Tuesday, October 17, 2017
Project co-funded by the European Commission in the framework of the 2nd Health Programme
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A.3.1. ACTIVITIES

A.3.1.1. Donor detection

1. A system to ensure that any deceased individual can be detected in an adequate period of time to perform an effective donation should be established between the TEs and the corresponding TE or ORHAs.

2. The TEs and the TE or ORHAs should establish a written agreement where the responsibilities of each party are defined.

3. The TE or ORHAs should perform an analysis of the potential donors, real donors, causes to reject a potential donor and all the statistics considered helpful to improve the detection system and increase donation efficacy.

4. The process efficacy review should be performed at least annually.

5. It is advisable to create a database shared by TE or ORHAs, TEs and blood establishments.  A list of donors rejected by a blood establishment due to blood analysis results may be helpful for tissue and organs centres.

A.3.1.1.1. Determination of death

1. The determination of death and the death certificate of a donor have to be based on the irreversible cessation of the cardio-respiratory functions (heart death) and encephalic functions (brain death).

2. The certification of death criteria will conform to the Member State’s regulation.

3. The death of the non-heart beating donor (NHBD) must be certified by a doctor independent of the retrieval team.  In case of deceased heart beating donors (HBD), it is necessary to take into account the relevant legislation related to determination of brain death.

A.3.1.1.2. Donor identification

1. Member States shall establish a system for the identification of human tissues and cells, in order to ensure the traceability of all human tissues and cells[1].

2. A codification system, physical and documental and / or electronic, should be in place to guarantee traceability and biovigilance from donor screening until tissue transplantation (e.g. the donor is identified with a wrist band and/or different labels attached to the body).  Both identification methods include the donor number. The donor code is applied to all tissues obtained after recovery.

3. The coding system should be designed so as to relate all transplants of a certain donor to a unique donor number in order to guarantee traceability and biovigilance from donor screening until tissue transplantation.

4. A (potential) donor should receive a donor identification number before any further procedures are started.  All documental and/or electronic data that are collected from this donor, should state this number.  All body materials (e.g. blood, tissue, fluid) that are collected from this donor, have to refer to the donor number.

5. The method of verifying the donor’s identity should be described in an identification procedure.  This procedure should be followed before starting the recovery and should enable the identity of the donor to be established beyond any doubt.  The verification should be performed based on at least two independent factors like date of birth and name, or name and hospital patient number.

6. The source of the donor’s identity has to be documented.  For living donors this could mean taking the number of the identity card.  For deceased donors, the presence of toe tags, wrist bands or other confirmation of the deceased’s identity should be noted.

7. A reliable identification of the deceased donor must always take place before starting the recovery.

A.3.1.1.3. Post Morten donor maintenance

1. To avoid deterioration of the corpse of a deceased donor, the body has to be brought into a cooled environment as soon as possible.  The eyes should be closed in case of cornea donation.

2. If the donor has not been cooled within six hours after death, the recovery should have commenced within 12 hours after heart death, unless a later time can be determined based on the tissue specific quality aspects.

3. If the refrigeration (1-10ºC) takes place during the first six hours, the recovery may start as late as 12 hours after death.  The maximum recovery delay has to be established per tissue type, based on the quality and contamination aspects of the specific tissue and the way it will be processed.

4. When the tissues derives from an organ donor, the corpse is maintained at a temperature >35ºC until the recovery of organs.  When the tissue recovery is performed immediately after organ donation, the corpse does not have to be refrigerated.  If not, the corpse is kept at 1-10ºC until the recovery.

5. Specific maximum time limits for recovery of different types of tissues and cells are incorporated into specific sections of quality.

6. The sampling of blood for testing must always be as short as possible.  The analytical samples should be taken within 24 hours after death to avoid the damage by cytolitical processes, unless validation of the post mortem testing allows otherwise.

 

 

Sampling

Refrigeration (around 4ºC) after death

Recovery after death

NHBD

≤ 24 hours

≤6 hours

≤ 24 hours

>6 hours or not refrigerated

≤ 12 hours

HBD

At the moment of the death diagnosis

 At the beginning of the organs recovery

Not necessary if recovery is performed immediately after organs retrieval

After organ recovery, (≤ 12 hours after aortic cross clamp)

If refrigerated after organ retrieval

≤6 hours from aortic cross clamp

≤ 24 hours from aortic cross clamp

>6 hours from aortic cross clamp

≤ 12 hours from aortic cross clamp

LIVING DONOR

At the time of donation -7 days after donation

N/A

N/A

 

A.3.1.2. Donor consent; judicial and familiar

1. Member States shall, in keeping with their national legislation, take all necessary measures to ensure that donors, their relatives or any persons granting authorisation on behalf of the donors are provided with all appropriate information as referred to in the Annex.[2]

2. Before the procurement of tissues and cells proceeds, an authorised person must confirm and record: (a) that consent for the procurement has been obtained in accordance with Article 13 of Directive 2004/23/EC; and (b) how and by whom the donor has been reliably identified.[3]

3. Evidence of consent or lack of opposition should be documented in the donor file.

4. The consent for all type of donors should be based on understandable information which at least contains items according to the table below

Explanation of the purposes of donation

Types of tissue that can be donated and general descriptions of the use of tissue transplants

Possible use for research or educational purposes

Possible involvement of for-profit organisations

Possible use for patients in other parts of Europe

Alternatives for treatment when no donation takes place.

Explanation of the risks or consequences

Of tissue donation

Physical consequences and risk of bodily harm

Relation with burial arrangements

Relation with autopsy and autopsy results

Relations with investigation of Medical examiner/Coroner

Explanation of the process op donation

Time frame of the donation decision process

Time frame of the procurement and processing of tissue

Need for information of the patient’s medical and social history

Need for testing of blood samples for tissue transmissible diseases

(Presumed) authorisation for the requirement of these data/testing

Description of the recovery and the possible reconstruction of the body including physical appearance

Information of possible movement of the donor

General information about processing/storage and distribution including risk of rejection of tissue.

Information, confidentiality and record keeping

Confidentiality of the medical / social information

Option for communication of the results of testing, donor screening and transplantation with the donor /next of kin/GP or treating physician including the protection of the privacy of patients

Record keeping for 30 years after transplantation

Contact data of the tissue bank/ tissue bank representatives

Explanation of costs involved and the fact that no charge will be made for the process.

 

 

A.3.1.2.1. Deceased donor

1. There should be an authorized person who confirms and records that consent has been obtained specifying organs or tissue donation, and for transplant or research purposes.  A clear differentiation should be done if consent is obtained from a living donor or a deceased donor.

2. Each country should take into account that different systems apply for obtaining consent for transplantation: an opting out system or opting in systems.  For both systems, a registry should be created in order to check if the person was opposed to donation when alive (opting-out) or showed the wishes to donate (opting-in).

3. The contents of the familiar interview should include, but not be limited to:

a)     The medical personnel, in collaboration with the responsible physician, will inform the family of the circumstances that have caused the death of the patient, ensuring the understanding of the explained facts.  Then, the transplant coordinator conducts the interview to obtain family consent, and guide the family in their questions or problems relating to the donation.

b)    The interview will be held respecting the privacy and intimacy of the family or the living donor.

c)     The scope and the purposes of the donation should be explained in detail and agreed with the family or the living donor.  Regarding deceased consent, different types should be differentiated:

                        i.     Donation of organs, tissues or both;

                       ii.     Donation for transplantation;

                     iii.     Donation of tissues for research with clinical application;

                     iv.     Donation of tissues for research with no clinical application;

                       v.     Donation of tissues for research and pharmaceutical manipulation and posterior marketing.

4. The medical / social evaluation should be performed during the interview if necessary, in the terms described in the paragraph 1.26.  The general (and tissue specific) exclusion criteria are used to determine whether tissues are suitable for donation or not.  In order to avoid any risk factors from transmissible diseases or behaviour, there should be a questionnaire addressed to the donor family.

a)     Medical records should show that all exclusion criteria have been appropriately investigated and applied.

b)    According to the EU Directive 2006/17 Annex IV the social history has to be sought from an individual that has known the donor well.  Mostly this is the reporting physician.  If this is not the case, this could be:

                        i.     General practitioner

                       ii.     Other treating physician

                     iii.     Family

                     iv.     Friends

c)     In case the social history cannot be traced with some certainty, the donor has to be rejected.  The social history contains information on the potential donor’s lifestyle, (e.g. alcohol abuse, use of drugs and other intoxications); if there is reason to suspect that the patient was at risk of a sexually transmitted disease, such as HIV, Hepatitis, etc., this forms a general contra-indication. Information on travel history is also sought.

5. In case a legal process applies; judicial consent will be obtained according to local regulations before starting any recovery activities.  When judicial authorization is needed due to an unknown cause of death, the transplant coordinator will be the person responsible to ask consent from the judge on call and in charge of the investigation.  Recovery will only carried out if it does not affect the judicial autopsy.

6. ‘All information must be given and all necessary consents and authorisations must be obtained in accordance with the legislation in force in Member States.

7. The confirmed results of the donor's evaluation must be communicated and clearly explained to the relevant persons in accordance with the legislation in Member States.[4]

A.3.1.2.2. Living donor

1. Informed consent shoukd be obtained for living donors.  The informed consent should include an explanation, in understandable terms, of all the reasonable risk and potential harm, both for the donor and recipient, as well as all the tests to be performed.  ‘The health professional responsible for obtaining the health history must ensure that the donor has:

a)    understood the information provided;

b)    had an opportunity to ask questions and been provided with satisfactory responses;

c)     confirmed that all the information provided is true to the best of his/her knowledge.

2. Information must be given prior to the procurement.

3. The information must be given by a trained person able to transmit it in an appropriate and clear manner, using terms that are easily understood by the donor.

4. The information must cover: the purpose and nature of the procurement, its consequences and risks; analytical tests, if they are performed; recording and protection of donor data, medical confidentiality; therapeutic purpose and potential benefits and information on the applicable safeguards intended to protect the donor.

5. The donor must be informed that he/she has the right to receive the confirmed results of the analytical tests, clearly explained.

6. Information must be given on the necessity for requiring the applicable mandatory consent, certification and authorisation in order that the tissue and/or cell procurement can be carried out.[5]

7. In case of minors donors or donor with no legal capacity the permission should be obtained from parents or legal representative.

A.3.1.3. Data protection and confidentiality

1. ‘Member States shall take all necessary measures to ensure that all data, including genetic information, collated within the scope of this Directive and to which third parties have access, have been rendered anonymous so that neither donors nor recipients remain identifiable.

2. For that purpose, they shall ensure that:

a)    data security measures are in place, as well as safeguards against any unauthorised data additions, deletions or modifications to donor files or deferral records, and transfer of information;

b)    procedures are in place to resolve data discrepancies;

c)     no unauthorised disclosure of information occurs, whilst guaranteeing the traceability of donations.

3. Member States shall take all necessary measures to ensure that the identity of the recipient(s) is not disclosed to the donor or his family and vice versa, without prejudice to legislation in force in Member States on the conditions for disclosure, notably in the case of gametes donation[6].

4. Besides autologous donation, anonymity between donor and recipient and vice versa must be strictly maintained.  An exception may exist for a living related donation.  An anonymous identification coding system of donation of tissues and cells must guarantee anonymity and traceability in the case of allogeneic donations.

A.3.1.4. Advertising

1. Member States shall take all necessary measures to ensure that any promotion and publicity activities in support of the donation of human tissues and cells comply with guidelines or legislative provisions laid down by the Member States.  Such guidelines or legislative provisions shall include appropriate restrictions or prohibitions on advertising the need for, or availability of, human tissues and cells with a view to offering or seeking financial gain or comparable advantage.

2. Member States shall endeavour to ensure that the procurement of tissues and cells as such is carried out on a non-profit basis.[7]

A.3.1.5. Prohibition of financial compensation for donors

1. ‘Member States shall endeavour to ensure voluntary and unpaid donations of tissues and cells.  Donors may receive compensation, which is strictly limited to making good the expenses and inconveniences related to the donation.  In that case, Member States define the conditions under which compensation may be granted.

2. Member States shall endeavour to ensure that the procurement of tissues and cells as such is carried out on a non-profit basis.

3. The donation of tissues and cells must be voluntary and unpaid. No financial gain or any other compensation can be done to the living donor or the deceased donor's family.  In case of unrelated living donors, an allowance to cover any costs incurred can be accepted.[8]

4. The extra medical costs incurred by the consideration of a deceased as a tissue donor (e.g. serological / bacteriological) cannot be charge to the donor.  These charges should be assumed by the tissue bank and never charged to the donor.

A.3.1.6. Donor evaluation; medical, social and physical

A.3.1.6.1. General

1. The activities related to tissue procurement shall be carried out in such a way as to ensure that donor evaluation and selection is carried out in accordance with the requirements referred to in Article 28(d) and (e) and that the tissues and cells are procured, packaged and transported in accordance with the requirements referred to in Article 28(f).

2. In the case of an autologous donation, the suitability criteria shall be established in accordance with the requirements referred to in Article 28(d).

3. The results of the donor evaluation and testing procedures shall be documented and any major anomalies shall be reported in accordance with the requirements referred to in the Annex.

4. The competent authority or authorities shall ensure that all activities related to tissue procurement are carried out in accordance with the requirements referred to in Article 28(f).

5. The competent authority or authorities shall take all necessary measures to ensure that tissue and cell procurement complies with the requirements referred to in Article 28(b), (e) and (f). The tests required for donors shall be carried out by a qualified laboratory accredited, designated, authorised or licensed by the competent authority or authorities.

6. An authorised person must collect and record the donor’s relevant medical and behavioural information according to the requirements described in section 1.4.

7. In order to acquire the appropriate information, different relevant sources must be used, including at least an interview with the donor, for living donors, and the following when appropriate:

a)    the medical records of the donor;

b)    an interview with a person who knew the donor well, for deceased donors;

c)     an interview with the treating physician;

d)    an interview with the general practitioner;

e)     the autopsy report.

8. In addition, in the case of a deceased donor, and in the case of a living donor when justified, a physical examination of the body must be performed to detect any signs that may be sufficient in themselves to exclude the donor or which must be assessed in the light of the donor’s medical and personal history.

9. The complete donor records must be reviewed and assessed for suitability and signed by a qualified health professional.[9]

10. The donor selection criteria should be based on the risk analysis associated with the properties and use of tissues and cells.  Physical examination, medical history and social behaviour, biological testing, post-mortem examination (for deceased donors) and other appropriate investigations provide the information to assess the presence of such risks.

11. The donor selection criteria should take into account those donor aspects that influence the safety of the donor and the safety and quality of a specific tissue.

12. Tissue specific contra-indications for donation have to be determined by the responsible person of the TE, based on the risk assessment linked to the given disorder.

13. The TE should have a procedure in place to evaluate the consequence for donor selection of emerging (infectious) diseases or advancing medical insights.  Evaluations have to be documented.

14. An authorised person must collect and record the donor’s relevant medical and behavioural information according to the requirements.

15. In order to acquire the appropriate information, different relevant sources must be used, including at least an interview with the donor for living donors, and for deceased donors an interview with a person who knew the donor well.  Furthermore, the following sources when appropriate:

a)        Medical records of the donor;

b)        Interview with the treating physician;

c)        Interview with the general practitioner;

d)        Autopsy report when applicable;

e)        Results of laboratory or imaging investigations;

f)         Medical information of the mother in case of a newborn donor.

16. ‘The health professional responsible for obtaining the health history must ensure that the donor or other relevant party has:

a. understood the information provided;

b. had an opportunity to ask questions and been provided with satisfactory responses

c. confirmed that all the information provided is true to the best of his/her knowledge. [10]  (Commission Directive 2006/17/EC, Annex IV Art 1.1.2)

17. In addition, in the case of a deceased donor, and in that of a living donor when justified, a physical examination of the body must be performed to detect any signs that may be sufficient in themselves to exclude the donor or which must be assessed in the light of the donor’s medical and personal history.

18. A qualified health professional assesses the available donor information for the presence of contraindications, before starting the recovery procedure.

19. The complete donor records must be reviewed and assessed for the absence of donor rejection criteria before release of the tissue for transplantation and signed by an authorized physician.

20. All donor data should be recorded and kept for 30 years after the use of the donated tissue.  Data should be protected from unauthorized viewing

A.3.1.6.2. Medical and social evaluation

1. The evaluation of the donor should contain all the necessary medical and social information to assess the presences of the following aspects:

            a) General contraindications concerning the safety of all donated tissue as stated in Directive 2004/23/EC Annex I.

            b) Additional safety related contraindications that are the result of risk assessments arising from health risks related to processing, donor population characteristics, emerging infectious diseases, or other relevant factors.

            c) Tissue specific contraindications that involve the quality of the donated tissue.

2. The final determination of the criteria for exclusion for tissue donation is the responsibility of the responsible person, in consultation with a medical advisor or medical advisory committee, if needed.  A list of mandatory and optional contraindications could be;

 

Medical evaluation

Weight and height

NTS (pre-screening)

If no exact weight and height are known, an estimate will suffice.

Active systemic. infections and vaccinations

NTS (pre-screening)

This includes all systemic infections (bacterial, viral, parasitical, prions).

Various circumstances are possible including:

1.   An infection at the time of death.

Please report:

§  the type of infection

§  lab results

§  whether cultures have been taken, including (provisional) results

§  antibiotic treatment, including duration and effectiveness of the treatment and if any, the results of the treatment (e.g. fever-free period).

2.   Suspicion of a systemic infection without supportive diagnostics. Please report the symptoms on which the suspicions are based.

3.    In case clinical signs are not highly suspect for an infection but infection cannot be ruled out, please report as such.

4.    Systemic infections of which the patient has been cured, but the cause is still (possibly latent) present (e.g. polio, hepatitis B-C, syphilis)

5.    Report vaccinations given with live attenuated virus, such as polio, mumps, measles, rubella and post exposure rabies vaccinations.

The criteria used to assess whether sepsis is present are in accordance with the internationally guidelines.

Clinical evidence or suspicion of neurodegenerative diseases with unknown aetiology, or other disorders possibly caused by prions

NTS (pre-screening)

The following apply:

§ All non-vascular or unexplained forms of dementia, such as Alzheimer’s disease;

§ ALS, multiple sclerosis, Parkinson

§  variant CJD or risk factors for prion disease such as familial CJD, the use of growth hormone and stay in the UK during 1980-1996.

Haematological malignancies or other haematological disorders

NTS (pre-screening)

All lymphoproliferative, myeloproliferative and other haemapoetic disorders, such as leukaemia, Morbus Kahler, non-Hodgkin disease, polycythemia vera and aplastic anaemia.

Other malignancies.

NTS (pre-screening)

Present at time of death or in the medical history.

Infection or signs of infection

All, also local, infections or signs of infection such as lab results, positive cultures, infiltration on X-thorax. Treatment with antibiotics?

Infections can be a tissue specific contraindication.

Bone marrow suppression due to medication in the last three months

Medication administered within three months before death with a proven bone marrow depression.  Mention which medication, indication, dose and last lab. results (Hb, leucocytes and platelets)

Chronic use of corticosteroids

Relevant in case of chronic use for more than six weeks. Provide details on indication, dosage and duration of use. Use of corticosteroids can be a tissue specific contra-indication.

Other medication

Please report all other medications that have been used.

Infusions and transfusions within the previous 48 hours

Only relevant if given for blood loss.  Please report type and quantity of all infused fluids (blood products, colloids, crystalloids, plasma replacement, plasma expanders etc.), as well how much and time of the infusions/transfusions

Social evaluation

Presence of risk factors for HIV, HTLV, Hepatitis B or C

This group includes donors belonging to known risk groups (either directly or through their sexual partners):

-   Persons who have used non-medical drugs intranasally in the last five years.

-   Persons who have ever injected non-medical drugs (intravenous, intramuscular or subcutaneous).

-  Persons with haemophilia or related clotting disorders who have received human-derived clotting factor concentrates before 1987.

-  Men who have had sex with another man in the preceding five years.

-  Men and women who have engaged in sex in exchange for money or drugs in the preceding five years.

-  Persons emigrated from countries where transfer of HIV infection through heterosexual contacts plays an important role in the spreading of the HIV virus, like countries in South East Asia, Caribbean and in countries in Africa below the Sahara.  Unless person has been in the Netherlands longer than one year and in that time has not been back to an endemic region.

-  Persons that, in the past six months, had sexual contact with persons of one of the above mentioned groups or were sexual partners of persons who are infected with HIV, HTLV or hepatitis C or B or who are suspected thereof.

-  Persons that, in the preceding six months, were exposed to (possibly) infected blood via accidental percutaneous puncture or through contact with an open wound and non-intact skin or mucous membrane.

-  Persons who are diagnosed or treated for SOA in past six months.

-  Children of 18 months or younger born to mothers with risk of HIV, or children from these mothers who were breastfed.

-  Tattoo: if the donor has had a tattoo, piercing or needle accident in the previous 6 months, there may be a reason for not accepting.  Please contact the BIS doctor on duty for evaluation. Piercings made with the use of shared needles or genital piercings shall not be accepted.

-  Persons who have jaundice of unknown but possibly infectious origin.

-  Persons who are in ‘Close contact; with another individual with infectious hepatitis, such as shared household (kitchen and toilet) or sexual partner during the last six months.

Intermittent haemodialysis

Intoxications

Includes alcohol abuse, drug abuse and long term exposure to heavy metals such as lead, mercury, chromium, arsenic, pesticides. Nicotine abuse is not relevant.

Risk of tropical diseases, for example as a result of travel.

Report risk for emerging diseases contracted during travel to foreign countries, such as SARS, Avian Flu, Malaria, Yellow fever etc.

Mention: which country, duration and date period of stay, vaccinations.

If unknown report as such.

Travel/Visit to the United Kingdom

Report if known whether duration of stay was longer than six months and between January 1980 and December 1996.

If unknown report as such.

     

 

3. For every potential donor, anamnestic data must be obtained from the available relevant sources, such as the living donor’s treating physician, general practitioner, next of kin or in the case of a deceased, other people who knew the donor well, and / or the donor's medical record included in the donor file.

4. When questioning donors or their relatives, it must be established that the phrasing of the questions is understood by the respondent.

A.3.1.6.3. Physical evaluation of cadaveric donors

1. The evaluation of the cadaveric donor should include a physical examination to detect signs:

a)   that are in themselves sufficient to the exclude the donor; or

b)  that may be an indication for further investigations; or

c)   are a contraindication for donation, when assessed in the light of the donor’s medical and social history.

2. The physical examination has to be performed by trained personnel, in a working area with sufficient light, and under the condition that the entire body surface is easy accessible for examination by the retrieval staff.

3. A written report on the findings during the physical examination should consist minimally of a check list of specific signs that have to be looked for.  Findings should also be drawn on a diagram of the body.

4. An example is given of a list of signs and their associated contraindications that indicate a (potential) cause for rejection of the donor for donation.

 

General impression

 

Describe the degree of care of the donor                                                                           

 

Inspection of the skin                      Description (including localisation, dimensions,

                                                                                type/aspect, signs of infection)

 

      Jaundice                                        r No r Yes                                                                     

 

      Tattoos / piercings                              r No r Yes      Old / new                                          

      Non-therapeutic needle wounds   r No r Yes                                                                     

 

      Skin abnormalities / petechiae       r No r Yes                                                                     

 

      Traumas / wounds / scars                             r No r Yes  Old / new                                              

 

      Lines (arterial / venous)                r No r Yes                                                                     

 

Specific inspection of

 

      Head / neck

      Abnormalities of eyes/sclera               r No r Yes  r Already enucleated              

 

      Abnormalities of oral cavity        

 

      Other facial abn. (e.g. infectious)  r No r Yes                                                                     

 

      Pathological lymph nodes             r No r Yes                                                                     

      (> 1 cm or abnormal consistency)

     

      Abn. of the ears (e.g. CSF, blood)      r No r Yes                                                    

      Torso & extremities

      Enlarged liver / spider naevi                r No r Yes                                                    

 

      Pathological lymph nodes             r No r Yes                                                                     

      (> 1 cm or abnormal consistency)

 

      Indications for auto-immune/        r No r Yes                                                                     

      connective tissue conditions

 

      Fractures                                       r No r Yes                                                                     

 

      Genitalia

      Abnormalities of the genitalia       r No r Yes                                                                     

 

Inspection of the rear side of the body

 

Skin abnormalities                               r No r Yes                                                          

 

Peri-anal abnormalities                      r No r Yes                                                

 

A.3.1.6.4. Exclusion criteria
A.3.1.6.5.1. Deceased donor

1. Cause of death unknown, unless autopsy provides information on the cause of death after procurement and none of the general criteria for exclusion set out in the present section applies.

2. History of a CNS disease of unknown aetiology.

3. Presence, or previous history, of malignant disease, except for primary basal cell carcinoma, carcinoma in situ of the uterine cervix, and some primary tumours of the central nervous system that have to be evaluated according to scientific evidence. Donors with malignant diseases can be evaluated and considered for cornea donation, except for those with retinoblastoma, haematological neoplasm, and malignant tumours of the anterior segment of the eye.

4. Risk of transmission of diseases caused by prions. This risk applies, for example, to:

a)    people diagnosed with Creutzfeldt-Jakob disease, or variant Creutzfeldt-Jacob disease, or having a family history of non-iatrogenic Creutzfeldt-Jakob disease;

b)    people with a history of rapid progressive dementia or degenerative neurological disease, including those of unknown origin;

c)      recipients of hormones derived from the human pituitary gland (such as growth hormones) and recipients of grafts of cornea, sclera, limbal cells / ossicular tympanomeatal allograft and dura mater, and persons that have undergone undocumented neurosurgery (where dura mater may have been used).[11]

For variant Creutzfeldt-Jakob disease, further precautionary measures may be recommended.

5. Specific precautionary measures regarding VCJD:

a)     Any person who stayed in Britain for six months or more between 1980 and 1996 (cumulatively) will be excluded as a donor.

6. Specific precautionary measures regarding prions diseases:

a)     The removal of tissue is excluded from:

                                 i.     potential donors with a transmissible spongiform encephalopathy confirmed or detected as probable;

                               ii.     potential donors with the presence or suspicion of a degenerative central nervous system including those of unknown origin;

                              iii.     potential donors with a family history of CJD, Gerstmann-Scheinker disease or fatal familial insomnia;

                              iv.     potential donors with a history of intracranial surgery (craniotomy syn.);

                               v.     potential donors who have receive treatment based on growth hormones extracted from human hypophyses;

                              vi.     potential donors who underwent implantation of ocular tissue;

                            vii.     potential donors who underwent implantation of dura mater allograft;

                           viii.     potential donors who underwent implantation of an ossicular tympanomeatal allograft.

7. Systemic infection which is not controlled at the time of donation, including bacterial diseases, systemic viral, fungal or parasitic infections, or significant local infection in the tissues and cells to be donated.  Donors with bacterial septicaemia may be evaluated and considered for eye donation but only where the corneas are to be stored by organ culture to allow detection of any bacterial contamination of the tissue.

8. History, clinical evidence, or laboratory evidence of HIV, acute or chronic hepatitis B (except in the case of persons with a proven immune status), hepatitis C and HTLV I/II, transmission risk or evidence of risk factors for these infections.

9. History of chronic, systemic autoimmune disease that could have a detrimental effect on the quality of the tissue to be retrieved.

10. Indications that test results of donor blood samples will be invalid due to:

a)        the occurrence of haemodilution, according to the specifications in Annex II, section 2, where a pre-transfusion sample is not available;

b)        treatment with immunosuppressive agents.

11. Evidence of any other risk factors for transmissible diseases on the basis of a risk assessment, taking into consideration donor travel and exposure history and local infectious disease prevalence.

12. Presence on the donor’s body of physical signs implying a risk of transmissible disease(s) as described in Annex IV, point 1.2.3.

13. Ingestion of, or exposure to, a substance (such as cyanide, lead, mercury, gold) that may be transmitted to recipients in a dose that could endanger their health.[12] 

14. Recent vaccination with living attenuated viruses whereby a risk for transmission can be suspected

15. Transplantation with xenografts.

A.3.1.6.5.2. Additional exclusion criteria for dead children donors

1. Any children born from mothers with HIV infection or that meet any of the exclusion criteria described in the previous section must be excluded as donors until the risk of transmission of infection can be definitely ruled out.

2. Children aged less than 18 months born from mothers with HIV, hepatitis B, hepatitis C or HTLV infection, or at risk of such infection, and who have been breastfed by their mothers during the previous 12 months, cannot be considered as donors regardless of the results of the analytical tests.

3. Children of mothers with HIV, hepatitis B, hepatitis C or HTLV infection, or at risk of such infection, and who have not been breastfed by their mothers during the previous 12 months and for whom analytical tests, physical examinations, and reviews of medical records do not provide evidence of HIV, hepatitis B, hepatitis C or HTLV infection, can be accepted as donors.[13]

A.3.1.6.5.3. Living donors
A.3.1.6.5.3.1. Allogeneic use donation

1. Allogeneic living donors must be selected on the basis of their health and medical history, provided on a questionnaire and through an interview performed by a qualified and trained healthcare professional with the donor, in compliance with point 4.

2. This assessment must include relevant factors that may assist in identifying and screening out persons whose donation could present a health risk to others, such as the possibility of transmitting diseases or health risks to themselves.

3. For any donation, the collection process must not interfere with or compromise the health or care of the donor.  In the case of cord blood or amniotic membrane donation, this applies to both mother and baby.

4. Selection criteria for allogeneic living donors must be established and documented by the tissue establishment (and the transplanting clinician in the case of direct distribution to the recipient), based on the specific tissue or cells to be donated, together with the donor’s physical status and medical and behavioural history and the results of clinical investigations and laboratory tests establishing the donor’s state of health.

5. The same exclusion criteria must be applied as for deceased donors with the exception of the concerning to the unknown cause of death.  Depending on the tissue or cell to be donated, other specific exclusion criteria may need to be added, such as:

a)     pregnancy (except for donors of umbilical cord blood cells and amniotic membrane and sibling donors of haematopoietic progenitors)

b)     breastfeeding

c)       in the case of haematopoietic progenitor cells, the potential for transmission of inherited conditions[14]

A.3.1.6.5.3.2. Autologous use donation

1. If the removed tissues and cells are to be stored or cultured, the same minimum set of biological testing requirements must apply as for an allogeneic living donor.  Positive test results will not necessarily prevent the tissues or cells or any product derived from them being stored, processed and reimplanted, if appropriate isolated storage facilities are available to ensure no risk of cross contamination with other grafts and/or no risk of contamination with adventitious agents and/or mix ups. [15]

A.3.1.6.6. Autopsy

1. If an autopsy of the donor has been required, the responsible doctor will examine the results before tissue release. 

A.3.1.7. Donor evaluation; biological

A.3.1.7.1. General

1. The tests must be carried out by a qualified laboratory, authorised as a testing centre by the competent authority in the Member State, using CE-marked testing kits where appropriate.  The type of test used must be validated for the purpose in accordance with current scientific knowledge.

2. The biological tests will be carried out on the donor’s serum or plasma; they must not be performed on other fluids or secretions such as the aqueous or vitreous humour unless specifically justified clinically using a validated test for such a fluid.

3. When potential donors have lost blood and have recently received donated blood, blood components, colloids or crystalloids, blood testing may not be valid due to haemodilution of the sample.  An algorithm must be applied to assess the degree of haemodilution in the following circumstances:

a)        ante-mortem blood sampling: if blood, blood components and/or colloids were infused in the 48 hours preceding blood sampling or if crystalloids were infused in the hour preceding blood sampling;

b)    post-mortem blood sampling: if blood, blood components and/or colloids were infused in the 48 hours preceding death or if crystalloids were infused in the hour preceding death.

4. TEs may accept tissues and cells from donors with plasma dilution of more than 50 % only if the testing procedures used are validated for such plasma or if a pre-transfusion sample is available.

5. In the case of a deceased donor, blood samples must have been obtained just prior to death or, if not possible, the time of sampling must be as soon as possible after death and in any case within 24 hours after death.  The testing method for cadaveric blood samples must be validated for cadaveric blood.

6. In the case of living donors (except allogeneic bone marrow stem-cell and peripheral blood stem-cell donors, for practical reasons), blood samples must be obtained at the time of donation or, if not possible, within seven days post donation (this is the ‘donation sample’).

7. Where tissues and cells of allogeneic living donors can be stored for long periods, repeat sampling and testing is required after an interval of 180 days. In these circumstances of repeat testing, the donation sample can be taken up to 30 days prior to and 7 days post donation.

8. Where tissues and cells of allogeneic living donors cannot be stored for long periods and repeat sampling is therefore not possible, point 6 above applies.

9. If in a living donor (except bone marrow stem-cell and peripheral blood stem-cell donors) the ‘donation sample’, as defined in point 6 above, is additionally tested by the nucleic acid amplification technique (NAT) for HIV, HBV and HCV, testing of a repeat blood sample is not required. Retesting is also not required if the processing includes an inactivation step that has been validated for the viruses concerned.

10. In the case of bone marrow and peripheral blood stem-cell collection, blood samples must be taken for testing within 30 days prior to donation.

11. In the case of neonatal donors, the biological tests may be carried out on the donor’s mother to avoid medically unnecessary procedures upon the infant.

12. In the case of living donors, see tissue specific paragraphs.[16]

A.3.1.7.2. Allogeneic Donation
A.3.1.7.2.1. Heart beating donors

1. The following biological tests must be performed for all heart beating donors as a minimum requirement:

a)     Anti-HIV 1 and 2 has to be negative (a positive test is a reason for exclusion);

b)    HBs Ag has to be negative (positive test is a reason for exclusion);

c)     Anti-HBc: if HBsAg test is negative and anti-HBc is positive, an anti-HBs test will be made.  If the test is also positive, it can be considered that the donor has recovered from a past infection, and the tissue can therefore be used.  If, by contrary, anti-HBs are negative or doubtful, then it should be rejected as a donor;

d)    Anti-HCV has to be negative (a positive test is a reason for exclusion);

e)     Testing for syphilis: a validated test result has to be negative (positive serological test is a reason for exclusion).

Table 1.

Serology test

Grounds for testing

Accepted result

S-TrpaAb

Exclusion of syphilis

Negative

S-HIV 1/2Ab

Exclusion of HIV

Negative

S-HIV Ag

Exclusion of HIV

Negative

S-HbsAg

Exclusion of acute HBV

Negative

S-HbcAb

Exclusion of past HBV

Negative

Positive g HBsAb g Positive

S-HCVAb

Exclusion of acute or past HCV

Negative

HIV1 NAT

Exclusion of acute HIV infection

Negative (not detectable)

HBV NAT

Exclusion of acute HBV infection

Negative (not detectable)

HCV NAT

Exclusion of acute HCV infection

Negative (not detectable)

 

2. Additional tests:

a)      HTLV-I antibody testing must be performed for donors living in, or originating from, high-incidence areas or with sexual partners originating from those areas or where the donor’s parents originate from those areas.

b)      A validated testing algorithm must be applied to exclude the presence of active infection with Treponema pallidum.  A non-reactive test, specific or non-specific, can allow tissues and cells to be released.  When a non-specific test is performed, a reactive result will not prevent procurement or release if a specific Treponema confirmatory test is non-reactive.  A donor whose specimen tests reactive on a Treponema-specific test will require a thorough risk assessment to determine eligibility for clinical use.[17]

c)       Anti-CMV: a positive test does not constitute a reason to reject the tissue. However, it is desirable not to use tissue from CMV positive donors in immunosuppressed recipients.

d)      Rh Factor: Some tissue donor Rh (D) positive antigen can sensitize a recipient Rh (D) negative. It is therefore advisable to avoid it in recipients belonging to the age where a pregnancy can still occur.  The decision on this issue, however, is the responsibility of the physician in charge of implantation.

e)       In certain circumstances, additional testing may be required depending on the donor’s history and the characteristics of the tissue or cells donated (e.g. RhD, HLA, malaria, CMV, toxoplasma, EBV, Trypanosoma cruzi)

f)          Anti-HTLV1 / 2 is recommended in donors who assume the risk.

g)        A second serology (anti-HIV1 and anti-HIV2 and anti-HCV)) is advisable for recipients three months after transplantation (back-screening).

A.3.1.7.2.2. Non-heart beating donors (Post-mortem removal)

1. In case of non-heart-beating donors, serological tests are performed on a blood sample taken within seven days before death (after identification) or by default on a blood sample taken immediately after death and never beyond 24 hours.

2. The minimum serological requirements for HBD are the same as for NHBD.  Additional tests, such as HIV1, HCV NAT, Anti-CMV, are recommended for non-heart beating donors in order to have an additional guarantee

A.3.1.7.2.3. Living donors

1. In case of living donors, the first serological tests are performed at the time of donation or seven days after donation when the first option is not possible.

2. Where tissues and cells of allogeneic living donors can be stored for long periods, repeat sampling and testing is required after an interval of 180 days. In these circumstances of repeat testing, the donation sample can be taken up to 30 days prior to and 7 days post donation.[18]

3. The serological minimum requirements are the same as for deceased donors.

4. In the case of living donors, a guarantee of tissue and cells must be obtained from:

a)     A test anti-HIV1 / 2 and anti-HCV, retested at least 180 days (six months) after sampling.  Only when the results of that test are known and proven to be negative, may the tissue be distributed for implantation: or

b)    NAT test HIV1, HBV and HCV performed on the sample taken at the time of donation. In this case, it is not necessary to retesting after six months: or

c)     A validated period of viral inactivation.  In this case, it is not necessary to retest after six months.

5. If at least one of three above mentioned conditions is completed, the tissues are kept in quarantine.

6. However, under exceptional circumstances, the doctor responsible for a tissue bank may repeal the quarantine (e.g. medical emergency) after reviewing the case and risk assessment. The decision must be explained decision and the transplant doctor, who can accept or reject the risk, informed.

A.3.1.7.3. Autologous Donations

1. In the case of autologous living donors, it is necessary to perform the same tests (serology) as for an allogeneic donor.

2. A positive result does not automatically exclude these tissues and cells.  However, a separate storage system must be provided.

A.3.1.7.4. Serum Bank

1. It is desirable to store the serum in a serum bank in order to complete serological tests that could be needed depending on the evolution of science.  The absence of a serum bank for a donation of tissues and cells does not constitute in itself a reason for rejection of these tissues or cells.

A.3.1.8. Documentation and release for recovery

A.3.1.8.1. General

1. The TE or ORHA must develop a system to maintain a record of each donation step; donor selection, collection, control, preparation, storage and distribution of tissues and cells.  The decision to release (i.e validation for human use) is taken on the basis of data contained in this dossier.

2. The records and documents must be completed in a legibly and indelibly manner.

3. The dossier and any other documentation can also be saved on a reliable system such as a digital or microfilm system.  When data is manage by the TE or ORHA personnel, a declaration must be made to the European Commission responsible for personal data protection according to current regulations.

4. The recording of relevant data in the dossier must allow identification of the author and the date of their entry.

5. Data security and confidentiality must be guaranteed.

 

A.3.1.8.2. Release

1. The items indicated in the Donor Screening File Contents should be required for the release or rejection of a donor for tissues/cells and thus should be documented.  The donor dossier should include the contents showed in Donor Screening File Contents section.

A.3.1.8.3. Donor Screening File Contents

1. The donor record will, at least, contain:

a)    The donor identification (first name, family name and date of birth — if a mother and child are involved in the donation, both the name and date of birth of the mother and the name, if known, and date of birth of the child);

b)    A unique identification code of the donation given by the TE or ORHA;

c)     Age, sex, medical and behavioural history (the information collected must be sufficient to allow application of the exclusion criteria, where required);

d)    Cause and certificate of death;

e)     Type of donor: living donor, NHBD or HBD;

f)     Type of donation: allogeneic, autologous;

g)     Evidence of informed consent (living donor): a copy of the original consent signed by the surgeon  or the no opposition (deceased donor), as the result of consulting the National Register;

h)    Outcome of body examination, where applicable;

i)      Identification of the recovery centre and the person responsible for donation and recovery;

j)      Haemodilution formula, where applicable;

k)    The consent/authorisation form (familiar and judicial), where applicable;

l)      Proof of consent for donation of the retrieved tissues/cells and its purpose;

m)   Clinical data, laboratory test results, and the results of other tests carried out;

n)    If an autopsy was performed, the results must be included in the record (for tissues and cells that cannot be stored for extended periods, a preliminary verbal report of the autopsy must be recorded);

o)    For haematopoietic progenitor cell donors, the donor’s suitability for the chosen recipient must be documented. For unrelated donations, when the organisation responsible for procurement has limited access to recipient data, the transplanting organisation must be provided with donor data relevant for confirming suitability;[19]

p)    Date and time of cardiac arrest (for deceased donor);

q)    Cooling time (for non-heart beating donors);

r)     Hospital discharge report, if applicable;

s)     Report of Biovigilance alerts, if applicable;

t)     Identification of the recovery centre and the person responsible for donation and recovery.

2. Other relevant information:

a)     ABO, Rh factor (if applicable);

b)    Serological results (HIV 1 & 2, HBV, HCV) and syphilis;

c)     Additional serological results, if any;

d)    Serum sample in the serum bank (desirable);

e)     Bacteriological results (aerobic and anaerobic) and mycological.

Access to registers and data must be restricted to persons authorised.  This File must be kept for a minimum of 30 years after clinical use.

A.3.1.9. Availability for inspection

1. The records must be accessible at any time for inspections conducted by the competent authority.  Donor identity and data related to it will be restricted to the sanitary establishment but must, if necessary, be available for inspectors.

A.3.1.10. Traceability

1. The TE or ORHA should be able to assure the traceability of the donor.

2. The traceability requirement applies to all relevant data related to the donor, critical products and materials coming into contact with the donor.

3. Corrections, changes or amendments made to a file should be carried out according to a written change control management procedure.

4. When electronic data is affected any critical change should be recorded and available through an audit trail.



[1] Directive 2004/23/EC of the European Parliament and of the Council (Art 25)

 

[2] Directive 2004/23/EC of the European Parliament and of the Council ( Art 13)

[3] Commission Directive 2006/17/EC (Annex IV)

 

[4] Directive 2004/23/EC of the European Parliament and of the Council ( Annex)

[5] Commission Directive 2004/33/EC ( Annex II)

[6] Directive 2004/23/EC of the European Parliament and of the Council (Art.13)

[7] Directive 2004/23/EC of the European Parliament and of the Council (Art.12)

[8] Directive 2004/23/EC of the European Parliament and of the Council (Art.12)

[9] Commission Directive 2006/17/EC (Annex IV)

[10] Commission Directive 2006/17/EC ( Anex IV)

[11] Commission Directive 2006/17/EC (Annex I)

[12] Commission Directive 2006/17/EC ( Annex I)

[13] Commission Directive 2006/17/EC ( Annex I)

[14] Commission Directive 2006/17/EC ( Annex II)

[15] Commission Directive 2006/17/EC ( Annex I)

[16] Commission Directive 2006/17/EC ( Annex II)

[17] Commission Directive 2006/17/EC ( Annex II)

[18] Commission Directive 2006/17/EC Annex II

[19] Commission Directive 2006/17/EC (Annex IV)

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