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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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PROPOSED LAW NO. 200 /X

Exhibition of Motives

The transplantation of human cells and tissues is an area of medicine that has had a

huge growth in recent years and which provides great possibilities

therapeutics to many patients. The availability of tissues and cells of human origin

for therapeutic purposes depends on the gift of the citizens.

The programmes for harvesting and application of tissues and cells should be based on the principles

of the free gift, altruism, solidarity, equity, transparency and accessibility, well

as in the general principality that the identity of the receiver or receptors should not be

revealed to the donor neither to the respective family and vice versa, except in the cases provided for in the

legislation in force.

The gift, harvesting, analysis, processing, preservation, storage and distribution of

tissues and cells of human origin intended for application in humans must

meet high standards of quality and safety, in order to ensure a high degree

of protection of public health and prevent the transmission of diseases through these tissues and

cells.

Considering the need to ensure that tissues and cells of human origin

intended for applications in humans to present quality and safety criteria

superpunishable in all Member States, the European Parliament and the Council of the

European Union adopted Directive No 2004 /23/CE of March 31, 2004, which

establishes quality and safety standards in relation to the donation, harvesting, analysis,

processing, preservation, storage and distribution of tissues and cells of origin

human. The Commission subsequently adopted Directive No 2006 /17/CE of 8 of

February 2006, which applies Directive No 2004 /23/CE of March 31, concerning

certain technical requirements applicable to the donation, harvesting and analysis of tissues and cells

of human origin, and Commission Directive No 2006 /86/CE of the Commission of October 24, 2006,

regarding traceability, notification of reactions and serious adverse incidents, and

certain technical requirements for the coding, processing, preservation,

storage and distribution of tissues and cells of human origin.

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This Law transposes to the Portuguese legal planning these directives. In your

wording has, still, met the Charter of Fundamental Rights of the European Union and the

Convention of the Council of Europe for the protection of the rights of man and of

dignity of the human being in the face of the applications of biology and medicine, signed in Oviedo

on April 4, 1997, and which came into force in Portugal in 2001.

With a view to compliance with community requirements and to promote effective implementation

of the provisions laid down in this Diploma, is established, still, a sanctions regime

applicable in the event of an infringement.

The National Data Protection Commission was heard.

They were heard, on the optional basis, the Order of Physicians, the INFARMED-Authority

National of Medication and Health Products, I. P., the Portuguese Society of

Transplantation, the National Council of Medically Assisted Procreation and the Council

National of Ethics for Life Sciences.

Thus:

Under the terms of the paragraph d) of Article 197 (1) of the Constitution, the Government presents to the

Assembly of the Republic the following proposal for a law:

CHAPTER I

General provisions

Article 1.

Subject

1-A This Law establishes the legal regime of quality and safety relating to the donation,

harvesting, analysis, processing, preservation, storage, distribution and application

of tissues and cells of human origin.

2-A This Law transposes to the internal legal order the Directives No. 2004 /23/CE, of the

European Parliament and of the Council of March 31, 2004, No 2006 /17/CE, of the

Commission, of February 8, 2006, and No. 2006 /86/CE of the Commission, 24 of

October 2006.

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Article 2.

Scope of application

1-The provisions of this Law shall apply:

a) To the gift, harvesting, analysis, processing, preservation, storage,

distribution and application of tissues and cells of human origin intended for

use in human beings, including hematopoietic stem cells of the

peripheral blood, the blood of the umbilical cord and bone marrow, residues

surgical, as well as to reproductive cells, fetal tissues and cells and to the

embryonic stem cells without prejudice to the provisions of the specific legislation;

b) To the gift, harvesting, analysis, processing, preservation, storage and

distribution of manufactured products derived from tissues and cells of origin

human intended for applications in human beings;

c) To tissues and cells of human origin, as long as it includes the application in beings

humans, in the framework of clinical trials.

2-A This Law shall not apply:

a) To tissues and cells used in autologous grafts in the framework of a single

surgical act;

b) To blood, its components and derivatives, within the meaning of the Decree-Law n.

267/2007 of July 24;

c) To organs or parts of organs that are used for the same purpose

that the entire organ in the human body;

d) To tissues and cells of human origin not intended to be applied in the body

human, as in research in animal models or in vitro .

3-Except for the provisions of the paragraph b) of the previous number, the harvest, analysis,

processing, storage, distribution and application of progenitor cells

hematopoietic.

4-To fabrics and cells intended for industrial manufacturing products, including the

medical devices, is applicable to this law only with respect to its gift,

harvesting and analysis, being the processing, preservation, storage and distribution

regulated by own legislation.

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Article 3.

Definitions

For the purposes of this Law, the technical terms used correspond to the definitions

constants of Annex I to this Law, of which it is an integral part.

CHAPTER II

Activity of the competent Authorities

Article 4.

Competent authorities

1-The competent authorities, responsible for verifying compliance with the

technical requirements set out in this Act, are the Authority for the Services of

Blood and Transplantation, abbreviately designated by ASST, and the National Council

of Medically Assisted Procreation, abbreviately designated by CNPMA.

2-A ASST, as the competent authority for transplantation services, has by

mission to ensure quality and safety in relation to the donation, harvesting and analysis of

tissues and cells of human origin, whatever their purpose, as well as in

relation to processing, storage distribution, including the activities of

import and export of tissues and cells, when they are intended for transplantation,

with the exception of reproductive cells and embryonic stem cells and when

such acts respect the application of medically assisted procreation techniques.

3-The CNPMA, as a competent entity, has for assignments guarantee the quality and

security in relation to the donation, harvesting, analysis, processing, storage and

distribution of reproductive cells and human embryonic stem cells from

agreement with points (s) a) , b) , c) and e) of Article 30 of Law No 32/2006 of July 26.

4-In the context of the action referred to in paragraph 2, it is incumbent upon ASST to coordinate, guide,

regulate and scrutinize, at the national level, the harvesting activity, analysis,

processing, storage, distribution and transplantation of tissues and cells of

human origin.

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5-Within the scope of the action referred to in paragraph 3, it is incumbent on the CNPMA to monitor the activity

of the centres where the medically assisted procreation techniques are given and the

centres where gametes or human embryos are preserved and scrutinise the

compliance with the law, in conjunction with the competent public entities, in the

terms set out in the paragraph c) of Article 30 of Law No 32/2006 of July 26.

Article 5.

Authorization

1-The activities referred to in paragraphs 2 and 3 of the preceding Article may only be carried out by

services that have been authorised, respectively, by ASST and in the terms of the n.

1 of Article 5 of Law No 32/2006 of July 26.

2-No activity regarding the harvesting of human and cell reproductive cells

embryonic stem or other cells and tissues harvested in the scope of the application of

medically assisted procreation techniques, can be carried out outside the centers

authorized in accordance with the conditions set by the CNPMA under the

provisions of Article 5 and (I) b) of Article 30, of Law No 32/2006 of July 26.

3-Exceptionally the harvesting of tissues and cells referred to in Article 2 (2)

previous may take place in unauthorised hospital units as units

of harvesting, provided that the tissues and cells are harvested by plant professionals

of authorized harvesting.

4-For the purposes of the provisions of the preceding paragraph the authorized harvesting units shall

ensure that the conditions are met so that the harvest can be carried out of

agreement with the provisions of this Law, including with respect to the traceability of the

donor and gift.

5-A harvesting of tissues and cells carried out in the situations referred to in paragraphs 3 and 4 shall be

communicated to ASST.

6-Compete to ASST:

a) Authorising the banks of tissues and cells with respect to harvesting activities,

analysis, storage and distribution in accordance with this Law;

b) Authorize the harvesting units with respect to harvesting activities;

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c) Authorize the services responsible for the application in human beings of fabrics or

cells;

d) Authorize the processes of preparation of tissues and cells that the tissue bank and

cells may carry out in accordance with the requirements referred to in the Annex

III to this Law, of which it is an integral part.

7-For the purpose of the authorisation provided for in the preceding paragraph shall be communicated to ASST

the information in accordance with the requirements referred to in Annexes II and III to the

present law, of which they form an integral part.

8-For consideration of the process leading to the issuance of the authorisation are examined the

agreements concluded between a bank and third parties including the harvesting units, to which

refers to Article 21.

9-The application for permission shall be submitted by the responsible body of the Institution

where to operate the service upon application addressed to ASST, from it

and must appear in the following information:

a) Identification of the responsible or responsible for the activities and their respective

curriculum vitae;

b) The processes for which you request permission;

c) Qualifications of the staff involved or to involve in the activities;

d) Identification of facilities, equipment, interdisciplinary relations or

inter-institutional, where applicable, relevant to the process;

e) Annual plan of activities;

f) Descriptive memory donde consents the nature of the application, the means available to it

the service for the realization of the requested activity, the type of tissue or cells to

that the said authorisation is requested.

10-A ASST, after confirming that the service brings together the constant requirements of the present

law, proceeds to the issuance of the authorization indicating which activities and processes of

preparation of authorised tissues and cells and under what conditions, all specified in

certificate issued for the purpose.

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11-Services shall not carry out any substantial change in their activities and

processes of preparation of tissues and cells without the prior written approval of the

ASST.

12-For the assessment of the process leading to the issuance of the permit are due rates of

amount to be fixed by dispatching from the Minister of Health.

13-A permission granted pursuant to paragraph 10 may be suspended or revoked by the

ASST if inspections or control measures carried out in the terms of the article

following prove that the service does not comply with the constant requirements of the present

law.

14-With respect to reproductive cells and embryonic stem cells and when

such acts are carried out in the framework of the application of procreation techniques

medically assisted, it is up to the CNPMA to exercise the skills referred to in paragraphs 6,

7, 8 and 11.

15-For the purpose of adopting the measures referred to in paragraph 13 a ASST shall proceed, always

That possible, at the hearing of the person concerned, pursuant to Articles 100 and following of the

Administrative Procedure Code.

16-The situations in which it may be suspended or revoked the operating permit

of the centres in which the medically assisted procreation techniques are delivered

are defined in a diploma of their own.

Article 6.

Inspection and control measures

1-In matters that are within its competence, ASST carries out, periodically, inspections

or other control measures appropriate to the harvesting units, to the banks of

tissues and cells and services responsible for its application, not owing the range

between the same exceeds two years, in order to ensure compliance with the provisions of the

present law.

2-For the purposes of the provisions of the preceding paragraph, ASST has the following powers:

a) Inspect the harvesting units, tissue and cell banks and services

responsible for its application, as well as the third-party facilities to whom the

holder of the authorisation has been entrusted with applying part of the procedures;

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b) Evaluate and verify the procedures and activities in the harvesting units, in the

tissue and cell banks, in the services responsible for their application and

third-party facilities;

c) Collect samples for examinations and analysis;

d) Examine any documents or other records relating to the object of the

inspection.

3-A ASST shall communicate in writing to the responsible of the services the result of the

inspections carried out in the terms of the preceding paragraphs.

4-A ASST sets out the guidelines regarding the conditions of inspection and measures of

control, as well as the training and qualification of professionals involved in order to

guarantee a high competence and performance.

5-In the event of adverse reactions or serious incidents or suspicion of the same, it shall

ASST to arrange inspections or other control measures, as it is more

suitable.

6-A ASST shall also carry out inspections or other control measures to

request from the competent authorities of another Member State, as long as justified,

in any case of incident or serious adverse reaction.

7-With respect to reproductive cells and embryonic stem cells and when

such acts are carried out in the framework of the application of procreation techniques

medically assisted, compete with the CNPMA, in articulation with the IGAS, exercise the

skills referred to above n. ºs 1, 2, 3, 4, 5, and 6.

8-Whenever requested by another Member State or by the European Commission, the ASST

and the CNPMA must provide information on the results of inspections and measures

of control related to the requirements set out in this Law.

CHAPTER III

National network of tissues and cells

Article 7.

Network

1-A National network of tissues and cells, hereinafter referred to as Network, consists of the

harvesting units, tissue banks and cells and services responsible for its

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application, irrespective of their legal nature, authorised by ASST to operate

in the national territory.

2-Harvesting units, tissues and cells and the services responsible for the

your application, can aggregate to cell harvesting coordination enclosures and

tissues for transplantation, in terms of regulating by Portaria to be approved by the

member of the Government responsible for the area of health.

3-A Network includes the Centres of Histocompatibility according to your assignments

defined by law.

4-The provisions in the previous figures are not applicable to reproductive cells, cells

embryonic stem and other cells or tissues collected in the scope of application

of medically assisted procreation techniques.

Article 8.

Traceability

1-harvested, processed, stored, and applied tissues and cells in the

national territory must be the subject of traceability from the donor to the receiver and

from this to the donor, as well as all relevant data relating to the products and

materials that come into contact with the tissues and cells.

2-For the purposes of the provisions of the preceding paragraph, the harvesting units, the banks of

tissues and cells and the services responsible for their application must implement a

donor identification system that ascribe a unique code to each donation and the

each product to it associated in accordance with that provided for in Article 12, and pursuant to

define by ASST and by the CNPMA.

3-All tissues and cells must be identified through a label with the

information or references that allow a link to the information referred to in

annex VIII to this Law, which of it forms an integral part.

4-The data required to ensure full traceability, referred to in Annex X to

present law, they are kept for at least 30 years after their clinical use,

regardless of the type of support and provided that we have safeguarded the respective

confidentiality.

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Article 9.

Import and export of tissues and cells of human origin

1-The tissues or cells intended for application in human beings can only be

imported from third countries when:

a) Have origin in tissues and cells authorized for such activities

and comply with the quality requirements provided for in this Law;

b) Ensure all the traceability requirements provided for in this Law;

c) Ensure a system of notification of serious adverse reactions and adverse events

equivalent to that provided for in this Law.

2-Imports imports of tissues or cells from third countries and exports

for third countries can only be done by tissue banks and cells that are

duly authorized for such activities, in accordance with this Law and

upon authorization, in accordance with their respective area of competence, of ASST and

of the CNPMA pursuant to the following n. 4 and 5.

3-All necessary measures shall also be adopted to ensure that the

exports of tissues and cells to third countries are made through banks of

tissues and cells authorized for such activities.

4-Applications for import of tissues and cells should mention the institution of

origin and are only permitted, in accordance with their respective area of competence, by the

ASST or by the CNPMA when:

a) There is proven benefit in the use of the tissues or cells that are intended

apply;

b) The purpose of tissues or cells is for human application;

c) There is no availability in the banks of national tissues or cells;

d) For reasons of justified compatibility by physician.

5-Applications for the export of tissues and cells must identify the institution of

destination and are only permitted, in accordance with their respective area of competence, by the

ASST or by the CNPMA when there is sufficient availability of tissues and cells in the

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banks of national fabrics or for reasons of justified compatibility.

6-In cases of emergency the import or export of tissues and cells may be

authorized directly, in accordance with its respective area of competence, by the

ASST or by the CNPMA provided that the supplier possesses accreditation, designation,

licensing or authorization as set out in this law or standards of

equivalent quality and safety.

7-The provisions of the preceding paragraphs shall apply to the circulation of tissues and cells of

third countries and the European Union.

Article 10.

Conservation of records

1-The tissue and cell banks and harvesting units must possess and maintain

updated a record of its activities, restricted and confidential access, which includes

the types and quantities of tissues and cells harvested, analyzed, processed,

preserved, stored and distributed or otherwise used, and the origin and

fate of tissues and cells intended for applications in human beings, in the terms

of Annexes II to VIII to this Law, of which they form an integral part.

2-Dealing with services responsible for the application of tissues and cells the register to which

refers to the previous number should include the clinical applications carried out, the data

necessary for the identification of the receptors of the transplanted tissues and cells and the

its origin in such a way as to ensure traceability under Annex X to this Law,

of which it is an integral part.

3-The records referred to in the preceding paragraphs shall be kept for a period

minimum of 30 years and destroyed as soon as they are not necessary for the purpose of

traceability.

4-The tissue and cell banks and the services responsible for their application must

present, in accordance with their respective area of competence, to ASST or to the

CNPMA an annual report of its activities which is an integral part of the

assessment necessary for the maintenance of the authorization of the activity of the activity.

5-Within the framework of their respective areas of expertise, ASST and the CNPMA must

institute and keep up to date a public record relating to authorised entities and

respective activities.

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Article 11.

Notification of incidents and serious adverse reactions

1-The tissue and cell banks and the harvesting units and the services responsible for

your application must have a system of notification, research, registration and dispatch

of information on adverse reactions and serious incidents that may interfere with the

quality and safety of tissues and cells and can be attributed to harvesting, analysis,

processing, storage and distribution of tissues and cells, as well as the

any serious adverse reaction observed during or after the clinical application, which

may be related to the quality and safety of tissues and cells.

2-A responsible person referred to in Article 14 shall ensure that they are notified,

according to their respective area of competence, to ASST and to the CNPMA all

adverse reactions or serious incidents referred to in the preceding paragraph and that is

presented a report of analysis of their causes and consequences, including the

measures adopted.

3-Any person or institution that uses tissues or cells of human origin in the

the terms of this Law shall communicate all the information pertinent to the units of

harvesting and the tissues and cells with activities in the field of donation,

harvesting, analysis, processing, storage and distribution of tissues and cells of

human origin, in order to facilitate traceability and ensure control of the

quality and safety.

4-The tissue and cell banks and the harvesting units and the services responsible for

your application must ensure the operation of a precise procedure, fast and

verifiable, which allows to withdraw from the distribution circuits any products that

may be related to adverse reactions or serious incidents.

5-In the case of assisted reproduction any type of incorrect identification or exchange of

gametes or embryos is considered to be a serious adverse incident, owing, all

the people and harvesting bodies responsible for their application in human beings

which carry out assisted reproduction, proceed to notification of such incidents to the

CNPMA.

6-For the purpose of notifying incidents and serious adverse reactions should be

used the models set out in Annex IX to this Law, of which it is part

member.

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CHAPTER IV

Of the requirements of the harvest

Article 12.

Harvesting of tissues and cells of human origin

1-The cell and tissue banks and harvesting units must have agreements

written with the staff or clinical teams responsible for the selection of donors, the

less that 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, of which it is part

integral, the types of tissues and cells, the samples to be spoon for analysis and the

protocols to be complied with.

2-The cell and tissue banks and harvesting units must dispose of

normalized operating procedures (PON) for verification of the following

elements:

a) Identity of the donor;

b) Details of the consent or authorisation of the donor or his / her family, of

agreement with the one established in the law;

c) Evaluation of donor selection criteria, as provided for in paragraph 1 of the

article 25;

d) Evaluation of laboratory analyses required of donors, as provided for in the

annexes VI and VII to this Law, of which they form an integral part.

3-There must also be PON that describe the procedures of harvesting,

packaging, labelling and transport of the tissues and cells up to the point of arrival in the

tissue bank or, in the case of direct distribution of tissues and cells, up to the team

clinic responsible for its application or, dealing with tissue and cell samples,

up to the laboratory for analysis, in the terms set out in Annex VIII to this Law, of the

which is an integral part.

4-A harvest must be carried out in proper facilities, respecting procedures that

reduce to a minimum the contaminations, namely bacterial, tissues and

cells harvested, in accordance with Annex VIII to this Law of which it is a part

member.

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5-Materials and equipment for harvesting must be managed in accordance with

the standards and specifications set out in paragraph 1.3 of Annex VIII to this Law, of the

which is an integral part, and taking into account regulation, standards and guidelines

relevant national and international, which cover the sterilization of medicines and

medical devices.

6-For the purposes of the provisions of the preceding paragraph, instruments and

sterile harvesting devices approved for the harvesting of tissues and cells.

7-A The harvesting of tissues and cells in living donors shall be carried out in an environment that

guarantee your health, safety and privacy.

8-A The harvesting of tissues and cells in corpse donors shall be made with respect to

dignity of dead donors, notably through the reconstitution of the body of

mode to which your appearance is as much as possible similar to your shape

original anatomic.

9-For the purposes of the provisions of the preceding number the cells and tissues and the

harvesting units shall make available the necessary personnel and equipment to the

reconstitution of the body of the deceased donor.

10-The donor and donated tissues and cells shall be assigned an identification code

single during harvesting or in the tissue bank and tissue cells, which ensure the

correct identification of the donor and the traceability of all the donated material.

11-For the purposes of the provisions of the preceding paragraph, a system of

identification of donors that assigns a unique code to each donation and to each product to

it associated with, in accordance with Annex II to this Law, of which it is an integral part,

without prejudice to the single system of European coding that comes to pass.

12-Encoded data must be introduced in a national register of the

liability of ASST or the CNPMA, according to the respective area of

competence.

13-A documentation relating to the donor shall be kept in accordance with the

set out in 1.4 of Annex VIII to this Law, of which it is an integral part.

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CHAPTER V

Provisions on the quality and safety of tissues and cells

Article 13.

Management of quality

1-Harvesting units, tissues and cells and the services responsible for the

your application should develop and maintain operational a system of quality and of

quality management based on good practices that includes at least the documentation

next:

a) Standard operating procedures of the authorized activities and of

critical processes;

b) Training and reference manuals;

c) Forms of transmission of information;

d) Registration of donors;

e) Information on the final fate of tissues or cells;

f) System for detection and communication of adverse reactions.

2-Harvesting units, tissues and cells and the services responsible for the

your application should adopt the necessary measures to ensure that the

documentation referred to in the preceding paragraph if it is available at the

inspections carried out, within the framework of their respective area of competence, by ASST or

by IGAS in articulation with the CNPMA.

Article 14.

Responsible person

1-The responsible for harvesting units, tissue and cell banking and by the services

responsible for your application must be a medical practitioner and possess experience of at least

two years in the area.

2-In the impossibility of fulfillment of the required in the preceding paragraph, the person

responsible can be assigned from among graduates in Pharmaceutical Sciences or

Biological who possess experience of at least three years in the activities of the area.

3-The provisions of the preceding paragraphs shall not apply to the centres in which they are provided

medically assisted procreation techniques.

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4-To the responsible designated in the terms of the previous figures compete:

a) Ensure that tissues and cells of human origin intended for applications in

human beings are harvested, analyzed, processed, stored, distributed

and applied in accordance with that established in this Law;

b) Provide ASST with all necessary information pursuant to this Act;

c) To ensure compliance with the requirements for personnel training,

quality system, documentation, preservation of records, traceability,

notification, data protection and confidentiality.

d) Ensuring that medical activities, inter alia, the selection of donors, the

analysis of laboratory clinical results, tissues and cells to be applied, and their

application are carried out under the responsibility and direct medical surveillance, with

experience.

5-The functions referred to in the preceding paragraph may be the subject of delegation, provided that the

delegate posits the qualifications referred to in paragraph 1.

6-The harvesting units, tissue banks and cells and the services responsible for their

application, shall communicate, within the framework of their respective area of competence, to ASST

or the CNPMA the name of the person responsible, as well as its substitute in case

of temporary or definitive absence.

Article 15.

Personnel

Personnel assigned to the harvesting units and to the tissues and cells and to the services

responsible for their application must possess the appropriate qualifications for the performance of the

their duties and receive adequate, timely and regular training.

Article 16.

Reception of tissues and cells

1-The tissue and cell banks shall ensure that:

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a) All tissue donors and cells of human origin are subjected to testing

in accordance with the requirements set out in Annexes VI and VII to this Law,

of which it is an integral part;

b) The selection and acceptance of tissues and cells are made according to the requirements

constants of Annexes V to VII of this Law, of which they form an integral part;

c) The tissues and cells of human origin and the respective documentation meet the

requirements set out in Annexes II to VIII to this Law, and to the regulations that

come to be approved in the terms set out in the paragraph c) of Article 32;

d) The packaging of the tissues and cells of human origin received has been made in

compliance with that provided for in Annex III to this Law, of which it is part

member.

2-The received tissues or cells that are not complying with the above requirements

in the previous figures should be rejected.

3-A The acceptance or rejection of the received tissues or cells must be documented.

4-The tissues and cells are to ensure that the tissues and cells of origin

human are always correctly identified over any phase of the

processing by assigning an identification code to each shipment or batch of

tissues or cells, in accordance with the provisions of Article 12 (10) and 11.

5-The tissues and cells remain quarantined until the requirements in respect of

analysis and information of the donor are satisfied in the terms of Annex VIII, of which

is an integral part.

Article 17.

Processing of tissues and cells

1-The tissue and cell banks must include in their operating procedures

standardised (PON) all processes that are likely to affect the quality

and safety, ensuring that the same arise under controlled conditions.

2-The tissue and cell banks shall ensure that the equipment used, the

work environment, the design, validation and conditions of control of the processes

are in accordance with the requirements set out in Annex II to this Law, of the

which is an integral part.

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3-The bank of tissues and cells shall include in its PON special provisions relating

to the handling of tissues and cells to be disposed of, so as to avoid contamination of

other tissues and cells, as well as the environment or personnel.

4-Any changes in the processes used in the preparation of tissues and cells must

observe the provisions of paragraph 1.

Article 18.

Conditions of storage of tissues and cells

1-The tissue and cell banks shall ensure that all procedures connected to the

storage of tissues or cells are documented in the PON and that the

storage conditions correspond to the requirements set out in Annex II to the

present law, of which it is an integral part.

2-The tissue and cell banks must establish and apply control procedures

of the packing and storage areas, so as to avoid any circumstances

likely to affect that of the subject fabrics and cells with a view to the end to which they are intended.

3-processed tissues or cells may not be distributed while they are not

met all the requirements set out in this Law.

4-In the event of a cessation of tissue bank activity and cells, the tissues and cells

stored are transferred to other services on the terms authorized by ASST.

5-A cessation of the activity of embryonic stem cell banking and other cells

or tissues collected in the scope of the application of medically procreation techniques

assisted is regulated by own diploma.

Article 19.

Labelling, documentation and packaging

Tissue and cell banks must ensure that the labelling, documentation and the

packaging of tissues and cells meet the requirements set out in Annexes III and VIII of the

present law, of which they form an integral part.

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Article 20.

Distribution

1-The tissues and cells banks shall ensure that the conditions of distribution of the

tissues and cells comply with the requirements set out in Annexes III and VIII to this Law,

of which they are an integral part, and of the regulations that come to be approved in the terms

of the points d) and e) of Article 32 para.

2-Within the scope of its area of competence, ASST may authorise the direct distribution of

certain tissues and cells from the place where the harvest is carried out until the

establishment of health care for immediate transplantation.

Article 21.

Relations between tissues and cells and third parties

1-The tissue and cell banks must enter into an agreement with third parties whenever

an external intervention is carried out and that such activity has an influence on the

quality and safety of treated tissues and cells, specifically in the following

circumstances:

a) When the tissue and cell bank assigns to third parties the responsibility for

one of the phases of harvesting, processing or analysis of tissues or cells;

b) Where third parties provide goods or services that may affect the warranty

of the quality and safety of the tissues and cells, including the distribution of the

same;

c) Whenever a bank of tissues and cells pay services to another tissue bank

and cells relatively to the given procedure for which it is not

authorized;

d) When a bank of tissues and cells distribute tissues or cells treated by

third parties.

2-A evaluation and selection of the third parties for the purpose of concluding the agreements referred to in

previous number are made based on your ability to comply with the requirements

constants of this Law.

3-The agreements referred to in paragraph 1 shall specify the responsibilities of the third parties

20

and provide for the procedures and protocols that each must comply with in respect of

contracted activity, including the terms of the remission procedure to which if

mentions the following number.

4-In case of resolution of the contract the contracted entity shall refer to the entity

contracting the documents, data, samples and all the information that may affect the

traceability, quality and safety of tissues and cells.

5-The tissue and cell banks must have an up-to-date list of the agreements

have concluded with third parties and provide a copy of them, in the framework of their

respective area of competence to ASST or to the CNPMA, whenever requested.

CAPITCHAPTER VI

Selection and evaluation of donors

Article 22.

Principles applicable to the donation of tissues and cells

1-A The donation of cells and tissues is voluntary and altruistic, there may not be, in

circumstance some, place for any economic compensation or remuneration, wants

for the donor wants for any individual or entity.

2-Without prejudice to the provisions of the preceding paragraph, living donors may receive a

compensation strictly limited to the reimbursement of the expenses incurred or the

damage immediately resulting from the donation, pursuant to Article 9 of the Law n.

22/2007, of June 29.

3-The conditions of which depends on the allocation of the compensation provided for in the number

previous are defined by dispatching from the Minister of Health.

4-Receivers may not be required for any payment by the subject fabrics or cells

received.

5-The activities developed by the harvesting units, tissue banks and cells and

services responsible for their application cannot have a lucrative character, owing

reflect exclusively the actual costs for the services provided.

6-A Promotion and advertising of the donation should always be carried out in generic terms,

without seeking benefits for concrete people, and evidencing their character

21

volunteer, selfless and disinterested.

7-It is considered misleading advertising to which induces in error about the actual usefulness of the

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 the strictures respect for the conditions set out in the Data Protection Act

Personnel, approved by Law No. 67/98 of October 26, the personal data concerning

to donors and receptors, their treatment and interconnection, are subject to secrecy

professional and appropriate measures of security and confidentiality of information.

2-To the donor and receiver is guaranteed the confidentiality of all related information

with your health, with the results of the analyses of your donations and with the

traceability of your gift.

3-Are expressly prohibited additions, suppressions or unauthorised changes

of the data set out in the fact sheets of the donors or the deletion records as well as the

unauthorized transfer of information, when they do not comply with the provision in the Act

n. 67/98 of October 26 (Personal Data Protection Act) on this matter.

4-The information systems of tissue and cell banks must ensure safety

of the data pursuant to this article and the necessary procedures for

troubleshode all data discrepancies.

5-The rights of access and opposition of the data holders to the information contained in us

systems for registration of donations and donors exercise in the terms and conditions referred to

in Articles 10 to 13 of Law No 67/98 of October 26, without prejudice to the provisions of the

legislation on the use and application of medically procreation techniques

assisted.

Article 24.

Consent

1-A harvesting of tissues and cells of human origin and their application in human beings

can only be carried out after all the mandatory requirements have been met

22

relating to the informed consent provided for in Article 8 of Law No 22/2007 of 29

of June, and in Annex IV to this Law, of which it is an integral part, without prejudice to the

provisions of legislation that regulates the use and application of techniques of

medically assisted procreation.

2-For the harvesting of surgical waste must obtain informed consent of the

donors, applying the same principles applicable to the living donor.

Article 25.

Selection, evaluation, harvesting and reception

1-Donor donors shall comply with the selection criteria set out in Annex V, of which

an integral part, and, in the case of reproductive cell donors, in Annex VII to the

present law, of which it is an integral part.

2-The donors of tissues and cells, with the exception of donor cells of reproductive cells,

shall be subjected to the biological analyses set out in paragraph 1 of Annex VI to the

present law, of which it is an integral part.

3-Reproductive Cell Donors are subjected to established biological analyses

in paragraphs 2 and 3 of Annex VII to this Law, of which it is an integral part.

4-The analyses referred to in paragraph 2 shall be carried out in accordance with the requirements

general set out in paragraph 2 of Annex VI to this Law, of which it is an integral part.

5-The analyses referred to in paragraph 3 shall be carried out in accordance with the requirements

general set out in paragraph 4 of Annex VII to this Law, of which it is an integral part.

6-The autologous donations must observe the selection criteria set out in paragraph 2.1.

of Annex V to this Law, of which it is an integral part.

7-The results of the donor evaluation and analysis procedures shall be

documented and any and all relevant anomaly detected must be notified of

agreement with Annex V to this Law, of which it is an integral part.

8-Required analyses of donors must be carried out by a certified laboratory

or accredited and authorized by ASST, to that end, with contractual relationship to the bank

of tissues and cells.

9-The procedures for donation and harvesting of tissues and cells, as well as their reception

in the bank of cells and tissues shall comply with the requirements set out in Annex VIII

23

to this Act, of which it is an integral part.

10-The provisions of paragraph 8 shall not apply to reproducing cells, stem cells

embryonic and other cells or tissues collected in the framework of the application of techniques

of medically assisted procreation.

CHAPTER VII

Exchange of information and reports

Article 26.

Reports

Within the framework of their respective areas of expertise, ASST and the CNPMA must submit to the

European Commission before April 7, 2009 and, subsequently, every three years, a

report on the activities developed in the context of the application of this Law,

including a relationship of the measures adopted in respect of inspection and control.

CHAPTER VIII

Of the offences and penalties

Article 27.

Counter-ordering

1-Without prejudice to civil or criminal liability, of the provisions of Articles 44 and 45.

of Law No. 32/2006 of July 26 and of the administrative measures to which there is place,

constitute counter-ordinances to the infringements of the norms of this Law pursuant to

predicted in the following numbers.

2-Constituts lightweight counterordinations:

a) The failure to comply with the provisions of Article 14 (6);

b) Failure to comply with the provisions of Article 21 (5).

3-Constituts serious counterordinations:

a) Failure to comply with the provisions of paragraph 1, 2, 3, 4, 5, 9, 9 and 11, of Article 5;

b) The failure to comply with the provisions of Article 10 (3) and (4);

c) The 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;

e) The failure to comply with the provisions of Article 13 (2);

f) The failure to comply with the provisions of Article 22 (6);

g) The failure to comply with the provisions of paragraphs 1, 2, 3 and 4, of Article 21;

h) The failure to comply with the determinations and instructions of the ASST or the CNPMA;

i) The resistance in the provision of information requested by ASST or by

CNPMA, as well as any and any behavior that translates into the lack of

collaboration with these entities.

j) The offences which have served to facilitate or cover up light offences.

l) The recidivism in the practice of light offences in the last six months;

m) The exercise of deceptive advertising as defined in Article 22 (7).

4-Constituts very serious counterordinations:

a) The exercise of activities not authorized by ASST or by the CNPMA in

disrespect continued by the provisions of paragraphs 1, 2, 3 to 4, 5, 7, 9 and 11 of Article 5.

b) The failure to comply with the provisions of Article 10 (1) and (2);

c) Failure to comply with the provisions of Article 9;

d) Failure to comply with the provisions of Articles 16;

e) Failure to comply with the provisions of 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 Article 20 (1);

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 Article 13 (1).

n) Failure to comply with the provisions of Article 11 (1 a) (11).

o) ) The failure to comply with the provisions of paragraphs 1, 2, 4, and 5 of Article 22;

25

p) The persistence of deceptive advertising as defined in Article 22 (7);

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 permit for other purposes various to those provided for therein;

t) The offences that affect the quality and safety of tissues and cells, and hence

has resulted in serious danger or damage to individual or public health;

u) The offences that have served to facilitate or cover up serious offences or

very serious;

v) The repeated failure to determine the determinations and instructions of the ASST or the

CNPMA;

x) The refusal in the provision of information requested by ASST or by the CNPMA,

as well as any and any behavior that translates into refusal of

collaboration with these entities;

z) The recidivism in the practice of serious offences in the last five years.

5-In the counter-ordinations provided for in the preceding paragraphs are punishable by negligence and the

attempt, being the amounts of the fines referred to in the following number reduced to

half.

Article 28.

Fines

The counter-ordinations provided for in the previous article are punishable with fines according to

the following graduation:

a) Lightweight counterorders are punishable by fines up to € 500;

b) Serious counterorders are punishable with fines from 500 a to € 1500, for

natural persons, and up to € 15000 for legal persons;

c) Very serious counterorders are punishable with fines since € 1500 a

€ 3500, for natural persons, and from € 15000 until € 44000, for people

collective.

26

Article 29.

Ancillary sanctions

Depending on the seriousness of the offence and the fault of the agent, they may be determined,

simultaneously with the fine, the following ancillary sanctions:

a) Suspension or partial revocation of the permission granted for the exercise of the

activity or a process of preparation of tissues and cells;

b) Termination of the service.

Article 30.

Supervision, instruction and application of fines

1-Compete to ASST to ensure monitoring of compliance with the constant provisions

of this Law and the application of the penalties provided for in this Chapter, except in what

respects the reproductive cells, embryonic stem cells and other cells or

tissues collected in the scope of the application of medically procreation techniques

assisted, in which the competence is of the CNPMA.

2-A Inspectorate-General for Health Activities (IGAS) is the competent entity for

instruct the counterordinance processes whose establishment has been determined by the

ASST or by the CNPMA.

Article 31.

Target of the product of the fines

The product of the fines provided for in this Law reverses:

a) In 60% for the State;

b) In 30% for ASST or for the CNPMA, according to their respective area of

competence;

c) In 10% for IGAS.

CHAPTER IX

Final and transitional provisions

Article 32.

Technical requirements and their adaptation to scientific and technical progress

1-They are the subject of regulation by porterie to be approved by the member of the Government

27

responsible for the area of health, the technical requirements and their adaptation to progress

following scientific:

a) Requirements for the authorisation of the harvesting units, of the banks of

tissues and cells and services responsible for their application;

b) Quality system;

c) Requirements for the procedure 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) Biovigilance.

Article 33.

Transient standard

1-Harvesting units, tissues and cells and the services responsible for the

your application already in operation have a period of twelve months counted to

from the date of the publication of this Law to adapt to the requirements therein

predicted.

2-Fishing the period referred to in the preceding number as the harvesting units, the banks

of tissues and cells and the services responsible for their application dispose of a

maximum period of thirty working days to apply for ASST the renewal of the application for

authorization of the activities in accordance with that provided for in this Law.

3-The provisions of the preceding paragraph shall not apply to the centres in which they are provided

medically assisted procreation techniques.

Article 34.

Abrogation standard

1-Are repealed Articles 7 and 8 of the Portaria No 31/2002 of January 8 on the part

concerning tissues and cells.

2-Are repealed in paragraphs 3 and 4 of Article 3 of Law No 22/2007 of June 29 on the Part

concerning tissues and cells.

28

Article 35.

Entry into force

This Law shall come into force on the day following that of its publication.

Seen and approved in Council of Ministers of April 24, 2008

The Prime Minister

The Minister of the Presidency

The Minister of Parliamentary Affairs

29

ANNEX I

Definitions

a) "Storage", the maintenance of the product under controlled conditions and

suitable up to the distribution;

b) "Human application", the use of tissues or cells on or within a

human receptor, as well as extracorporeal applications;

c) "Bank of tissues and cells", a bank of tissues, or unit of a hospital or

another body where activities related to processing are carried out, the

preservation, storage or distribution of tissues and cells of origin

human, without loss of power also being in charge of harvesting or analysis

of tissues and cells;

d) "Cells", the individual cells or a set of cells of human origin, no

linked to each other by any type of connective tissue;

e) "Reproductive cells", all tissues and cells intended to be used for

assisted reproduction effects;

f) "Harvesting", a process in which tissues or cells are made available;

g) "Dador", any human source, living or dead, of cells or tissues of origin

human;

h) "Dádiva" means any donation of tissues or cells of human origin intended for

applications in the human body;

i) "Gift between partners", the gift of reproductive cells between a man and a

woman who declares to maintain an intimate physical relationship;

j) "Distribution", the transport and supply of tissues or cells intended for

application in human beings;

k) "Allogeneic purposes", those of cells or tissues harvested in a person and applied

nother person;

l) "Autologous purposes", those of the harvested cells or tissues and subsequently applied

in the same person;

30

m) "Serious adverse incident", a harmful occurrence during harvesting, analysis,

processing, storage and distribution of tissues and cells, susceptible to

lead to the transmission of an infectious disease, to death or to put life in danger,

to lead to a disability or disability of the patient, or to provoke, or

prolong the hospitalization or morbidity;

n) "Organ", a differentiated and vital part of the human body, consisting of several

tissues, which largely maintain their structure, vascularization

and ability to develop physiological functions;

o) "Preservation", the use of chemical agents, the change of conditions

environmental or other means at the processing to prevent or retard the

biological or physical deterioration of cells or tissues;

p) "Normalized operating procedures" (PON), written instructions that

describe the steps of a specific process, including the materials and the

methods to be used and the final product expected;

q) "Processing", all the operations involved in the elaboration, handling,

preservation and packaging of tissues or cells intended for use in the being

human;

r) "Quarantine", the situation of the harvested tissues or cells, or of the insulated tissue

physically, or through other effective means, pending a decision

about your approval or rejection;

s) "Traceability", the ability to locate and identify the tissue or cell during

any step, from its harvest, going through processing, analysis and the

storage, up to the distribution to the receiver or disposal, including the

ability to identify the donor and the tissue and cell bank or the facilities of

manufacturing that they receive, process or store the tissue or cell, the capacity of

identify the receptors in the medical facilities that apply the tissue or cells to the

receivers and the ability to find and identify all relevant data from

products and materials that come into contact with these tissues and cells;

t) "Serious adverse reaction", an unexpected response, including an infectious disease

31

of donor or recipient, associated with the harvesting or human application of tissues and

cells, which cause death or put life in danger, lead to a disability

or disability, or that provokes, or prolongs, hospitalization or

morbidity;

u) "surgical residue", organs, tissues and cells removed during a procedure

surgical, with therapeutic targets and not to obtain tissues or cells. In this

procedure for obtaining tissues or cells there are no additional risks to the

donor specifically related to the harvesting of the same. Applies the same

definition of the harvesting of fetal membranes (amnion and corion) after childbirth;

v) "Quality system", the organizational structure, the definition of responsibilities,

procedures, processes and resources aimed at the application of quality management,

including all activities that contribute, directly or indirectly, to the

quality;

w) "Service responsible for the application of cells or tissues in human beings", a

health care service, public or private, which proceed to applications in

human beings from tissues and cells of human origin;

x) "Tissue", all constitutive parts of the human body formed by cells;

y) "Harvesting unit" an establishment of health care or a unit

of a hospital or any other body that performs activities of

harvesting of tissues and cells of human origin and that you do not find yourself authorized

as a bank of tissues and cells;

z) "eventual autologous use", that of cells or tissues harvested with the purpose of

be preserved for a hypothetical future use in the same person, without which

there is a medical indication at the time of harvesting and preservation;

aa) "Direct use" means any procedure by which the cells are

donated and used without being stored in a bank;

bb) "Validation" (or "approval" in the case of equipment or environments), the

establishment of documented data that provide a high degree of

safety that a process, PON, a piece of equipment or an environment

specific produce, in a consistent manner, a product that fulfils

specifications and quality attributes previously determined, in order to evaluate

32

the performance of a system with respect to its effectiveness for the use

intended.

33

ANNEX II

Requirements for the authorisation of the harvesting units, of the banks of

tissues and the services responsible for the application of the same

A. Organization and Management

1-Must be appointed a person responsible with the qualifications and responsibilities

provided for in Article 14 of this Law.

2-All services have to have access to a doctor appointed for advice and

supervision of the medical activities of the service, referred to in para. e) of the Article 3 (3)

14.

3-Services have to have operating procedures appropriate to the activities for

which is requested authorization.

4-There has to be an organizational framework that clearly defines the hierarchy and the

notification relations.

5-There has to be a documented quality management system applied to the activities

for which permission is requested, in accordance with the standards set out in the

present law.

6-Services have to ensure that the risks inherent in the use and handling of

biological materials, including those related to procedures, environment,

staff health status, be identified and consistently minimized

with the maintenance of a suitable quality and safety to the end to which they are intended

the tissues and cells.

7-Agreements between tissue banks and third parties, where applicable, have to comply with the

provisions of Article 21 of this Law.

8-There has to be a documented system, supervised by the person responsible, to

ratify that the tissues and cells comply with the appropriate safety specifications and

quality for release and respective distribution.

9-There has to be a documented system that ensures the identification of all the

tissue or cell units at all stages of the activities for which it is requested

34

authorization.

B. Staff

1-The personnel of the harvesting units, the tissue banks and the responsible services

by the application of the same, must be in sufficient number and possess the qualifications

necessary for the tasks they perform.

2-A the staff's competence shall be assessed at appropriate intervals specified in the

quality system.

3-All personnel shall have a description of clear, documented and

updated. Their tasks, responsibilities and accountability have to be

clearly documented and fully understood.

4-All personnel shall receive initial and continuous training, appropriate to their respective

tasks. The Training Programme has to ensure in a properly documented manner

that each professional:

a) Demonstrated competence in the implementation of the respective assigned tasks;

b) Has appropriate knowledge and understanding about the processes and

scientific and technical principles, relevant to the tasks assigned to it;

c) It comprises the organisational framework, the quality system and the standards of

health and safety of the service where it performs its functions;

d) It is conveniently informed of the ethical, legal and regulatory context more

broad of your work.

C. Equipment and Material

1-All equipment and material have to be designed and maintained to serve the end

predicted and has to minimise any risk to donors, recipients and staff.

2-All critical technical equipment and devices have to be identified and

validated, regularly inspected and subject to preventive maintenance, of agreement

with the specifications of the manufacturer.

3-Whenever the equipment or the material affects critical processing parameters

or storage, such as temperature, pressure, particle count, levels of

microbial contamination, has to be identified and submitted, if necessary, to

monitoring, alerts, alarms and appropriate corrective actions in the sense of detecting

35

dysfunctions and defects, in such a way as to ensure the permanent maintenance of the parameters

critics within acceptable limits.

4-All equipment with a critical measurement function shall be calibrated second

a perfectly identifiable standard, if available.

5-The new and repaired equipment has to be tested when installed, validated before

of their use, and the respective results are documented.

6-A maintenance, assistance, cleaning, disinfection and hygienization of all equipment

critical have to be carried out regularly and registered.

7-They have to be available procedures for the operation of each component

of critical equipment, which specifies in detail the measures to be taken in the event of

dysfunction or failure.

8-Procedures for the activities for which you are requesting permission have to

describe in detail the specifications for all critical materials and reagents.

It has to be defined, inter alia, specifications for additives, such as

solutions, and packaging materials. Critical reagents and materials have to comply

documented requirements and specifications and, if that is the case, the provisions of the legislation

specific about medical devices.

D. Facilities / Locations

1-The Services have to possess adequate facilities to carry out the activities for the

which one requests permission, in accordance with the standards set out in the present

law.

2-Where the activities in the tissue bank include the processing of tissues and

cells in exposure to the environment, the same should unfold in a medium

environment with specified air quality and cleaning, in the sense of minimizing the risk

of contamination, including cross contamination between donations. The effectiveness of these

measures should be validated and monitored.

3-Except in the situations specified in the following number, whenever the subject fabrics and

cells are exposed to the environment during processing, without a process

subsequent of microbial inactivation, an air quality is required with

count of particulate matter and microbial colonies equivalent to those of Grade A, such as

defined in Annex I to the European Manufacturing Best Practice Guide, with a means

general environment suitable to the processing of the tissues or cells involved but,

36

at least, equivalent to those of Grade D of the Guide in terms of particle counting and

of microbial counting.

4-It may be acceptable a less rigorous environment than specified in the

previous number, whenever:

a) A process of microbial inactivation or final sterilization is applied

validated; or

b) It is shown that exposure to an environment of Grade A has an effect

detrimental on the required properties of the tissues or cells involved; or

c) It is shown that the mode and the way of application of the tissue or cell in the receptor

implies a significantly lower risk of transmission of bacterial infection

or fungal to the receiver than with cell and tissue transplantation; or

d) It is not technically possible to carry out the required process in an environment of

Grade A, namely, 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 it has to be specified an environment.

It has to be demonstrated and documented that the chosen environment achieves the

quality and safety required, having at least taken into account the intended end, the way of

application and the immune status of the receiver. They have to be provided clothing and

appropriate personal protective and hygiene equipment in each workplace

relevant from the tissue bank and cells, along with written instructions about

hygiene and use of protective clothing.

6-Where the activities for which you request permission involve the

storage of tissues and cells, they have to be defined the conditions of

storage necessary for the maintenance of the properties of the tissues and cells,

including relevant parameters such as temperature, humidity or air quality.

7-The critical parameters, such as temperature, humidity and air quality, have to

be controlled, monitored and registered, in the sense of substantiation of their

compliance with the specified conditions of storage.

8-Have to dispose of storage facilities that separate and distinguish clearly

tissues and cells prior to their release or quarantine of those who are

authoritative and those who are rejected, in the sense of avoiding exchanges and contaminations

37

cross between them. They have to have assigned separate areas physically or devices

of storage or secure segregation within the device, in places of

storage of tissues and cells in quarantine or released, in the sense of maintaining

certain tissues and cells harvested in accordance with special criteria.

9-The tissue and cell bank has to possess written policies and procedures in

controlled access, cleaning and maintenance, disposal of waste and of

reorganization of services in emergency situations.

E. Documentation and Records

1-There has to be a system that provides for clearly defined and effective documentation,

correct records and Normalized Operative Procedures (PON) for the

activities for which permission is requested.

2-Documents have to be reviewed regularly and comply with the standards set out in the

present law.

3-The system has to ensure that the work carried out is standardised and that all phases

are traceable, namely, the coding, eligibility of the donor, harvesting,

processing, preservation, storage, transport, distribution, application or

elimination, including aspects related to control and quality assurance.

4-For each critical activity, the materials, equipment and personnel involved have to be

identified and documented.

5-In the harvesting units, tissue and cell banks, and services responsible for its

application, all changes to the documents have to be reviewed, dated, approved,

documented and implemented quickly by the authorized personnel.

6-There has to be a documentary control procedure, in the sense of ensuring the

history of the revisions to the documents and the changes and ensure that they are only

used the updated versions of the documents.

7-Records need to be shown to be credible, reliable and reliable.

8-Records have to be legible and indelible, and may be manuscripts or transferred

for another validated system, such as computer system or microfilm.

9-Without prejudice to the provisions of Article 8 (4), the records, including original data,

which are critical for the safety and quality of tissues and cells should be

38

kept for at least ten years after the date of validity, clinical use or

elimination.

10-Records have to comply with the confidentiality requirements set out in Article 23.

of this Law. Access to records and data has to be limited to authorised persons

by the person in charge and ASST for inspection and control measures.

F. Quality System

1-There has to be an audit system in respect of the activities for which if

requests authorization. The audit has to be conducted in an independent manner by

trained persons, of recognized competence, at least every two years, in the

sense of checking compliance with approved protocols and requirements

regulatory.

2-The non-conformities and corrective actions have to be documented.

3-Failure to comply with quality and safety standards shall lead to investigations

documented, which include a decision on possible actions, corrective or

preventive.

4-The fate of non-compliant tissues and cells has to be decided in accordance with

written procedures, supervised by the person responsible and registered. All the

affected tissues and cells have to be identified and accounted for.

5-Corrective actions have to be documented, initiated and completed in a way

timely and effective. Preventive and corrective actions should be assessed in relation

to the effectiveness after it is implemented.

6-The harvesting units, tissue banks and services responsible for their application

must have processes to analyse the performance of the management system of the

quality, in the sense of ensuring continuous and systematic improvement.

39

ANNEX III

Requirements for the authorisation of tissue preparation processes and cells in the

tissue and cell banking

ASST authorizes each process of preparation of tissues and cells after the evaluation of the

criteria for selection of donors, harvesting procedures, protocols for each

process phase, the quality management criteria and the quantitative criteria and

final qualitative for cells and tissues. This assessment has to comply with at least the

requirements set out in this Annex.

A. Reception in the Banks of Tecids and cells

The reception of the subject fabrics and cells shall comply with the requirements set out in Article 16 of the

present law.

B. Processing

Where the activities for which you request permission to include the processing

of tissues and cells, the procedures have to meet the following criteria:

1-Critical processing procedures have to be validated and cannot make

the clinically ineffective or harmful tissues or cells for the receptor. This

validation may be based on studies carried out by the service itself or in data

of published studies or, for well-established processing procedures,

in a retrospective evaluation of the clinical results for the tissues provided

by the service.

2-It has to be demonstrated that the validated process can be carried out in a way

consistent and effective by the staff in the environment of the tissue bank and cells.

3-Procedures have to be documented in PON that have to be in

compliance with the validated method and with the standards set out in this Law,

in accordance with that set out in E, paragraphs 1 a to 4, of Annex II.

4-It has to be ensured that all processes are carried out in compliance with the

PON approved.

5-If, in the tissues or cells, a microbial inactivation procedure is used,

such a procedure shall be specified, documented and validated.

6-Before any significant change to the processing is applied, the process

40

changed has to be validated and documented.

7-Procedures for prosecutions have to be subject to an assessment

periodic critique, including procedures, means or equipment of use in

routine, in order to ensure that they continue to lead to the intended results.

8-Procedures for the disposal of tissues and cells have to prevent contamination

of other donations and products, the environment of processing or the personnel, in

compliance with the legislation in force.

C. Storage and Release of Products

Where the activities for which you request permission to include storage

and release of tissues and cells, the authorized procedures of the tissue banks and

cells have to meet the following criteria:

1-According to the conditions of storage, the period of

maximum storage, in order to guarantee the necessary properties.

2-There has to be an inventory system for the tissues and cells to ensure that it does not

they may be released until all the requirements set out in the

present law.

3-There has to be a standardised operative procedure that defines in detail the

circumstances, responsibilities and procedures for the release of tissues and cells

for distribution.

4-There has to be a system for identification of tissues and cells along any

phase of processing in the tissue bank and cells, which has to allow a

unambiguous distinction between released products, quarantined and eliminated.

5-Records have to show that, prior to the release of the tissues and cells, they are

complied with all appropriate specifications, namely that all forms

of current statement, relevant medical records, processing records and

results of analyses were verified in accordance with a procedure written by

an authorised person for this task, by the responsible person referred to in Article 14.

of this Law.

6-Should you use an informatics support to release the results of the laboratory, the

41

responsible for the respective release must be able to be identified.

7-After the introduction of any new criteria for selection of donors, clinical or

analytical as well as any significant change of a phase of the processing

that it improves safety or quality, a risk assessment has to be carried out

documented, approved by the responsible person referred to in Article 14º of this Law,

in the sense of determining the fate of all tissues and stored cells.

D. Distribution and Retreat

Where the activities for which it is requested to be allowed to include the distribution of

tissues and cells, the authorized procedures have to meet the following criteria:

1-There have to be defined transport conditions, such as temperature and time frame, with

a view to the conservation of the necessary properties of the tissues and cells.

2-The container or packaging has to be safe and ensure that the tissues and cells are

kept under the conditions specified. All containers and packaging need

of being validated as appropriate to the end they are intended for.

3-If the distribution is entrusted by contract to third parties, there has to be an agreement

documented that ensures the observance of the required conditions.

4-In the tissue and cell bank authorized to assess the need for tissue withdrawal

and cells and to trigger and coordinate the necessary actions.

5-There has to be an effective withdrawal procedure that provides for the description of the

responsibilities and measures to be taken. Such a procedure has to provide for

notification of ASST.

6-Whenever a donor may have contributed to cause a reaction in the receiver,

measures must be taken within pre-established time frames, which

must include trace of the tissues and cells and, if applicable, cover the research of the

origin in such a way as to identify the available tissues and cells from such

donor and to notify the recipients and receptors of the subject fabrics and cells

of that same donor, should they be at risk.

7-There have to be procedures for the treatment of tissue and cell applications. The

standards for the allocation of tissues and cells to certain patients or institutions

42

of health care have to be documented and be made available to the parties

interested whenever requested.

8-There must be a documented system for the treatment of returned products,

including criteria for their acceptance in the inventory, if any.

E. Final labelling for distribution

1-The label of the primary container of the subject fabrics and cells should indicate:

a) The type of tissues and cells, identification number or tissue code or

cells, and number of the lot or group, if any;

b) Identification of the tissue bank;

c) Period of validity;

d) In the case of autologous donation, this fact has to be specified: " for use

autologous ", and the receiver donor has to be identified;

e) In the event of direct donations, the receiver shall be identified;

f) When it is known that the tissues or cells are positive for a marker of

a relevant infectious disease, mention should be included: " DANGER

BIOLOGICAL ".

g) In case it is not possible to add to the primary container label the information

mentioned in the points d) and and ), these must be provided in a document

separate that will accompany the primary container. This document should be

packaged together with the primary container in order to ensure that

remain together.

2-The data listed below have to appear on or from the label, or the documentation that the

accompanies:

a) Description, definition and, if relevant, the dimensions of the tissue-based product or

cells;

b) Morphology and functional data, if any;

c) Date of distribution of tissues or cells;

d) Biological tests performed on the donor and the respective results;

e) Recommendations on storage;

43

f) Instructions for the opening of the container, packaging or any handling or

necessary reconstitution;

g) Period of validity after opening or handling;

h) Instructions for notification of serious adverse reactions and adverse incidents, such as

defined in Article 11 of this Law.

i) Presence of potentially hazardous waste (antibiotics, ethylene oxide,

etc.).

F. Outdoor labelling of the transport container

For transport, the primary container has to be placed in a transport container

whose label contains at least the following information:

a) Identification of tissue bank and source cells, including abode and number

of telephone;

b) Identification of the target body responsible for application in beings

humans, including abode and telephone number;

c) A reference that the packaging contains human tissues or cells, and includes

the mention: "HANDLE WITH CARE";

d) Whenever living cells are needed for transplant functions, such as

stem cells, gametes and embryos, the following expression has to be added:

"NOT IRRADIATE";

e) Recommended transport conditions (position, temperature, etc.).

f) Safety instructions or refrigeration method, where applicable.

44

ANNEX IV

Consent and Information regarding the donation and application of fabrics and

cells

A. Living donors

1-The consent of the donor shall be free, enlightened, informed and unequivocal.

2-The consent is provided before the doctor, designated in accordance with the provisions of the n.

2 of Article 8 of Law No 22/2007 of June 29.

3-Treating to smaller donors, consent must be provided by parents, since

that non-inhibited from the exercise of parental power, or, in the event of inhibition or lack of

both, by the court.

4-A gift of tissues or cells from minors with an ability to understand and to

manifestation of will lacks also the concordance of these.

5-A harvesting of tissues or cells in larger incapable for reasons of psychic abnormality

can only be done by judicial authorization.

6-The consent of the donor or of whom the represent legally is always provided by

written, being freely revocable except in the case in which, by the prep preparation

transplant already carried out, the life of the recipient is put at risk.

7-The person responsible for the donation process shall ensure that, at a minimum, the donor or

who lawfully represent him, has been adequately informed of the aspects concerning the

donation and the collection described in paragraph 6 and 10 of this Annex.

8-A information has to be provided prior to the donation.

9-A information must be provided by a health professional with specific training

in this area, able to transmit it in a proper and clear way, using terms easily

understandable by the donor.

10-A The information should mention the purpose and nature of the collection and its

consequences and risks, laboratory examinations, if they are carried out, the registration and

protection of data relating to the donor, medical secrecy, therapeutic target and the

potential benefits, as well as information on the applicable safeguards

intended to protect the donor and the receiver.

45

11-The donor, or who represents it legally, shall be informed that he / she has the right

to receive the confirmed results of the laboratory tests and to receive explanations

clear about these results.

12-Information must be provided on the need for the mandatory to exist the

consent for the collection of tissues or cells to be able to take place.

B. Donors cadaver

Information, consent and authorizations, must be provided and obtained in agreement

with that provided for in Law No 22/2007 of June 29.

C. Reproductive cell donors

Information, consent and authorizations, must be provided and obtained in agreement

with that provided for in Law No 32/2006 of July 22.

D. Receptor of tissues and cells

1-A The application of tissues or cells in human beings has to be preceded by the

free, enlightened, informed and unequivocal consent of the recipient.

2-The consent is provided before the doctor, designated in accordance with the provisions of the n.

2 of Article 8 of Law No 22/2007 of June 29.

3-Consent is always provided in writing and freely revocable.

4-Treating minor recipients, consent must be provided by the parents,

provided that it is not inhibited from the exercise of parental power, or, in the event of inhibition or lack

of both, by the court.

5-A application of tissues or cells in minors with an ability to understand and to

manifestation of will lacks also the concordance of these.

6-A application of tissues or cells in larger incapable for reasons of anomaly

psypical can only be done by judicial authorization.

46

ANNEX V

Criteria for selection of tissue and cell donors (EXCEPT DONORS OF

REPRODUCTIVE CELLS)

The donor selection criteria are based on an analysis of the risks related to the

application of specific tissues or cells. Indicators of these should be identified

risks by physical examination, an analysis of medical and behavioural background, analyses

biological, examination post mortem and other appropriate indagations, in the case in the case of donors

corpse. 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 donations from donors to which the constant criteria of the figures apply

following:

1. Body daters:

1.1. General exclusion criteria:

1.1.1. Cause of undetermined death, unless the autopsy reveals information about the

cause of death after harvesting and that do not apply any of the general criteria of

exclusion provided for in this number.

1.1.2. Background of disease of unknown etiology.

1.1.3. Existence or antecedents of malignant disease, except basocellular carcinoma

primary, carcinoma of the cervix in situ and some primary tumors of the nervous system

central, which should be assessed according to scientific data. For the gift of cornea,

may be taken into account and evaluated donors with malign-disease, except

retinoblastoma, hematological neoplasias and malign-like tumors in the anterior segment of the

eye.

1.1.4. Risk of transmission of diseases caused by prions. This risk applies,

namely, a:

a) People diagnosed with Creutzfeldt-Jakob disease, or with the variant

of this disease or with a family background of Creutzfeldt-Jakob disease no

iatrogen;

47

b) People with a background of rapid progressive dementia or with disease

neurodegenerative, including those of unknown origin;

c) People treated with hormones derived from human hypophysis (eg.

hormone growth hormone) and transplant recipients from the cornea, sclerotic and

hard-mater as well as people who have been subjected to intervention

undocumented neurosurgical (in which it may have been used hard-máter).

1.1.4.1. The variant of the Creutzfeldt-Jakob disease, referred to in para. a) of the number

previous, additional precautionary measures may be recommended.

1.1.5. Uncontrolled systemic infection at the time of donating, including infections

bacterials, viral infections, fungal or systemic parasites, or significant local infection

in the tissues and cells to donate. In the regard to the donations of eyes, they can be taken in

consideration and evaluated donors with bacterial septicaemia, but only when the corneas

are stored by culture of organs, so as to detect any contamination

bacterial of the tissue.

1.1.6. Background, clinical data or laboratory results that demonstrate the existence

of risk of transmission of HIV, acute or chronic hepatitis B, except in the case of persons

with a status of proven immunity, hepatitis C and HTLV I/II or presence of

risk factors of these infections.

1.1.7. Antecedents of chronic, systemic and autoimmune disease, capable of damaging the

quality of the fabric to be spoon.

1.1.8. Indications that the results of the analyses of the donor's blood samples did not

are valid, due:

a) To the occurrence of hemodilution, in accordance with the specifications described

in 2 of Annex VI, when a pre-transfusion sample is not available; or

b) To the treatment with immunosuppressive agents.

1.1.9. Data from other risk factors of communicable diseases on the basis of a

assessment of risks taking into account the donor's background in travel and

exposure, as well as the prevalence of local infectious diseases.

1.1.10. Presence, in the body of the donor, of physical signs that have swirted risk of disease

48

communicable.

1.1.11. Ingestion of substances or exposure to substances, such as cyanide, lead,

mercury, gold, which can be transmitted to the receptors in doses likely to be put

at risk to your health.

1.1.12. Recent background of vaccination with live attenuated viruses, when if

consider that there is risk of transmission.

1.1.13. Transplantation with xenotransplants.

1.2. Supplementary criteria for exclusion of dead donor children:

1.2.1. They should be excluded from dators, until the risk of transmitting infection can be

definitely sidelined, all children whose mothers are infected by HIV or

meet any of the exclusion criteria described in 1.1. of this Annex.

a) They cannot be considered as dayers, regardless of the results of the

analyses, children younger than 18 months of age whose mothers are

infected or present risk factors of HIV infection, hepatitis B,

hepatitis C or HTLV and which have been breastfed by their respective mothers in the

12 previous months;

b) They can be accepted as a donor the children whose mothers are infected or

present risk factors of infection, by HIV, hepatitis B, hepatitis C or

HTLV and who have not been breastfed by their respective mothers in the 12 months

previous and whose analyses, physical examinations and analysis of clinical records do not

demonstrem infection by HIV, hepatitis B, hepatitis C or HTLV.

2. Living Dators:

2.1. Live donor for autologous purposes:

2.1.1. Whether the removed cells or tissues are intended to be stored or placed in

culture, should apply the same minimum set of biological analyses that applies to the

living donors for allogeneic purposes. The fact that the results of the analyses are positive

is not an impediment that the tissues or cells or any other product thereof derived

are stored, processed and redeployed, provided that there are facilities of

insulated and appropriate storage that guarantee the non-risk of contamination

crusade for other transplants and / or contamination with adventitious agents and / or

49

product exchanges.

2.2. Living donor for allogeneic purposes:

2.2.1. Living donors for allogeneic purposes should be selected on the basis of their

background sanitary and medical, provided in a questionnaire and by interview

held to the donor by a qualified and trained health care professional, in

compliance with the provisions of 2.2.5. of this Annex.

2.2.2. The assessment referred to in the preceding paragraph shall include relevant factors that

can help to identify and exclude people whose donations could present a risk

for the health of third parties, such as the possibility of transmission of diseases, or for their

own health.

2.2.3. Whatever the gift, the process of harvesting should not interfere with or

compromising the health of the donor nor the care to be provided to him.

2.2.4. In the case of donations of the umbilical cord or the amniotic membrane, the willing us

previous figures apply to both the mother and the baby.

2.2.5. The criteria for selection of living donors for allogeneic purposes should be

established and documented by the tissue and cell bank and the responsible practitioner

by transplants, in the case of direct distribution to the receiver, on the basis of tissue or

specific cells to donate, together with the physical state of the donor, the antecedents

physicians and behavioural, the results of clinical investigations and analyses

laboratory that determines the state of health of the donor.

2.2.6. The exclusion criteria to be applied shall be the same as those used in the case of

dead donors, with the exception of the provisions of 1.1.1. of this Annex. In function of the

tissue or cell to donate, other specific exclusion criteria may be required, such

how to:

a) Pregnancy, except for blood cell donors from the umbilical cord blood, from the

amniotic membrane and donor siblings of hematopoetic progenitor cells;

b) Breastfeeding;

c) In the case of hematopoetic progenitor cells, the potentials of transmission

of inherited affections.

50

ANNEX VI

Laboratory analysis required of donors (EXCEPT DONOR CELLS

REPRODUCTIVAS)

1. Biological analyses required of donors:

1.1. It constitutes a minimum requirement to submit all donors to biological analyses to

follow indicated:

a) VIH 1 and 2 (Anti-VIH-1, 2);

b) Hepatitis B (HBsAg; Anti-HBc)

c) Hepatitis C (Anti-HCV-Ab)

d) Syphilis, pursuant to paragraph 1.4. of this Annex.

1.1.1. For hepatitis B, Hepatitis C and HIV should always carry out nucleic acid tests.

In urgent situations these tests can be carried out at a posteriori.

1.2. The analyses of HTLV I/II antibodies are to be performed in the case of donors who

they live or come from areas with high incidence, or with sexual partners

coming from those areas, or in the case that the donor's parents come from those

zones.

1.3. When the anti-HBc analysis is positive and HBsAg is negative, they should proceed

the investigations, upon assessment of the risks, in order to determine eligibility for

clinical use.

1.4. A validated analysis algorithm should apply, in order to exclude the presence of

active infection with Treponema pallidum . A non-reactive analysis, specific or not, may

allow acceptance of tissues and cells. When to perform a non-specific analysis, a

reactive result does not prevent harvesting or acceptance, should a specific analysis for

confirmation of Treponema is non-reactive. If a sample of the donor is reactive to a

specific analysis for detection of Treponema, a thorough evaluation of the

risks, in order to determine eligibility for clinical use.

1.5. In certain circumstances, additional analyses may be required, in function

of the antecedents of the donor and the characteristics of the donated tissue or cells, such as

RhD, HLA, malaria, CMV, toxoplasma, EBV, Trypanosoma cruzi .

1.6. In relation to donors for autologous purposes, the provisions of 2.1 of Annex V shall apply.

51

2. General requirements to be observed in the determination of biological markers:

2.1. The analyses must be carried out by an approved laboratory as a centre of analysis

by the responsible authority, using, if necessary, the test kits with the marking

CE. The type of analysis used must be validated for the purpose, in accordance with the

current scientific knowledge.

2.2. Biological analyses are carried out in the donor's serum or plasma; they must not be

performed in other fluids or secretions, such as aqueous or vitreous mood, unless such

if warranted from the clinical point of view, a validated analysis should be used for that

fluid.

2.3. Should potential donors have lost blood and received recently blood,

blood components, colloids or crystalloids coming from donations, the analysis of the

blood may not be valid due to the hemodilution of the sample. Must apply for a

algorithm in order to evaluate the degree of hemodilution in the following circumstances:

a) Sampling of blood ante mortem : if the infusion of blood was carried out,

blood components and / or colloids in the 48 hours leading up to

blood sampling or if it carried out the infusion of crystalloids at the time that

preceded the said harvest;

b) Sampling of blood post mortem : if the infusion of blood was carried out,

blood components and / or colloids in the 48 hours leading up to the death or

if it carried out the infusion of crystalloids at the time that preceded the death.

2.3.1. Tissue and cell banks can only accept tissues and donor cells with

plasma dilution greater than 50%, if the analysis procedures used are

validated for that plasma or if they dispose of a pre-transfusion sample.

2.4. In the case of a corpse donor, blood samples must be obtained immediately

before death or, if it is not possible, sampling must be carried out the most

quickly possible after death and never after after decorations 24 hours.

2.5.

52

a) In the case of living donors, except, for reasons of practical order, the donors of

bone marrow stem cells and from peripheral blood stem cells

for allogeneic purposes, blood samples must be obtained at the time of

gift, or, if it is not possible, in the period of 7 days later than the donation (the

called "sample of gift");

b) If the tissues and cells of living donors for allogeneic purposes can be

stored for long periods, it is necessary to make a repeat of the

sample and analyses after a range of 180 days. In these circumstances, of

repeat probes, the donation sample can be taken in a period

understood between 30 days before the donation and 7 days after the donation;

c) If the tissues and cells of living donors for allogeneic purposes cannot be

stored for long periods and, consequently, it is not possible to do

a repeat of the sample harvest, the provisions of the paragraph shall apply. a) from the

present number.

2.6. If, in a living donor, except for bone marrow stem cell donors and

stem cells from peripheral blood, the "donation sample", as defined in the

a) from the previous number, is further analyzed for determination of HIV, HBV and HCV, by the

nucleic acid amplification technique (NATou TAA), it is not necessary to repeat the analysis

of new blood sample. It is also not necessary to conduct new analyses when the

processing include an inactivation phase that has been validated for the viruses in

cause.

2.7. In the case of bone marrow harvesting and peripheral blood cells, the samples of

blood should be harvested for analysis in the 30 days prior to the donation.

2.8. In the case of neonatal donors, biological analyses to the donor can be carried out in the

mother of the donor, in order to avoid medically unnecessary procedures for the baby.

53

ANNEX VII

Criteria for selection and laboratory analysis required of donors

of reproductive cells

1. Treating donations between partners for direct use, it is not necessary to apply the

criteria for selection of donors.

2. In the case of donations between partners for non-direct use, reproductive cells

that are processed or stored and the reproductive cells that give rise to the

cryopreservation of embryos, must comply with the following criteria:

2.1. The practitioner responsible for the donor must determine and document, based on the

medical background and in the therapeutic indications of the patient, the justification for the donation

and the safety of this for the receiver and for the children who can come to be born.

2.2. The following biological analyses must be carried out in order to assess the risk of

cross contamination:

a) VIH 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 indicated

in 2.2. or if it is known that the donor constitutes a source of risk of infection, it must be

designed a separate storage system.

2.4. Probes of HTLV I/II antibodies should be performed on donors living or

coming from areas with high incidence or with sexual partners coming from

of these areas or in the case that the donor's parents come from those areas.

2.5. In certain circumstances, additional analyses may be required, in function

of the donor's background in respect of travel and eventual exposure to agents

infectious and the characteristics of donated tissue or cells, such as RhD, malaria, CMV,

T. Cruzi.

2.6. The fact that the results are positive is not necessarily impeditive to donation

54

between partners, of harmony with the legis artis legally defined.

3. In the case of donations not sourced from partners, the use of reproductive cells

should respect the following criteria:

3.1. Donors must be selected on the basis of age, health and medical background,

provided in a questionnaire and by personal interview conducted by doctor with

experience. This assessment should include relevant factors that contribute to identifying

and exclude persons whose donations may present a risk to the health of third parties, such as

the possibility of transmission of diseases, such as sexually transmitted infections,

or for your own health, such as hyperovulation, sedation, or the risks associated with

procedure of egg harvesting or the psychological consequences of being dador.

3.2. The donors must be negative for HIV-1 and 2, HCV, HBV and syphilis in a sample

of serum or plasma, analyzed in accordance with point 1.1 of Annex II, and the donors

of sperm must still have negativity for the Chlamydia in a sample of urine analyzed

by the technique of amplification of nucleic acids (NAT).

3.3. Probes of HTLV I/II antibodies should be carried out in donors living or

are from areas with high incidence or with sexual partners coming from

of these areas or in the case that the donor's parents come from those areas.

3.4. In certain circumstances, additional analyses may be required, in function

of the antecedents of the donor and the characteristics of the donated tissue or cells, such as

RhD, malaria, CMV, T. Cruzi.

3.5. In relation to donors for autologous purposes, the provisions of 2.1 of Annex V shall apply.

3.6. Must proceed to genetic screening for determination of recessive genes

autossomics, which, according to international scientific data, are prevalent in the

background of the ethnicity of the donor, and to an assessment of the risk of disease transmission

hereditary, which is known to be present in the family, after obtaining the consent.

Full information should be provided on the associated risks and on the measures

taken for their mitigation, which must be communicated and clearly explained to the

receiver.

4. General requirements to be observed in the determination of biological markers:

4.1. The analyses shall be carried out in accordance with the provisions of 2.1. and 2.2. of the

annex VI.

55

4.2. Blood samples must be obtained at the time of the donation.

4.3. Sperm donations do not come from partners should be quarantined, in the

minimum, for 180 days. After the course of this period, the analyses shall be repeated

with new blood sample.

4.3.1. If, in a donor, the blood donation sample is analyzed also for

determination of HIV, HBV and HCV, by the technique of amplification of nucleic acids

(NAT), it is not necessary to test a new blood sample.

4.3.2. It is not necessary to conduct new analyses when the processing includes a phase of

inactivation that has been validated for the viruses in question.

56

ANNEX VIII

Donation and harvesting procedures of cells and tissues and reception

in the Bank of tissues and cells

1. Proceedings of donation and harvesting:

1.1. Consent and identification of the donor:

1.1.1. Prior to proceeding with the harvesting of tissues and cells, an authorised person

must confirm and register:

a) That the consent to the harvest was obtained in accordance with the provisions of

in Article 24 of this Law; and

b) In what way and by whom the donor has been correctly assessed.

1.1.2. In the case of living donors, the health professional responsible for obtaining the

background of health must ensure that the donor:

a) Understood the information provided;

b) Had the opportunity to ask questions and who obtained satisfactory answers;

c) It confirmed that, as far as it is given to know, all the information it has provided

are true.

1.2. Evaluation of the donor:

1.2.1. An authorised person shall collect and record the medical information and

relevant behavioural of the donor, according to the requirements described in 1.4.

1.2.2. In order to obtain the appropriate information, different sources should be used

relevant, including at least an 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 well, in the case of donors

corpse;

c) An interview with the attending physician;

d) An interview with the general practitioner;

57

e) The autopsy report.

1.2.3. In the case of a cadaver donor and, when warranted, in the case of a living donor,

must also be made a physical examination of the body in order to detect any signs that

may suffice to exclude the donor, or should be assessed in the context of the antecedents

doctors and personnel of the donor.

1.2.4. All donor records must be analyzed and evaluated to determine from your

suitability and signed by a qualified health professional.

1.2.5. The provisions of paragraphs 1.2. to 1.2.4. of this Annex shall not apply to donations between

reproductive cell partners or donors for autologous purposes.

1.3. Procedures for collection of tissues and cells:

1.3.1. There shall be appropriate harvesting procedures to the type of donor and the type of

gift of tissues or cells, and that protect the safety of the living donor.

1.3.2. The harvesting procedures shall conserve the properties of the subject fabrics or

cells required for their clinical purpose and simultaneously reduce to a minimum

microbiological contamination in the course of this process, in particular when the subject fabrics and

cells cannot subsequently be sterilized.

1.3.3. In the case of donations from cadaver donors, the access area must be

restricted.

1.3.3.1. A sterile working area must be used, upon use of fields

sterilized.

1.3.3.2. The professionals who proceed to the harvest must be dressed appropriately

for the type of harvest.

1.3.3.3. The staff must wash and properly scrub their hands and arms, wear clothing

and sterile gloves, facials and protective masks.

1.3.4. In the case of a corpse donor, the place of harvest shall be registered and the period which

mediated between death and harvesting should be specified, in order to ensure the conservation of the

necessary biological and physical properties of the tissues and cells.

1.3.5. Once the tissues and the cells of the body of a corpse donor, the body

must be reconstituted in such a way that its appearance is as much as possible

similar to its original anatomical form.

58

1.3.6. All adverse reactions taking place must be recorded and examined during

harvesting and who harm or have impaired a living donor, as well as the

results of investigations aimed at determining the causes.

1.3.7. There must be policies and procedures that reduce to a minimum the risk of

contamination of tissues and cells by personnel likely to be infected with disease

communicable.

1.3.8. They must be used, in the harvesting of tissues and cells, instruments and devices

sterile. The instruments or the devices must be of good quality, validated or

specifically certified and subject to regular maintenance for the purpose of harvesting

tissues and cells.

1.3.9. For reusable instruments there must be a cleaning procedure and

sterilization validated for the removal of infectious agents.

1.3.10. Where possible, only CE-branded medical devices should be used

and all the personnel involved must have received adequate training on the use of these

devices.

1.4. Documentation relating to the donor:

1.4.1. For each donor there must be a record containing the following elements:

a) Identification of the donor: own name, surname and date of birth. In the case of the

donations involve mother and child, the name and date of birth of the mother and the name, if

known, and the date of birth of the son.

b) Age, sex, medical background and behavioural. The information collected

should be sufficient to allow the application of the exclusion criteria, if

required;

c) Results of the examination of the body, if applicable;

d) Hemodilution formula, if applicable;

e) Form of consent or authorization, if applicable;

f) Clinical data, results of laboratory analyses and results of other analyses

carried out;

g) Should an autopsy be performed, your results should be included in the register.

In relation to tissues and cells that cannot be stored during periods

59

protracted, a preliminary oral autopsy report should be recorded;

h) In the case of hematoipoetic progenitor cell donors, the suitability of the

dador chosen for the receiver must be documented. Treating yourself to donations

no relation of kinship, when the organization responsible for harvesting has

limited access to the recipient's data, must be provided to the body which

carries out the transplantation the data of the donor that are relevant to confirm the

suitability.

1.4.2. The body carrying out the harvest shall set up a harvest report, which is

transmitted to the tissue bank and cells, from it owing to at least the following

elements:

a) Identification, name and address of the tissue bank and cells that will receive the

cells or tissues;

b) Identification of the donor, including the way it has been identified and by whom;

c) Description and identification of harvested tissues and cells, including samples for

analysis;

d) Identification of the person responsible for the harvesting session, including signature;

e) Date, time (when pertinent, start and end), location of the harvest and procedure

(PON) used, including possible incidents occurred; where necessary,

environmental conditions of the harvesting facility (description of the physical area in which if

proceeded to harvest);

f) In relation to corpse donors, the conditions under which the corpse is kept:

refrigerated (or not), time of the start and the term of the refrigeration;

g) Identification / batch numbers of reagents and transport solutions used.

h) When possible, the date and time of death.

1.4.2.1. When harvesting sperm at home, the harvest report must register this

fact and contain only the following elements:

a) Name and address of the tissue bank and cells that will receive the cells or

tissues;

b) Identification of the donor, and, if possible, the date and time of the harvest;

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1.4.3. All registrations must be clear and legible, protected against prohibited changes,

conserved and readily accessible under these conditions throughout their period of

conservation specified, in accordance with the provisions of the Data Protection Act

Personal.

1.4.4. The donor records required to guarantee a full traceability must be

kept for at least 30 years after clinical use, or date of validity,

in a suitable file, acceptable by ASST.

1.5. Packaging:

1.5.1. After harvesting, all tissues and harvested cells must be packaged in a way

reduce to the minimum the risk of contamination and stored at temperatures that preserve

the necessary characteristics and biological function of cells or tissues. The packaging shall

also prevent the contamination of those responsible for the packaging and transport of

tissues and cells.

1.5.2. Packaged fabrics or cells must be sent in a suitable container for the

transport of biological materials and to maintain the safety and quality of the subject fabrics or

cells in it contained.

1.5.3. All tissue or blood samples for analysis that accompany them must be

labelled with correctness in order to ensure the identification of the donor, and shall include the

record of the time and place on which the sample was taken.

1.6. Labeling of the harvested tissues or cells:

1.6.1. At the time of harvesting, each packaging that contains tissues and cells shall be

labeled.

1.6.2. The primary container of tissues or cells must indicate the identification or the code

of donations and the type of tissues and cells.

1.6.3. When the size of the packaging allows it, it should be provided still

following information:

a) Date of the donation and, if possible, time;

b) Warnings of danger;

c) Nature of any additives (if used);

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d) In the case of donations for autologous purposes, the label must state " Only for

autologous use ";

e) In the event of direct donations, the label must identify the receiver to which if

are intended.

1.6.4. In case it is not possible to include in the label of the primary packaging the information

mentioned in the points a) a e) of the preceding paragraph shall be provided on a sheet

separate that accompanies the primary packaging.

1.7. Labelling of the transport container-If the tissues or cells are transported

by an intermediary, the transport containers must contain on the respective labels,

at least the following elements:

a) The mention: "TISSUES AND CELLS" and "HANDLE WITH CARE";

b) Identification of the establishment from which the packaging is transported

(address and telephone number) and the name of the person to be contacted in case of

problems;

c) Identification of the tissue bank and target cells (address and number of

telephone) and person to contact for the receipt of the container;

d) Date and time of the start of the transport;

e) Specifications relating to transport conditions that are important for the

quality and safety of tissues and cells;

f) In the case of all cellular products, the following mention should be included:

"NOT IRRADIATE"; and

g) If one lears that a product is positive to a marker of an infectious disease

relevant, the mention should be included: "BIOLOGICAL DANGER";

h) In the case of donors for autologous purposes, the following mention should be included:

"ONLY FOR AUTOLOGOUS PURPOSES";

i) Specifications relating to storage conditions, such as " NO

FREEZE ".

2. Reception of tissues or cells in the tissue bank and cells:

2.1. When tissues or cells arrive at the tissue and cell bank, they must proceed to the

62

verification and documenting that the shipment, including the conditions of carriage, the

packaging, labeling and associated documentation and samples, respect the requirements

of this Annex and the specifications of the receiver service.

2.2. Each tissue and cell bank must ensure that the tissues and cells received

are quarantined until they are inspected or checked, as well as the

respective documentation, in compliance with the requirements. The analysis of the information

relevant relating to the donor and harvesting and, therefore, to the acceptance of the donation,

shall be carried out by authorised persons.

2.3. Each tissue and cell bank must have a policy and specifications

documented, which will serve as a comparison term when checking each

shipment of tissues and cells, including samples. Of them must appear technical requirements and

other criteria that the tissue and cell bank considers essential for maintenance

of an acceptable quality.

2.3.1. The tissue and cell bank must have documented procedures for the

management and separation of non-compliant consignments or for which it is not available

of results of complete analyses, in order to ensure the non-risk of

contaminate other tissues and cells that are being processed, preserved or

stored.

2.4. The data that is to be recorded in the tissue and cell bank, except in the case of

reproductive cell donors intended for donations between partners, include the following

elements:

a) Consent or consent, including the possible uses of the subject fabrics and

cells (such as therapeutic or research purposes, or both) and all instructions

specific for disposal, should the tissue or cells not be used for the

purposes for which consent has been obtained;

b) All records required in relation to the harvesting and the antecedents of the donor,

as described in paragraph 1.4. of this Annex.

c) Results of the physical examination, laboratory or other analyses, such as the

autopsy report, if it has been used in accordance with paragraph 1.2.2.

of this Annex;

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d) In the case of donors for allogeneic purposes, correctly documented analysis of the

full assessment of the donor, depending on the selection criteria, by a person

authorized and formed;

e) In the case of cell cultures intended for use for autologous purposes,

documentation of the eventuality of the recipient being allergic to medicines.

2.5. In the case of reproductive cells intended for donations between partners, the data that

are to be recorded in the tissue bank and cells include the following elements:

a) Consent or consent, including the possible uses of the subject fabrics and

cells, such as for reproductive purposes only or for therapeutic or

research, and all specific instructions for disposal, if the tissue or the

cells are not used for the purposes for which you obtained the

consent;

b) Identification and characteristics of the donor: type of donor, age, sex and presence of

risk factors;

c) Identification of the partner;

d) Location of the harvest;

e) Tissues and cells obtained and relevant characteristics.

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ANNEX IX

System of Biovigilance

FACT SHEET FOR BIOVIGILANCE

INCIDENTS

WHO DECLARES: DATA______/______/________

SERVIÇO______________________________________________

INSTITUITION______________________________________

COORDINATION______________________________

1. PERSON WHO NOTIFIES

1.1 Identification 1.2 contacts

Name Telephone

Mobile Phone Cargo

Fax Service

And mail

Address

2. Tecido, cells, organ or other related product

2.1 Nature of the graft or the product put in contact with the graft

Tissue Organ

Related Product Cell

2.2. # of identification (reference, Lot)

3. Description of the incident

3.1 Date of detection of the incident ___________/_________/______

65

3.2 Type of incident. Description

3.3Classificação of the incident

Phase in which

occurred the

incident

CAUSE OF THE INCIDENT

Lack of

documentaç

on

Deficit

From

Identifies

tion

Failure in the

equipamen

to

Failure

in

material

Error

Human

the

Other

(specify)

Selection of the donor

Harvest

Analyses

Laboratory

Transport

Processing

Storage

Distribution

Other

(specify)

4. Analyses. Corrective and preventive actions

4.1 Investigations and 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 Subscription of who filed this fact sheet

67

FACT SHEET FOR BIOVIGILANCE

ADVERSE REACTIONS

WHO DECLARES: DATA______/______/________

SERVIÇO______________________________________________

INSTITUITION______________________________________

COORDINATION______________________________

1. PERSON WHO NOTIFIES

1.1 Identification 1.2 contacts

Name Telephone

Mobile Phone Cargo

Fax Service

And mail

Address

2. Tecido, cells, organ or other related product

2.1 Nature of the graft or the product put in contact with the graft

Tissue Organ

Related Product Cell

2.2. # of identification (reference, Lot)

3. Utente affected (Dador or Receiver)

3.1 Dador (Identification Code)

3.1.1 Dator Type: Autologo Sim_______Nion_______

3.1.2 Gender H_____ M______ 3.1.3Data of Birth _____/_____/____

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3.1.4 Date of Colheita______/______/____ 3.1.5 Institution Colheita_______________

3.2 Receiver (Identification Code)

3.2.1 Gender H_____ M______ 3.2.2Data of Birth _____/_____/____

3.2.3 Date of

Transplante_____/_____/____

3.2.4 Surgeon responsible for the Implant

3.1.1 Service and Institution where the transplant performed

4. Description of the Adverse Reaction

4.1 The detection date of the Reaction Adversa___________/_________/______

4.2. Type of Reaction Adverse. (transmission of viral or bacterial infection, parasitic, tumor,

by ex.) Description

4.3. Effective or possible consequences. Research and final conclusions

4.3.1 Severity

1 percent (full recovery) 3 percent graduated (Sequels Graves)

2 percent (minor Sequels) 4 percent (Death)

4.3.2 Imputability

Not avaliable

0 (Deleted) thereof

1 (Improbable) thereof

2 (Possible)

3 (Provably)

4 (Certa)

5. Corrective and Preventive Actions

69

5.1. Description of Applied Measures

5.2 Other Coordinators Informed

Don't _______ Yes _______Precision Which

5.3 Other Responsible Persons

Don't _______ Yes _______Precision Which

5.4 Other Informed Transforming Teams

Don't _______ Yes _______Precision Which

4.3 Date of Communication ________/________/__________

4.4 Entity to whom the Communication was made

Date and Subscription of who filed this fact sheet

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ANNEX X

Information on the minimum data about the donor / receiver to be kept,

as required in Article 8 para.

A. By harvesting units and tissue and cell banks

Identification of the donor

Identification of the donation that will include at least:

-Identification of the harvesting organism or the tissue bank and cells

-Single number of identification of donations

-Date of harvest

-Place of harvest

-Type of donation (for example, a tissue or various tissues; autologous or allogeneic;

living donors or dead donors)

Identification of the product that will include at least:

-Identification of tissue bank and cells

-Type of tissue based product / cells (basic nomenclature)

-Number of the pool (if applicable)

-Number of fractionation (if applicable)

-Date of validity

-Status of tissues or cells (e.g., in quarantine, suitable for use,

etc.)

-Description and origin of products, steps of applied processing, materials and

additives that came into contact with the tissues and cells and which influence their

quality and / or safety

-Identification of the installation that issues the final label

Identification of application in human beings that will include at least:

-Date of distribution or elimination

-Identification of the Clinic or end user / Installation

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B. By The Services responsible for the application of tissues and cells in human beings

a) Identification of the tissue bank and cells or harvesting units

suppliers.

b) Identification of the Clinic or end user / Installation

c) Type of tissues and cells

d) Identification of the product

e) Identification of the receiver

f) Date of application

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ANNEX XI

Information contained in the European coding system

( a ) Identification of donations:

-Single number of identification

-Identification of tissue bank and cells

( b ) Identification of the product:

-Product code (basic nomenclature)

-Number of fractionation (if applicable)

-Date of validity