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SOHO V&S Vigilance and Surveillance of Substances of Human

Origin

(A project co-funded by the EU Programme of Community Action in the Field of Health)

ISCT ANNUAL MEETING18 MAY 2011

Dr Fewzi TeskratSpecial advisor for Human Products

SOHO V&S WP 5 Vigilance in ART

Inspections and Companies DepartmentAFSSAPS

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General Aim of the Project:General Aim of the Project:

To support EU Member States in theTo support EU Member States in the establishment of effective Vigilance &

Surveillance systems for tissues and cells used in transplantation and in assisted

reproduction.

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SOHO V&SSpecific Objectives

1. To provide guidance to EU Competent Authorities on the investigation and management of Serious Adverseinvestigation and management of Serious Adverse Reactions and Events associated with tissues and cells for transplantation and for assisted reproduction

2 To provide training to EU Competent Authority officers in2. To provide training to EU Competent Authority officers in the investigation and management of Serious Adverse Reactions and Events associated with tissues and cells for transplantation and for assisted reproduction

3. To provide guidance for professionals working in EU hospitals and clinics on their roles and responsibilities in relation to supporting traceability and vigilance of tissues pp g y gand cells for transplantation and assisted reproduction

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Specific Objectives

4. To increase awareness and transparency among p y gregulators, professionals and the general public regarding risks associated with human tissues and cells and the steps taken to mitigate themcells and the steps taken to mitigate them.

5. To promote global standardisation and p gcommunication in vigilance and surveillance of tissues and cells for transplantation and assisted reproductionreproduction

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PartnersCo-ordinating Partner: CNT

Steering CommitteeSteering Committee• Donor Action Foundation• Irish Medicines Board Inspectorate Department• National Transplant Organisation (ONT) Spain• National Transplant Organisation (ONT) Spain • Agence de la Biomedecine, France • AFSSAPS, France • National Centre for Tissue and Cell Banking Poland• National Centre for Tissue and Cell Banking Poland • Human Fertilisation and Embryology Authority UK • Human Tissue Authority

World Health Organisation• World Health Organisation

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Collaborating Partners (26)

• Bulgarian Executive Agency for

• EBMT• EATBAgency for

Transplantation • Danish Medicines Agency• Federal Ministry of Health,

Austria

• EATB• ESHRE• EEBA• WMDA• AATB• Paul Ehrlich Institute,

Germany• Ministry of Health and

Social Welfare, Croatia• Assisted Reproduction

• AATB• AABB• FDA• PHAC• US CDC• Assisted Reproduction

Registry, Italy• Healthcare Products

Inspectorate, the Netherlands

• US CDC• University of Ottawa• University Hospital Bratislava, Slovakia• Public Health Agency, UK• TRIP the Netherlands• Ministry of Health Malta

• Slovenia Transplant• Ministry of Health, Cyprus

• TRIP, the Netherlands

• International Haemovigilance Network (IHN)

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Planned Project Outputs• Report of a survey of EU V&S systems (CAs)• Guidance Document on V&S in ART in the EU• Enhancement of Eurocet platform to include vigilance• Report on serious adverse reactions in living donorsReport on serious adverse reactions in living donors

of tissues and cells.• Guidance for EU regulators on the detection and

management of Illegal and Fraudulent Activity in g g yTissues and Cells

• Guidance Document on investigation and communication of Serious Adverse Reactions and Events in Tissues and Cells

• Training course model for investigators of Serious Adverse Reactions and Events

• V&S Guidance for Clinical Units

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SOHOV&S Project ShapeKey Technical Activities

Phase 1: Exploration Phase II: Guidance Phase III: Dissemination and 

TrainingWP4 Questionnaire Survey Report g

WP5 ART donor V&S Workshop Guidance

WP1 Eurocet Enhanced Platform

WP5 Review of Living Donor V&S

WP7Guidance

for R l t

ReportWP8

Training Course

WP6 Review of Illegal and Fraudulent Activity

RegulatorsGuidance

WP8Training

Course

WP7 I t ti lWP2

Global V&S ConferenceWP9

Guidance for Cli i l U

WP7 International Workshop on Investigation

and Reporting (Notify)Report

WP9 Consultation with professionals in TEs and

Cinical Users

Clinical Users of Tissues and Cells

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Objective of Work Package 6

• Review cases of suspected or proven illegalReview cases of suspected or proven illegal and fraudulent activities (IFA) related to tissues and cells

• Develop guidance to aid in detecting / identifying, investigating and managing such situations.

• Draw upon the experience and findings from EU M b St t d thi d t iEU Member States and third countries

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( )Fraudulent and illegal activity (IFA)

• CoE definition : Illegal and fraudulentCoE definition : Illegal and fraudulent activities in organs, tissues and cells occurs when there is the illicit procurement, preparation, storage, offering, distribution, brokerage, transport or implantation of

ti d llorgans, tissues and cells.

The prevention and détection of IFA is a major issue because of the serious damage that IFA cause to the image of donation and transplantationimage of donation and transplantation.

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Guidance for Competent Authorities on Illegal and Fraudulent Activity• (Work package 6 - led by AFSSAPS)• 3 meetings since May 2010 (Paris, Dublin, Vienna)• Outline guidance structure agreed

Questionnaire designed for EU Competent• Questionnaire designed for EU Competent Authorities – distributed in July –

• The questionnaire has collected valuable information – information on current practices and enforcement powers– Individual descriptions of instances of IFA with information

on how they were managed by regulators - lessons learned 16 b itt d– 16 cases submitted.

• Drafting group will meet in May 2011 in Vienna.

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CConsiderations re IFA• Commercial activities which generate an g

important financial gain

• Needs higher than available supplies

• Insufficient inspection of the procurement establishments

• Lack of specific training of the inspectors on IFAIFA

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CConsiderations re IFA• Insufficient compliance with regulationsInsufficient compliance with regulations

• Insufficient cooperation in the fieldInsufficient cooperation in the field

• Trafficking in tissues is easier• Trafficking in tissues is easier

• Demand for tissues by the pharmaceutical• Demand for tissues by the pharmaceutical industry

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Ethical aspects re IFA

• Exploitation of vulnerable groups p g p

• Search for unclaimed bodies at morguesg

• Lack of information and consent from next of kin

F l ifi ti f t f• Falsification of consent forms

R i b t f bl• Reimboursement of unreasonnable expenses

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Ethical aspects re IFA

Payment issuesPayment issues

• Medical teamed ca tea

• Next of kin (e.g. for the burial expenses)

• Personnel at the morgues

• Brokers (in the case of cord blood)

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Safety and security aspects re IFASafety and security aspects re IFA

• Non respect of donor selection criteria

• Falsification of the donor testing results

Di t ib ti f ti ith t f t d t• Distribution of tissues without safety data

• Lack of a cross-check of donor records with those ot the TE

• Insufficient audit of procurement activities by tissue bank

• Relabelling of products after expiry dateRelabelling of products after expiry date

• Exportation and importation without authorization

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Analysis and synthesis of the existing documentation• Charter of fundamental rights of the European Union

(2000)

• CoE : The Additional Protocol supplements the• CoE : The Additional Protocol supplements the Council of Europe Convention on Human Rights and Biomedicine (Oviedo) (2004)

• United Nations (Preventing, combating and punishing ( g, g p gtrafficking in human Organs - Report of the Secretary-General) (2006)

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Analysis and synthesis of the existing documentation• United Nations : The report on Vienna forum to fight

human trafficking (2008)

• CoE : Trafficking in organs tissues and cells and• CoE : Trafficking in organs, tissues and cells and trafficking in human beings and the replies to the questionnaire for Member States on organ and tissue trafficking (2009)trafficking (2009)

• WHO : Resolutions and decisions of the Executive Board for Human organ and tissue transplantation (2009)*

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Aims of the questionnaire• To identify the legislative & operational tools that y g p

support Competent Authorities in this area

• To gather information about nature & extent of IFA problem in the European Union

• Scope - Directive 2004/23/EC on tissues & cells used in transplantation & assisted reproductionused in transplantation & assisted reproduction

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QuestionnaireTo the Competent Authorities of EU Member StatesTo the Competent Authorities of EU Member States

Legislation in place at Member State levelMember State level

Measures in place at CA level

Experience with IFA of tissues and cellstissues and cells

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P li i Fi diPreliminary Findings

32 Countries responded32 Countries responded

27 EU Member States5 Others

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Instances of IFA- contacts with CAs

– How the fraudulent activity was detectedHow the fraudulent activity was detected

– How the situation has been managedHow the situation has been managed

What action was taken (penalties others )– What action was taken (penalties, others,..)

What was the follow up and results– What was the follow up and results

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OOther contacts

Contacts and meeting with others officialContacts and meeting with others official instances

- Europol/Interpol

- justice (Eurojust)j ( j )

(sharing experiences on other types of IFA)(sharing experiences on other types of IFA)

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IFA CasesTissue / cell /

No Cause of suspicion How detected / identified/

Cord blood / Cord blood stem cells/

6 • Serious adverse eventreported

• Brochures distributed to

• Use of ‘customer’ to inquire aboutthe service and personnel admittedthis service provided for a while.stem cells/

cord tissue Brochures distributed to clinics

• Alerted by a civilian

this service provided for a while.• Not part of Directory of locally

licensed establishments• Serious adverse event reported to

established reporting system• Unable to verify the source of stem

cellsBones 3 • Complaint by recipients • Following site inspectionBones 3 • Complaint by recipients

• Information provided by a former member of establishment

• Following site inspection• After reviewing patient records• Interviews with person involved in

procurement• Interviews with person responsible

for exportation of products

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IFA CasesTissue / cell / N

oCause of suspicion How detected / identified

Musculoskele 1 Questionable records • Inspections and interviews atMusculoskeletal tissue

1 Questionable records • Inspections and interviews atrecovery site

• Examination of donor records

Gametes / embryos / oocytes / Sperm cells.

4 • Payment of eggdonors from thirdcountry

f

Examination of donor recordsDonor interviews

Sperm cells. • Recurrent use ofsame donors fromthird countriesN li ti f• No application forsite authorisation

None reported

13p

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CAdvice to the CAs• Avoiding manipulation by the pressAvoiding manipulation by the press

• Avoiding manipulation by stakeholdersAvoiding manipulation by stakeholders

• Care in handling information (cross check)• Care in handling information (cross check)

• Awareness of « business intelligence »• Awareness of « business intelligence »

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Acknowledgements

• Frances Delaney (Afssaps project advisor)Frances Delaney (Afssaps project advisor)

• Deirdre Fehily (CNT)• Deirdre Fehily (CNT)

• Teena Chowdhury (HTA)• Teena Chowdhury (HTA)

Type tissue / cell involvd

Suspicion /Issue How detected / identified

Prescribed activity involved

Who investigated Final outcome

Cord blood Local procurement Brochures of import Police Pending court

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Cord  blood Local procurement and storage in another MS in a non‐licensed TE

Brochures of Establishment were distributed to Clinics

Competent

import Police Pending court decision for prosecution

Competent authority contacted the CA of the MS that the cord blood was stored. Verified the absence of License

Cord  blood Brought to the attention of inspectorate by civilian

Applied for licensing the activity after CA enquired about such activity

Activity involved procurement, testing, processing, storage

CA and police Pending court decision

y

Before CA enquiry to the TE, we used dummy customer to inquire about this 

g

service and the TE personnel admitted that they provide this service for a while.

bones Complains from Complain from Import By the police and The importer has

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bones Complains from patients who have been affected after transplantation (quality defect of the final products)

Complain from many recipient

After reviewing the patient records• no medical 

Import By the police and CA (inspection done on sites)

The importer has been judged and put in jail and has been obliged to pay a important amount of money p )

record of the procurement

establishment• serological 

test were 

yto the justice

missing or not done

• quality defect of the bones after surgery which injured and affected many patients

use of bones after expiry date

no traceability data

Musculoske CA notified by one  Inspection  Tissue Recovery – CA + police Procurement 

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letal tissue, including bone and skin

of the processors who received tissue recovered by this firm.  The processor had questions 

conducted at the recovery firm.  Inspectors interviewed the president/owner 

tissues were being recovered without adequate donor screening and testing.

organization team have been put in jail

regarding the records provided by the recovery firm.  For example, the telephone numbers f h d ’

and several employees, obtained statements and collected donor 

d d hof the donors’ physicians were incorrect for over 25 donors.

records and other relevant evidence.  Investigators also performed inspections at 

l f lseveral funeral homes involved in the case, and obtained death certificates from State and localState and local authorities.

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SO O & SSOHO & VS

Th k f tt tiThank you for your attention