EN Official Journal of the European Union L 93/56

COMMISSION DIRECTIVE (EU) 2015/566

of 8 April 2015

implementing Directive 2004/23/EC as regards the procedures for verifying the equivalent standards of quality and safety of imported tissues and cells

(Text with EEA relevance)

THE EUROPEAN COMMISSION,

Having regard to the Treaty on the Functioning of the European Union,

Having regard to Directive 2004/23/EC of the European Parliament and of the Council of 31 March 2004 on setting standards of quality and safety for the donation, procurement, testing, processing, preservation, storage and distribution of human tissues and cells (1), and in particular Article 9(4) thereof,

Whereas:

(1) Directive 2004/23/EC lays down standards of quality and safety for the donation, procurement, testing, processing, preservation, storage and distribution of all human tissues and cells intended for human application, and for the donation, procurement, and testing of human tissues and cells contained in manufactured products intended for human application where those products are covered by other Union legislation, so as to ensure a high level of human health protection in the Union.

(2) Exchanges of tissues and cells increasingly take place on a worldwide basis and Directive 2004/23/EC therefore requires that imports of tissues and cells are undertaken by tissue establishments accredited, designated, authorised or licensed by Member States for that purpose. Exceptions to that requirement are laid down in Article 9(3) of Directive 2004/23/EC allowing competent authorities to directly authorise the import of specific tissues and cells under the conditions laid down in Article 6 of Commission Directive 2006/17/EC (2) or in case of emergency. These exceptions are regularly used, but not limited to, allowing the import of haematopoietic stem cells from bone marrow, peripheral blood or cord blood which is used in the treatment of a number of life-threatening conditions.

(3) Directive 2004/23/EC, furthermore, requires Member States and importing tissue establishments to ensure that imports of tissue and cells meet standards of quality and safety equivalent to the ones laid down in Directive 2004/23/EC and calls for the establishment of procedures to verify the equivalency of the quality and safety standards of imports of tissues and cells. Those procedures should be laid down in this Directive without prejudice to the Union legislation on customs.

(4) In particular, it is appropriate to establish authorisation and inspection schemes mirroring the verification process in place for activities related to tissues and cells carried out within the Union. It is also appropriate to lay down the procedures to be followed by importing tissue establishments in their relations with their third country suppliers.

(5) With the exception of imports directly authorised by competent authorities pursuant to Article 9(3) of Directive 2004/23/EC, all imports of tissues and cells from third countries must be undertaken by importing tissue establishments. Where competent authorities do directly authorise imports pursuant to Article 9(3) of Directive 2004/23/EC, the responsibility to ensure that such imports meet quality and safety standards equivalent to those laid down in that Directive falls upon the competent authorities.

(6) Tissues and cells should normally be imported by tissue banks or units of hospitals which are accredited, designated, authorised or licensed as importing tissue establishments for the purpose of their import activities. Tissue banks or units of hospitals should be considered to be importing tissue establishments where they are a party to a contractual agreement with a third country supplier for the import of tissues and cells. Where an organisation offering brokerage services is a party to a contractual agreement with a third country supplier to facilitate the import of tissues and cells but not for the import itself, it should not be considered to be an importing tissue establishment. Member States may choose to regulate such services outside the scope of this Directive.

(7) Where other bodies such as organisations responsible for human application, manufacturers of advanced therapy medicinal products, clinical practitioners or individuals are a party to a contractual agreement with a third country supplier for the import of tissues and cells, they should be considered to be an importing tissue establishment. They must comply with the requirements of this Directive as well as with all relevant provisions of Directive 2004/23/EC and be accredited, designated, authorised or licensed as importing tissue establishments for the purpose of their import activities by their relevant competent authorities. Where, subsequent to the import, they also undertake testing, processing, preservation, storage or distribution of the imported tissues and cells they must also be accredited, designated, authorised or licensed by their relevant competent authorities for the purpose of those activities and comply with the requirements of Directive 2004/23/EC. Alternatively they may obtain tissues and cells originating from third countries from tissue banks or units of hospitals located within the Union which are accredited, designated, authorised or licensed as importing tissue establishments by their relevant competent authorities.

(8) Where importing tissue establishments are also accredited, designated, authorised or licensed as tissue establishments for the activities they carry out within the Union, Member States may align their authorisation, inspection and reporting procedures provided the procedures laid down in this Directive are followed.

(9) In order to facilitate the distribution within the Union of imported tissues and cells including where such distribution is cross-border in nature, the competent authority or authorities should issue the certificate attesting the accreditation, designation, authorisation, or licence of the importing tissue establishment.

(10) Inspection measures play an important role in the verification of the equivalency of imported tissues and cells with the quality and safety standards laid down in Directive 2004/23/EC. Member States are therefore encouraged, where appropriate to also inspect third country suppliers and cooperate with other Member States into which imported tissues and cells are likely to be distributed. Member States in which the importing tissue establishments are located retain the responsibility for deciding on the most appropriate measures to be undertaken and for decisions on whether on-site inspections of third country suppliers are needed.

(11) The Operational Manual for Competent Authorities on inspections has been updated to take into account inspections of importing tissue establishments and their third country suppliers and is available to Member States as a guidance document when undertaking such inspection measures.

(12) Importing tissue establishments should verify that the standards of quality and safety of the tissues and cells they import into the Union are equivalent to the standards of quality and safety laid down in Directive 2004/23/EC. Written agreements with third country suppliers and the documentation to be provided and made available to competent authorities are key elements in ensuring such verification takes place and in particular providing traceability back to the donor and ensuring that the principle of voluntary and unpaid donation is adhered to in line with Directive 2004/23/EC. Importing tissue establishments are also encouraged to audit their third country suppliers as part of this verification process.

(13) Importing tissue establishments should ensure that the Single European Code is applied to imported tissues and cells in line with Commission Directive 2006/86/EC (3), either by carrying out this task themselves or delegating it to third country suppliers as part of the terms of their written agreements with such suppliers.

(14) Member States should be allowed to exempt one-off imports from the requirements laid down in this Directive in respect of documentation and written agreements. Such one-off imports should, however, be carried out by accredited, designated, authorised or licensed importing tissue establishments and as a general rule should not take place on a regular or repeated basis from the same third country supplier. The use of such exemptions should be limited to situations where a person or persons has or have had tissues and cells stored in a third country for their future use, in particular in cases of partner donations of reproductive cells, of autologous donations, or donations directed to close relatives, and subsequently, wishes to have such tissues or cells imported into the Union on their behalf. Such an import of any specific type of tissue or cell should normally not occur more than once for any given recipient and should not include tissues or cells for third parties.

(15) This Directive does not prevent Member States from maintaining or introducing more stringent measures relating to imports of tissues and cells, in particular in order to ensure the principle of voluntary and unpaid donation is respected, provided that the provisions of the Treaty are met.

(16) The measures provided for in this Directive are in accordance with the opinion of the Tissues and Cells Regulatory Committee established by Article 29(3) of Directive 2004/23/EC,

HAS ADOPTED THIS DIRECTIVE:

CHAPTER I

GENERAL PROVISIONS

Article 1

Scope

1. This Directive shall apply to the import into the Union of:

(a) human tissues and cells intended for human application; and

(b) manufactured products derived from human tissues and cells intended for human applications, where those products are not covered by other Union legislation.

2. Where the human tissues and cells to be imported are intended to be used exclusively in manufactured products which are covered by other Union legislation, this Directive shall only apply to the donation, procurement and testing which takes place outside of the Union as well as to contributing to ensuring traceability from donor to recipient and vice versa.

3. This Directive shall not apply to:

(a) the import of tissues and cells referred to in Article 9(3)(a) of Directive 2004/23/EC which are directly authorised by the competent authority or authorities;

(b) the import of tissues and cells referred to in Article 9(3)(b) of Directive 2004/23/EC which are directly authorised in case of emergencies;

(c) blood and blood components as defined by Directive 2002/98/EC;

(d) organs or parts of organs, as defined in Directive 2004/23/EC.

Article 2

Definitions

For the purposes of this Directive, the following definitions apply:

(a) ‘emergency’ means any unforeseen situation in which there is no practical alternative other than to urgently import tissues and cells from a third country into the Union for immediate application to a known recipient or known recipients whose health would be seriously endangered without such an import;

(b) ‘importing tissue establishment’ means a tissue bank or a unit of a hospital or another body established within the Union which is a party to a contractual agreement with a third country supplier for the import into the Union of tissues and cells coming from a third country intended for human application;

(c) ‘one-off import’ means the import of any specific type of tissue or cell which is for the personal use of an intended recipient or recipients known to the importing tissue establishment and the third country supplier before the importation occurs. Such an import of any specific type of tissue or cell shall normally not occur more than once for any given recipient. Imports from the same third country supplier taking place on a regular or repeated basis shall not be considered to be ‘one-off imports’;

(d) ‘third country supplier’ means a tissue establishment or another body, established in a third country, which is responsible for the export to the Union of tissues and cells it supplies to an importing tissue establishment. A third country supplier may also carry out one or more of the activities, which take place outside of the Union, of donation, procurement, testing, processing, preservation, storage or distribution of tissues and cells imported into the Union.

CHAPTER II

OBLIGATIONS ON MEMBER STATES' AUTHORITIES

Article 3

Accreditation, designation, authorisation or licensing of importing tissue establishments

1. Without prejudice to Article 1(3), Member States shall ensure that all imports of tissues and cells from third countries are undertaken by importing tissue establishments accredited, designated, authorised or licensed by a competent authority or authorities for the purposes of these activities.

2. The competent authority or authorities, having obtained the information set out in Annex I to this Directive and, having verified that the importing tissue establishment complies with the requirements of this Directive, shall accredit, designate, authorise or license the importing tissue establishment to import tissues and cells and indicate any conditions which apply such as any restrictions of the types of tissues and cells to be imported or the third country suppliers to be used. The competent authority or authorities shall issue the accredited, designated, authorised or licensed importing tissue establishment with the certificate set out in Annex II to this Directive.

3. The importing tissue establishment shall not undertake any substantial changes to its import activities without the prior written approval of the competent authority or authorities. In particular, any changes to the type of tissues and cells imported, the activities undertaken in third countries which may have an influence on the quality and safety of imported tissues and cells or the third country suppliers used shall be considered as substantial changes. Where an importing tissue establishment undertakes a one-off import of tissues or cells originating from a third country supplier not covered by its existing accreditation, designation, authorisation or licence, such an import shall not be considered as a substantial change if the importing tissue establishment is authorised to import the same type of tissues or cells from another third country supplier or suppliers.

4. The competent authority or authorities may suspend or revoke the accreditation, designation, authorisation, or licence, in part or in full, of an importing tissue establishment if, in particular, inspections or other control measures demonstrate that such an establishment no longer meets the requirements of this Directive.

Article 4

Inspections and other control measures

1. Member States shall ensure that the competent authority or authorities organise inspections and other control measures of importing tissue establishments and, where appropriate, their third country suppliers and that importing tissue establishments carry out appropriate controls in order to ensure the equivalency of the quality and safety standards of the tissues and cells to be imported with the standards laid down in Directive 2004/23/EC. The interval between inspections of any given importing tissue establishment shall not exceed 2 years.

2. Such inspections shall be carried out by officials representing the competent authority or authorities who shall:

(a) be empowered to inspect importing tissue establishments and, where appropriate, the activities of any third country suppliers;

(b) evaluate and verify the procedures and activities carried out in importing tissue establishments and the facilities of third country suppliers that are relevant to ensuring the equivalency of the quality and safety standards of the tissues and cells to be imported with the standards laid down in Directive 2004/23/EC;

(c) examine any documents or other records that are relevant for this evaluation and verification.

3. Member States shall, upon a duly justified request from another Member State or the Commission, provide information on the results of inspections and other control measures relating to importing tissue establishments and third country suppliers.

4. Member States into which tissues and cells are imported shall, upon a duly justified request from another Member State into which imported tissues and cells are subsequently distributed, consider carrying out inspections or other control measures on importing tissue establishments and the activities of any third country suppliers. The Member State in which the importing tissue establishment is located shall decide on the appropriate measures to take following consultation with the Member State which made such a request.

5. Where an on-site inspection takes place following such a request, the competent authority or authorities of the Member State in which the importing tissue establishment is located shall agree with the competent authority or authorities of the Member State which made such a request on whether and how the Member State which made such a request shall participate in the inspection. The final decision on any such participation shall rest with the Member State in which the importing tissue establishment is located. The reasons for any decision to refuse such participation shall be explained to the Member State which made such a request.

CHAPTER III

OBLIGATIONS ON IMPORTING TISSUE ESTABLISHMENTS

Article 5

Applications for accreditation, designation, authorisation or licensing as an importing tissue establishment

1. Importing tissue establishments, having taken measures to ensure that any imports of tissues and cells meet standards of quality and safety equivalent to the ones laid down in Directive 2004/23/EC and that imported tissues and cells can be traced from the donor to the recipient and vice versa, shall apply for an accreditation, designation, authorisation or licence as an importing tissue establishment by:

(a) providing to the competent authority or authorities the required information and documentation as set out in Annex I to this Directive;

(b) making available and, when requested by the competent authority or authorities, providing the documentation listed in Annex III to this Directive.

2. Member States may choose to not apply the documentation requirements of Annex I, part F and Annex III to this Directive to one-off imports as defined in Article 2 of this Directive, provided they have suitable national measures in place to regulate such imports. Those national measures shall ensure the following:

(a) traceability from donor to recipient and vice versa; and

(b) imported tissues and cells are not applied to anyone other than their intended recipients.

Article 6

Updated information

1. Importing tissue establishments shall seek the prior written approval of the competent authority or authorities for any planned substantial changes to their import activities, and in particular those substantial changes described in Article 3(3), and inform the competent authority or authorities of their decision to cease their import activities in part or in full.

2. Importing tissue establishments shall notify, without delay, the competent authority or authorities of any suspected or actual serious adverse events or reactions, reported to them by third country suppliers and which may influence the quality and safety of the tissues and cells they import. The information laid out in Annexes III and IV to Directive 2006/86/EC shall be included in such notifications.

3. The importing tissue establishment shall notify, without delay, the competent authority or authorities of:

(a) any revocation or suspension, in part or full, of a third country supplier's authorisation to export tissues and cells; and

(b) any other decision taken for reasons of non-compliance by the competent authority or authorities of the country in which the third country supplier is based and which may be relevant to the quality and safety of imported tissues and cells.

Article 7

Written agreements

1. Importing tissue establishments shall have in place written agreements with third country suppliers where any of the activities of donation, procurement, testing, processing, preservation, storage or export to the Union of tissues and cells to be imported into the Union are carried out outside of the Union.

Member States may choose to not apply this requirement to one-off imports as defined in Article 2 of this Directive, provided they have suitable national measures in place to regulate such an imports. Those national measures shall ensure the following:

(a) traceability from donor to recipient and vice versa; and

(b) imported tissues and cells are not applied to anyone other than their intended recipients.

2. The written agreement between the importing tissue establishment and the third country supplier shall specify the quality and safety requirements to be met to ensure the equivalency of the quality and safety standards of the tissues and cells to be imported with the standards laid down in Directive 2004/23/EC. In particular, the written agreement shall include, as a minimum, the contents listed in Annex IV to this Directive.

3. The written agreement shall establish the right of the competent authority or authorities to inspect the activities, including the facilities, of any third country suppliers during the duration of the written agreement and for a period of 2 years following its termination.

4. Importing tissue establishments shall provide copies of written agreements with third country suppliers to the competent authority or authorities as part of their application for accreditation, designation, authorisation or licensing.

Article 8

Register of importing tissue establishments

1. Importing tissue establishments shall keep a record of their activities, including the types and quantities of tissues and cells imported, and on their origin and destination. This record shall also include the same information for any one-off imports carried out. The annual report referred to in Article 10(1) of Directive 2004/23/EC shall include information about those activities.

2. The competent authority or authorities shall include importing tissue establishments in the publicly accessible register of tissue establishments laid down in Article 10(2) of Directive 2004/23/EC.

3. Information on the accreditations, designations, authorisations or licences of importing tissue establishments shall also be made available through the network of registers referred to in Article 10(3) of Directive 2004/23/EC.

CHAPTER IV

FINAL PROVISIONS

Article 9

Transposition

1. Member States shall adopt and publish the laws, regulations and administrative provisions necessary to comply with this Directive by 29 October 2016 at the latest. They shall forthwith communicate to the Commission the text of those provisions.

They shall apply those provisions from 29 April 2017.

When Member States adopt those provisions, they shall contain a reference to this Directive or be accompanied by such a reference on the occasion of their official publication. Member States shall determine how such reference is to be made.

2. Member States shall communicate to the Commission the text of the main provisions of national law which they adopt in the field covered by this Directive.

Article 10

Entry into force

This Directive shall enter into force on the twentieth day following that of its publication in the Official Journal of the European Union.

Article 11

Addresses

This Directive is addressed to the Member States.

Done at Brussels, 8 April 2015. For the Commission The President Jean-Claude JUNCKER

(1) OJ L 102, 7.4.2004, p. 48.

(2) Commission Directive 2006/17/EC of 8 February 2006 implementing Directive 2004/23/EC of the European Parliament and of the Council as regards certain technical requirements for the donation, procurement and testing of human tissues and cells (OJ L 38, 9.2.2006, p. 40.)

(3) Commission Directive 2006/86/EC of 24 October 2006 implementing Directive 2004/23/EC of the European Parliament and of the Council as regards traceability requirements, notification of serious adverse reactions and events and certain technical requirements for the coding, processing, preservation, storage and distribution of human tissues and cells (OJ L 294, 25.10.2006, p. 32.)

ANNEX I Minimum requirements concerning the information and documentation to be provided by importing tissue establishment applicants when applying to be accredited, designated, authorised or licensed for the purpose of import activities When applying for an accreditation, designation, authorisation or licence for the purpose of import activities, the importing tissue establishment applicant shall, unless already provided as part of previous applications for accreditation, designation, authorisation or licensing as a tissue establishment or importing tissue establishment, provide the most up-to-date information and, for part F, documentation on the following: A. General Information on the Importing Tissue Establishment (ITE) 1. Name of the ITE (Company name). 2. Visiting address of the ITE. 3. Postal address of the ITE (if different). 4. Status of the applicant ITE: It should be indicated if this is the first application for accreditation, designation, authorisation or licensing as an ITE or, where applicable, whether this is a renewal application. Where the applicant is already accredited, designated, authorised or licensed as a tissue establishment, the TE compendium code should be provided. 5. Name of the applying unit (if different from the company name). 6. Visiting address of the applying unit. 7. Postal address of the applying unit (if different). 8. Name of the site of reception of imports (if different from the company name and applying unit). 9. Visiting address of the site of reception. 10. Postal address of the site of reception (if different). B. Contact Details for the Application 1. Name of contact person for the application. 2. Telephone number. 3. E-mail address. 4. Name of Responsible Person (if different from contact person). 5. Telephone number. 6. E-mail address. 7. URL of ITE website (if available). C. Details of Tissues and Cells to be Imported 1. A list of the types of tissues and cells to be imported, including one-off imports of specific types of tissues or cells. 2. The product name (where applicable, in accordance with the EU generic list) of all types of tissues and cells to be imported. 3. The trade name (if different to the product name) of all types of tissues and cells to be imported. 4. The name of the third country supplier for each type of tissue and cell to be imported. D. Location of Activities 1. A list specifying which of the activities of donation, procurement, testing, processing, preservation or storage are carried out prior to import by the third country supplier per type of tissue or cell. 2. A list specifying which of the activities of donation, procurement, testing, processing, preservation or storage are carried out prior to import by sub-contractors of the third country supplier per type of tissue or cell. 3. A list of all activities carried out by the ITE subsequent to import per type of tissue or cell. 4. The names of the third countries in which the activities prior to import take place per type of tissue or cell. E. Details of Third Country Suppliers 1. Name of third country supplier(s) (company name). 2. Name of contact person. 3. Visiting address. 4. Postal address (if different). 5. Telephone number including international dialling code. 6. Emergency contact number (if different) 7. E-mail address. F. Documentation to Accompany the Application 1. A copy of the written agreement with the third country supplier(s). 2. A detailed description of the flow of imported tissues and cells from their procurement to their reception at the importing tissue establishment. 3. A copy of the third country supplier's export authorisation certificate or, where a specific export authorisation certificate is not issued, certification from the relevant third country competent authority or authorities authorising the third country supplier's activities in the tissue and cells sector including exports. This documentation shall also include the contact details of the third country competent authority or authorities. In third countries where such documentation is not available, alternative forms of documentation shall be provided such as reports of audits of the third country supplier.

ANNEX II Certificate of Accreditation, Designation, Authorisation or Licence to be issued by the competent authority or authorities to importing tissue establishments

ANNEX III Minimum requirements concerning the documentation to be made available to the competent authority or authorities by tissue establishments intending to import tissues and cells from third countries With the exception of one-off imports as defined in Article 2 of this Directive which have been exempted from these documentation requirements, the applicant importing tissue establishment shall make available and, unless already provided as part of previous applications for accreditation, designation, authorisation or licensing as an importing tissue establishment or tissue establishment, shall provide when requested by the competent authority or authorities the most up-to-date version of the following documents regarding the applicant and its third country supplier(s). A. Documentation relating to the importing tissue establishment 1. A job description of the Responsible Person and details of his/her relevant qualifications and training record as laid down in Directive 2004/23/EC; 2. A copy of the primary label, repackage label, external package and transport container; 3. A list of relevant and up-to-date versions of standard operating procedures (SOPs) relating to the establishment's import activities including SOPs on applying the Single European Code, reception and storage of imported tissues and cells at the importing tissue establishment, management of adverse events and reactions, management of recalls and traceability from donor to recipient. B. Documentation relating to the third country supplier or suppliers 1. A detailed description of the criteria used for donor identification and evaluation, information provided to the donor or donor family, how consent is obtained from the donor or donor family and whether the donation was voluntary and unpaid or not; 2. Detailed information on the testing centre(s) used by third country suppliers and the tests performed by such centres; 3. Detailed information on the methods used during the processing of the tissues and cells including details of the validation for the critical processing procedure; 4. A detailed description of the facilities, critical equipment and materials and criteria used for quality control and control of the environment for each activity carried out by the third country supplier; 5. Detailed information on the conditions for release of tissues and cells by the third country supplier or suppliers; 6. Details of any sub-contractors used by the third country suppliers including the name, location and activity undertaken; 7. A summary of the most recent inspection of the third country supplier by the third country competent authority or authorities including the date of the inspection, type of inspection and main conclusions; 8. A summary of the most recent audit of the third country supplier carried out by, or on behalf of, the importing tissue establishment; 9. Any relevant national or international accreditation.