaluation

PMF’s (Product Master Files / Design Dossiers)

FDA Approval; 21 CFR 800: Food & Drug Administration:Pre-Market Notification / Submission / Approval (PMA), 510k Registration

ISO 62304 & 21 CFR 11 – Software validation


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Supplementary Standards to be applied cont.

cGMP: Current Good Manufacturing Practice (if administering medication)

WHO: World Health Organisation Pharmaceutical Requirements (if administering medication)

ISO / EN 10993: Series of Standards for Biological Evaluation & Biocompatibility

ISO 11737-1, -2: Microbiological Population Estimation Series

EN60601 & IEC Series

Harmonised Standards (Technical) – a myriad of them; as applicable

(European Commission Site)


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MDD 93/42/EEC explained

‘The MDD is one of the EU’s most difficult mandates to decipher’, it also ‘makes FDA approval look like

child’s play in comparison’ – Les Schnoll, Director of KPMG Quality Registrar.

Medical Device Manufacturers &/or their Authorised Representatives must demonstrate compliance

with the Directive’s applicable Two Sections; Articles & Annexes:

Section 1: 23 Articles:

Define rules and routes for compliance

Classification description

Pointers to Section 2.

Section 2: 12 Annexes:

Provide details relevant to different Risk Class Devices

Annex I: - Essential requirement, applicable to all devices

Annex VII: - EC Declaration of Conformity


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Product Master File / Design DossierTechnical Documentation required, for review by Notified Body / Competent Authority

• EC Declaration of Conformity

• General Description of Products and Variants

• RM and Component Documentation

• Intermediate Product and Subassembly Documentation

• Final Product Documentation

• Packaging and Labelling Documentation

• Design Verification

• Risk Analysis Results

• Compliance with Essential Requirements (Annex I) and Harmonised Standards

(technical, product specific)

• Clinical Data & / or Scientific Literature

• Records (manufacturing, Inspection, Testing; proving compliance with procedures and

applicable Specifications)


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ISO 13485 Specific Notes

•Risk Analysis: can be conducted using ISO 14971 (EN 1441), FMEA, FTA etc. as a

guide.

•Design Verification: Includes Clinical Investigations; which can encompass

Scientific Literature, Historical evidence of safe designs and materials used that the

device performs as intended.

•Biocompatibility Data: from test results / literature

•Software Integrity: data output integrity to be maintained

•Labeling: ID of person performing final Labeling is to be recorded

•Inspection & Testing: ID of person performing ANY Inspection & Testing - recorded

•Delivery & Distribution: Records to be kept by Authorised Representative


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Training required

Quality & Product Safety Awareness

QM - Quality Management

ISO Knowledge – various; 9001, 13485 (14001, 18001 etc.)

CE & MDD 93/42/EEC – 2007/47/EEC (or applicable directive)

FDA (21CFR)

Internal Auditing

Risk Analysis - ISO 14971, FMEA, FTA


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Challenges / Pitfalls of MEDDEV Registration

• Traceability; RM � Finished product; materials / electrical componentry

• Manufacturing environment

• Subcontract Manufacturers

• Auditors – Local vs International – expense & availability

• Administration of Accreditation / Notified Bodies / FDA

• Device Registration – “Prescribed Requirements” unclear

• Marketing

• Authorised Representative


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Solutions

• Notified Body: SA Government Involvement;

International ISO/TC210 N732

• Development of Skills Base

• Centre(s) of Competence

• Skills Development links with Academia

• Marketing; Companies for various small MEDDEV Manufacturers

• SMEDP Incentive funding (DTI - EIP, MCEP etc.)

• Business Management Optimisation through

Strategic Innovation

Medical Device and IVD Regulatory Conference Device and IVD Regulatory Conference 2015 Licencing...

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