Ethics and Regulation of Human Cell and Tissue Transplantation

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941Bulletin o the World Health Organization | December 2007, 85 (12)

IntroductionFrom its origins with the rst successultransplant o banked cadaveric tissuein the rst hal o the 20th century, thetransplantation o human tissues (Hs)has become a widely practised surgical

procedure.1 oday, Hs are transplantedacross the globe not only to save lives,but also to improve lives through recon-structive and cosmetic interventions.Due to the growing demand or Hsand the increasing quality and saetystandards required in tissue banking,many o the original hospital-based tis-sue banks, designed to meet local needs,have been replaced by national or mul-tinational H organizations which selltheir products internationally and mayoperate on a or-prot basis.

In parallel, the transplantation ohuman cells (HCs) haematopoieticprogenitor cells in particular hasevolved into a widely used clinical ac-tivity. Ater the rst successul bonemarrow transplants in the 1960s, sub-sequent advances in immunosuppres-sive and antibiotic therapy have madehaematopoietic progenitor cell trans-plantation an established treatment or

Abstract The transplantation o human cells and tissues has become a global enterprise or both lie-saving and lie-enhancingpurposes. Yet current practices raise numerous ethical and policy issues relating to inormed consent or donation, prot-making,and quality and saety in the procurement, processing, distribution, and international circulation o human cells and tissues. Thispaper reports on recent developments in the international debate surrounding these issues, and in particular on the attentioncell and tissue transplantation has received in WHOs ongoing process o updating its 1991 Guiding principles on human organtransplantation. Several o the organizers o an international working group o stakeholders rom a wide range o backgroundsthat convened in Zurich in July 2006 summarize the areas o normative agreement and disagreement, and identiy open questionsregarding acts and undamental concepts o potential normative signicance. These issues must be addressed through developmento common medical, scientic, legal and ethical requirements or human cell and tissue transplantation on a global basis. Whileguidance must accommodate the distinct ethical issues raised by activities involving human cells and tissues, consistency withnormative rameworks or organ transplantation remains a prime objective.

Bulletin o the World Health Organization 2007;85:941948.

Une traduction en ranais de ce rsum fgure la fn de larticle. Al fnal del artculo se acilita una traduccin al espaol.

International perspectives on the ethics and regulation ohuman cell and tissue transplantationAnnette Schulz-Baldes,a Nikola Biller-Andorno a & Alexander Morgan Capron b

.

a Institute o Biomedical Ethics, Center or Ethics, University o Zurich, Zollikerstr. 115, 8008 Zurich, Switzerland. Correspondence to Annette Schulz-Baldes (e-mail:[email protected]).

b Gould School o Law, University o Southern Caliornia, Los Angeles, CA, United States o America.

doi: 10.2471/BLT.06.038703

(Submitted: 10 November 2006 Revised version received: 3 July 2007 Accepted: 15 July 2007)

a wide variety o genetic and malignantdiseases.2 As with H, haematopoieticprogenitor cells are exchanged globallytoday,3 driven by the need to nd adonor that closely matches the humanleucocyte antigen type o the recipient.

Prot-making has also been introducedinto the eld with the establishmento or-prot (private) autologous cordblood banks and a growing number oclinics oering experimental cell trans-plants.4,5

Current practices in HC/H trans-plantation raise several questions thatneed to be addressed jointly by clini-cians, scientists, health regulators andethicists as well as representatives o civilsociety, in particular HC/H donorsand recipients. Te increasing com-mercialization o HC/H productshas multiplied opportunities or prot-making and increased the risk o clini-cally unsae and unethical practices(particularly in H procurement).Recent scandals in the United Stateso America6,7 and other countries 8,9involving nonconsented procurementunderline the urgent need or a com-mon global technical and ethical rame-

work. Although a number o regulations

on HC/H transplantation have beenadopted in the past several years or arecurrently under discussion,1012 nationalregulation and oversight o HC/Htransplantation is nonexistent or ine-cient in many countries.

Moreover, regulation is no longermerely a national matter because HCs/Hs can be processed, preserved andeasily transported around the globe.

While the international circulation oHCs/Hs can acilitate access, it canalso spread tainted material, create globalinequities in donation or accentuateinequities in access to HC/H services.Te lack o ethical guidance and the ex-istence o unmonitored or unregulatedHC/H procurement and distributionrepresent a serious international risk toboth donors and recipients o cells andtissues.

WHO has given special attentionto human cell and tissue transplanta-tion in the process o updating its1991 Guiding principles on human organtransplantation,13 an activity which hasbeen ongoing since 2004.14 As parto this process, WHOs Departmentso Essential Health echnologies andEthics, rade, Human Rights and


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942 Bulletin o the World Health Organization | December 2007, 85 (12)

Policy and practiceEthics and regulation o human cell and tissue transplantation Annette Schulz-Baldes et al.

Health Law held a meeting jointlywith the Institute o Biomedical Ethics,University o Zurich, in July 2006. Temeeting involved an international groupo experts on transplantation medicine,nursing, ethics, social sciences, law and

policy-making. Meeting participantswere: suyoshi Awaya (Okayama Uni-versity, Japan), Nikola Biller-Andorno(University o Zurich, Switzerland),

Arlinke Bokhorst (Bio Implant Services,Leiden, Netherlands), Alexander Capron(WHO, Geneva, Switzerland), MarCarmona (WHO, Geneva, Switzerland),Francis Delmonico (ransplantationSociety, Boston, MA, United States),Deirdre Fehily (Centro Nazionale ra-pianti, Rome, Italy), Gregorio GarridoCantarero (Organizacin Nacional

de rasplantes, Madrid, Spain), JensGobrecht (WHO, Geneva, Switzer-land), Alois Gratwohl (University oBasel, Switzerland), Bernadette Haase-Kromwijk (Dutch ransplant Founda-tion, Leiden, Netherlands), MarisaHerson (Asociacion Latinoamericanade Bancos de ejidos, Sao Paulo, Brazil),Roman Hitchev (Osteocentre BulgariaEAD, Soa, Bulgaria), Liisa Kok (DutchMinistry o Health, Netherlands), JanKoller (Central issue Bank, Bratislava,Slovakia), Teo Le Roux (University oPretoria National issue Bank, South A-rica), Nabila Metwalli (WHO EMRO,Cairo, Egypt), Conrad Mller (Swis-stransplant, Berne, Switzerland), Ales-sandro Nanni Costa (Centro Nazionalerapianti, Rome, Italy), Aziz Nather(National University o Singapore,Singapore), Luc Noel (WHO, Geneva,Switzerland), Jan Pierce (American As-sociation o issue Banks, McLean,VA, United States), Virender Sangwan(LV Prasad Eye Institute, Hyderabad,

India), Volker Schmidt (National Uni-versity o Singapore, Singapore), AnnetteSchulz-Baldes (University o Zurich,Switzerland), Naoshi Shinozaki (CorneaCenter, Ichikawa, Japan), Magi Sque(University o Southampton, UnitedKingdom), Caroline rouet (Euro-pean Commission, Brussels, Belgium),

Yongyudh Vajaradul (Siriraj Hospital,Bangkok, Tailand), Rdiger vonVersen (German Institute or Cell andissue Replacement, Berlin, Germany)and Kathryn Wood (ransplantation

Society, Oxord, United Kingdom). Temeeting ocused on tissues notablybone, skin, tendon and ascia as well ascornea, pericardium, heart valves, arteries

and veins, procured or clinical use romdeceased persons and haematopoieticstem cells rom cord blood and adultliving donors. Issues relating to HCs/Hs retained or research or educationpurposes, HCs/Hs rom human em-

bryos or rom animals, human blood orblood products and human reproductivecells, such as oocytes and spermatocytes,

were not addressed.Te aim o the meeting was to

delineate areas o normative consensusand divergence about HC/H trans-plantation. Drawing on the ReectionDocument that resulted rom the meet-ing,15 this paper provides the perspectiveo several o the meetings organizerson the agreements and disagreementsamong stakeholders that emerged re-

garding normative issues, as well as actsand undamental concepts o potentialnormative signicance.

Current ethical and policyissues in HC/HT transplanta-tion areas o agreementand disagreement1. Consent or removal o humancells and tissuesIn line with universal ethical principles,

the meeting participants agreed that in-ormed consent was necessary wheneverobtaining human cells and tissues. Withregard to living donors, this conclusion

was unambiguous: HCs/Hs shouldonly be procured ater the donor hasgiven inormed and voluntary consent,or, in rare cases when a minor is a donoro haematopoietic progenitor cells to aclose relative, a surrogate has consentedand the minor has assented ater careuldeliberation and proessional scrutiny.

While donors should be able to with-draw consent at any time beore actualprocurement, withdrawal can be highlyproblematic when, or example, the re-cipient is already immunosuppressed ortransplantation o haematopoietic pro-genitor cells. Tis should be made clearto the donor at the time o consent.

Yet consent in and o itsel was notconsidered sufcient to justiy HC/Hprocurement rom living donors whichcan cause serious, even irreversible harm.Participants thereore agreed that live

HC/H donation should not be prac-tised unless there is no easible alterna-tive and means are in place to eectivelyprotect the donors health and saety.

Te implications or deceased Hdonation were less straightorward. Sub-stantial normative disagreement existedabout whether presumed consent isethically equivalent to actual inormedconsent, mirroring the longstanding de-

bate regarding consent or post-mortemorgan donation. However, participantsbroadly agreed concerning the practicalchallenges o presumed consent systems;namely, how to conduct public debates,to veriy a positive societal attitudetowards donation and to incorporatesuitable measures or continued publiceducation about the donation process,its implications and the procedures orindividuals to opt out.

Meeting participants also agreedthat, irrespective o the consent scheme,

bereaved next o kin or legal representa-tives must be approached by speciallytrained proessionals who are compe-tent in sensitively discussing deceasedH donation (including the donorshistory) and providing ollow-up sup-port. As ar as possible, participantsthought the inormation given in thedonation discussion should reect theinormational needs o the consentingparty. Te exact amount and depth oinormation, however, were contentious.Because inormation about the proce-

dures o HC/H activities is complexand continuously changing, requiringully-inormed consent rom an emo-tionally distressed person seemed overlyarduous to some. It was particularly con-troversial whether inormation shouldbe provided that relates to whether theprocessing or distribution o cells or tis-sues would produce a prot or surplus.Some suggested a nuanced approachthat would require inorming the nexto kin or legal representatives only ithe institutions involved in HC/H

processing or distribution dispenseprots among owners or shareholders.Views also varied on the need to inormabout the possibility that donated cellsor tissues would be used abroad or orcosmetic purposes. Yet all participantsconcurred that consent cannot be validi the consenting party is deceived ordonates under alse assumptions.

Mirroring ongoing debates aboutprocurement o organs, participants alsodisagreed about whether next o kin shouldbe allowed to veto the choice a person had

made to donate tissue ater death or, in apresumed consent system, the donationthat would occur when the deceased hadnot opted out. Some meeting participants


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Policy and practiceEthics and regulation o human cell and tissue transplantationAnnette Schulz-Baldes et al.

argued that, to increase donation rates,the wishes o designated donors shouldbe respected even i the next o kin object.Others asserted that doing so would beunacceptable, particularly in societies

where amily ties are strong.

2. Confdentiality o donor dataCondentiality o donor data was con-sidered a requirement or all activitiesinvolving HCs/Hs. However, par-ticipants acknowledged exceptions inthe case o testing results which indicatea high risk o serious and preventableharm to third parties and agreed thatdonors or next o kin should be inormedaccordingly in the donation discussion.Ideally, consent should be sought ordisclosing results which indicate a condi-

tion that cannot be treated due to resourceconstraints (e.g. anti-retroviral treatmentin resource-poor countries).

3. Unpaid donationBy analogy to organ donation, all meet-ing participants concurred that dona-tion o cells and tissues should remainunpaid, because payment can undulyinduce vulnerable and poor living do-nors or constitute a conict o interestor next o kin or legal representatives indeceased donation, and is likely to result

in inequities in donation. Some alsoworried that paying or cells or tissuesincreases the likelihood o inaccurateresponses on donor-history question-naires, resulting in transplanted materi-als carrying an undetected disease. Atthe same time, the need to removenancial disincentives or HC/Hdonation was recognized as it has beenor organ donation. Participants there-ore concluded that only compensationor travel expenses, loss o earningsor other expenses actually incurred in

donation may be allowed and must betransparent and regularly audited. Gen-eral consensus also existed that or-protorganizations should not be involved inpromoting cell and tissue donation, ordiscussing it with potential donors, toavoid conicts o interest.

More generally, although HC/Hprocurement and transplantation havebecome quite common, the undamen-tal legal, economic and philosophicalconcepts o body ownership remainsurprisingly vague or both living and

deceased persons. Tis is startling con-sidering that undamental agreed normsabout ownership are a general precondi-tion or ordinary transactions. Te lack

o an overarching concept o body own-ership also has practical implicationsbecause legal and regulatory denitionso human cells and human tissues re-main to some extent arbitrary, althoughthey heavily inuence practices.

4. Fair procurement o cells andtissuesTere was broad agreement that do-nors should be identied and selectedaccording to air and explicit criteria,above all medical eligibility, equally and

without explicit or implicit discrimi-nation based on social status, race orgender. Meeting participants recognizedthat the geographical location o HC/H procurement acilities inevitablyaects procurement where donation

programmes are not well developed andresources are limited. Tere was alsobroad agreement that consent proce-dures and the methods or approachingpotential donors should be standard-ized, transparent and subject to regularexternal auditing, given that vulnerablegroups are at risk or subtle or overtmanipulation regarding the decision todonate HCs/Hs.

A controversial issue was how tis-sue and organ procurement should becoordinated in those deceased donors

who are medically suitable to donateboth organs and HCs/Hs. Some par-ticipants believed that prot-makingopportunities could bias in avour oprocuring Hs rather than organs (e.g.heart valves instead o the entire heart),

whereas others regarded such scenariosas practically irrelevant. Yet all partici-pants recognized the need to coordinateprocurement, while supporting the gen-eral priority o procuring organs overHs, i clinically appropriate, because

o the greater scarcity o organs andbecause organs are more requently usedor lie-saving purposes. Nonetheless,disagreement remained whether thispriority should be binding.

5. Stewardship or donated cellsand tissues

All meeting participants agreed that HC/H organizations have a responsibil-ity to act as stewards o the donationsentrusted to them or the benets oothers. Most participants concurred that

HC/H activities should, to the extentpossible, ull the intentions or expecta-tions expressed in the consent to donateregarding the uture clinical, research and

educational uses o donated HCs/Hs,the making o prot rom the processingand distribution o the cells and tissues,and their circulation outside the country.Consensus existed that donors or nexto kin should be given the opportunity

to veto uture HC/H use or research,education and training. However, not allmeeting participants supported the rightto veto HC/H circulation abroad or useor cosmetic purposes because o the prac-tical difculties in implementing suchrequests and the concern that includingull inormation about such choices maybe too complex or too emotionally bur-densome or bereaved relatives or otherlegal representatives. Yet all concurredthat procurement organizations shouldnot implement donors instructions to

discriminate against individual recipi-ents, in particular on racial or religiousgrounds.

Participants also endorsed that,in addition to respecting the non-discriminatory wishes o individual do-nors, HC/H institutions and the proes-sion should set priorities or clinical useso HCs/Hs in light o their compatibil-ity with general donor intent. However,even this common perspective did notyield straightorward conclusions. For ex-ample, it remained problematic whether

HC/H use or cosmetic purposes shouldbe rigorously rejected, given that thedistinction between reconstructive andcosmetic interventions is not clear-cutand a decline in certain preparations thatcan be used or both reconstructive andcosmetic purposes could imperil the careo patients in need.

Meeting participants ound it overlysimplistic to rame stewardship by con-trasting or-prot with not-or-protorganizations. For one thing, what itmeans or an organization to be or-

prot is, in many cases, unclear, andprot-making is a descriptive, not aninherently moral attribute. All organiza-tions that process or distribute HCs/Hscan produce a surplus o income overexpense, but the ramework or usingthis surplus diers. Not-or-prot orga-nizations are, at least in theory, subjectto rules that tightly control the extent to

which individuals may receive nancialand material benets; accordingly, sur-pluses must be used in ways consistent

with the organizations purpose, such as

in improving HC/H services or sup-porting other services when the HC/Hactivity is a unit within a publicly undedhealth system. In or-prot organiza-


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tions, in contrast, surpluses that are notreinvested are distributed among theowners (such as the shareholders o cor-porations) and/or lead to higher salariesor the managers.

However, the apparent distinction

between or-prot and not-or-protinstitutions is oten blurred in practice.Not-or-prot institutions may own orcollaborate with or-prot subsidiaries,16and in countries where HC/H orga-nizations do not receive public unding,patients may have to rely on services oor-prot institutions to access neces-sary medical care. Furthermore, or-prot organizations are sometimes in abetter position to invest in high-qualityacilities and/or research and develop-ment, and may thereby promote e-

cient use o donated HCs/Hs andimprovement o services. Tis can helpto ensure enhanced benets rom thedonation or patients, which is also anethical imperative.

Finally, the institutional structureitsel does not indicate the amount oincome. For-prot institutions can gen-erate little prot, while not-or-protinstitutions can have large surpluses.

What matters rom a normative per-spective is the way income is managedand the eects that eorts to generate

surplus revenues have on stewardship,efciency, transparency, accountability,air pricing, responsiveness to local ornational health needs and air alloca-tion. Tese criteria are more importantin evaluating HC/H organizationsnormatively than their ormal prot-making status.

All participants recognized that be-ing operated on a or-prot basis cancreate conicts o interest or at leastthe appearance o such conict. Hence,

the participants agreed that or-protHC/H organizations should not beinvolved in the promotion o donationor the interviewing o donors, surrogatesor next o kin. In addition, regulationsthat minimize commercial conicts ointerest in the processing and possiblythe distribution o cells and tissues wereconsidered necessary.

However, there was considerabledispute as to how a prot-making ori-entation might inuence processingdecisions. Although respective evidence

does not exist, it is conceivable that or-prot institutions would be more proneto process HCs/Hs into the mostprotable products, thereby imperilling

equitable access to services (e.g. acellulardermis products rather than minimallyprocessed skin or burn care).

Meeting discussions yielded theollowing preliminary ethical criteria ororganizations processing or distribut-

ing cells or tissues with a prot-makingorientation: donors, surrogates, next okin or legal representatives should beinormed accordingly; the quality, saetyand price o cells and tissues should beat least comparable to those rom not-or-prot organizations; and the prot-making orientation should not compro-mise equitable access to HC/H services.

6. Quality and saety o HC/HTprocurement and processing

All meeting partic ipants considered

compliance with recent internationalquality and saety standards manda-tory to guarantee the saety o recipients,even i this implies a reduced availabil-ity o HCs/Hs.17,18 raceability (thatis, the capacity to trace cells and tissuesrom the donor to recipients and viceversa) and long-term ollow-up o livingdonors and recipients o cells and tissuesare central elements o saety and qualitymanagement. Many participants envis-aged or the uture the ability to coordi-nate the traceability o organs and tissues

in a common surveillance system withuniversal donor identication numbers,as many organ donors also donate tissues;however, such aspirations were distant orparticipants rom resource-poor coun-tries. Te latter urged the internationalcommunity to adopt minimal standardsor procurement and processing as thesurest way o helping them to balancequality, saety and HC/H availability.

Quality and saety were consid-ered a particular concern in or-protautologous cord blood banking, where

practices are oten substandard. In ad-dition, autologous cord blood bankingis not an evidence-based practice today,but a speculative private investment.4Participants thereore agreed that suchservices should only be oered i qualitystandards correspond to those appliedin allogeneic not-or-prot cord bloodbanks and i parents are ully inormedabout the currently limited clinical ap-plication o autologous cells.

7. Fair distribution o processed

cells and tissuesAlthough the scarcity o HCs/Hs isless marked than the scarcity o organs,there was broad agreement that HCs/

Hs should be distributed airly. Par-ticipants concurred that a air HC/Hdistribution could only be achievedthrough the regulated implementationo transparent allocation criteria andprioritization rules which balance util-

ity and equity considerations in thedistribution process. While participantswere committed to medical need as theprimary consideration in distributingHCs/Hs, because donors generally giveHCs/Hs with the intention to helpothers, they recognized that medicalneed is vague and context-dependent.

Although distribution according tomedical need would imply prioritizingHC/H use or lie-saving purposes overlie-enhancing or cosmetic purposes,participants recognized the practical

limitations in eectuating such prioriti-zation. HC/H processing institutionsrequently do not know where andhow their products will be used. Eveni better oversight was achieved, useo small amounts o cells and tissuesin numerous clinical settings poses aclear practical limitation on designing,much less implementing, sophisticatedallocation schemes even in resource-richcountries. Some also questioned theneed or elaborate algorithms becausemost HCs/Hs can be stored, used as

necessary and imported in case o short-age; moreover, some medical productsor devices only contain traces o HCs/Hs. Nonetheless, all participants agreedthat allocation rules should be generallyand explicitly structured; examples inthis direction already exist.19

Participants also appreciated thatactors other than medical need caninuence the distribution o HCs/Hs,provided they have been dened in a airprocess. Regional balance, waiting time,the number o waiting patients, and

reciprocity o services between procure-ment and processing institutions werementioned (and partially criticized).However, all participants rejected dis-criminatory criteria in the distributionprocess, such as ethnicity and religion.

Some controversy arose about howa prot-making orientation aects HC/H distribution. Several participants

were convinced that or-prot institu-tions should not be involved in distribu-tion, while others denied the assumedconicts o interest in distribution.

Tis disagreement could not be resolvedbecause little is currently known aboutHC/H distribution and the actorsthat inuence the availability o, and


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Table 1. Eight o the central ethical issues in the regulation o human cell (HC) and human tissue (HT) transplantation

Issue Agreement Disagreement

Consent or HC/HT removal No HC/HT removal without consent Inormed consent or donation rom living donors Disclosure o possible limitations to withdrawing

consent

Inormed versus presumed consent in deceaseddonation?

Role o the next o kin (amily veto) in deceased

donation?Obligation to inorm about possible prot-making,

international circulation or cosmetic applications?

Condentiality o donor data Condentiality o donor data (with exceptions)

Unpaid HC/HT donation Unpaid donation Removal o nancial disincentives or donation

Only not-or-prot institutions in donationdiscussions and the promotion o donation

Fair HC/HT procurement Fair criteria or donor identication and selection Binding priority o organ over HC/HT recovery?

Stewardship or donatedHC/HT

Obligation to honour and realize donor intent Option to veto HC/HT use or research or education No discriminatory restrictions o HC/HT use

Stewardship, eectiveness, accountability, airpricing, responsiveness to local and/or nationalneeds and air allocation are more important thaninstitutional or-prot/not-or-prot structure

Option to veto HC/HT use abroad or or cosmeticapplications?

Quality and saetymanagement

Necessity o quality and saety management Long-term ollow-up o donors and recipients

Balance between quality, saety and HC/HTavailability in resource-poor settings?

Fair distribution o processedHC/HT

Need or allocation criteria and prioritization rulesdespite limited scarcity

General priority o HC/HT use or lie-saving overlie-enhancing and cosmetic purposes

General priority o local and/or national sel-suciency

Scope o allocation criteria and prioritizationrules: institutional, national, subregional?

Institutional reciprocity as an allocation criterion? For-prot organizations in HC/HT distribution? General priority o subregional sel-suciency? International HC/HT circulation to subsidize public

health care?

Consent or HC/HTtransplantation

No HC/HT transplantation without voluntary andinormed consent

Obligation to inorm recipients about prot-making and international circulation?

Limits o consent or medically contested uses?

normative agreement or disagreement was analogous to that for organ transplantation;

normative agreement or disagreement was specic or HC/HT transplantation.

equitable access to, HC/H services, aswell as about the impact o internationalcirculation, legal denitions and regula-tory requirements.

Whether the scope o allocationrules should be institutional, national,subregional or international was equally

controversial. While trade in human cellsand tissues can help address patientsneeds worldwide, it can arguably aggra-vate global inequities both in donationand access to services. It is important torecognize that H/HC organizations in particular those with a prot-makingorientation can experience a conict ointerest between providing HCs/Hsto the donating population and gen-erating income, inter alia by exportingHCs/Hs. o reduce the potential orsuch inequities, participants concludedthat local or national sel-sufciencyshould have a general priority over in-ternational solidarity and that HCs/Hs

should be exported only i exportationactivities are controlled and transpar-ent. Te University o Pretoria Nationalissue Bank, or example, will export amaximum o 10% o its stock providedthat the remaining supply is sufcientto cover national need or three months.

Te idea o subregional sel-sufciency,however, was controversial: some par-ticipants rom resource-poor countriesargued that the international exportationo HCs/Hs ater national needs havebeen met is needed to subsidize publiclyunded national health care.

Finally, meeting participants em-phasized that achieving equity in accessto HCs/Hs is not only a matter o airdistribution but also o health care in-rastructure. ransplant tourism occurs

when people in resource-poor countriesare unable to obtain needed cell or tis-sue transplants locally. Tereore, toachieve sel-sufciency in the provision

o HC/H services, national develop-ment o HC/H organizations shouldbe ostered as ar as resources allow.

8. Consent or HC/HTtransplantation

All meeting participants considered in-ormed and voluntary consent by or onbehal o the recipient a necessary require-ment or HC/H transplantation. Validconsent requires inorming the patientthat a planned intervention contains hu-man material with specic risks, i any, as

well as what is known about the interven-tions eectiveness. Yet the extent to whichrecipients should be inormed aboutall aspects o HC/H procurement,processing and distribution was conten-tious. Participants agreed, however, thatconsent alone is not sufcient to validateexperimental (and medically contested)transplants o cells or tissues as therapy(so-called miracle cures).


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Table 2. Preliminary ethical ramework or the regulation o human cell (HC) andhuman tissue (HT) transplantation

Fundamentalethical principle

Specifcation in the context oHC/HT transplantation

Respect or persons Inormed and voluntary consent or living HC/HT removal Explicit consent during lietime or presumed consent or

deceased HC/HT removal Option to veto uture uses o donated HC/HT or research and

education (and/or cosmetic applications and/or internationalcirculation)

Stewardship or donated HCs/HTs Inormed and voluntary consent or HC/HT transplantation

Non-malecence Minimal quality and saety standards or HC/HT procurement,processing and transplantation

Long-term ollow-up o living donors and transplant recipients

Justice Fair criteria or donor identication and selection Unpaid donation to reduce inequities in donation Fair HC/HT distribution General priority o local and/or national sel-suciency to

reduce global inequities in donation o and access to HCs/HTs

ConclusionTe Zurich symposium was the rst in-ternational meeting on the ethical andpolicy issues in human cell and tissuetransplantation. By selecting, analysingand structuring relevant issues, it aimed

to provide a rst step towards the neededcomprehensive global ramework orHC/H transplantation. In the ollow-ing remarks the authors o this paper

wish to highlight, rom their perspective,the key insights o the meeting to guideuture eorts in this direction.

First, the practice o HC/H trans-plantation has reached a global dimen-sion. Activities o national and interna-tional HC/H organizations and the

worldwide circula tion o HCs/Hsaect the way we practise medicine

and trade health goods and serviceson a global level. Tey also entail in-ternational health risks and have thepotential to create global inequities inaccess to HCs/Hs. For this reason,health authorities and proessionalsrom all countries need to develop andimplement a common normative basisor HC/H transplantation.

Second, activities involving organtransplantation are inherently con-nected with those involving cells andtissues. Many ethical and policy issues in

HC/H transplantation mirror thoseidentied regarding organ transplanta-tion. At the same time, HC/H activi-ties raise distinct questions relating toprot-making, cosmetic applicationsand extensive global exchange and trad-ing. While the regulation o cell and tis-sue transplantation must accommodatethese particularities, consistency withnormative rameworks or organ trans-plantation remains a prime objective.

Tird, the current spectrum opractices in HC/H transplantation is

wide and difcult to pinpoint. It is hardto assess how practices inuence na-tional and international availability o,and equitable access to, cells and tissues.Research on the actual uses and dis-tribution o HCs/Hs in particularon the impact o prot-making andinternational circulation, and on appro-priate allocation schemes is urgentlyneeded.

Fourth, there was considerablenormative agreement among meetingparticipants (able 1), which is encour-

aging or uture work. Some points oagreement may seem trivial consideringthe nuanced debates about the ethicsand regulation o organ transplantation.

However, it should be recognized thatsome o these points contrast starkly

with current practices. For example, atpresent criteria or the identication andselection o potential donors are typi-cally not explicit; or-prot institutionsare requently involved in donation dis-cussions; the ideal o stewardship otenremains rhetorical; allocation criteriaand prioritization rules are exceptional;and cells and tissues are commonlytransplanted without ull disclosure torecipients.

Fith, general points o normativeagreement are difcult to speciy withregard to the large variety o HC/Hproducts. Tere seems to be a dierencebetween transplanting large pieces o in-tact bone and composite tissues suchas entire hands or signicant parts oaces and transplanting orthopaedicscrews that contain traces o bone dust

to speed healing. Te moral signicanceo this intuitive dierence and impli-cations, or example or donor andrecipient consent and air distribution,requires urther inquiry.

Sixth, although the meeting wasnot designed to reach a consensus state-ment, the authors o this paper thinkthat the present areas o normativeagreement render a preliminary ethicalramework or HCs/Hs that remainsto be scrutinized and/or specied (able2). It is based on the three undamental

ethical principles o respect or persons,non-malecence and justice, and in ourview corresponds to the existing normsin organ transplantation.13

Certainly, more work is needed inthis complex area o applied ethics andpolicy-making. It seems clear, however,that the only way orward is movingtowards consistent regulation o, as wellas common medical, scientic, legal andethical requirements or, human cell,tissue and organ transplantation on aglobal basis. Te revised WHO Guiding

principles on human organ transplanta-

tion will be an important step in thatdirection.

AcknowledgementsWe are grateul to all participants othe meeting on Human Cell and issueransplantation An InternationalSymposium on Ethical and Policy Issues(Zurich, 1719 July 2006) or theircritical and pertinent comments on thebackground paper and the ReectionDocument as well as a productive discus-sion during the meeting. In particular,

we thank Deirdre Fehily, Luc Nol (whowas the principal WHO organizer o thesymposium) and Francis Delmonico orvaluable input on earlier versions o thismanuscript. We also grateully acknowl-edge the comments and suggestions othe anonymous reviewers.

Funding: Te meeting was organizedwith WHO, which provided substantialunding, thanks to the generous supporto the Ministry o Health and Con-sumer Aairs o Spain. Te authors also

thank the University o Zurich or host-ing and supporting the symposium.

Competing interests: None declared.


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Rsum

Points de vue internationaux sur lthique et la rglementation de la transplantation de cellules et detissus humainsLa transplantation de cellules et de tissus humains est devenueune entreprise dampleur mondiale, visant sauver des vies et

amliorer des existences. Bien que les pratiques actuellessoulvent de nombreuses questions thiques et politiquesconcernant le consentement inorm au don, ainsi que larentabilit, la qualit et la scurit des processus dacquisition,de traitement, de distribution et de circulation internationaledes cellules et tissus humains. Le prsent article rapporte lesaits marquants rcents dans le dbat international autour de cesquestions et notamment lattention accorde la transplantation decellules et de tissus dans le cadre du processus actuellement menpar lOMS dactualisation des 1991 Guiding principles on humanorgan transplantation . Plusieurs des organisateurs dun groupe

de travail international ayant runi des participants issus dhorizonstrs divers en juillet 2006 Zrich rsument les domaines daccord

et de dsaccord sur le plan normati et identient les questionsrestant ouvertes concernant les aits et concepts ondamentauxpouvant avoir une importance dans la normalisation. Il auttraiter ces questions en dveloppant des exigences mondialescommunes sur les plans mdical, scientique, juridique et thiquepour la transplantation de cellules et de tissus humains. Mme siles recommandations doivent prendre en compte les direntesquestions thiques souleves par les activits aisant appel descellules et tissus humains, la cohrence avec les cadres normatisde la transplantation dorganes reste un objecti primordial.

ResumenPerspectivas internacionales sobre la tica y la regulacin del trasplante de clulas y de tejidos humanosEl trasplante de clulas y tejidos humanos se ha convertidoen una gran empresa mundial que aspira tanto a salvar vidascomo a mejorar la calidad de vida. Sin embargo, las prcticasactuales suscitan numerosas cuestiones ticas y normativas enrelacin con el consentimiento inormado para las donaciones,la obtencin de lucro, y la calidad y seguridad en materiade adquisicin, procesamiento, distribucin y circulacininternacional de clulas y tejidos humanos. En este artculose inorma sobre las ltimas novedades registradas en eldebate internacional sobre estas cuestiones, y en particular

sobre la atencin que ha suscitado el trasplante de clulas ytejidos en el proceso seguido actualmente por la OMS paraactualizar sus Principios rectores sobre el trasplante de rganos

humanos, de 1991. Varios de los organizadores de un grupo detrabajo internacional de interesados directos con muydiversas experiencias que se reuni en Zurich en julio de 2006resumen aqu las reas de acuerdo y desacuerdo normativo yplantean interrogantes por resolver sobre hechos y conceptosundamentales de eventual trascendencia normativa. Estos temasdebern abordarse ormulando requisitos mdicos, cientcos,legales y ticos comunes para el trasplante de clulas y tejidoshumanos a nivel mundial. Si bien las indicaciones deben tener encuenta los aspectos ticos peculiares que plantean las actividades

en que se manejan clulas y tejidos humanos, la coherencia conlos marcos normativos para el trasplante de rganos sigue siendoun objetivo primordial.

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.1991

2006 /

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at: http://www.bisoundation.org/cms/index.php?page=allocationcriteria

Ethics and Regulation of Human Cell and Tissue Transplantation

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