Establishes The Legal Regime Of The Quality And Safety On The Donation, Procurement, Testing, Processing, Preservation, Storage, Distribution And Application Of Human Tissues And Cells, Transposing To The Internal Legal Order Directives N

Original Language Title: Estabelece o regime jurídico da qualidade e segurança relativa à dádiva, colheita, análise, processamento, preservação, armazenamento, distribuição e aplicação de tecidos e células de origem humana, transpondo para a ordem jurídica interna as Directivas n

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Read the untranslated law here: http://app.parlamento.pt/webutils/docs/doc.pdf?path=6148523063446f764c3246795a5868774d546f334e7a67774c336470626d6c7561574e7059585270646d467a4c316776644756346447397a4c334277624449774d4331594c6d527659773d3d&fich=ppl200-X.doc&Inline=false

1 PROPOSAL of law No. 200/X explanatory memorandum the transplantation of human cells and tissues is an area of medicine that has been a huge growth in recent years and that provides great therapeutic possibilities to many patients. The availability of human tissues and cells used for therapeutic purposes depends on the gift from the citizens. Harvest programs and application of tissues and cells shall be based on the principles of free donation, altruism, solidarity, fairness, transparency and accessibility, as well as the general principle that the identity of the receiver or receivers should not be disclosed to the donor or their family and vice versa, except in the cases provided for in the legislation in force. The donation, procurement, testing, processing, preservation, storage and distribution of human tissues and cells intended for human application must meet high standards of quality and safety, in order to ensure a high level of protection of public health and avoid the transmission of diseases by these tissues and cells. Considering the need to ensure that human tissues and cells intended for human applications present comparable quality and safety criteria in all Member States, the European Parliament and the Council of the European Union adopted the Directive 2004/23/EC of 31 March 2004 laying down standards of quality and safety for the donation , procurement, testing, processing, preservation, storage and distribution of human tissues and cells. Subsequently, the Commission adopted Directive 2006/17/EC of 8 February 2006 implementing Directive 2004/23/EC of 31 March, for certain technical requirements for the donation, procurement and testing of human tissues and cells, and Directive No. 2006/86/EC of 24 October 2006 with regard to traceability, notification of serious adverse reactions and incidents, and certain technical requirements for the coding, processing, preservation, storage and distribution of human tissues and cells.


2 this law transposes to the Portuguese legal system these directives. In drafting your answer-if the Charter of fundamental rights of the European Union and the Council of Europe Convention for the protection of human rights and dignity of the human being with regard to the application of biology and medicine, signed at Oviedo on 4 April 1997, and entered into force in Portugal in 2001. With a view to compliance with Community requirements and to promote the effective implementation of the provisions of the present law, is established a sanctions regime applicable in the event of infringements. Was heard the National Commission for Data Protection. Were heard, on an optional basis, the order of Doctors, INFARMED-National Authority of Medicine and health products, I. P., Portuguese society of Transplantation, the National Council of medically assisted procreation and the National Council of ethics for the life sciences. So: under d) of paragraph 1 of article 197 of the Constitution, the Government presents to the Assembly of the Republic the following Bill: chapter I General provisions Article 1 subject-matter 1-this law establishes the legal regime of the quality and safety on the donation, procurement, testing, processing, preservation, storage, distribution and application of human tissues and cells. 2-this law transposes to the internal legal order directives n° 2004/23/EC of the European Parliament and of the Council of 31 March 2004, n° 2006/17/EC of 8 February 2006, and 2006/86/EC of 24 October 2006.


3 article 2 scope 1-the provisions of this law shall apply: a) the donation, procurement, testing, processing, preservation, storage, distribution and application of human tissues and cells intended for use in humans, including haematopoietic stem cells from peripheral blood, umbilical cord blood and bone marrow, surgical residues, as well as the reproductive cells , the foetal tissues and cells and embryonic stem cells without prejudice to the provisions of specific laws; (b)) the donation, procurement, testing, processing, preservation, storage and distribution of manufactured products derived from human tissues and cells intended for human applications; c) tissues and cells of human origin, provided that it contains the human application, in the context of clinical trials. 2. this law shall not apply to: a) tissues and cells used as an autologous graft within the framework of a single surgical procedure; (b)), its components and derivatives, in accordance with Decree-Law No. 267/2007 of 24 July; c) the organs or parts of organs that are used for the same purpose as the entire organ in the human body; d) tissues and cells of human origin intended for application in the human body, as in research in animal models or in vitro. 3-the exception to the provisions of subparagraph (b)) of the preceding paragraph, the procurement, testing, processing, storage, distribution and application of hematopoietic progenitor cells. 4-The tissues and cells intended for industrially manufactured products, including medical devices, this law shall apply only with respect to your donation, procurement and testing, and the processing, preservation, storage and distribution regulated by legislation of its own.


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Article 3 definitions for the purposes of this law, the technical terms used correspond to the definitions in annex I to this Act, which is an integral part. CHAPTER II activities of competent authorities article 4 competent Authorities 1-the competent authorities responsible for verifying compliance with the technical requirements laid down in this law, are the authority for blood and transplantation, briefly designated by ASST, and the National Council on medically assisted procreation, as designated by CNPMA. 2-the ASST, while competent authority for transplantation services, aims to guarantee the quality and safety for the donation, procurement and testing of human tissues and cells, whatever your purpose, as well as in relation to the processing, storage, distribution, including the activities of import and export of tissues and cells, when intended for transplantation with the exception of reproductive cells and embryonic stem cells and when such acts comply with the application of techniques of medically assisted procreation. 3-CNPMA, as competent authority, shall ensure the quality and safety for the donation, procurement, testing, processing, storage and distribution of reproductive cells and human embryonic stem cells in accordance with (a)), b), c) and (e)) of article 30 of law No. 32/2006, of July 26. 4-within the framework of the action referred to in paragraph 2 ASST is responsible for coordinating, guiding, regulate and monitor, at the national level, the activities of collection, testing, processing, storage, distribution and transplantation of tissues and cells of human origin.


5 5-within the framework of the action referred to in paragraph 3 the CNPMA follow the activities of the centres where they are taught the techniques of medically assisted procreation and the centers where preserved gametes or human embryos and monitor compliance with the law, in conjunction with the competent public bodies, under the conditions laid down in subparagraph (c)) of article 30 of law No. 32/2006 , July 26.

Article 5 1 Authorization-the activities referred to in paragraphs 2 and 3 of the preceding article may only be performed by services that are authorized, respectively, by the ASST and pursuant to paragraph 1 of article 5 of law No. 32/2006, of July 26. 2-no activity related to the collection of human reproductive cells and embryonic stem cells or other cells and tissues collected in the context of the application of techniques of medically assisted procreation, can be performed outside of the approved centres in accordance with the conditions laid down by the CNPMA under the provisions of article 5 and in article 30 (b)), of law No. 32/2006 , July 26. 3-exceptionally the collection of tissues and cells referred to in paragraph 2 of the preceding article may be achieved in unauthorized hospital units as units of harvest, since the tissues and cells are collected by sampling units authorized professionals. 4-for the purposes of the preceding paragraph the harvest authorized units must ensure that the conditions for which the harvest can be carried out in accordance with the provisions of this law, including the respect of the traceability of the donor and donation. 5-the tissue and cell procurement held in situations referred to in paragraphs 3 and 4 shall be communicated to the ASST. 6-ASST is responsible for: a) Authorise the tissue and cell banks with regard to the activities of collection, testing, storage and distribution in accordance with this law; b) authorise the harvesting units as regards harvesting activities;


6 c) Authorize the services responsible for human application of tissues or cells; d) to authorize the preparation processes of tissues and cells that the Bank of tissues and cells can be carried out in accordance with the requirements referred to in annex III to this law, which is an integral part. 7-for the purposes of the authorization referred to in paragraph 1 shall be communicated to ASST the information in accordance with the requirements referred to in annexes II and III to this Act, which shall form an integral part. 8-For assessing the process leading to the issuance of the authorization are examined the agreements concluded between a Bank and third parties including procurement, referred to in article 21. 9-the application for authorisation shall be submitted by the body in charge of the institution where the work the service upon request directed to the ASST, and should be included, obligatorily, be it the following information: a) identification of the person (s) responsible for the activities and their curriculum vitae; b) the processes for which authorisation requests; c) qualification of personnel or to engage in activities; d) identification of facilities, equipment, interdisciplinary or interinstitutional relations, where applicable, relevant to the process; e) annual activity Plan; f) descriptive document where stating the nature of the application, the means available to carry out the service requested activity, the type of tissue or cells so that authorization is requested. 10-ASST, after confirming that the service meets the requirements of this law, shall issue the authorization indicating which activities and processes of preparation of tissues and cells and under what conditions, all specified in certificate issued to that effect.



7 11-cannot make any substantial change in their activities and processes of preparation of tissues and cells without the prior approval in writing of the ASST. 12-by the appreciation of the process leading to the issuance of the authorization are due amount to be fixed rates by order of the Minister of health. 13-the authorisation granted under paragraph 10 may be suspended or revoked by the ASST if inspections or control measures carried out in accordance with article following proving that the service does not meet the requirements laid down in this law. 14-in the case of reproductive cells and embryonic stem cells and when such acts are carried out in the context of the application of techniques of medically assisted procreation, the CNPMA exercise the powers referred to in paragraphs 6, 7, 8 and 11. 15-for the purpose of adopting the measures referred to in paragraph 13 the ASST shall, whenever possible, the hearing of the person concerned, in accordance with articles 100 et seq. of the code of administrative procedure. 16-the situations in which may be suspended or revoked the operating permit of the centres in which they are taught the techniques of medically assisted procreation are set in own diploma. Article 6 inspection and inspection measures 1-in matters that are of your competence, ASST performs periodically, inspections or other measures of control appropriate to the harvest units, tissue and cell banks and services responsible for your application, and the interval between them exceeds two years, in order to ensure compliance with the provisions of this law. 2-for the purposes of the preceding paragraph, the ASST has the following powers: a) Inspect the harvest units, tissue and cell banks and the services responsible for your application, as well as the facilities of third parties to whom the permit holder has commissioned to apply part of the procedures;


8 b) Evaluate and verify the procedures and activities in harvest units, on the banks of tissues and cells, in the services responsible for your application and third-party facilities; c) take samples for examination and analysis; d) examine any documents or other records relating to the subject matter of the inspection. 3-ASST shall communicate in writing to officials at the result of the inspections conducted in accordance with the preceding paragraphs. 4-ASST establishes the guidelines relating to the conditions of inspection and control measures, as well as the training and qualification of professionals involved in order to ensure a high level of competence and performance. 5-In case of adverse reactions or serious incidents or suspicion thereof, should the ASST organize inspections or other control measures, as more appropriate. 6-ASST should also carry out inspections or other control measures at the request of the competent authorities of another Member State, since justified, in any case of incident or serious adverse reaction. 7-in the case of reproductive cells and embryonic stem cells and when such acts are carried out in the context of the application of techniques of medically assisted procreation, the CNPMA, in conjunction with the IGAS, exercise the powers referred to paragraphs 1, 2, 3, 4, 5, and 6. 8-whenever requested by another Member State or by the European Commission, the ASST and CNPMA should provide information on the results of inspections and control measures related to the requirements laid down in this law. CHAPTER III National Network of tissues and cells article 7 1 Network-the national network of tissues and cells, hereinafter referred to as the network shall consist of the sampling units, tissue and cell banks and services responsible for your 9 application, regardless of your legal status, authorized by the ASST to operate on the national territory. 2-harvest units, tissue and cell banks and the services responsible for your application, you can add it if the coordination offices of harvest of cells and tissues for transplantation, in terms to regulate by Ordinance to be approved by the Member of Government responsible for healthcare. 3-the network includes Histocompatibility centres according to their duties defined by law. 4-the preceding paragraphs shall not apply to reproductive cells, embryonic stem cells and other cells or tissues collected in the context of the application of techniques of medically assisted procreation. Article 8 1 Traceability-tissues and cells collected, processed, stored, distributed and applied in the national territory shall be subject to traceability from the donor to the recipient and to the donor, as well as all relevant data relating to products and materials coming into contact with tissues and cells. 2-for the purposes of the preceding paragraph, the sampling units, tissue and cell banks and the services responsible for your application should implement a donor identification system which assigns a unique code to each donation and to each product to it associated as provided for in article 12, and in accordance with the set by ASST and at CNPMA. 3-all tissues and cells must be identified through a label with the information or references allowing a link to the information referred to in annex VIII of this law, which is an integral part. 4-the data needed to ensure full traceability, listed in annex X to the present law, shall be kept for at least 30 years after your clinical use, regardless of the type of support and since confidentiality safeguarded.


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Article 9 import and export of human tissues and cells 1-tissues or cells intended for human application can only be imported from third countries when: a) originate in tissue and cell banks authorized for such activities and comply with the quality requirements provided for in this law; b) Ensure all traceability requirements provided for in this law; c) Ensure a system of notification of serious adverse reactions and incidents equivalent provided for in this law. 2-imports of tissues or cells from third countries and exports to third countries may only be made by banks of tissues and cells that are properly authorized for these activities, in accordance with this law and with the permission, according to your respective area of competence, the ASST and CNPMA pursuant to paragraphs 4 and 5 below. 3-Should be also adopted all the necessary measures to ensure that exports of tissues and cells to third countries are made through tissue and cell banks authorized for such activities. 4-applications for imports of tissues and cells must mention the institution of origin and shall be authorized only in accordance with your respective area of competence, by the ASST or by CNPMA when: there are proven benefit in the use) of the tissues or cells to be applied; (b)) the purpose of the tissues or cells is for human application; c) there is no availability on the banks of tissues or cells; (d)) for compatibility reasons justified by doctor. 5-applications for export of tissues and cells must identify the target institution and shall be authorized only in accordance with your respective area of competence, by the ASST or by CNPMA when there is sufficient availability of tissues and cells in 11 national tissue banks or for compatibility reasons justified. 6-in case of emergency, the import or export of tissues and cells may be authorised directly, according to your respective area of competence, by the ASST or at CNPMA provided that the supplier has accreditation, designation, authorisation or licensing as set out in this Act or equivalent standards of quality and safety. 7-the preceding paragraphs shall apply to the movement of tissues and cells from third countries and the European Union. Article 10-keeping 1-tissue and cell banks and harvest units must have and keep updated a register of their activities, restricted access and confidential, including the types and quantities of tissues and cells harvested, analyzed, processed, preserved, stored and distributed, or otherwise used, and the origin and destination of the tissues and cells intended for human applications in accordance with annex II to VIII of this law, which shall form an integral part. 2-in the case of enforcement of tissues and cells register referred to in the preceding paragraph shall include the clinical applications, the data necessary for the identification of recipients of transplanted tissues and cells and your origin so as to ensure traceability in accordance with annex X to the present law, which is an integral part. 3-The records referred to in the preceding paragraphs shall be kept for a minimum period of 30 years and destroyed as soon as you are not required for the purposes of traceability. 4-The tissue and cell banks and the services responsible for your application must be in accordance with your respective area of competence, to ASST or CNPMA an annual report of its activities which is an integral part of the evaluation required the maintenance of activity exercise. 5-in the context of their respective areas of competence, the ASST and CNPMA shall establish and maintain an updated public register relating to authorised and their activities.


12 article 11 notification of serious adverse reactions and incidents 1-tissue and cell banks and harvest units and the services responsible for your application should have a system of notification, investigation, registration and transmission of information on adverse reactions and serious incidents which may interfere with the quality and safety of tissues and cells and can be assigned to collection , testing, processing, storage and distribution of tissues and cells, as well as any serious adverse reaction observed during or after clinical application which may be linked to the quality and safety of tissues and cells. 2-the person responsible referred to in article 14 shall ensure that they are notified, according to your respective area of competence, to ASST and CNPMA all adverse reactions or serious incidents referred to in the preceding paragraph and which is a report of the analysis of its causes and consequences, including the measures taken. 3-Any person or institution that uses tissues or cells of human origin under this law shall communicate all relevant information to harvest units and tissue and cell banks with activities in the field of the donation, procurement, testing, processing, storage and distribution of human tissues and cells, in order to facilitate traceability and ensure quality control and safety. 4-The tissue and cell banks and harvest units and the services responsible for your application shall ensure the functioning of a procedure need, fast and controllable, allowing the distribution circuits any products that might be related to adverse reactions or serious incidents. 5-in the case of assisted reproduction any type of identification or gametes or embryos Exchange is regarded as a serious adverse event, and all the persons and bodies responsible for harvesting your human application performing assisted reproduction, carry out notification of such incidents at CNPMA. 6-for the purposes of notification of serious adverse events and reactions shall be used the models set out in annex IX to this law, which is an integral part.



13 CHAPTER IV to the requirements of article 12 crop Harvest of human tissues and cells 1-banks of cells and tissues and harvest units shall have written agreements with the staff or clinical teams responsible for donor selection, unless they are part of the staff of that body or service, specifying the procedures to be followed in accordance with annex V to this law , which is an integral part, the types of tissues and cells, the samples to be taken for analysis and the protocols to be observed. 2-the banks of cells and tissues and harvest units must have standard operating procedures (SOPS) for verification of the following elements: the Identity of the donor); b) details of the consent or permission of the donor or of your family, in accordance with the law; c) evaluation of donor selection criteria, as provided for in paragraph 1 of article 25; d) evaluation of the laboratory tests required for donors, as laid down in annexes VI and VII to this Act, which shall form an integral part. 3-also should be SOPS describing the procedures for procurement, packaging, labelling and transportation of the tissues and cells to the point of arrival in the tissue bank or, in the case of direct distribution of tissues and cells, to the clinical team responsible for your application or, in the case of samples of tissues and cells, to the laboratory for analysis, as referred to in annex VIII to the present law , which is an integral part. 4-harvesting shall take place in appropriate facilities, in compliance with procedures that minimise bacterial contamination, in particular, of tissues and cells procured in accordance with annex VIII to this law which is an integral part.


14 5-materials and equipment for harvesting should be managed in accordance with the standards and specifications set out in paragraph 1.3 of annex VIII to the present law, which is an integral part, and having regard to the instruments, standards and relevant national and international guidelines, covering the sterilisation of medicines and medical devices. 6-for the purposes of the preceding paragraph, must use sterile instruments and sampling devices approved for tissue and cell procurement. 7-the tissue and cell procurement in living donors must be carried out in an environment that ensures health, your security and privacy. 8-the collection of tissues and cells donors corpse must made with respect for the dignity of the deceased donor, in particular through the reconstitution of the body so that your appearance is as much as possible similar to your original anatomical form. 9-for the purposes of the preceding paragraph the banks of cells and tissues and harvest units should provide the personnel and the equipment necessary for the reconstitution of the body of the dead donor. 10-to the donor and the donated tissues and cells must be assigned a unique identification code during the harvest or the tissue bank and tissue cells, which ensures the correct identification of the donor and the traceability of all donated material. 11-for the purposes of the preceding paragraph, is created at the national level a donor identification system which assigns a unique code to each donation and to each product to her associate, in accordance with annex II to this law, which is an integral part, without prejudice to the single European coding system to be approved. 12-the encoded data must be entered in a national register by the ASST or CNPMA, according to their area of competence. 13-the donor documentation shall be kept in accordance with the established in 1.4 of annex VIII to the present law, which is an integral part.


15 chapter V provisions concerning the quality and safety of tissues and cells quality management article 13 1-harvest units, tissue and cell banks and the services responsible for your application should develop and maintain a quality system operating and quality management based on best practices that include at least the following documentation : a) standard operating procedures authorized activities and critical processes; b) training manuals and reference; c) forms of transmission of information; d) register of donors; e) information on the final destination of tissues or cells; f) system for the detection and reporting of adverse reactions. 2-harvest units, tissue and cell banks and the services responsible for your application should adopt the necessary measures to ensure that the documentation referred to in the preceding paragraph is available during the inspections carried out, within the framework of your respective area of competence, by the ASST or at IGAS in conjunction with the CNPMA. Article 14 responsible person 1-responsible for harvest units, tissue and cell banks and by the services responsible for your application must be doctor and possess at least two years experience in the area. 2-the impossibility of compliance required in the preceding paragraph, the person responsible may be designated from among graduates in Pharmaceutical or Biological Sciences with at least three years experience in the activities of the area. 3-the preceding paragraphs shall not apply to the centres in which they are taught techniques of medically assisted procreation.



16 4-The responsible designated pursuant to the preceding paragraphs shall: a) ensuring that human tissues and cells intended for human applications are collected, analyzed, processed, stored, distributed and implemented in accordance with the provisions of this law; b) provide the ASST all necessary information in accordance with this law; c) ensure compliance with the requirements for staff training, quality system, documentation, preservation of records, traceability, notification, data protection and confidentiality. d) ensure that medical activities, namely, the selection of donors, the clinical laboratory results, analysis of tissues and cells to be applied, and your application are carried out under the responsibility and direct medical supervision, with experience. 5-the functions referred to in the preceding paragraph may be delegated, provided that the delegate has the qualifications referred to in paragraph 1. 6-harvest units, tissue and cell banks and the services responsible for your application, shall communicate, within the framework of your respective area of competence, to ASST or CNPMA the name of the person responsible, as well as your replacement in the event of temporary or definitive absence.

Article 15 crew Personnel to harvest units and tissue and cell banks and services responsible for your application should possess appropriate qualifications to their duties and receive adequate training, regular and timely. Article 16 Reception of tissues and cells 1-tissue and cell banks should ensure that: the 17) all donors of human tissues and cells are subjected to tests in accordance with the requirements laid down in annexes VI and VII to this Act, which shall form an integral part of it; b) the selection and acceptance of tissues and cells are made in accordance with the requirements laid down in annexes V to VII of this Act, which shall form an integral part; c) tissues and cells of human origin and documentation meet the requirements laid down in annexes II to VIII of this law, and the rules that may be adopted in accordance with subparagraph (c)) of article 32; d) the packaging of tissues and cells of human origin received was made in accordance with the provisions in annex III to this law, which is an integral part. 2-the tissues or cells received which do not comply with the requirements referred to in the preceding paragraphs must be rejected. 3-the acceptance or rejection of received tissues/cells shall be documented. 4-cell and tissue banks shall ensure that human tissues and cells are correctly identified throughout any phase of processing, assign an identification code to each consignment or batch of tissues or cells, according to the provisions of paragraphs 10 and 11 of article 12 5-tissues and cells remain in quarantine until the requirements for analysis and information of the donor are met in accordance with annex VIII, which shall form part. Article 17 1 Processing of tissues and cells-tissue and cell banks shall include in their standard operating procedures (SOPS) all processes which are likely to affect the quality and safety, ensuring that they take place under controlled conditions. 2-cell and tissue banks shall ensure that the equipment used, the working environment, the design, validation and control conditions are processes in accordance with the requirements laid down in annex II to this law, which is an integral part.


18 3-the Bank of tissues and cells must include in their PON special provisions for the handling of tissues and cells to eliminate in order to prevent the contamination of other tissues and cells, as well as the environment or personnel. 4-Any modifications to the processes used in the preparation of tissues and cells should comply with the provisions of paragraph 1. Article 18 Conditions of storage of tissues and cells 1-cells and tissue banks shall ensure that all procedures associated with the storage of tissues or cells are documented in SOPs and that the storage conditions comply with the requirements set out in annex II to this law, which is an integral part. 2-tissue and cell banks should establish and apply procedures for the control of packaging and storage areas, in order to avoid any circumstances likely to affect the tissues and cells with a view to their intended purpose. 3-The processed tissues or cells shall not be distributed until you are satisfied all the requirements of this law. 4-In case of cessation of activity of Bank of tissues and cells, stored tissues and cells shall be transferred to other services in accordance with authorized by ASST. 5-the cessation of activity of Bank of embryonic stem cells and other cells or tissues collected in the context of the application of techniques of medically assisted procreation is governed by its own diploma. Article 19 Labelling, documentation and packaging tissue and cell banks shall ensure that labelling, documentation and packaging of tissues and cells comply with the requirements laid down in annexes III and VIII of this law, which shall form an integral part.




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Article 20 1-Distribution of tissues and cells shall ensure that the conditions of distribution of tissues and cells comply with the requirements set out in annexes III and VIII to this law, which shall form an integral part, and regulation to be adopted pursuant to points (a) (d)) and e) of the article 32 2-within the framework of your area of competence , ASST may authorise the direct distribution of certain tissues and cells from the harvest to the health care establishment for immediate transplantation. Article 21 relationship between tissue and cell banks and third parties 1-tissue and cell banks should conclude an agreement with third parties whenever an external intervention and that this activity has influence on the quality and safety of tissues and cells processed, in particular in the following circumstances:) When the tissue and cell bank assign to third parties the responsibility for one of the phases of crop , processing or analysis of tissues or cells; b) if third parties providing goods or services that may affect the warranty of the quality and safety of tissues and cells, including the distribution of same; c) whenever a Bank of tissues and cells providing services to another bank of tissues and cells for certain procedure for which is not authorized; d) when a Bank of tissues and cells distribute tissues or cells processed by third parties. 2-the evaluation and selection of third parties for the purposes of concluding the agreements referred to in the preceding paragraph are made based on your ability to meet the requirements of this law. 3-the agreements referred to in paragraph 1 shall specify the responsibilities of third parties and 20 provide the procedures and protocols that each must meet regarding the contracted activity, including the terms of reference referred to in the following paragraph. 4-In case of termination of the contract the contractor entity should refer to the contracting authority the documents, data, and all information that may affect the traceability, quality and safety of tissues and cells. 5-cell and tissue banks shall keep an updated list of agreements concluded with third parties and provide a copy of the same, within the framework of your respective area of competence to ASST or CNPMA, where requested.

CHAPTER VI donor selection and evaluation article 22 Principles governing the donation of tissues and cells 1-the donation of cells and tissues is voluntary and altruistic, and cannot be, under any circumstances, place any economic compensation or remuneration for the donor or for any individual or entity. 2-Notwithstanding the previous paragraph, the living donors may receive compensation strictly limited to reimbursement of the costs incurred or damage immediately resulting from the donation, in accordance with article 9 of law No. 22/2007 of 29 June. 3-the conditions for the allocation of compensation provided for in the preceding paragraph are defined by order of the Minister of health. 4-receptors cannot be required any payment for tissues or cells received. 5-the activities carried out by the units of harvest, tissue and cell banks and services responsible for your application may not be profitable, and should reflect only the actual costs for services rendered. 6-the promotion and advertising of the donation must be always in generic terms, without seeking benefits to specific people, and highlighting the 21 volunteer nature, your selfless and disinterested. 7-it is considered misleading advertising that misleads about the real utility of obtaining, processing, preservation and storage of human cells and tissues, when this is not scientifically supported. Article 23 protection and confidentiality of data 1-In compliance with the strict conditions laid down in the law of protection of personal data, approved by law No. 67/98 of 26 October, the personal data relating to donors and recipients, your treatment and interconnection, are subject to professional secrecy and the appropriate measures of security and confidentiality of information. 2-The donor and recipient is guaranteed the confidentiality of all information related to your health, with the results of the analyses of their gifts and the traceability of your gift. 3-Are expressly forbidden, deletions or additions unauthorized changes of the data contained in the donor records or delete records, as well as the unauthorized transfer of information, when failing to comply with the provisions of law No. 67/98 of 26 October (Law of protection of personal data).

4-information systems of tissue and cell banks should ensure the security of data under this article and the procedures necessary to resolve data discrepancies. 5-access rights and opposition of the data subjects to information contained in the registration systems of donations and donors engaged in the terms and conditions laid down in articles 10 to 13 of law No. 67/98 of 26 October, without prejudice to the provisions of the legislation on the use and application of techniques of medically assisted procreation. Article 24 1 Consent-the harvest of human tissues and cells and your application in humans may be carried out only after having been fulfilled all mandatory requirements



22 relating to informed consent as provided for in article 8 of law No. 22/2007, of June 29, and annex IV to this Act, which is an integral part, without prejudice to the provisions of the legislation governing the use and application of techniques of medically assisted procreation. 2-For the collection of surgical residues must obtain the informed consent of donors, applying the same principles apply to the living donor. Article 25 Selection, evaluation, collection and reception 1-donors must meet the selection criteria set out in annex V, which forms an integral part, and, in the case of donors of reproductive cells, in annex VII to this law, which is an integral part. 2-donors of tissues and cells, except donors of reproductive cells, must be subject to biological tests set out in paragraph 1 of annex VI to the present law, which is an integral part. 3-donors of reproductive cells undergo the biological tests set out in paragraphs 2 and 3 of annex VII to the present law, which is an integral part. 4-the analysis referred to in paragraph 2 shall be carried out in accordance with the General requirements set out in paragraph 2 of annex VI to the present law, which is an integral part. 5-the analyses referred to in paragraph 3 shall be carried out in accordance with the General requirements set out in paragraph 4 of annex VII to the present law, which is an integral part. 6-autologous donations must meet the selection criteria set out in paragraph 2.1. Annex V to the present law, which is an integral part. 7-the results of the evaluation and analysis procedures of the donor must be documented and any relevant abnormality detected shall be notified in accordance with annex V to this law, which is an integral part. 8-the analyses required for donors shall be carried out by a laboratory certified or accredited and authorized by ASST, for this purpose, with contractual relationship to the Bank of tissues and cells. 9-donation and procurement procedures for tissues and cells, as well as your reception at Bank of cells and tissues must meet the requirements set out in annex VIII to this law, 23 of which it forms an integral part. 10-the provisions of paragraph 8 shall not apply to reproductive cells, embryonic stem cells and other cells or tissues collected in the context of the application of techniques of medically assisted procreation.

CHAPTER VII exchange of information and reports article 26 Reports within their respective areas of competence, the ASST and CNPMA shall submit to the European Commission before 7 April 2009 and subsequently every three years a report on the activities carried out in the context of the application of this Act, including a statement of the measures adopted on health inspection and monitoring. CHAPTER VIII infringements and sanctions article 27 administrative offences 1-Without prejudice to the civil or criminal liability, the provisions of articles 44 and 45 of the law No. 32/2006, of July 26, and the administrative measures that there is place, constitute infringements of the contravention of this Act in accordance with standards set out in the following paragraphs. 2-light: offences Constitute failure to comply with the) paragraph 6 of article 14; b) failure to comply with the provided for in paragraph 5 of article 21. 3-Constitute serious offenses: a) non-compliance with the provisions paragraphs 1, 2, 3, 4, 5, 7, 9 and 11, article 5; b) failure to comply with the laid down in paragraphs 3 and 4, article 10; c) failure to comply with the provisions of paragraphs 1, 2, 4 and 5 of article 14;


24 d) failure to comply with the provisions of article 15; and failure to comply with the) paragraph 2 of article 13; f) failure to comply with the provisions of paragraph 6 of article 22; g) the failure to comply with the provisions of paragraphs 1, 2, 3 and 4 of article 21; h) non-observance of the regulations and instructions of the ASST or CNPMA; I) resistance in providing information requested by ASST or at CNPMA, as well as any and all behavior resulting in lack of collaboration with these entities. j) offences which have served to facilitate or cover up infringements. l) recidivism in light offences in the last six months; m) the exercise of misleading advertising as defined in paragraph 7 of article 22. 4-Constitute serious offenses: a) the unauthorized activities by ASST or at CNPMA in continued disregard by the provisions of paragraphs 1, 2, 3 4, 5, 7, 9 and 11 of article 5; b) failure to comply with the provisions paragraphs 1 and 2 of article 10; c) failure to comply with the provisions of article 9; d) failure to comply with the provisions of articles 16; and failure to comply with the provisions of the) article 17; f) failure to comply with the provisions of article 18; g) failure to comply with the provisions of article 19; h) the failure to comply with the provisions of paragraph 1 of article 20; I) failure to comply with the provisions of article 12; j) failure to comply with the provisions of article 25; l) failure to comply with the provisions of article 8; m) failure to comply with the provisions of paragraph 1 of article 13. n) failure to comply with the provisions of paragraphs 1 to 5 of article 11. the failure to comply with the provisions of)) in paragraphs 1, 2, 4, and 5 of article 22;


25 p) the persistence of misleading advertising as defined in paragraph 7 of article 22; q) failure to comply with the provisions of article 23; r) failure to comply with the provisions of article 24; s) the use of the license for other purposes other than those provided for therein; t) offences affecting the quality and safety of tissues and cells, and hence have a result serious danger or damage to public or individual health; u) the infringements which have served to facilitate or cover up serious or very serious; v) non-compliance determinations and reiterated instructions of ASST or CNPMA; x) refusal to provide information requested by ASST or at CNPMA, as well as any and all behavior resulting in refusal of collaboration with these entities; z) recidivism in serious offences over the past five years. 5-in the contravention referred to in the preceding paragraphs are punishable neglect and attempting, with the amounts of the fines referred to in number following halved.


Article 28 Penalties The administrative offences provided for in the preceding article are punishable with fines in accordance with the following: a) The minor offenses are punished with fines up to € 500; (b) serious offences are punished), with fines from € 500 to € 1 500, for individuals, and up to € 15 000 for legal persons; c) The very serious offenses are punished with fines from € 1 500 € 3 500, for natural persons, and from € 15 000 up to € 44 000 for legal persons.


26 article 29 penalties depending on the gravity of the offence and the guilt of the agent, can be determined simultaneously with the fine, the following penalties: the) suspension or revocation of the authorization granted partial to the activity or process of preparation of tissues and cells; b) Closure of the service. Article 30 Supervision, instruction and imposition of fines 1-ASST is responsible for ensuring the enforcement of the provisions of this Act and the application of the sanctions provided for in this chapter, except in the case of reproductive cells, embryonic stem cells and other cells or tissues collected in the context of the application of techniques of medically assisted procreation, in which jurisdiction is of the CNPMA. 2-the General Inspectorate of Health Activities (IGAS) is the competent authority to instruct a misdemeanour procedures whose introduction has been determined by the ASST or at CNPMA. Article 31 destination of the product of the fines the proceeds of fines provided for in this Act reverts: a) In 60% to the State; b) In 30% to the ASST or CNPMA, according to your respective area of competence; c) In 10% to the IGAS. CHAPTER IX transitional and final provisions article 32 technical requirements and their adaptation to scientific and technical progress 1-Are regulated by Ordinance to be approved by the 27 Government member responsible for healthcare, technical requirements and your adaptation to scientific progress: a) authorization requirements of harvest, tissue and cell banks and services responsible for your application; b) quality system; c) procedural requirements of preparation of tissues and cells; d) processing, storage and distribution of tissues and cells; e) requirements for the direct distribution to the recipient of specific tissues and cells; f) Biomonitoring. Article 33 Transitional Standard 1-harvest units, tissue and cell banks and the services responsible for your application already in operation have a period of 12 months from the date of publication of this law to adapt to the requirements laid down therein. 2-on expiry of the period referred to in the preceding paragraph harvest units, tissue and cell banks and the services responsible for your application have a maximum of thirty working days to request the renewal of the application for ASST authorisation of operations in accordance with the provisions of this law. 3-the provisions of the preceding paragraph shall not apply to the centres in which they are taught techniques of medically assisted procreation. Article 34 set 1-Standard Are revoked the articles 7 and 8 of ministerial order No. 31/2002, of 8 January, in the part relating to tissues and cells. 2-Are deleted paragraphs 3 and 4 of article 3 of law No. 22/2007 of 29 June, in part concerning tissues and cells.


28 article 35 entry into force this law shall enter into force on the day following your publication.

Seen and approved by the Council of Ministers of 24 April 2008 the Prime Minister, the Minister of Parliamentary Affairs Minister Presidency 29 ANNEX I definitions a) «Storage», maintaining the product under appropriate controlled conditions until distribution; b) "human application" means the use of tissues or cells on or in a human recipient and extracorporal applications; c) ' tissue and cell Bank», a tissue bank or a unit of a hospital or another body where activities with the processing, preservation, storage or distribution of human tissues and cells, without prejudice to can also be responsible for the collection or analysis of tissues and cells; d) «Cells», individual human cells or a collection of human cells when not bound by any form of connective tissue; e) ' reproductive cells», all tissues and cells intended to be used for the purpose of assisted reproduction; f) «harvest», a process by which tissue or cells are made available; g) donor, every human source, whether living or deceased, of human cells or tissues; h) «Gift», any donation of tissues or cells intended for human applications; I) «partners» donation, the donation of reproductive cells between a man and a woman who state keep an intimate physical relationship; j) ' distribution ' means the transport and delivery of tissues or cells intended for human application;

k) ' allogeneic ' means cells or tissues removed from one person and applied to another; l) ' autologous use ' shall mean cells or tissues removed from and applied in the same person;



30 m) ' serious adverse event ' shall mean any untoward occurrence associated with the procurement, testing, processing, storage and distribution of tissues and cells that might lead to the transmission of a communicable disease, to death or life-threatening, disabling or incapacitating conditions for patients, or in, or prolongs hospitalisation or morbidity; n) ' Organ ' means a differentiated and vital part of the human body, formed by different tissues, that maintains your vascularisation the structure, vascularization and capacity to develop physiological functions; the) «Preservation», the use of chemical agents, the change in environmental conditions or other means during processing to prevent or retard biological or physical deterioration of cells or tissues; p) ' standard operating procedures ' (SOPS), written instructions describing the steps in a specific process, including the materials and methods to be used and the expected end product; q) ' Processing ' means all operations involved in the preparation, manipulation, preservation and packaging of tissues or cells intended for use in human beings; r) "Quarantine" means the status of harvested tissues or cells, or tissue isolated physically or by other effective means, whilst awaiting a decision on your approval or rejection;

s) ' Traceability ' means the ability to locate and identify the tissue or cell during any step, from your collection, processing, analysis and storage, to the distribution to the recipient or disposal, including the ability to identify the donor and the tissue and cell bank or manufacturing facilities that receive, process or store the tissue or cell the ability to identify the receptors in medical facilities applying the tissue or cells to recipients and the ability to locate and identify all relevant data for products and materials coming into contact with these tissues and cells; t) "serious adverse reaction" means an unintended response, including a communicable disease 31 in the donor or in the recipient associated with the procurement or human application of tissues and cells that is fatal, life-threatening, disabling, incapacitating, or which results in, or prolongs, hospitalisation or morbidity; u) ' waste ' surgical, organs, tissues and cells removed during a surgical procedure with therapeutic goals and not get tissues or cells. In this procedure of obtaining of tissues or cells no additional risks to the donor specifically related to the harvest. The same definition applies to collection of fetal membranes (amnion and corion) after delivery; v) "quality system" means the organisational structure, the definition of responsibilities, procedures, processes and resources for implementing quality management, including all activities that contribute, directly or indirectly, to the quality; w) «Service responsible for application of cells or tissues in human beings ', a health care service, public or private, to carry out human applications of tissues and cells of human origin; x) «Fabric», all the constituent parts of the human body formed by cells; y) «harvest unit ' means a health care establishment or a unit of a hospital or any other body which carries out activities of harvest of human tissues and cells and which is not authorized as Bank of tissues and cells; z) ' autologous Use possible», the cells or tissues collected for the purpose of being preserved for a hypothetical future use in the same person, without a medical indication at the time of collection and preservation; AA) ' direct use ' means any procedure where cells are donated and used without being stored in a bank; BB) ' Validation ' (or ' approval ' in the case of equipment or environments) means the establishment of documented data that provide a high degree of assurance that a process, PON, a piece of equipment or a specific environment consistently produce a product that meets specifications and quality attributes previously determined, in order to evaluate the performance of a system 32 as regards your effectiveness for intended use.


33 ANNEX II authorization requirements of harvest, tissue banks and the enforcement thereof. Organisation and management 1-Should be appointed a responsible person with the qualifications and responsibilities provided for in article 14 of this law. 2-all services must have access to a doctor named for counseling and supervision of medical service activities, referred to in point (e)) of paragraph 3 of article 14 3-the services must have operating procedures appropriate to the activities for which authorization is requested. 4-there must be an organizational framework that defines clearly the hierarchy and relationships of notification. 5-there must be a documented quality management system applied to activities for which authorization is requested, in accordance with the rules laid down in this law. 6-the services must ensure that the risks inherent in the use and handling of biological materials, including those related to the procedures, environment, staff health status are identified and minimized consistent with the maintenance of a quality and safety appropriate to the intended purpose the tissues and cells. 7-the agreements between tissue banks and third parties, where applicable, must comply with the provisions of article 21 of this law.

8-there must be a documented system, overseen by the person responsible for ratifying that tissues and cells meet appropriate specifications for safety and quality for release and distribution. 9-there must be a documented system that ensures the identification of every unit of tissue or cells at all stages of the activities for which requests



34 authorization. B. Personnel 1-harvest units, tissue banks and the enforcement thereof, must be in sufficient number and qualifications required for the tasks they perform. 2-staff competence shall be assessed at appropriate intervals specified in the quality system. 3-all personnel must have a functional description clear, documented and updated. Their tasks, responsibilities and accountability must be clearly documented and fully understood. 4-all personnel should receive initial and continuing training, suited to their tasks. The training programme must ensure so documented that each professional: a) Demonstrated competence in the execution of their designated tasks; b) Has knowledge and proper understanding about processes and scientific and technical principles, relevant to the tasks assigned; c) understands the organizational framework, quality system and health and safety standards of the service from which carries out its functions; d) is conveniently informed of ethical, legal and regulatory context wider than your work. C. equipment and supplies 1-all the equipment and material must be designed and maintained to serve the order and must minimise any hazard to donors, recipients and people. 2-all critical equipment and technical devices must be identified and validated, regularly inspected and subject to preventive maintenance according to the manufacturer's specifications. 3-whenever the equipment or materials affect critical processing or storage parameters, such as temperature, pressure, particle counts, microbial contamination levels, must be identified and submitted, if necessary, monitoring, alerts, alarms and corrective actions appropriate to detect malfunctions and defects, 35 to ensure permanent maintenance of critical parameters within acceptable limits. 4-all equipment with a critical measuring function shall be calibrated according to a discernible standard, if available. 5-the new and repaired equipment must be tested when installed, validated prior to your use, and the results be documented. 6-the maintenance, service, cleaning, disinfection and sterilization of all critical equipment must be carried out regularly and recorded. 7-procedures must be available for the operation of each component of critical equipment, which specify in detail the measures to be taken in the event of malfunction or failure. 8-procedures relating to activities for which authorization is requested must describe in detail the specifications for all critical materials and reagents. Has to be defined, in particular, specifications for additives, such as solutions, and packing materials. The critical reagents and materials must meet documented requirements and specifications and, where appropriate, the specific legislation on medical devices. D. facilities/Locations 1-the services must have adequate facilities to carry out the activities for which authorization is requested, in accordance with the rules laid down in this law. 2-where the tissue bank activities include processing of tissues and cells in exposure to the environment, the same should take place in an environment with air quality and cleanliness, in order to minimize the risk of contamination, including cross-contamination between donations. The effectiveness of these measures must be validated and monitored. 3-Except in situations specified in the following paragraph, where tissues and cells are exposed to the environment during processing, without a subsequent microbial inactivation process, an air quality is required with particle counts and microbial colony equivalent to those of grade A, as defined in annex I to the European Guide to good manufacturing practice with a general environment suitable for the processing of tissues or cells involved but, at least, equivalent to 36 of Degree D of the guide in terms of particle counting and microbial count. 4-Can be acceptable an environment less strict than specified in the preceding paragraph, where: a) Is a microbial inactivation process or final validated sterilization; or b) Is shown that exposure to a grade A environment has a detrimental effect on the required properties of the tissues or cells involved; or c) Is shown that the method and the application of the tissue or cell in the receiver means a significantly lower risk of transmission of bacterial or fungal infection to the receiver than with transplantation of cells and tissues; or (d)) is not technically possible to carry out the required process in a grade A environment, in particular due to requirements for specific equipment in the area of processing that are not fully compatible with grade A. 5-in the situations referred to in the preceding paragraph must be specified a environment. It has to be demonstrated and documented that the chosen environment achieves the quality and safety required, taking into account at least the order referred to, the application and the immune status of the receiver. Must be provided clothing and protective equipment and personal hygiene appropriate in each relevant workplace Bank of tissues and cells, along with written instructions about hygiene and use of protective clothing. 6-when the activities for which authorization is requested involves the storage of tissues and cells, must be defined the storage conditions required for maintaining the properties of tissues and cells, including relevant parameters such as temperature, humidity or air quality. 7-The critical parameters, such as temperature, humidity and air quality must be controlled , monitored and recorded, in order to verify your compliance with the specified conditions of storage. 8-must have storage facilities which separate and distinguish tissues and cells clearly before your release or placing in quarantine of those that are permitted and which are rejected, in order to avoid exchanges and contamination



37 crossed between them. Must have assigned physically separate areas or storage devices or secured segregation within the device in places of storage of tissues and cells in quarantine or released, in order to keep certain tissues and cells procured in accordance with special criteria. 9-the Bank of tissues and cells must have written policies and procedures regarding controlled access, cleaning and maintenance, waste disposal and reorganisation of services in emergency situations. E. documentation and records 1-there must be a system which envisages clearly defined and effective documentation, correct records and standard operating Procedures (SOPS) for the activities for which authorization is requested. 2-the documents must be reviewed regularly and meet the standards laid down in this law. 3-the system must ensure that the work done is normalized and that all phases are traceable, inter alia, the coding, donor eligibility, procurement, processing, preservation, storage, transport, distribution, application or disposal, including aspects relating to the monitoring and quality assurance. 4-for each critical activity, the materials, equipment and personnel involved must be identified and documented. 5-in the harvest, tissue and cell banks, and services responsible for your application, any changes to documents must be reviewed, dated, approved, documented and implemented rapidly by authorized personnel. 6-there must be a document control procedure to ensure the history of revisions of the documents and the changes and ensure that only used the updated versions of the documents. 7-the records must demonstrate to be credible, reliable and trustworthy. 8-the records must be legible and indelible, and may be handwritten or transferred to another validated system, such as computer system or microfilm. 9-Without prejudice to the provisions of paragraph 4 of article 8, the records, including original data, which are critical to the quality and safety of tissues and cells should be 38 kept for at least 10 years after the expiration date, clinical use or disposal. 10-the records must meet the requirements of confidentiality laid down in article 23 of this law. Access to registers and data must be limited to persons authorized by the person responsible and the ASST for inspection and control measures. F. 1-quality system there must be an audit system in respect of activities for which authorization is requested. The audit must be conducted independently by people trained, recognized competence, at least every two years, in order to verify conformity with the approved protocols and the regulatory requirements. 2-The non-conformities and corrective actions must be documented. 3-non-compliance with the standards of quality and safety must lead to documented investigations, which include a decision on possible corrective or preventive actions,. 4-the fate of non-conforming tissues and cells must be decided in accordance with written procedures, supervised by the person responsible and registered. All affected tissues and cells must be identified and accounted for. 5-corrective actions must be documented, initiated and completed in a timely and effective manner. The preventive and remedial actions should be evaluated with respect to effectiveness after your implementation. 6-harvest units, tissue banks and services responsible for your application should have processes to analyze the performance of the quality management system, to ensure a continuous and systematic improvement.


39 ANNEX III requirements for the authorization of processes of preparation of tissues and cells in the tissue and cell banks the ASST authorizes each process of preparation of tissues and cells after the assessment of the criteria for donor selection, sampling procedures, protocols for each stage of the process, the quality management criteria and final quantitative and qualitative criteria for cells and tissues. This assessment has to meet at least the requirements laid down in this annex. A. Reception on the banks of the tissues and cells tissues and cells must comply with the requirements set out in article 16 of this law. B. the Processing activities for which authorization is requested include processing of tissues and cells, the procedures must meet the following criteria: 1-critical processing procedures must be validated and may not render the tissues or cells clinically ineffective or harmful to the receiver. This can be based on validation studies carried out by the service itself or on data from published studies or, for well established processing procedures, in a retrospective evaluation of clinical results relating to the tissues supplied by the service. 2-it must be shown that the validated process can be carried out consistently and effectively by staff in the environment the Bank of tissues and cells. 3-procedures must be documented in SOPS which must conform to the validated method and with the rules laid down in this law, in accordance with the established and paragraphs 1 to 4 of annex II. 4-you have to ensure that all processes are carried out in accordance with the SOPS approved. 5, in the tissues or cells, using a microbial inactivation procedure, such a procedure must be specified, documented, and validated. 6-Before any significant change to be applied to the processing, the process



40 changed must be validated and documented. 7-The processing procedures must be subject to periodic review, including review procedures, means and equipment for use in routine, in order to ensure that they continue to lead to desired results. 8-procedures for disposal of tissues and cells must prevent the contamination of other donations and products, the processing environment or personnel, in accordance with the legislation in force. C. storage and release of Products where the activities for which authorization is requested include the storage and release of tissues and cells, the authorised tissue and cell banks must meet the following criteria: 1-according to the storage conditions, must be specified the maximum storage period, in order to ensure the required properties. 2-there must be an inventory system for tissues and cells in order to ensure that they cannot be released until they have been met all requirements established in this Act. 3-there has to be a standard operating procedure that defines in detail the circumstances, responsibilities and procedures for the release of tissues and cells for distribution.

4-there must be a system for the identification of human tissues and cells throughout any phase of processing in the tissue and cell Bank, which has to allow a clear distinction between products released, quarantined and disposed of. 5-the records must demonstrate that, prior to the release of tissues and cells, all appropriate specifications are met, in particular that all current declaration forms, relevant medical records, processing records and test results were verified in accordance with a written procedure by a person authorised for this task, by the person responsible referred to in article 14 of this law. 6-If you use a computer-readable form to release the results of the laboratory, the 41 responsible for their release should be able to be identified. 7-after the introduction of any new donor selection criteria, or analytical, clinical as well as any significant change from one stage of processing that enhance safety or quality, must be made a documented risk assessment approved by the responsible person referred to in article 14 of this law, in order to determine the fate of all stored tissues and cells. D. distribution and Removal whenever the activities for which authorization is requested to include the distribution of tissues and cells, the authorised procedures must meet the following criteria: 1 it must be transport conditions, such as temperature and the period, with a view to the conservation of required properties of tissues and cells. 2-the container or packaging must be safe and ensure that the tissues and cells are kept under the conditions specified. All containers and packages need to be validated as suitable for the intended purpose.

3-If the distribution is entrusted by contract to third parties, there must be a documented agreement to ensure compliance with the requirements. 4-in the tissue and cell bank authorised to assess the need for the removal of tissues and cells and trigger and coordinate the necessary actions. 5-there must be an effective withdrawal procedure that provides for the description of the responsibilities and the measures to be taken. This procedure must provide for the notification of the ASST. 6-whenever a donor may have helped to cause a reaction in the receiver, must be taken within pre-set time periods, which must include the screening of tissues and cells and, if applicable, include the source research in order to identify the tissues and cells available from such donor and to notify recipients and recipients of tissues and cells from the same donor If they can be at risk. 7-exist procedures for processing applications of tissues and cells. The rules for allocation of tissues and cells to certain patients or 42 health care institutions must be documented and be made available to interested parties where requested. 8-there must be a documented system for the treatment of returned products including criteria for acceptance in your inventory, if applicable. E. final labelling for distribution 1-the primary container label of the tissues and cells must indicate: the) type of tissues and cells, identification number or code of the tissue or cells, and lot number or group, if applicable; b) identification of the tissue bank; c) expiry date; d) in the case of autologous donation, this fact must be specified: ' for autologous use», and the donor recipient has to be identified; e) in the event of direct donations, must be identified by the receiver; f) when Word gets out that the tissues or cells are positive for a relevant infectious disease marker, it must be included the words: «BIOHAZARD». g) if it is not possible to include in the primary container label the information referred to in points (a) to (d)) and e) should be provided in a separate document that will accompany the primary container. This document should be packed along with the primary container in such a way as to ensure that they remain together. 2-the following data must be entered or the label or the accompanying documentation: a) Description, definition and, if relevant, the dimensions of the product based on cells or tissues; b) morphology and functional data, if applicable; (c)) date of distribution of the tissue or cells; (d) biological Tests performed on the donor) and their results; e) storage recommendations;



43 f) Instructions for opening the container, packaging or any manipulation or reconstitution required; g) shelf life after opening/manipulation; h) instructions for the notification of serious adverse reactions and incidents, as defined in article 11 of this law. I) presence of potentially dangerous waste (antibiotics, ethylene oxide, etc.). F. external Labelling of the shipping container for transport, the primary container must be placed in a shipping container whose label contains at least the following information: a) identification of the tissue bank and cells, including address and phone number; b) identification of the target organism responsible for human application, including address and phone number; c) a reference to the package contains human cells or tissues, and include the words ' HANDLE with CARE '; d) where living cells are required for the transplant, such as stem cells, gametes and embryos must be added as follows: ' DO NOT IRRADIATE '; and recommended Transport Conditions) (position, temperature, etc.). f) safety instructions or cooling method, where applicable.


44 ANNEX IV, consent and information about organ donation and tissue and cell application a. living donors 1-the consent of the donor must be free, enlightened, informed and unequivocal. 2-the consent is provided before doctor, designated pursuant to paragraph 2 of article 8 of law No. 22/2007 of 29 June. 3-in the case of smaller donors, the consent must be given by the parents, provided that they are not inhibited from exercising parental authority, or, in the case of inhibition or absence of both, by the Court. 4-the donation of tissues or cells for minors with capacity of understanding and of manifestation of will also lacks the consistency of these. 5-the harvest of tissues or cells in larger unable for reasons of psychic anomaly can only be done by judicial authorization. 6-the consent of the donor or of who represents it legally is always rendered in writing, being freely revocable except in the case where, for preparing pre-transplant ever performed, the receiver's life is put at risk. 7-in charge of the donation process shall ensure that, at a minimum, the donor or who represents it legally, was properly informed of the aspects relating to the donation and the collection described in paragraphs 6 and 10 of this annex. 8-the information must be provided before the donation. 9-the information should be provided by a health professional with special training in this area, able to transmit properly and clear, using terms easily understood by the donor.

10-the information shall state the purpose and the nature of the collection and its consequences and risks, the laboratory tests, if they are carried out, the registration and protection of donor data, doctor-patient confidentiality, the therapeutic objective and the potential benefits, as well as information on the applicable safeguards intended to protect the donor and recipient.


45 11-the donor, or who represents legally, must be informed that he has the right to receive the confirmed results of the laboratory tests and receive clear explanations about these results. 12-information must be given on the necessity of the requirement for the consent for the collection of tissues or cells can be carried out. B. body Donors the information, consents and authorisations must be provided and obtained in accordance with the provisions of law No. 22/2007 of 29 June. C. donors of reproductive cells, consents and authorizations information must be provided and obtained in accordance with the provisions of law No. 32/2006, of July 22. D. Receiver of tissues and cells 1-the application of tissues or cells in human beings must be preceded by free consent, savvy, informed and unequivocal. 2-the consent is provided before doctor, designated pursuant to paragraph 2 of article 8 of law No. 22/2007 of 29 June. 3-the consent is always provided in writing and freely revocable. 4-in the case of smaller receivers, the consent must be given by the parents, provided that they are not inhibited from exercising parental authority, or, in the case of inhibition or absence of both, by the Court. 5-the application of tissues or cells on minors with capacity of understanding and of manifestation of will also lacks the consistency of these. 6-the application of tissues or cells in larger unable for reasons of psychic anomaly can only be done by judicial authorization.


46 ANNEX V criteria for the selection of donors of tissues and cells (EXCEPT DONORS of REPRODUCTIVE CELLS) The donor selection criteria are based on an analysis of the risks related to the implementation of specific tissues or cells. Indicators of these risks must be identified by physical examination, a review of past medical history and behavioral, biological analyses, post-mortem and other appropriate questions, in case in case of body donors. Unless it is justified on the basis of a documented risk assessment approved by the responsible person referred to in article 14 of this law, shall not be accepted gifts of donors to which to apply the criteria given in the following paragraphs: 1. cadaver Donors: 1.1. General criteria for exclusion: 1.1.1. Cause of death undetermined, unless the autopsy reveal information about the cause of death after harvest and that it does not apply any of the general criteria for exclusion set out in this paragraph. 1.1.2. History of disease of unknown aetiology. 1.1.3. Presence or history of malignant disease, except for primary basal cell carcinoma, cervical carcinoma in situ and some primary tumours of the central nervous system, which should be evaluated according to scientific data. For cornea donation, may be taken into consideration and evaluated donors with malignant diseases, hematologic neoplasms and retinoblastoma, except malignant tumors in the anterior segment of the eye.

1.1.4. Risk of transmission of diseases caused by prions. This risk applies, inter alia, to: a) people diagnosed with Creutzfeldt-Jakob disease, or variant of this disease or family history of Creutzfeldt-Jakob not iatrogenic;



47 b) People with a history of rapid progressive dementia or with neurodegenerative diseases, including those of unknown origin; c) people treated with hormones derived from the human pituitary gland (e.g. growth hormones) and recipients of transplants of the cornea, sclera and dura mater, as well as people that have undergone undocumented neurosurgery intervention (which may have been used dura). 1.1.4.1. with regard to variant Creutzfeldt-Jakob disease, referred to in subparagraph (a)) of the preceding paragraph, may be recommended additional precautions. 1.1.5. systemic Infection is not controlled at the time of the donation, including bacterial infections, viral infections, fungal or parasitic infection significant local or systemic in the tissues and cells to donate. As regards the donation of eyes, can be taken into consideration and evaluated donors with bacterial septicaemia, but only where the corneas are stored by organ culture, so as to detect any bacterial contamination of the tissue. 1.1.6. background, clinical data or laboratory findings that demonstrate the existence of risk of transmission of HIV, acute or chronic hepatitis B, except for people with a proven immune status, hepatitis C and HTLV I/II or presence of risk factors of these infections. 1.1.7. History of chronic disease, autoimmune and systemic, able to impair the quality of the fabric in the middle.

1.1.8. Indications that the results of the analyses of the samples of blood from the donor are not valid, because: a) the occurrence of haemodilution, in accordance with the specifications described in 2 annex VI, when not available a sample pré-transfusão; or b) to treatment with immunosuppressive agents. 1.1.9. Data from other risk factors for transmissible diseases, based on a risk assessment that takes into account the antecedents of the donor in the field of travel and exposure, as well as the prevalence of infectious disease sites. 1.1.10. Presence in the body of the donor, of physical signs that suggest risk of 48 communicable diseases. 1.1.11. Ingestion of substances or exposure to substances such as cyanide, lead, mercury, gold, which may be transmitted to recipients in doses which may endanger your health. 1.1.12. recent Antecedents of vaccination with live attenuated virus, when you consider that there is a risk of transmission. 1.1.13. Transplantation with xenotransplantes. 1.2. Additional criteria of exclusion of children dead donors: 1.2.1. Should be excluded from donors until the risk of transmission of infection can be definitely removed, all children whose mothers are HIV-infected or meet any of the exclusion criteria described in 1.1. of this annex. the) cannot be considered as donors regardless of the results of the analyses, children under 18 months of age whose mothers are infected or present risk factors for HIV infection, hepatitis B, hepatitis C or HTLV and who have been breastfed by their mothers in the 12 previous months; b) can be accepted as donors children whose mothers are infected or present risk factors for infection with HIV, hepatitis B, hepatitis C or HTLV and who have not been breastfed by their mothers in the 12 previous months and whose tests, physical examinations and analysis of medical records do not demonstrate HIV infection, hepatitis B, hepatitis C or HTLV. 2. Living donors: 2.1. Living donor for autologous purposes: 2.1.1. If the cells or tissues removed are to be stored or placed in culture, should apply the same minimum set of biological analyses that apply to allogeneic living donor. The fact that the test results are positive it's not preventing that the tissues or cells or any other product derived from them are stored, processed and redeployed, provided that their isolated and appropriate storage facilities to ensure that there is no risk of cross-contamination to other transplants and/or contamination with adventitious agents and/or trading of 49 products. 2.2. allogeneic living donor: 2.2.1. The allogeneic living donors must be selected on the basis of their health and medical background, provided on a questionnaire and through interview to the donor by a qualified health care professional and formed, in accordance with the willing in 2.2.5. of this annex. 2.2.2. The assessment referred to in the preceding paragraph must include relevant factors that may help to identify and exclude persons whose donation could present a health risk to third parties, such as the possibility of transmitting diseases, or for your own health. 2.2.3. Whatever the gift, the harvest process must not interfere with or compromise the health of the donor or the care you. 2.2.4. In the case of donation of umbilical cord blood or amniotic membrane, the preceding paragraphs applies both to the mom and the baby. 2.2.5. The selection criteria for allogeneic living donors must be established and documented by the Bank of tissues and cells and by responsible for clinical transplants, in the case of direct distribution to the recipient, based on specific cells or tissue to donate, along with the physical state of the donor, medical and behavioral history, the results of clinical investigations and laboratory analyses to determine the State of health of the donor. 2.2.6. Exclusion criteria to be applied should be the same as those used in the case of deceased donors, except as provided in 1.1.1. of this annex. Depending on the tissue or cell to donate, it may take other specific exclusion criteria, such as: a) Pregnancy, except for donors of umbilical cord blood cells, amniotic membrane and sibling donors of hematopoietic progenitor cells; b) breastfeeding; c) in the case of hematopoietic progenitor cells, the potential for transmission of inherited disorders.



50 ANNEX VI laboratory tests required the donors (EXCEPT DONORS of REPRODUCTIVE CELLS) 1. Biological tests required for donors: 1.1. Is a minimum requirement to submit all donors at the following biological analyses: HIV 1 and 2) (HIV-1.2); b) Hepatitis B (HBsAg; Anti-HBc) c) Hepatitis C (Anti-HCV-Ab) d) Syphilis, in accordance with point 1.4. of this annex. 1.1.1. For hepatitis B, hepatitis C and HIV must be always nucleic acid tests. In emergency situations, these tests can be conducted afterwards. 1.2. The analysis of antibody to HTLV I/II shall take place in the case of living donors or from high incidence areas or with sexual partners from these areas, or in the case of the parents of the donor to be from these areas. 1.3. When analyzing anti-Hbc is positive and HBsAg is negative, should be pursuing investigations, by means of risk assessment, in order to determine eligibility for clinical use. 1.4. Should apply a validated analysis algorithm in order to exclude the presence of active infection with Treponema pallidum. A proactive rather than reactive, specific analysis or not, can allow the acceptance of tissues and cells. When you perform a non-specific analysis, a reactive result does not prevent the collection or acceptance, if a specific analysis for confirmation of Treponema is not responsive. If a sample of the donor is responsive to a specific analysis for detecting Treponema, will require a comprehensive evaluation of risks in order to determine eligibility for clinical use. 1.5. In certain circumstances, additional tests may be required depending on the donor's background and characteristics of the tissue or cells donated, such as RhD, HLA, malaria, CMV, toxoplasma, EBV, Trypanosoma cruzi. 1.6. in the case of autologous donors, in 2.1 shall apply. of annex V.


51 2. General requirements to be observed in determining the biological markers: 2.1. The analyses must be carried out by an approved laboratory as analytical center by the responsible authority, using, if necessary, the test kits with CE marking. The type of analysis used should be validated for the purpose, in accordance with current scientific knowledge. 2.2. biological analyses are carried out on the donor's serum or plasma; should not be performed on other fluids or secretions such as the aqueous or vitreous humour unless justified clinically, and should use a validated analysis for that fluid. 2.3. If the potential donors have lost blood and recently received blood, blood components, colloids or crystalloids coming from donations, the blood may not be valid due to hemodilution. Should apply an algorithm to assess the degree of hemodilution in the following circumstances: a) ante-mortem blood sampling: whether the infusion of blood, blood components and/or colloids in the 48 hours preceding blood sampling or whether the infusion of crystalloids in the hour preceding the said collection; b) post-mortem blood sampling: whether the infusion of blood, blood components and/or colloids in the 48 hours preceding death, or whether the infusion of crystalloids in the hour preceding death.

2.3.1. The banks of tissues and cells can only accept tissues and cells from donors with plasma dilution of more than 50%, if the analysis procedures used are validated for this plasma or if have a pré-transfusão sample. 2.4. In the case of a donor, blood samples should be obtained immediately prior to death or, if not possible, sampling should take place as soon as possible after death and not later than after 24 hours. 2.5. the 52) in the case of living donors, except, for practical reasons, donors of bone marrow stem cells and stem cells allogeneic peripheral blood, blood samples must be obtained at the time of the donation, or, if not possible, within 7 days after the gift (the so-called "donation sample"); b) tissues and cells of allogeneic living donors cannot be stored for long periods, it is necessary to do a repeat of the sample and the analysis after an interval of 180 days. In these circumstances, of repeat analyses, the donation sample can be collected in a period from 30 days before the donation and 7 days after donation; c) tissues and cells of allogeneic living donors cannot be stored for long periods and, consequently, it is not possible to do a repeat specimen collection, shall apply the provisions of subparagraph (a)) of this paragraph.

2.6. If in a living donor, except for donors of bone marrow stem cells and peripheral blood stem cells, the "donation sample» as defined in point (a)) of the preceding paragraph, is still considered to determination of HIV, HBV and HCV, the nucleic acid amplification technique (NATou TAA), it is not necessary to repeat the analysis of new blood sample. Also it is not necessary to perform new analyses when processing include an inactivation phase that has been validated for the viruses concerned. 2.7. In the case of collection of bone marrow and peripheral blood cells, blood samples must be collected for analysis in the 30 days prior to donation. 2.8. In the case of neonatal donors, the biological analysis to the donor may be carried out on the donor's mother, in order to avoid medically unnecessary procedures for the baby.



53 ANNEX VII selection criteria and laboratory tests required the donors of reproductive cells 1. In the case of gifts between partners for direct use, it is not necessary to apply the criteria for donor selection. 2. In the case of gifts between partners for direct use, reproductive cells that are processed or stored and reproductive cells that give rise to the embryo cryopreservation, must meet the following criteria: 2.1. The clinician responsible for donor must determine and document, based on past medical history and the patient's therapeutic indications, the justification for the donation and the safety of this to the receiver and to the children who may come to be born. 2.2. the tests must be carried out following biological, in order to assess the risk of cross-contamination: the HIV 1 and 2) (anti-HIV-1, 2); b) Hepatitis B (HBsAg; Anti-HBc); c) Hepatitis C (Anti-HCV-Ab). 2.3. If they are not available or are positive the results of the analyses referred to in 2.2. or if you know that the donor constitutes a source of risk of infection, should be designed a separate storage system. 2.4. analysis should be conducted of HTLV I/II antibodies in donors living or originating from high incidence areas or with sexual partners from these areas or where the donor's parents originate from those areas.

2.5. In certain circumstances, additional analyses may be required, depending on the background of the donor in respect of travel and possible exposure to infectious agents and the characteristics of the tissue or cells donated, such as RhD, malaria, CMV, t. Cruzi. 2.6. The fact that the results are positive is not necessarily detracts from 54 gift between partners, in accordance with the legis artis legally defined. 3. In the case of gifts not from partners, the use of reproductive cells must respect the following criteria: 3.1. Donors must be selected on the basis of age, health and past medical history, provided on a questionnaire and through a personal interview performed by a doctor with experience. This assessment must include relevant factors that contribute to identify and exclude people whose donations might constitute a risk to the health of third parties, such as the possibility of transmitting diseases, such as sexually transmitted infections, or for your own health, such as hiperovulação, sedation or the risks associated with the procedure of collection of ova or the psychological consequences of being a donor. 3.2. Donors must be negative for HIV-1 and 2, HCV, HBV and syphilis on a serum or plasma sample, analyzed in accordance with point 1.1 of annex II, and sperm donors must still be negativity to Chlamydia on a urine sample analyzed by nucleic acid amplification technique (NAT). 3.3. Must perform analyses of HTLV I/II antibodies in donors living or originating from high incidence areas or with sexual partners from these areas or where the donor's parents originate from those areas. 3.4. In certain circumstances, additional tests may be required depending on the donor's background and characteristics of the tissue or cells donated, such as RhD, malaria, CMV, t. Cruzi. 3.5. in the case of autologous donors, in 2.1 shall apply. Annex v. 3.6. It must be genetic screening to determine recessive gene autossómicos, which, according to international scientific data, are prevailing in the ethnic background of the donor, and an assessment of the risk of transmission of hereditary diseases, which are known to be present in the family, after obtaining the consent. Should be given complete information about the risks and the measures taken for easing your, which must be communicated and clearly explained to the receiver. 4. General requirements to be observed in determining the biological markers: 4.1. The analyses should be carried out in accordance with the provisions of 2.1. and 2.2. of annex VI.


4.2 55. Must obtain blood samples at the time of the donation. 4.3. sperm donations from partners must be quarantined for at least 180 days. After the expiry of this period shall be repeated the tests with new blood sample. 4.3.1. If a donor, the blood sample is analysed also for determination of HIV, HBV and HCV, the nucleic acid amplification technique (NAT), it is not necessary to test a new blood sample. 4.3.2. It is not necessary to perform new analyses when processing include an inactivation phase that has been validated for the viruses concerned.


56 ANNEX VIII donation and procurement Procedures of cells and tissues and reception at the tissue and cell Bank 1. Donation and procurement procedures: 1.1. Consent and identification of the donor: 1.1.1. Before proceeding with the collection of tissues and cells, an authorized person must confirm and record: a) that consent for the harvest was obtained in accordance with the provisions of article 24 of this law; and b) how and by whom the donor has been properly evaluated. 1.1.2. In the case of living donors, the health professional responsible for obtaining the health history must ensure that the donor: a) understood the information provided; b) had the opportunity to ask questions and who obtained satisfactory answers; c) confirmed that, as much as it is given to know, all the information provided are true. 1.2. donor Evaluation: 1.2.1. An authorized person must collect and record the relevant behavioral and medical information of the donor in accordance with the requirements described in 1.4. 1.2.2. In order to obtain the appropriate information, different sources are used, including at least one interview with the donor, in the case of living donors, and, where appropriate, the following: a) The medical records of the donor; b) an interview with a person who knew the donor, in the case of cadaver donors; c) an interview with the doctor; d) an interview with the general practitioner;



57 e) the autopsy report. 1.2.3. In the case of a donor and, when appropriate, in the case of a living donor, must also do a physical examination of the body, in order to detect any signs that may be enough to exclude the donor or should be evaluated in the context of medical and personal background of the donor. 1.2.4. All donor records should be reviewed and evaluated to determine of your fitness and signed by a qualified health professional. 1.2.5. The provisions of paragraphs 1.2. the 1.2.4. of this annex shall not apply to the donation of reproductive cells between partners or autologous donors. 1.3. procedures for the collection of tissues and cells: 1.3.1. Sampling procedures shall be appropriate to the type of donor and the type of donation of tissues or cells, and to protect the safety of the living donor. 1.3.2. sampling procedures should retain the properties of the tissues or cells necessary for your purpose and simultaneously minimising microbiological contamination in the course of this process, particularly when tissues and cells cannot subsequently be sterilized. 1.3.3. In the case of donations from donors, the access zone should be restricted. 1.3.3.1. Must use a sterile work area, using sterile fields. 1.3.3.2. Professionals undertaking the harvest must be dressed appropriately for the type of harvest. 1.3.3.3. personnel should wash and scrub their hands and arms properly, use clothing and sterile gloves, face shields and protective masks. 1.3.4. In the case of a donor, the location of harvest should be recorded and the period that mediated between the death and the harvest must be specified in order to ensure the conservation of biological and physical properties required of the tissues and cells. 1.3.5. Once harvested tissues and body cells from a donor cadaver, the body must be reconstituted so that your appearance is as much as possible similar to your original anatomical form.


58 1.3.6. Shall be recorded and examined all adverse reactions that occur during the harvest and that undermine or have harmed a living donor, as well as the results of investigations designed to determine the causes. 1.3.7. There must be policies and procedures that minimise the risk of contamination of tissues and cells for people likely to be infected with communicable diseases. 1.3.8., should be used on tissue and cell procurement, sterile instruments and devices. The instruments or devices must be of good quality, validated or specifically certified and subject to regular maintenance for the purpose of tissue and cell procurement. 1.3.9. For reusable instruments must exist a validated cleaning and sterilization procedure for removal of infectious agents. 1.3.10. Wherever possible, use only medical devices with CE mark and all personnel involved must have received adequate training on the use of these devices. 1.4. Donor documentation: 1.4.1. For each donor must be a register that contains the following elements: the Identification of the donor): name, surname and date of birth. In the case of organ donation involving mother and child, the name and date of birth of the mother and the name, if known, and date of birth of the child. b) age, sex, medical and behavioral background. The information collected must be sufficient to permit the application of the exclusion criteria, if necessary; c) results of the examination of the body, if applicable; d) haemodilution formula, if applicable; and consent or authorization form), if applicable; f) clinical data, results of laboratory tests and results of other analyses; g) if perform an autopsy, the results should be included in the register. In relation to tissues and cells that cannot be stored for prolonged periods 59, should be recorded an oral preliminary autopsy report; h) in the case of hematoipoéticas progenitor cells donors, donor suitability is chosen for the receiver should be documented. In the case of gifts without relation, when the organization responsible for the crop have limited access to the data of the receiver, must be provided to the agency making the transplantation of donor data that are relevant to confirm the adjustment. 1.4.2. the body carrying out the harvest must create a crop report, which is transmitted to the Bank of tissues and cells, and should appear in it at least the following information: a) ID, name and address of the tissue and cell bank that will receive the cells or tissues; b) identification of the donor, including how it was identified and by whom; c) description and identification of procured tissues and cells, including samples for analysis; d) identification of the person responsible for the sampling session, including signature; e) date, time (where relevant, start and end), harvest location and procedure (SOP) used, including any incidents that occurred; When necessary, environmental conditions of the installation of collection (description of the physical area in which proceeded to harvest); f) for body donors, the conditions under which the cadaver is kept: refrigerated (or not), time of the beginning and the end of the chilling; g) identification/batch numbers of reagents and transport solutions used. h) where possible, the date and time of death. 1.4.2.1. When you harvest sperm at home, the sampling report shall record this fact and contain only the following elements: a) the name and address of Bank of tissues and cells that will receive the cells or tissues; b) identification of the donor, and, if possible, the date and time of collection;


1.4.3 60. All records must be clear and readable, protected against changes prohibited, preserved and readily accessible under these conditions throughout your period of specified conservation, in accordance with the provisions of the Personal Data Protection Act.


1.4.4. donor records required to ensure full traceability must be kept for a minimum of 30 years after clinical use, or expiration date, a suitable file acceptable by the ASST. 1.5. Packing: 1.5.1. After the harvest, all tissues and cells procured must be packed in such a way as to minimize the risk of contamination and stored at temperatures that preserve the required characteristics and biological function of cells or tissues. The packaging must also prevent contamination of those responsible for the packaging and transport of tissues and cells. 1.5.2. The packaged cells or tissues must be shipped in a container suitable for the transport of biological materials, and that maintains the safety and quality of tissues or cells it contains. 1.5.3. Any tissue or blood samples for analysis that follow must be accurately labelled to ensure identification of the donor, and must include the record of the time and place where the sample was taken. 1.6. Labelling of tissues or cells harvested: 1.6.1. At the time of harvest, each package containing tissues and cells must be labelled. 1.6.2. The primary container of tissues or cells must indicate the ID or the code of the donation and the type of tissues and cells. 1.6.3. When the packing dimension, must provide the following information: a) Date of the donation and, if possible, time; b) Warnings of danger; c) nature of any additives (if used);


61 d) in the case of autologous donations, the label must indicate ' autologous use only '; e) in the event of direct donations, the label must identify the intended receiver. 1.6.4. If it is not possible to include on the label of the primary packaging the information mentioned under (a))) of the preceding paragraph, shall be provided on a separate sheet accompanying the primary container. 1.7. Labelling of the shipping container – if the tissue or cells are transported by an intermediary, transport containers shall bear on their labels, at least, the following elements: a) the words ' tissues and cells ' and ' HANDLE with CARE '; b) identification of the establishment from which packaging is transported (address and phone number) and the name of the person to contact in case of problems; c) identification of the tissue and cell Bank of destination (address and phone number) and contact person for the reception of the container; d) date and time of the beginning of the transport; e) specifications for transport conditions that are important to the quality and safety of tissues and cells; f) in the case of all cellular products, the following shall be added: ' do not IRRADIATE '; and (g)) If you know that a product is positive for a relevant infectious disease marker, it must be included the words: «BIOHAZARD»; h) in the case of autologous donors, the following shall be added: «only for AUTOLOGOUS USE»; I) Specifications concerning storage conditions such as "DO NOT FREEZE". 2. Reception of tissues or cells in the tissue and cell bank: 2.1. When the tissues or cells reach the Bank of tissues and cells must be 62 and document verification that the consignment, including the transport conditions, packaging, labelling and associated documentation and samples, comply with the requirements of this annex and the specifications of the service receiver. 2.2. Each Bank of tissues and cells must ensure that the tissue and cells received are quarantined until they are inspected or verified, as well as its documentation, in accordance with the requirements. The analysis of the relevant information concerning the donor and the harvest and, therefore, the acceptance of the donation, must be carried out by authorised persons. 2.3. Each Bank of tissues and cells must have a documented policy and specifications, which will serve as a term of comparison when checking each consignment of tissues and cells, including samples. Of them should contain technical requirements and other criteria that tissue and cell Bank consider essential to the maintenance of an acceptable quality. 2.3.1. The Bank of tissues and cells must have documented procedures for the management and the separation of non-compliant shipments or for which no complete analysis results are available, in order to ensure that no risk of infecting other tissues and cells being processed, preserved or stored. 2.4. The data shall be recorded in the Bank of tissues and cells, except donors of reproductive cells intended for partner donation, include the following elements: a) consent or authorization, including the possible use of tissues and cells (such as therapeutic or research, or both) and all the specific instructions for disposal if the tissue or cells are not used for the purposes for which obtained the consent; b) all records required in relation to the harvest and the background of the donor, as described in paragraph 1.4. of this annex. c) results of physical examination, of laboratory tests or other, such as the autopsy report, if used in accordance with paragraph 1.2.2. of this annex;


63 d) for allogeneic donors, correctly documented analysis of the complete assessment of the donor, in the light of the selection criteria, by an authorized person and formed; e) in the case of cell cultures intended for autologous use, documentation of the event that the receiver be allergic to medications. 2.5. In the case of reproductive cells intended for partner donation, the data shall be recorded in the tissue and cell bank include the following elements: a) consent or authorization, including the possible use of tissues and cells, such as for reproductive purposes only or for therapeutic or research purposes, and any specific instructions for disposal if the tissue or cells are not used for the purposes for which obtained the consent; b) donor identification and characteristics: type of donor, age, sex and the presence of risk factors; c) identification of the partner; d) Local harvesting; e) tissues and cells obtained and relevant characteristics.


64 ANNEX IX CERTIFICATE BIOMONITORING Biomonitoring system INCIDENTS


Who DECLARES: date _ _ _ _ _ _/_ _ _ _ _ _/_ _ _ _ _ _ _ _ SERVICE _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ INSTITUTION _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ COORDINATION OFFICE _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 1. PERSON who NOTIFIES 1.1 Identification 1.2 Contact Name Phone Phone Fax and mail Service Office Address 2. Tissue, cells, organ or other related product 2.1 nature of graft or put in contact with the Cell Tissue Organ graft related product 2.2. ID number (reference, Batch) 3. 3.1 description of the incident Date incident detection _ _ _ _ _ _ _ _ _ _ _/_ _ _ _ _ _ _ _ _/_ _ _ _ _ _ 65 3.2 type of incident. 3.3 description of incident Classification phase in which the incident occurred BECAUSE of the lack of INCIDENT will lack of documentation Identifies tion equipment failure to Human Error material Failure the Other (specify) Selection Harvest donor Processing Distribution Storage Transport Laboratory Analyses Other (specify) 4. Analyses. Corrective and preventive actions and Investigations 4.1 conclusions 4.2 description of the measures implemented 4.3 date of communication _ _ _ _ _ _ _ _/_ _ _ _ _ _ _ _/_ _ _ _ _ _ _ _ _ _ 66 4.4 Entity to whom the Communication was made date and signature of who filled out this form 67 BIOMONITORING SHEET ADVERSE REACTIONS who DECLARES: date _ _ _ _ _ _/_ _ _ _ _ _/_ _ _ _ _ _ _ _ SERVICE _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ INSTITUTION _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ COORDINATION OFFICE _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 1. PERSON who NOTIFIES 1.1 Identification 1.2 Contact Name Phone Phone Fax and mail Service Office Address 2. Tissue, cells, organ or other related product 2.1 nature of graft or put in contact with the Cell Tissue Organ graft related product 2.2. ID number (reference, Batch) 3. Affected user (donor or Recipient) 3.1 Donor (Identification Code) 3.1.1 type of Donor: Autologous ____ Yes _ _ _ No _ _ _ _ _ _ _ 3.1.2 Genus H _ _ _ _ _ M _ _ _ _ _ _ 3.1.3 BirthDate _____/_____/_____ 3.1.4 68 date of Harvest _ _ _ _ _ _/_ _ _ _ _ _/_ _ _ _ 3.1.5 Institution Harvest _____ _ _ _ _ _ _ _ _ _ _ 3.2 receiver (Identification Code) 3.2.1 Genus H _ _ _ _ _ M _ _ _ _ _ _ 3.2.2 date of birth _____/_____/_____ 3.2.3 transplant Date _____/_____/____ 3.2.4 the implanting Surgeon 3.1.1 service and institution where the transplant took place 4. 4.1 adverse reaction Date description of detecting adverse reaction _ _ _ _ _ _ _ _ _ _ _/_ _ _ _ _ _ _ _ _/_ _ _ _ _ _ 4.2. Type of adverse reaction. (transmission of viral or bacterial, parasitic infection, tumor, for ex.) 4.3 description. Actual or possible consequences. Research and findings 4.3.1 Severity 1 (full recovery)   3 (Sequels) 2 (minor Sequelae)   4 (death) 4.3.2 Accountability Not available 0 (deleted)   1 (unlikely) 2 (possible)    3 (probable) 4 () 5. Corrective and preventive actions 5.1 69. Description of the measures implemented 5.2 other coordinators informed Not _ _ _ _ _ _ _ Yes _ _ _ _ _ _ _ Need Which other officials Informed 5.3 Not _ _ _ _ _ _ _ Yes _ _ _ _ _ _ _ Need Which 5.4 other teams Informed transplant Not _ _ _ _ _ _ _ Yes _ _ _ _ _ _ _ Need Which 4.3 date of communication _ _ _ _ _ _ _ _/_ _ _ _ _ _ _ _/_ _ _ _ _ _ _ _ _ _ 4.4 Entity to whom the Communication was made date and signature of who filled out this form Annex X 70 minimum data information about the donor/recipient to be kept as required in article 8. harvest units and banks of tissues and cells of donor Identification Identification of which shall include, at least: — identification of the procurement organisation or the Bank of tissues and cells — unique identification Number of donations — date of collection — the harvest Site — type of donation (for example, a cloth or tissues; or allogeneic autologous; living donor or deceased donor) product identification that will include at least: — identification of Bank of tissues and cells — a product of tissues/cells (basic nomenclature) — pool number (if applicable) — split number (if applicable) — expiration date — status of tissues or cells (for example, quarantined, suitable for the use, etc.) — description and origin of the products, processing steps applied, materials and additives that came into contact with tissues and cells and influencing your quality and/or safety — Identification of the installation which emits the final label human application identification that will include at least: — date of distribution or elimination — identification of the Clinician or end user/facility b. 71 By enforcement of tissues and cells in humans) identification of the tissue and cell bank or harvest energy units. b) identification of the Clinician or end user/facility c) type of tissues and cells d) and product ID) identification of the receiver f) date of application 72 ANNEX XI information contained in European coding system (a) identification of donations: — identification — identification number from the Bank of tissues and cells (b) product ID: — product code (basic nomenclature) — split number (if applicable) — expiration date