PART 1

The General European OMCL

Network (GEON)

More than 70 national Official Medicines

Control Laboratories (OMCLs) from 40+

countries

together in a pan-European network

for public and animal health protection

1Oct 2018

Outline

What is an OMCL?

What is the GEON?

The GEON’s Quality Management System

The GEON’s Surveillance Programmes & Testing Activities

Zoom in on Falsified Medicines Testing Activities

“My OMCL”

2

What is an OMCL?

Definition

Objectives & Missions

Scope of analysed products

Roles of OMCLs in Europe

OMCLs’ stakeholder environment

3

Definition

Official Medicines Control Laboratories are:

Independent public laboratories

Established and nominated by National

Authorities

Analysing medicinal products, already or to

be marketed, for human and veterinary use

What is an OMCL?

4

Mission and Objectives

OMCL Mission:

Support national regulatory authorities in quality control of medicines for human and veterinary use

Ensure quality, safety and efficacy of medicines to enhance patient and animal welfare

OMCL Objectives:

Test medicines independently from manufacturers

React quickly in times of crisis to perform tests and investigate issues

What is an OMCL?

5

Products List of medicinal products analysed by OMCLs

What is an OMCL?

Medicines for human and veterinary use:

Chemical products Biological products:

vaccines, blood and plasma derivatives, immunological products

Herbal medicines Homeopathic medicines

Including:

Stockpiled medicines

Ingredients, products, preparations:

Active Pharmaceutical Ingredients (APIs)

Excipients Radiopharmaceutical

products Allergens and gene

therapy products Falsified and other illegal

medicines including “Medicines in disguise”

Other pharmaceutical preparations

6

ProductsAnalysed medicines for human

and veterinary use

What is an OMCL?

Chemical products Biological products

Vaccines

Immunological products

Blood

Plasma derivatives

Herbal medicines Homeopathic medicines Stockpiled medicines 7

ProductsAnalysed ingredients, preparations…

What is an OMCL?

Radiopharmaceuticalproducts

Active Pharmaceutical

Ingredients and excipients

Allergen products (for diagnosis and

treatment)

Medicines

Falsified medicines and medicines in disguise

Gene therapy products

8

Products List of Non-medicinal products analysed by OMCLs

Primary packaging

materials

Medical devices

Diagnostic products

Food supplements

Premixes for medicated

feeding stuffs for veterinary

use

Cosmetics

Tattoo ink

What is an OMCL?

9

Roles of OMCLs in Europe OMCLs’ main activities:

Pre- and Post-marketing test programmes:

Sampling and Analysis

Emergency testing e.g. in case of adverse reactions of medicines

Laboratory testing of medicines & active ingredients:

Innovator medicines

Generic medicines and biosimilars

Unlicensed/unauthorised products

Suspected falsified/illegal medicines

Packaging and labelling controls

OMCLs adopt a risk-based approach in all their planned testing

activities (detailed slide 29)

What is an OMCL?

10

Roles of OMCLs in Europe

OMCLs’ activities lend support to:

Marketing Authorisation Dossiers (in evaluating the quality

part)

Test methods to be included in the European

Pharmacopoeia

Good Manufacturing Practice inspections (as laboratory

experts)

Quality defect report evaluation

Pharmacovigilance investigations

What is an OMCL?

11

OMCLs’ stakeholdersGovernment-type Stakeholders (e.g. Regulators and Other Groups)

The Heads of Medicines Agencies (HMA)

Agency Inspectorates, Assessors and Pharmacovigilance Groups

Police/Customs Groups & Forensic Laboratories/Customs Labs

Food Inspectorates & Food Testing Laboratories

Cosmetics Inspectorates and related Testing Laboratories

External Stakeholders

The General Public

Healthcare Professionals

The Pharmaceutical Industry

What is an OMCL?

12

Benefits of OMCL Testing

What is an OMCL?

13

What is the GEON?The General European OMCLs Network

GEON set-up & history

Composition/Membership

Objectives and benefits

of the GEON

The GEON Pillars and risk-

based approach

The GEON Tools and Key

programmes and support

activities

14

HistoryThe GEON creation & set

up:

Devised in 1994 by the EU Commission & Council of Europe

To promote the collaboration ofOMCLs across Europe (andbeyond) in the area of quality controlof marketed medicinal products forhuman and veterinary use

Set up in 1995 by the European Directorate for the Quality of Medicines & HealthCare (EDQM)

With financial support from the EU

The GEON organisation:

Annual work programmes decidedwith National Authorities and theEuropean Medicines Agency (EMA)

EDQM: Secretariat and co-ordination of the Network activitiesand joint programmes

What is the GEON?

2014: 20th Anniversary of the GEON

15

What is the GEON?OMCLs within regulatory

environment

16

What is the GEON?OMCLs within regulatory

environment

17

CompositionMore than 70 OMCLs from 40+

countries

Members and Observers of the

European Pharmacopoeia Convention

Full, associate or limited

membership

List available on EDQM site

PA/PHOMCL (09)45 R27 (annex 3

to GEON Terms of Reference

See map next slide

What is the GEON?

GEON

OMC

L

OMC

L

OMC

L

OMC

L

OMC

L

OMC

L

OMC

L

OMC

L

OMC

L

27 out of the 28 EU countries (except

Malta)

6 European non-EU countries:

Belarus, Bosnia & Herzegovina,

Russian Federation, Serbia, The

Former Yugoslav Republic of

Macedonia, Ukraine

Norway (EEA) & Switzerland (MRA)

7 non-European partners (Australia,

Canada, Israel, Kazakhstan, Morocco,

Singapore and Taiwan FDA): associate

members as observers to Ph. Eur.

ConventionStatus: April 2018 18

Status: April 2018 19

Membership criteria

There are defined Terms of Reference and specific criteria for gaining accession to the OMCL Network (GEON):

Independence, impartiality, no conflicts of interest regarding the testing and control of medicines

Ph. Eur. implementation as a common standard in the national rules governing medicines (strictly applied for full membership)

Clear mandate from the Competent Authority regarding the lab’s responsibilities and duties

Implementation of a Quality Management System based on ISO/IEC 17025: General requirements for the competence of testing and calibration laboratories

What is the GEON?

20

Who are we?

21st GEON Annual Meeting 2016, Paris

21

Who are we?

23rd GEON Annual Meeting 2018, Sarajevo

22

What we do?

23

Where does the GEON meet?

EDQM - Council of Europe, 7 allée Kastner, CS 30026 F-67081 Strasbourg FRANCE

Telephone: + 33 3 88 41 30 30

Fax: + 33 3 88 41 27 71 24

Objectives

Protecting public and animal health through independent surveillance testing of medicines (and selected products)

The GEON works to…

Promote and facilitate work-sharing among the OMCLs

Continue to foster/promote the mutual recognition of test results

Achieve harmonisation in testing standards and laboratory controls

Facilitate the exchange of knowledge and expertise Provide a platform for sharing scientific information

and surveillance strategies

What is the GEON?

25

Objectives (cont.)

Protecting public and animal health through independent surveillance testing of medicines (and other products)

The GEON works to…

Reduce duplication in testing => reducing costs and focusing on other products / testing more products

Facilitate risk-based approaches in market surveillance testing

Promote and facilitate the use of novel scientific methods and technologies in surveillance work,e.g. API Fingerprinting, Chemometrics, etc.

Raise public awareness about the importance of medicines surveillance testing

What is the GEON?

26

Benefits of networking

The GEON is designed to allow OMCLs to network and collaborate…this is achieved in many ways:

Annual Meetings

Working Groups

Mutual Joint Visits and Mutual Joint Audits

Symposia and other seminars

Co-ordinated sampling and testing – e.g. CAP and MRP/DCP products

Sample exchange activities and collaborative testing

This all helps achieve meaningful and value-added surveillance for all,

exemplified by the MRP & DCP programme (see slides 46-47)

What is the GEON?

27

Pillars of the GEON

What is the GEON?

Policies and Rules:

Terms of Reference

Procedures

Guidelines

Other General Docs

Risk-based Approaches

Human Resources:

Plenum Groups (discussions and

decision-making)

Advisory Groups (advice & planning)

Expert Groups (elaboration of

guidelines, procedures, etc.)

EDQM Secretariat (co-ordination)

Harmonised Quality Management Systems (QMS): According to the ISO/IEC 17025 standard

In compliance with Ph. Eur. requirements

Supported by OMCL Quality Guidelines 28

Incorporation of a risk-based approach in Market

surveillance testing of OMCLs

What is the GEON?

Risk-based approaches in place within the OMCL Network for

surveillance testing activities

This helps ensure that funding, resources and laboratory capacity

are well managed so that high-risk products receive the greatest

focus

Risk assessment tools in use to help select products for testing

Continuously working to optimise the risk-based approach, the OMCL

Network is currently heavily engaged in a Heads of Medicines Agency

(HMA) project to develop a new risk-based tool for surveillance

work:

Pilot Project on new HMA risk assessment tool in 2015-2016

The OMCL Network took the leading role in analysing the

results of that pilot

The OMCL Network will be involved during the implementation

phase 29

Tools of the GEON

What is the GEON?

Educational

Programmes: Technical and QMS

training

Training on IT tools

Training visits to

laboratories

Surveillance of the Quality Management Systems:

Programme to support the implementation of the QMS in OMCLs

Audit Programme (peer audits, alternative to accreditation)

Proficiency Testing Schemes (PTSs) - chemical and biological

Secure IT platforms (restricted

access):

Extranet (dissemination of

information, documents, reports…)

Databases (exchange of information

on technical competencies, test

results, annual reports, certificates of

quality status, scopes contacts…)30

What is the GEON?

Key programmes

& support activitiesQuality Management

Activities

Publishing OMCL Network

Guidelines, Procedures, etc.

See Slide 36

The MJV/MJA programme

See Slide 37

The Proficiency Testing Scheme

(PTS)

See Slide 38

Training & Educational Activities

See Slides 39-40

The SUP (Suspicious Unknown

Products) Programme

See Slide 62

Working Groups

API Working Group

See Slide 58

Gene Therapy Working Group

See Slide 59

Counterfeit and Illegal Medicines

Working Group

See Slides 60-63

31

What is the GEON?

Joint programmes

The GEON operates several different

surveillance programmes and engages

in a wide range of support activities…these are all

co-ordinated by the EDQM

CAP Sampling & Testing Programme

MRP/DCP Post-Marketing Surveillance Scheme

MSS Programme (Ph. Eur. monograph

elaboration as “spin-off”/positive consequence)

OCABR/OPBR Programme

32

The GEON’s

Quality Management System

Importance of QMS in OMCLs

QMS-related activities in the GEON:

OMCL Guidelines

MJA/MJV

PTS

Training

33

Importance of QMS

The established and harmonised Quality Management System across all OMCLs, based on the same ISO Standard and set of common guidelines, has many advantages:

High confidence in test results => mutual recognition of results

Testing processes under control => reduces the risk of errors

Full traceability of all testing and other activities

Facilitates co-operation/exchanges/harmonisation between OMCLs

Makes good use of resources => reduces costs

Helps to protect public and animal health

The GEON’s QMS

34

GEON QMS activities

The OMCLs work to one common QM system

This QM system is based on internationally recognised standards: ISO/IEC 17025 “General requirements for the competence of testing and calibration laboratories” and:

OMCL Guidelines/Documents: to complement/interpret ISO/IEC 17025 and respond to specific needs of OMCLs (GEON’s interpretation of standards)

the legal standards laid down in the European Pharmacopoeia (Ph. Eur.)

The QM system is supported by:

Audits

Proficiency Testing Schemes (PTSs)

Training and educational activities

The GEON’s QMS

35

OMCL Guidelines

Specific guidelines/documents have been elaborated by experts of the OMCL Network to complement and interpret the ISO/IEC 17025 standard and facilitate the implementation of its requirements.

All QMS OMCL Guidelines are officially adopted by the OMCL Network and can be found on the EDQM website.

They are not legally binding but deviations must have a sound scientific/technical justification.

In addition, there are so-called “recommendation documents” which should provide help to improve the QMS. They can also be found on the EDQM website.

Note: Not all of the GEON’s Guidelines concern Quality-related topics… there are also Guidelines on general policies and other topics

The GEON’s QMS

36

OMCL AuditsPeer audits by qualified auditors

Mutual Joint Visits (MJV): aimed at helping OMCLs implement a QMS if not yet in place, or giving recommendations for improvement if QMS is under development

Mutual Joint Audit (MJA): once the QMS is established, its compliance is periodically verified with respect to the requirements stated in ISO/IEC 17025, the OMCL Guidelines and the Ph. Eur.

NB: the EDQM is not an accreditation body

The GEON’s QMS

37

Proficiency Testing Scheme

Aimed at assessing the analytical performance of the OMCLs.

PTSs are a further means to ensure harmonisation, confidence and

mutual recognition within the OMCL Network.

ISO/IEC 17025, clause 5.9 requires that laboratories implement

quality control procedures for monitoring the validity of tests => one

possibility is the participation in proficiency-testing

programmes/schemes such as PTS. The revised norm in its

December 2017 version has reinforced this notion in clause 7.7.2.

Separate physico-chemical and biological programmes are offered

free of charge to OMCLs and subject to fees to external labs.

The GEON’s QMS

38

Training activities

Training Visits

The EDQM organises visits of OMCL staff members to the facilities of

other OMCLs to receive practical training on QM or technical topics

Training Courses (examples)

QM training courses

Technical training on Chemical/Biological topics, e.g. falsified/illegal

medicines testing

Training courses and workshops for experienced auditors or

candidate auditors

Database training

The GEON’s QMS

39

Training agenda

Workshop for auditors/trainees of the MJA/MJV

Scheme of the OMCL Network

Workshops on technical topics and training on the

QMS Guidelines

Hands-on(practice) training for OMCLs on

falsified medicines

Chemometrics Training

Workshops on computerised systems (e.g.

CombiStats)

The GEON’s QMS

40

Zoom in on GEON’s

Surveillance programme

& other Testing activities Surveillance programmes

Other Testing activities

41

The CAP ProgrammeFor innovative biological/biotech products as well as IVMPs (Immunological

Veterinary Medicinal Products) and for products including new active

substances authorised via the Centralised procedure.

• Overall responsibility lies with the European Medicines Agency (EMA)

• Operational support from EU/EEA OMCL Network, National

Inspectorates & the EDQM

• Each annual sampling and testing plan is established by the EMA with

the input of the CAP Advisory Group - Risk-based criteria are applied

• Plan is approved by the EMA scientific committees (CHMP & CVMP)

• Sampling and testing are co-ordinated by the EDQM in collaboration with

the MAH concerned, nationally appointed samplers and the OMCLs

• The EDQM co-ordinates reporting of the test results and the EMA

manages any required follow-up actions

2014: CAP programme expanded to cover CAP generic products

2019-2023: Further programme expansions: e.g. Formal authenticity checks

of Parallel Distributed CAPs, CAP Biosimilars testing, CAP API testing

Surveillance

programmes

42

The CAP ProgrammeStatistics

Surveillance

programmes

0

10

20

30

40

50

60

Nu

mb

er

of

pro

du

cts

Year

Repartition of the products tested

V/Chem

V/Imm

H/Chem

H/Bio

Generics

Meloxicam

vet generics:

ANMV (8

products/ 11

batches)

Vet chemical CAP tested by ANMV in 2002 (1), 2003 (1), 2004 (2), 2009 (1), 2011 (1), 2012 (1), 2013 (1), 2016 (1)

43

The MRP/DCP Programme

For medicines authorised via the European Mutual Recognition

Procedure (MRP) and the Decentralised Procedure (DCP)

This surveillance programme is restricted to EU/EEA members (because

these procedures are only in use in the EU/EEA)

• Sampling and testing plans are established by the individual OMCLs

participating in this programme and performed on a national level

• Information about planned testing activities and test results is shared

via a secure IT platform with access restricted to OMCLs and

Medicines Agencies

• Whenever possible national programmes are adapted and samples

are exchanged - applying the principle of work-sharing - to avoid

overlap testing

• The majority of products tested under this programme in EU/EEA

countries are generics (already implemented)

Surveillance

programmes

44

The MRP/DCP Programme

Statistics (H & V)

Surveillance

programmes

Total completed Projects

Countries Testing Benefiting

Austria 471 3469

Belgium 0 2888

Bulgaria 38 1487

Croatia 4 279

Cyprus 42 1255

Czech Republic 437 2814

Denmark 57 3692

Estonia 69 1790

Finland 439 3073

France 856 2770

Germany 1504 4715

Greece 203 2466

Hungary 91 2390

Iceland 0 1394

Ireland 122 2713

Italy 9 3306

Latvia 26 1820

Liechtenstein 0 36

Lithuania 32 1920

Luxembourg 0 2366

Malta 0 850

The

Netherlands 7 3745

Norway 270 2039

Poland 1957 3527

Portugal 509 3585

Romania 27 1705

Slovak

Republic 243 2575

Slovenia 50 1785

Spain 40 2769

Sweden 420 3161

United

Kingdom 258 3375

8181 75759

Testin

g

Bene

fiting

0

500

1000

1500

2000

2500

3000

3500

4000

4500

5000

Austr

iaB

elg

ium

Bulg

aria

Cro

atia

Cypru

sC

zech R

epu

blic

De

nm

ark

Esto

nia

Fin

land

Fra

nce

Germ

any

Gre

ece

Hu

nga

ry

Icela

nd

Irela

nd

Ita

ly

La

tvia

Lie

chte

nste

in

Lithu

ania

Lu

xe

mbo

urg

Ma

lta

The

Neth

erla

nds

No

rwa

y

Pola

nd

Port

ug

al

Ro

man

ia

Slo

vak R

epub

lic

Slo

ven

ia

Spain

Sw

ede

n

Un

ite

d K

ing

dom

471

038 4 42437

5769439

856

1504

20391

0 1229 26

0 320

0 7270

1957

509

27 243

5040

420

258

3469

2888

1487

279

1255

2814

3692

1790

3073

2770

4715

24662390

1394

2713

3306

1820

36

1920

2366

850

3745

2039

35273585

1705

2575

1785

2769

31613375

Testing

Benefiting

In total: 8181 projects

Benefits Ratio: 1:9

Status: May 2017

45

The MRP/DCP Programme

Statistics

46

Surveillance

programmes

In total: 9472 projects

Benefits Ratio: 1:9 (status : june 2018)

For 1 product tested, result concerns 9 countries

0

1000

2000

3000

4000

5000

6000

AT BE BG CY CZ DE DK EE EL ES FI FR HR HU IE IS IT LI LT LU LV MT NL NO PL PT RO SE SI SK UK

601

0 41 58

520

1602

63 73273

81

479

920

33 1451640 9 0 36 0 33 0 22

318

2230

589

29

439180276258

3968

3301

1793

1491

3282

5313

4151

2140

2809

37363465

3255

489

2749

3084

1584

3779

40

2220

2666

2154

1024

4253

2312

40994082

2085

3542

2175

2895

3886

Benefits - Global

Testing

Benefits

Caroline Offerlé©2018

EDQM, Council of Europe.

All rights reserved.

General figures

Life-cycle of projects

Project content

Information sharing

Batch information

Benefits

Benefits Vet

For 2017,

Ratio VET 1:17Ratio HUM 1:10

FR in this slide = ANMV

Cut-off date: 27/04/2018

0

20

40

60

80

100

120

AT BE BG CY CZ DE DK EE EL ES FI FR HR HU IE IS IT LI LT LU LV MT NL NO PL PT RO SE SI SK UK

40 0 0

44

60 0

16

9

1

18

0

27

0 0 0 0 0 0 0 0 0 0

11

0 0 0

7

0 0

96102

5255

97

105

79

56

93

116

61

101

16

108 106

19

110

4

69

79

65

20

96

43

112107

72

57

7680

116

Benefits Vet 2017Testing

Benefiting

Increased Focus on

Generics & Biosimilars• Many countries increasingly rely on generic medicines within their

national health programmes

• Many new Marketing Authorisations are now generic or biosimilar (≈

generic of a biological medicine: none in vet domain in France until 2018)

About 90% of MRP/DCP products are generics (or hybrids)

About 40% of CAP products are generics or biosimilars

• These factors required a change in the design of surveillance

programmes

– While the MRP/DCP programme always involved generics testing,

the CAP programme previously focused mainly on branded

medicines

– Now, more and more CAPs are either generic or biosimilar

medicines

– These medicines are also controlled by testing

– It makes sense to combine efforts from different programmes,

Surveillance

programmes

48

Increased Focus on

Generics & Biosimilars cont.• The GEON has responded to this trend by developing a wide-scale

generics testing programme

– It is independent of the MA type – MRPs, DCPs and CAPs are

tested at the same time

– Approx. 1000 MRP/DCP products are tested every year &

around 900 of these are generics!

– Since 2014, 1-2 families of CAP generic medicines have been

tested each year in the MSS programme (e.g. Temozolomide,

Irbesartan, Telmisartan, Pramipexole, Repaglinide, Leflunomide,

Meloxicam…)

– Approx. 10 different medicines (mostly generics) are tested in

each family, and the originator branded medicine is also tested

– One test methodology is generally used for all products

(including the originator), allowing comparison of the quality of

the product family

Surveillance programmes

49

Increased Focus on

Generics & Biosimilars cont.• Further developments:

A new CAP generics programme will start in 2019

Approx. 3 generic product families will be covered each year

Ways to combine this testing with other surveillance programmes

will be further facilitated

• These programmes allow assessment of the overall quality of

generics

• They help improve the confidence of patients and health

professionals in generic medicines generally

• In 2016, a feasibility study on biosimilars testing was completed…

– It concluded that the co-ordinated surveillance testing of these

products is possible

– A biosimilar test programme is being planned for implementation

in 2019 (it will form part of the CAP programme)

Surveillance programmes

50

The MSS ProgrammeThis is a type of Market Surveillance Programme that focuses on:

• Testing product groups (e.g. a series of generics, a series of herbal

drugs...)

• Specific pharmaceutical forms (e.g. modified-release tablets,

inhalators, intra-mammary suspensions...)

• Performing specific tests (e.g. heavy metals, uniformity of dosage

units...)

The products are tested according to a common protocol established

by a scientific advisor on the project

Sampling is done on a national level and is the responsibility of the

participating OMCLs/member states

A common test report is established at the end of the study

The MSS programme allows for a high degree of flexibility - other types

of products (e.g. medical devices) can also be tested, and the overall

run time of the studies has been reduced for “atypical MSS”

Surveillance

programmes

51

The MSS Programme

- Multiple Benefits• MSS studies have the ability to cover a wide range of products on the

European market

• MSS studies allow products registered by national MA scheme, but also MRP/DCP products, to be tested

• Sampling activities are logistically simple – all sampling is performed according to national rules

• The results of MSS studies are used, where appropriate, for revision of the relevant Ph. Eur. monograph and/or general chapters and test methods – this leads to continual improvement in the testing of those medicines. The results give also an overview of the quality of the focused products on European market.

• Selection of specific quality topics is not necessarily limited to

medicines or even the test parameters listed in the product

specification as all OMCLs of the Network can participate

Surveillance

programmes

52

Comparison of “Classical” MSS programmes

Surveillance

programmes

1- MSS 2- MRP/DCP 3- CAP

Focus on National MA on

behalf of NCA; (MRP/DCP

products are also tested)

Focus on MA via MR/DC procedures

on behalf of NCA

Focus on MA via Centrally Authorised

Procedure on behalf of EMA

Whole OMCL Network EU/EEA OMCL Network EU/EEA OMCL Network

Variable no. participants

(many testing OMCLs)

Variable no. participants

(as a rule 1 testing OMCL/MA/year)

Defined no. participants (1 OMCL for

chemicals, 2 for biologicals)

Variable no. samples Variable no. samples Defined no. samples

Protocol established by

Scientific Advisor of the

MSS project

Protocol based on the MA dossier +

SOPs of manufacturer, or internal

method or compendial

Protocol based on MA dossier + SOPs

from manufacturer or “generic”

methods

Type of products depend

on local market

Major group: Generics Major group: innovative

biological/biotech products as well as

IVMPs and new APIs 53

OCABR/OBPR Programme

• This programme involves the independent testing, examination and release of batches of human biological medicinal products (vaccines, blood and plasma derivatives) and immunological veterinary medicinal products (IVMPs)

• These products are included because of the recognised variability inherent in the products themselves, and in their production and test methods

• The programme is also important given the way these medicines are used - i.e. in prevention campaigns for healthy children and in helping compromised individuals e.g. blood clotting factors for haemophilia patients

• The batches are officially ‘released’ for marketing after testing/examination by the Competent Authority or OMCL

• This is known as Official Control Authority Batch Release (OCABR) and Official Batch Protocol Review (OBPR applies to IVMPs only)

• This surveillance programme is based on:

– Article 114 of EU Directive 2001/83/EC as amended (for human vaccines and medicinal products derived from human blood and plasma) : all batches tested

– Articles 81 & 82 of EU Directive 2001/82/EC, as amended, for immunological veterinary medicinal products (IVMPs) : only products from an agreed list are tested

Surveillance

programmes

54

OCABR/OBPR cont’dHow the programme works…

• OMCLs receive samples of a batch from the manufacturer or MAH before the batch

is placed onto the market. A batch is tested/examined in only 1 OMCL

• The OMCL also reviews the manufacturers’ batch production records and test

results

• The OMCL performs a set of commonly agreed tests to independently check the

quality of the batch

• The goal is to check if the batches comply with the specifications as defined in the

relevant approved marketing authorisation dossier

• Compliant batches are issued an EU OCABR certificate by the testing OMCL/CA.

Failed batches receive a non-compliance notice and this is shared with all network

members

Surveillance

programmes

55

OCABR/OBPR cont’dMutual Recognition underpins/support this programme

• The batch release certificate is mutually recognised within the EU/EEA,

Switzerland and Israel (human vaccines only), and is also recognised as a sign

of quality in other parts of the world.

• The MAH uses the OCABR certificate to apply to the local CAs for permission

to actually place the batch onto the local market

• Note: Only certain IVMPs are eligible for OCABR.

– This is determined by common agreement across the Network.

– Otherwise OBPR, based on a protocol review only, can be applied to

IVMPs, resulting in an OBPR certificate recognised throughout the network.

– See Benefits of official batch control and surveillance for immunological

VMPs, www.topra.org, Regulatory Rapporteur – Vol 13, No 4, April 2016

Surveillance

programmes

56

The OCABR/OBPR Programme

Statistics

Surveillance

programmes

B = blood, V = vaccine, FP = Final Product, BUP = upstream product i.e. plasma pool viral safety screen

Nu

mb

er

of

ba

tch

es t

este

d

OMCLs

Human Biological OCABR Activity 201616 OMCLs performedOCABR for the Network in 2016

OMCLs have different profiles and different capacities

Total vaccine = 4197 batches (146 monovalent bulks )

Total blood = 7396 batches

Total plasma pools = 11308

Work-sharing spreads theload and allows all member states access to independently controlled batches

0

500

1000

1500

2000

2500

3000

A B C D E F G H I J K L M N O P

BFP

BUP

VFP

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API SurveillanceWorking Group on API Testing was established in 2011

At least one meeting per year; around 15 group members

Tasks of the group: fostering collaboration between OMCLs in the

quality control and “fingerprint analysis” of APIs on the European

market and raising awareness of the valuable OMCL contributions in

this field

This is achieved by

• Sharing information via a common API testing database (module of

MRP/DCP database)

• Developing sampling strategies/RB selection of API samples

• Running market surveillance programmes applying, amongst others,

chemometric methods

• Organising training for Network members

• Drafting relevant OMCL Network documents

Other Testing activities

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Gene Therapy Products

Other Testing activities

Working Group created in 2008 to foster collaboration between

OMCLs active in the field of GTP testing

11 active OMCL members (status 2017)

Goals of the WG:

• Sharing of knowledge and latest technologies

• Establishment of methods and reference standards

• Centres of Excellence

Target vectors:

Adenovirus-associated vectors (AAV), Plasmids, Poxvirus

vectors, Retro-/lentivirus vectors, Non-replicative adenovirus

vectors (AV), HSV1-based vectors

Need for more manpower: more OMCLs and/or include external

partners, i.e. academia/manufacturers, in collaborative studies

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Zoom in on

activities to detect and combat

falsified and illegal medicines At OMCL level

At GEON level

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OMCL

Falsified Medicine Testing ActivitiesOMCLs routinely collaborate with customs, police, law courts

and health authorities in a number of member states on the

identification and quantification of falsified/illegal medicines.

e.g. they support forensic/customs labs with complementary testing,

and they act as technical experts at court

A decision was made in 2004 to better co-ordinate the work of the

individual OMCLs in the field of falsified/illegal medicines testing, to

share information between all GEON members and to set up

common programmes with the help of the Secretariat (EDQM)

This helped achieve increased levels of collaboration with the

above stakeholder groups

FM testing at OMCLs’ level

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GEON’s

“Anti-Falsified medicines” activities

– Counterfeit/Illegal Medicines Working Group

Operational since 2011; 2 meetings per year

• Falsified Medicines Documents for the GEON

Internal and public OMCL documents including “Aide memoire for the testing of suspected illegal and counterfeit medicines”

– “Falsified Medicines Report” Data Pool – Know-X database

More than 3,600 OMCL case reports uploaded by December 2017

• Suspicious Unknown Products (SUP) Project

8 studies finalised by the end of 2017

• Falsified/Illegal Medicines Testing Training and Symposia

3 symposia and 13 hands-on training sessions for OMCLs by October 2017

• Market Surveillance Studies on Suspected Illegal Products (MSSIP)

3 MSSIPs by December 2017

– Novel Approaches – the API Fingerprinting Project

Third MSSFP launched in 2017

FM testing at GEONs’ level

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Benefits

“Anti-Falsified medicines” activities

– Facilitates the sharing of technical know-how and

expertise on the detection of falsified/illegal medicines

– Facilitates the sharing of intelligence and information

in this area between OMCLs and NCAs

– Helps OMCLs develop competencies in falsified

medicines testing activities

– Offers a forum for OMCLs active in this area to

exchange information with other stakeholders

– Speaks as one voice with stakeholders

FM testing at GEONs’ level

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PART 2

OMCL specific

information

Anses, Agence Nationale du Médicament Vétérinaire (ANMV)

UNITÉ SURVEILLANCE DU MARCHÉ

8 rue Claude Bourgelat (lab : 10 B rue Claude Bourgelat BioAgroPolis)

Parc d’activité de la Grande Marche Javené CS 70611

F-35306 FOUGERES CEDEX

FRANCE

OMCL contact for Fougères lab : jocelyne.verdon@anses.fr

TEL: +33 2 99 94 78 49

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2 OMCL in Anses !

- One OMCL in Fougères (see next slides)

- One OMCL in Nancy (OCABR for rabbies vaccines),

certificates delivered by ANMV as CA (not detailed here)

Jean-Pierre Orand, director

N., deputy director

Gérard Moulin, deputy director

Sylvie Goby, executive secretary

European and international affairs

N.

Legal affairs

Paule Carnat-Gautier

Quality management

Valérie Colin

Health and safety

Jérôme Blot

I.T.

N.

Library

Emmanuelle Chiffoleau

Registration unit

Maryse Georgeais

Registration unit

Maryse Georgeais

Pharmaceuticals assessment

unit

Laure Baduel

Pharmaceuticals assessment

unit

Laure Baduel

Immunologicals assessment

unit

Jean-Claude Rouby

Immunologicals assessment

unit

Jean-Claude Rouby

Inspection unit

Grégory Verdier

Inspection unit

Grégory Verdier

Business licence unit

Nathalie Legrand

Business licence unit

Nathalie Legrand

Market surveillance unit

Flore Demay

Market surveillance unit

Flore Demay

Marketing authorisation department

Sophie BarreteauPharmacovigilance department

Sylviane Laurentie

Inspection and market surveillance

department

Mickaëlle Sachet

Administrative, financial and technical

department

Frédéric Mokrab

HR : Sarah Salmon

OMCL

OMCL presentationFrench agency for veterinary medicinal products

OMCL presentation :

ANMV Fougères (OMCL-

FR_Anses-F) Vet OMCL – only pharmaceuticals (no vaccines)

3 HPLC/DAD – 1 spectrometer Raman –

classical tests (pH, density, loss on drying, Karl

Fisher,…) - label check

MJA recognition versus ISO 17025 (2007-2011-

2014 - 2019 (planned)) (certificate available on OMCL

database and on request)

Screening methods for API content in series of

finished products (same API and pharmaceutical

form)66

OMCL presentation 50 to 80 products/year (62 batches in 2018)

Most of the time, sampling at wholesalers, on

site or after selection on a list, by an

inspector from the same unit of the OMCL

Program with RB (Risk Based) quotation with

extensions to make series (+ other

departments demands and OOS follow up)

Active in MRP/DCP (18 products in 2017).

The only one vet OMCL to accept samples

from other OMCL in 2017 (see next slide)

67

30

25

20

15

10

5

0

5

10

15

20

2017

Batches accepted as TOMCL Batches supplied as POMCL

Sample exchanges:2017

Caroline Offerlé©2018

EDQM, Council of Europe.

All rights reserved.

General figures

Life-cycle of projects

Project content

Information sharing

Batch information

Benefits

OMCL presentation

Counterfeiting

Development of a database of vet products using regular

programme samples,

Use spectrometer Raman to test samples from internet

Centrally Authorised Product testing

Try to candidate to one project every year.

In 2017, participation, with HU vet OMCL, to the first

generic CAP program : testing of meloxicam vet

products (11 batches of solutions for injection + 5

batches of API)

69

OMCL presentation

Active in the GEON (General European OMCL

Network)

Participation to all annual meetings

Frequent presentations during annual meetings,

EDQM conferences or workshops,

J. Verdon elected to Advisory group in 2013 (4

years)

J. Verdon : MJA technical auditor

Participation to different working groups for

years, the last one being the Risk Based

quotation group.

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For more information on the activities of the General European OMCL Network please consult the section “OMCL Network” on www.edqm.eu

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