Commission Directive 2006/86/ECShow full title

ANNEX I Requirements for accreditation, designation, authorisation or licensing of tissue establishments as referred to in Article 3

A. ORGANISATION AND MANAGEMENT

1. A responsible person must be appointed having qualifications and responsibilities as provided in Article 17 of Directive 2004/23/EC.

2. A tissue establishment must have an organisational structure and operational procedures appropriate to the activities for which accreditation/designation/authorisation/licensing is sought; there must be an organisational chart which clearly defines accountability and reporting relationships.

3. Every tissue establishment must have access to a nominated medical registered practitioner to advise on and oversee the establishment’s medical activities such as donor selection, review of clinical outcomes of applied tissues and cells or interaction as appropriate with clinical users.

4. There must be a documented quality management system applied to the activities for which accreditation/designation/authorisation or licensing is sought, in accordance with the standards laid down in this Directive.

5. It must be ensured that the risks inherent in the use and handling of biological material are identified and minimised, consistent with maintaining adequate quality and safety for the intended purpose of the tissues and cells. The risks include those relating in particular to the procedures, environment, staff health status specific to the tissue establishment.

6. Agreements between tissue establishments and third parties must comply with Article 24 of Directive 2004/23/EC. Third party agreements must specify the terms of the relationship and responsibilities as well as the protocols to be followed to meet the required performance specification.

7. There must be a documented system in place, supervised by the responsible person, for ratifying that tissues and/or cells meet appropriate specifications for safety and quality for release and for their distribution.

8. In the event of termination of activities the agreements concluded and the procedures adopted in accordance with Article 21(5) of Directive 2004/23/EC shall include traceability data and material concerning the quality and safety of cells and tissues.

9. There must be a documented system in place that ensures the identification of every unit of tissue or cells at all stages of the activities for which accreditation/designation/authorisation/licensing is sought.

B. PERSONNEL

1. The personnel in tissue establishments must be available in sufficient number and be qualified for the tasks they perform. The competency of the personnel must be evaluated at appropriate intervals specified in the quality system.

2. All personnel should have clear, documented and up-to-date job descriptions. Their tasks, responsibilities and accountability must be clearly documented and understood.

3. Personnel must be provided with initial/basic training, updated training as required when procedures change or scientific knowledge develops and adequate opportunities for relevant professional development. The training programme must ensure and document that each individual:

(a)

has demonstrated competence in the performance of their designated tasks;

(b)

has an adequate knowledge and understanding of the scientific/technical processes and principles relevant to their designated tasks;

(c)

understands the organisational framework, quality system and health and safety rules of the establishment in which they work, and

(d)

is adequately informed of the broader ethical, legal and regulatory context of their work.

C. EQUIPMENT AND MATERIALS

1. All equipment and material must be designed and maintained to suit its intended purpose and must minimise any hazard to recipients and/or staff.

2. All critical equipment and technical devices must be identified and validated, regularly inspected and preventively maintained in accordance with the manufacturers' instructions. Where equipment or materials affect critical processing or storage parameters (e.g. temperature, pressure, particle counts, microbial contamination levels), they must be identified and must be the subject of appropriate monitoring, alerts, alarms and corrective action, as required, to detect malfunctions and defects and to ensure that the critical parameters are maintained within acceptable limits at all times. All equipment with a critical measuring function must be calibrated against a traceable standard if available.

3. New and repaired equipment must be tested when installed and must be validated before use. Test results must be documented.

4. Maintenance, servicing, cleaning, disinfection and sanitation of all critical equipment must be performed regularly and recorded accordingly.

5. Procedures for the operation of each piece of critical equipment, detailing the action to be taken in the event of malfunctions or failure, must be available.

6. The procedures for the activities for which accreditation/designation/authorisation/licensing is sought, must detail the specifications for all critical materials and reagents. In particular, specifications for additives (e.g. solutions) and packaging materials must be defined. Critical reagents and materials must meet documented requirements and specifications and when applicable the requirements of Council Directive 93/42/EEC of 14 June 1993 concerning medical devices(1) and Directive 98/79/EC of the European Parliament and of the Council of 27 October 1998 on in vitro diagnostic medical devices(2).

D. FACILITIES/PREMISES

1. A tissue establishment must have suitable facilities to carry out the activities for which accreditation/designation/authorisation or licensing is sought, in accordance with the standards laid down in this Directive.

2. When these activities include processing of tissues and cells while exposed to the environment, this must take place in an environment with specified air quality and cleanliness in order to minimise the risk of contamination, including cross-contamination between donations. The effectiveness of these measures must be validated and monitored.

3. Unless otherwise specified in point 4, where tissues or cells are exposed to the environment during processing, without a subsequent microbial inactivation process, an air quality with particle counts and microbial colony counts equivalent to those of Grade A as defined in the current European Guide to Good Manufacturing Practice (GMP), Annex 1 and Directive 2003/94/EC is required with a background environment appropriate for the processing of the tissue/cell concerned but at least equivalent to GMP Grade D in terms of particles and microbial counts.

4. A less stringent environment than specified in point 3 may be acceptable where:

(a)

a validated microbial inactivation or validated terminal sterilisation process is applied;

(b)

or, where it is demonstrated that exposure in a Grade A environment has a detrimental effect on the required properties of the tissue or cell concerned;

(c)

or, where it is demonstrated that the mode and route of application of the tissue or cell to the recipient implies a significantly lower risk of transmitting bacterial or fungal infection to the recipient than with cell and tissue transplantation;

(d)

or, where it is not technically possible to carry out the required process in a Grade A environment (for example, due to requirements for specific equipment in the processing area that is not fully compatible with Grade A).

5. In point 4(a), (b), (c) and (d), an environment must be specified. It must be demonstrated and documented that the chosen environment achieves the quality and safety required, at least taking into account the intended purpose, mode of application and immune status of the recipient. Appropriate garments and equipment for personal protection and hygiene must be provided in each relevant department of the tissue establishment along with written hygiene and gowning instructions.

6. When the activities for which accreditation/designation/authorisation or licensing is sought involve storage of tissues and cells, the storage conditions necessary to maintain the required tissue and cell properties, including relevant parameters such as temperature, humidity or air quality must be defined.

7. Critical parameters (e.g. temperature, humidity, air quality) must be controlled, monitored, and recorded to demonstrate compliance with the specified storage conditions.

8. Storage facilities must be provided that clearly separate and distinguish tissues and cells prior to release/in quarantine from those that are released and from those that are rejected, in order to prevent mix-up and cross-contamination between them. Physically separate areas or storage devices or secured segregation within the device must be allocated in both quarantine and released storage locations for holding certain tissue and cells collected in compliance with special criteria.

9. The tissue establishment must have written policies and procedures for controlled access, cleaning and maintenance, waste disposal and for the re-provision of services in an emergency situation.

E. DOCUMENTATION AND RECORDS

1. There must be a system in place that results in clearly defined and effective documentation, correct records and registers and authorised Standard Operating Procedures (SOPs), for the activities for which accreditation/designation/authorisation/licensing is sought. Documents must be regularly reviewed and must conform to the standards laid down in this Directive. The system must ensure that work performed is standardised, and that all steps are traceable; i.e. coding, donor eligibility, procurement, processing, preservation, storage, transport, distribution or disposal, including aspects relating to quality control and quality assurance.

2. For every critical activity, the materials, equipment and personnel involved must be identified and documented.

3. In the tissue establishments all changes to documents must be reviewed, dated, approved, documented and implemented promptly by authorised personnel.

4. A document control procedure must be established to provide for the history of document reviews and changes and to ensure that only current versions of documents are in use.

5. Records must be shown to be reliable and a true representation of the results.

6. Records must be legible and indelible and may be handwritten or transferred to another validated system, such as a computer or microfilm.

7. Without prejudice to Article 9(2), all records, including raw data, which are critical to the safety and quality of the tissues and cells shall be kept so as to ensure access to these data for at least 10 years after expiry date, clinical use or disposal.

8. Records must meet the confidentiality requirements laid down in Article 14 of Directive 2004/23/EC. Access to registers and data must be restricted to persons authorised by the responsible person, and to the competent authority for the purpose of inspection and control measures.

F. QUALITY REVIEW

1. An audit system must be in place for the activities for which accreditation/designation/authorisation/licensing is sought. Trained and competent persons must conduct the audit in an independent way, at least every two years, in order to verify compliance with the approved protocols and the regulatory requirements. Findings and corrective actions must be documented.

2. Deviations from the required standards of quality and safety must lead to documented investigations, which include a decision on possible corrective and preventive actions. The fate of non-conforming tissues and cells must be decided in accordance with written procedures supervised by the responsible person and recorded. All affected tissues and cells must be identified and accounted for.

3. Corrective actions must be documented, initiated and completed in a timely and effective manner. Preventive and corrective actions should be assessed for effectiveness after implementation.

4. The tissue establishment should have processes in place for review of the performance of the quality management system to ensure continuous and systematic improvement.

(1)

OJ L 169, 12.7.1993, p. 1. Directive as last amended by Regulation (EC) No 1882/2003 of the European Parliament and of the Council (OJ L 284, 31.10.2003, p. 1).

(2)

OJ L 331, 7.12.1998, p. 1. Directive as amended by Regulation (EC) No 1882/2003.