Regulation on the application of good manufacturing practice in the manufacture of medicinal products and active substances and on the application of good technical practice in the manufacture of products of human origin

Original Language Title: Verordnung über die Anwendung der Guten Herstellungspraxis bei der Herstellung von Arzneimitteln und Wirkstoffen und über die Anwendung der Guten fachlichen Praxis bei der Herstellung von Produkten menschlicher Herkunft

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Regulation on the application of good manufacturing practice in the manufacture of medicinal products and active substances and on the application of good technical practice in the manufacture of products of human origin (medicinal products and drugs) Active substance production regulation-AMWHV)

Unofficial table of contents

AMWHV

Date of completion: 03.11.2006

Full quote:

" Pharmaceutical and active substance manufacturing regulation of 3 November 2006 (BGBl. 2523), as last amended by Article 1 of the Regulation of 28 June 2008. October 2014 (BGBl. 1655).

Status: Last amended by Art. 1 V v. 28.10.2014 I 1655

For more details, please refer to the menu under Notes

Footnote

(+ + + Text evidence from: 10.11.2006 + + +) 
(+ + + Official note from the norm-provider on EC law:
Implementation of the
ERL 20/2001 (CELEX Nr: 301L0020)
EWGRL 412/91 (CELEX Nr: 391L0412)
ERL 82/2001 (CELEX Nr: 301L0082)
ERL 83/2001 (CELEX Nr: 301L0083)
ERL 94/2003 (CELEX Nr: 303L0094)
EGRL 33/2004 (CELEX Nr: 304L0033)
EGRL 23/2004 (CELEX Nr: 304L0023)
ERL 61/2005 (CELEX Nr: 305L0061)
ERL 62/2005 (CELEX Nr: 305L0062)
EWGRL 167/90 (CELEX Nr: 390L0167) + + +)

The V was defined as Article 1 of the V v. 3.11.2006 I 2523 by the Federal Ministries of Health and Food, Agriculture and Consumer Protection in agreement with the Federal Ministries of Economy and Technology, for Environment, Nature Conservation and Reactor safety, for health and with the consent of the Federal Council. She's gem. Art. 6 sentence 1 of this V entered into force on 10 November 2006.
This Regulation shall be used to implement the
-
Commission Directive 91 /412/EEC of 23 July 1991 laying down the principles and guidelines of good manufacturing practice for veterinary medicinal products (OJ L 327, 31.12.1991, p. EC No OJ L 228, p. 70),
-
Directive 2001 /20/EC of the European Parliament and of the Council of 4 April 2001 on the approximation of the laws, regulations and administrative provisions of the Member States relating to the application of good clinical practice in the conduct of clinical trials with Medicinal products for human use (OJ EC No L 121 p. 34),
-
Directive 2001 /82/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to veterinary medicinal products (OJ L 327, 30.12.2001, p. EC No 1), as amended by Directive 2004 /28/EC of the European Parliament and of the Council of 31 March 2004 (OJ L 311, 28.11.2004, p. EU No L 136 p. 58),
-
Directive 2001 /83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal products for human use (OJ L 311, 28.11.2001, p. EC No 67), as last amended by Directive 2004 /27/EC of the European Parliament and of the Council of 31 March 2004 (OJ L 311, 28.11.2004, p. EU No L 136 p. 34),
-
Commission Directive 2003 /94/EC of 8. October 2003 laying down the principles and guidelines of good manufacturing practice for medicinal products for human use and investigational medicinal products intended for human use (OJ L 327, 28.12.2003, p. EU No L 262 p. 22),
-
Commission Directive 2004 /33/EC of 22 March 2004 on the implementation of Directive 2002/98/EC of the European Parliament and of the Council as regards certain technical requirements for blood and blood components (OJ L 327, 30.4.2004, p. EU No L 91 p. 25),
-
Directive 2004 /23/EC of the European Parliament and of the Council of 31 March 2004 laying down quality and safety standards for the donation, procurement, testing, processing, preservation, storage and distribution of human tissues and cells (OJ EU No 102 p. 48),
-
Commission Directive 2005 /61/EC of 30 September 2005 on the implementation of Directive 2002/98/EC of the European Parliament and of the Council as regards requirements for traceability and notification of serious incidents and serious incidents Adverse reactions (OJ C 327, EU No 32),
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Commission Directive 2005 /62/EC of 30 September 2005 on the implementation of Directive 2002/98/EC of the European Parliament and of the Council as regards Community standards and specifications for a quality system for Blood establishments (OJ L 327, 30.4.2004 EU No L 256 p. 41),
-
Council Directive 90 /167/EEC of 28 March 1990 laying down the conditions for the production, placing on the market and use of medicated feedingstuffs in the Community (OJ No L 73, 27.3.1990, p. 1). EC No 42).
Unofficial table of contents

Content Summary

Section 1
Scope and definitions
§ 1 Scope
§ 2 Definitions
Section 2
General requirements
§ 3 Quality management system, good manufacturing practice and good professional practice
§ 4 Staff
§ 5 Operating rooms and equipment
§ 6 Hygiene measures
§ 7 Storage and transport
§ 8 Livestock farming
§ 9 Activities on behalf of
§ 10 General documentation
§ 11 Self-inspections and supplier qualification
Section 3
Medicinal products, blood products and other blood components and products of human origin
§ 12 Personnel in a leading position and in a responsible position
§ 13 Manufacture
§ 14 Audit
§ 15 Marking
§ 16 Marketing authorisation
§ 17 Marketing and imports
§ 18 Reset Pattern
§ 19 Complaints and recall
§ 20 Documentation retention
Section 4
Active substances not of human origin
Section 21 Organization Structure
Section 22 Manufacture
Section 23 Audit
§ 24 Marking
Section 25 Marketing authorisation
Section 26 Marketing and imports
§ 27 Reset Pattern
§ 28 Complaints and recall
§ 29 Documentation retention
Section 5
Special provisions
§ 30 Supplementary rules for medicated feedingstuffs
Section 31 Supplementary rules for blood establishments
Section 5a
Special requirements for removal and tissue establishments and for tissue laboratory laboratories
Section 32 Additional general requirements
§ 33 Determination of the suitability of the donor and laboratory tests required for the production
Section 34 Extraction of tissue by the removal device
§ 35 Transport to be used or processed and received in the tissue equipment
§ 36 Working or processing and storage by the tissue device
Section 37 Testing of tissue and tissue preparations
§ 38 Release by tissue equipment
§ 39 Placing on the market, importation and transport by tissue equipment
§ 40 Notification of serious adverse reactions and serious adverse events and recall
Section 41 Documentation retention
Section 6
Irregularities
§ 42 Irregularities
Section 7
Final provisions
Section 43 Transitional arrangements

Section 1
Scope and definitions

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§ 1 Scope

(1) This Regulation shall apply to establishments and establishments which:
1.
Medicinal products,
2.
active substances intended for the manufacture of medicinal products which are human or of animal or microbial origin or which are produced by genetic engineering;
2a.
Tissue within the meaning of § 1a No. 4 of the Transplantation Act as amended by the Notice of 4 September 2007 (BGBl. 2206),
3.
substances of human origin intended for the manufacture of medicinal products;
4.
Substances other than those referred to in paragraph 2 which are intended for the manufacture of medicinal products; or
5.
Substances other than those referred to in paragraph 3 and intended for the manufacture of medicinal products for human use, insofar as they are the subject of appropriate good manufacturing practice, in accordance with the guidelines of the European Commission pursuant to Article 47 (5) of Directive 2001 /83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal products for human use (OJ L 327, 30.12.2001, p. 67), as last amended by Directive 2011 /62/EU (OJ L 311, 28.11.2011, p. 74), which has been amended (auxiliary substances),
Manufacture, test, store, place on the market, place in or out of the scope of the Medicines Act, import or export. It shall also apply to persons who carry out these activities professionally. (1a) Section 3 of this Regulation shall not apply to the collection and tissue establishments and tissue establishments ' laboratories. (2) The Regulation shall also apply to:
1.
Pharmacies, the retail trade of medicinal products outside pharmacies, persons who are doctors or otherwise authorised to exercise the medicine in human beings, dentists, veterinarians, veterinary medicinal products and wholesalers of medicinal products, to the extent that: they require permission in accordance with § 13 or § 72 (1) of the German Medicines Act, and
2.
Pharmaceutical companies according to § 4 (18) of the Medicines Act,
3.
Establishments and establishments or persons acting with active substances for the manufacture of medicinal products intended for use in humans.
(3) The requirements of this Regulation shall not apply to:
1.
substances in accordance with the homeopathic pharmacopoeia which are used for the preparation of homeopathic preparations as starting materials,
2.
active substances which are or contain substances within the meaning of Article 3 (1), (2) or (3) of the Medicines Act, in so far as they are not subject to the requirements of the EC-GMP Guide,
3.
(dropped)
4.
(dropped)
5.
(dropped)
6.
Active substances for ectoparasitic agents for use in animals, and
7.
Active substances for medicinal products intended solely for use in pet animals in accordance with § 60 of the Medicines Act and which are approved for circulation outside pharmacies.
In the case of the first sentence, compliance with comparable standards and procedures shall ensure that the quality of manufacture and testing is equivalent to the requirements laid down in Sections 2 to 4. (4) The Regulation shall apply No application to establishments and facilities which require a permit pursuant to Section 72 (2) of the Medicines Act. The Regulation does not apply to persons and entities collecting medicinal products. (5) This Regulation does not apply to active substances, excipients and intermediates intended solely for the purpose of placing them in countries which do not Member States of the European Union or other States Parties to the Agreement on the European Economic Area shall be designated and under customs supervision and without manufacturing steps within the meaning of Article 46a (1) of the Directive 2001 /83/EC or Article 50a (1) of Directive 2001/82/EC Parliament and of the Council of 6 November 2001 on the establishment of a Community code relating to veterinary medicinal products (OJ L 327, 31.12.2001, p. EC No 1), as amended by Directive 2004 /28/EC of the European Parliament and of the Council of 31 March 2004 (OJ L 311, 28.11.2004, p. EU No (6) The provisions of the Implementing Regulation (EU) No 520/2012 of the European Parliament and of the Council of the European Parliament and of the Council of the European Parliament and of the Council of the European Union Commission of 19 June 2012 on the implementation of the pharmacovigilance activities provided for in Regulation (EC) No 726/2004 of the European Parliament and of the Council and of Directive 2001 /83/EC of the European Parliament and of the Council (OJ L 139, 30.4.2012, p. 5) shall remain unaffected. Unofficial table of contents

§ 2 Definitions

For the purposes of this Regulation
1.
Products of human origin for the manufacture of medicinal products are active substances within the meaning of Article 4 (19) of the Medicinal Products Act, which are of human origin, or substances within the meaning of Section 3 (3) of the Medicinal Products Act, which are human Origin are, in processed or unprocessed state, excluding blood products within the meaning of § 2 No. 3 of the Transfusion Act, as amended by the Notice of 28 August 2007 (BGBl. 2169) and other blood components,
2.
Excipient shall be any component of a medicinal product, with the exception of the active substance or the packaging material,
3.
is the EC-GMP Guide (BAnz. 6887) of the Guide to Good Manufacturing Practice for medicinal products and investigational medicinal products, including its annexes, by which the European Commission shall adopt the detailed guidelines referred to in Article 47 of Directive 2001 /83/EC and Article 51 of Directive 2001 /23/EC of the European Parliament and of the Council of the European Communities Directive 2001 /82/EC and on the interpretation of the principles and guidelines of good manufacturing practice as laid down in Article 3 (2) of Commission Directive 2003 /94/EC of 8 June 2001 on the implementation of the principles and guidelines of good manufacturing practice. October 2003 laying down the principles and guidelines of good manufacturing practice for medicinal products for human use and investigational medicinal products intended for human use (OJ L 327, 28.12.2003, p. EU No 22) and in accordance with Article 3 of Commission Directive 91 /412/EEC of 23 July 1991 laying down the principles and guidelines of good manufacturing practice for veterinary medicinal products (OJ L 262, 27.9.1991, p. EC No 70); the Federal Ministry of Health is aware of the current version of the guide in German in the Federal Gazette (Bundesanzeiger),
4.
Quality management system (QM system) is a system that includes quality assurance, good manufacturing practice or good professional practice, including quality control and periodic product quality reviews,
5.
specifications and requirements to which starting materials or intermediate products for the preparation of medicinal products or active substances, active substances, medicinal products or tissues must comply; they shall serve as the basis for the quality assessment,
6.
Inspection checks carried out during manufacture are carried out in order to monitor and, where necessary, adapt the process and ensure that the product complies with its specification,
7.
Investigational medicinal products are medicinal products within the meaning of § 3 (3) of the GCP Regulation of 9 August 2004 (BGBl. 2081), as amended by the Regulation of 15 March 2006 (BGBl. 542),
8.
is the management of the production or management of the quality control of the directors or the director of the production or quality control within the meaning of Section 14 (1) (2) of the Medicines Act,
9.
Blood donation establishment is a facility within the meaning of § 2 No. 2 of the Transfusion Act, which takes blood or blood components, tests, processes, characterizes, packs, releases, stores, in the sense of Section 4 (17) of the Medicines Act in the Transport, imports, exports or imports into or out of the scope of the Medicines Act,
10.
Tissue establishment shall be a body exercising the activities listed in Section 20c (1) or section 72b (1) of the Medicinal Products Act, or the tissue or tissue preparations from Member States of the European Union or of other States Parties to the (a) Agreement on the European Economic Area in or out of the scope of the Medicines Act; provided that the tissue establishment also wins tissues, it shall also be a withdrawal device within the meaning of point 11; the tissue establishment shall also provide the necessary laboratory tests, it is also a tissue laboratory within the meaning of point 13,
11.
Removal means is a device which, for use in humans, acquires certain tissues within the meaning of Section 1a (4) of the transplant law, including any measures intended to be used to ensure that the tissue is placed in a particular tissue in the form of a tissue. to be able to identify, clearly identify and transport,
12.
is a person who donates a donation within the meaning of Section 2 (1) of the Transfusion Act or a donation to a tissue donation
13.
Tissue laboratory laboratory is a laboratory which carries out the laboratory tests required for tissue recovery;
14.
Job descriptions are written definitions of the specific tasks, responsibilities and responsibilities assigned to the individual employees of an establishment or establishment of their respective lines. have been assigned,
15.
standard working instruction (SOP) is a written instruction to describe the individual steps of recurrent operations (standard working methods), including the materials and methods to be used,
16.
Validation is the application of a documented proof that proves with high certainty that a specific process or standard working method produces a product that will meet the pre-established specifications and the quality characteristics,
17.
Qualification is the provision of a documented proof that proves with high certainty that a specific item of equipment or a specific environmental condition for the manufacture of a product which has been determined beforehand specifications and quality characteristics, is appropriate,
18.
are critical manufacturing or testing procedures that can have a significant impact on the quality or safety of the products, and critical additives materials that can have such an impact,
19.
critical equipment or devices are those that come into contact with the products or which may have a different impact on the quality or safety of the products.

Section 2
General requirements

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§ 3 Quality Management System, Good Manufacturing Practice and Good Professional Practice

(1) The establishments and facilities must operate a functioning quality management system (QM system) in accordance with the nature and scope of the activities carried out. In the cases referred to in paragraph 2, the QM system shall include good manufacturing practice and, in the cases referred to in paragraph 3, good professional practice and the active participation of the management of the establishments and establishments and the staff of the individual areas affected. All areas involved in the creation, maintenance and implementation of the QM system shall be adequately staffed with competent personnel and with appropriate and adequate premises and equipment. The QM system must be fully documented and must be checked for its functionality. (2) For the interpretation of the principles of good manufacturing practice, medicinal products, blood products within the meaning of § 2 No. 3 of the Transfusion Act and Other blood components as well as products of human origin of Part I of the EC-GMP Guide. For the interpretation of the principles of good manufacturing practice and good distribution practices, the active substances of Part II of the EC-GMP guide apply. For the interpretation of the principles and for the risk assessment of appropriate good manufacturing practice for excipients, the guidelines adopted by the European Commission in accordance with Article 47 (5) of Directive 2001 /83/EC should be observed. The Federal Ministry of Health is aware of the current version of the guidelines in the Federal Gazette (Bundesanzeiger). (3) Paragraph 2 does not apply to removal and tissue facilities as well as tissue pendulating laboratories, which carry out their activities according to the standards of good professional practice. Unofficial table of contents

§ 4 Staff

(1) The establishments and establishments must have adequate and suitably qualified staff in sufficient numbers. Staff may only be used in accordance with their training and knowledge, and must be shown to be subject to the diligence shown in the respective activities at the beginning and thereafter on a continuous basis. The instruction must relate in particular to the theory and application of the concept of quality assurance and good manufacturing practice or in the cases of Section 3 (3) of Good Practice as well as to the specific features of the product group, which is manufactured, tested or stored. The success of the training is to be examined. (2) The duties of the employees in a senior or responsible position, which are responsible for the observance of good manufacturing practice in the cases of § 3 para. 2 or in the cases of § 3 para. 3 of the good professional practice, must be defined in job descriptions. There must be no gaps or unsubstantiated overlaps between the responsibilities of the staff. The hierarchical relationships are to be described in an organization scheme. Organisational schemes and job descriptions must be approved by internal procedures. The staff referred to in the first sentence shall be given sufficient powers to enable them to fulfil their responsibilities. Unofficial table of contents

§ 5 Operating rooms and equipment

(1) The operating rooms shall be suitable for the intended purposes by type, size, number and equipment and shall be designed and used in such a way as to reduce the risk of errors to the smallest possible extent and to ensure that each of the quality of the Product impairing effect is avoided. The operating rooms should be arranged in such a way that the production can be carried out in logically successive steps, in accordance with the sequence of the operations and, if necessary for the product quality, the cleanliness classes of the rooms. (2) To the extent that the operating rooms and their equipment are used for manufacturing operations in products of sections 3 and 5 which are of crucial importance for product quality, they must be checked for their suitability (qualification). (3) The operating rooms must be in a proper construction condition . They must be sufficiently illuminated and have suitable climatic conditions. The operating rooms must be protected by appropriate measures against the access of unauthorized persons. (4) The premises and their equipment must be thoroughly cleaned and maintained in order to ensure that impurities and cross-contamination as well as any other to avoid the quality of the product's adverse effect. Before each processing operation, it shall be ensured that the working area and the equipment are clean and free of all the starting materials, products, product residues, documents and other materials which are not required for the planned operations . Unofficial table of contents

§ 6 hygienic measures

(1) Operating rooms and their equipment must be cleaned regularly and, where necessary, disinfected or sterilized. It shall be adopted in accordance with a written hygiene plan in which, in particular,
1.
the frequency of the measures;
2.
the cleaning, disinfection or sterilization procedures to be carried out, and the equipment and tools to be used,
3.
where applicable, the method of sampling for the verification of the effectiveness of the measures; and
4.
the persons responsible for supervision
shall be established. The effectiveness of purification and sterilisation procedures shall be validated in so far as it requires the production process or the product. (2) Without prejudice to the hygiene plan referred to in paragraph 1, written hygiene programmes shall be provided to: activities to be carried out. They shall, in particular, contain provisions on health, hygiene and protective clothing of the staff. (3) Where animals are used for the manufacture and testing of products to which this Regulation relates, the following shall be: in their position, the hygiene requirements are respected. Unofficial table of contents

§ 7 Storage and transport

(1) Starting materials, intermediate and end products, as well as recovery patterns, shall be stored in such a way that their quality is not adversely affected and any confusion is avoided. Critical storage and transport parameters must be checked and recorded in order to confirm compliance with the requirements. The first sentence shall apply to containers, outer coverings, labelling material and, where used, also for package leaflets. Special precautions must be taken in the case of printed packaging and marking materials. (2) The storage containers and the internal transport containers must be such that the quality of the contents is not is affected. They must be marked with clear inscriptions, which clearly indicate the content. To the extent that names are determined and published by the Federal Institute for Drugs and Medical Devices in accordance with Section 10 (6) No. 1 of the Medicinal Products Act, these are to be used. The content shall be marked by additional information to the extent that this is necessary to avoid confusion. The right of access to the containers referred to in the first sentence shall be restricted by means of appropriate measures on persons authorized to do so. (3) Paragraph 2 shall apply to containers for the delivery of intermediate or final products. Where products are dispatched for further processing by other establishments outside the manufacturer ' s control, their containers shall be sealed in such a way as to enable them to be opened at the same time. (4) The Storage responsible person has to be convinced at regular intervals that the products and materials are stored properly. (5) The procedures for storage and transport must be laid down in writing. In so far as they may have an influence on the quality of the starting materials and intermediate products for the manufacture of medicinal products or for the medicinal products, the suitability of the procedures shall be proved. (6) During transport to the date of delivery in the The responsibility of the recipient is to ensure that there is no unauthorised access and that the quality of the products is not compromised. Unofficial table of contents

§ 8 Animal husbandry

(1) The state of health of animals kept for the manufacture or testing of medicinal products or active substances shall be subject to continuous control by a veterinarian. (2) Insofar as a quarantine is required before the use of the animals, they are to be placed in a quarantine stable and monitored by a veterinarian. The quarantine period shall be at least two weeks for small animals, at least three weeks for cattle, pigs, sheep and goats, and at least four for one-howls and for other large animals, and at least six weeks for monkeys. The quarantine stables must be separated from the rest of the stables. The persons responsible for the care and maintenance of the animals placed under the quarantine barn shall not be employed in other areas without adequate measures, in particular to prevent the transmission of possible infections. (3) In the manufacture and testing of products to which this Regulation applies, only animals which, according to the outcome of the veterinary examination, do not show signs of communicable diseases and shall not be used for the manufacture and testing of products to which this Regulation applies may be used. Diseases that have a negative effect on manufacturing or testing (4) holdings and establishments holding animals as referred to in paragraph 1 shall keep separate records of the animals by animal species which contain at least information on:
1.
the origin and date of the acquisition;
2.
race or tribe,
3.
Number,
4.
Marking,
5.
the beginning and end of the quarantine period,
6.
the result of the veterinary examinations,
7.
type, date and duration of use and
8.
Whereabouts of the animals after use.
(5) Rooms in which animals are kept must be separated from other areas and have their own entrance as well as their own ventilation systems. Unofficial table of contents

§ 9 Activities on behalf of

(1) For each activity on the contract, in particular the manufacture, testing and placing on the market or any associated operation carried out on behalf of the contract, a written contract must exist between the contracting authority and the contractor. In the contract, the responsibilities of each side must be clearly defined and, in particular, the observance of good manufacturing practice in the cases of § 3 para. 2 or of good professional practice must be regulated in the cases of § 3 para. 3. (2) The The contracting authority must ensure that the contractor carries out the activity in accordance with the prescribed instructions and has permission to do so, insofar as this is required in accordance with § § 13 and 72 of the German Medicines Act. (3) The Contractor shall not be allowed to carry out any work entrusted to it by the contracting entity without its written consent Permission granted to third parties. In the event of an order or order examination, it must comply with the principles and guidelines of good manufacturing practice or good professional practice, and in particular the specified production and testing instructions. Unofficial table of contents

§ 10 General Documentation

(1) establishments and facilities shall maintain a documentation system in accordance with the activities carried out. The totality of the documents shall enable the tracing and placing on the market of each batch and the changes made in the course of the development of a test product to be followed. The documents shall be clear, clear, error-free and up-to-date. The original content of an entry must not be made illegible. No changes may be made which do not indicate whether they have been made at the time of the original registration or only later. The documents may only be accessible to authorised persons. (2) If the recordings are made with electronic, photographic or other data processing systems, the system shall be sufficiently validated. At least it must be ensured that the data are available during the period of retention and can be made legible within a reasonable period of time. The stored data must be protected against loss and damage. Where a system is used for the automatic processing or transmission of data, the person responsible shall, instead of the personal signature of the persons responsible, be able to reproduce their names if it is ensured in a suitable manner that only authorized persons shall be responsible for the reproduction of the data. (3) The records of the placing on the market shall be arranged in such a way as to allow the immediate recall of the product in question. Unofficial table of contents

Section 11 Self-inspections and supplier qualification

(1) In order to ensure compliance with the provisions of this Regulation, self-inspections must be carried out on a regular basis in accordance with a programme set out in advance. Records must be kept and kept by means of the self-inspections and the corrective measures subsequently taken. (2) The qualification of suppliers for starting materials and primary and secondary packaging materials, which shall be used for the The use of medicinal products shall be carried out in accordance with the procedure laid down in writing in the framework of the QM system of the processing operation. (3) The procedure referred to in paragraph 2 shall, in so far as it concerns active substances for the manufacture of medicinal products, have to be carried out , in order to establish proper production
1.
provide for the carrying out of verifications by the manufacturer on the spot (audits) by adequately trained staff of the manufacturer of medicinal products; instead of their own audits, the manufacturer may have recourse to appropriate third party knowledge, provided that the requirements for carrying out the audits correspond to those of the own QM system, and
2.
the verifications include that the manufacturer of the active substance for the manufacture of medicinal products for human use, provided that the latter is situated in a country, the Member State of the European Union or any other State Party to the Agreement on the European Economic Area, is registered with the competent authority.
The number 1 and 2 of the first sentence shall also apply to importers and distributors, in so far as they are active substances for the manufacture of medicinal products intended for human use. (4) In order to ensure the suitability of the excipients for the manufacture of medicinal products, the following shall apply: of medicinal products intended for use in humans, the procedure referred to in paragraph 2 shall provide for a formalised risk assessment by the manufacturer of medicinal products. The risk assessment shall, in particular, verify compliance with the rules of appropriate good manufacturing practice in the manufacture of the excipients, their origin and their intended use, and any knowledge of (5) The specifications of the medicinal products and active substances shall reflect the manufacturer and supplier accepted by the company. (6) The provisions of paragraphs 2, 3 (1) and (5) shall apply to other critical Starting materials for the preparation of active ingredients accordingly.

Section 3
Medicinal products, blood products and other blood components and products of human origin

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§ 12 Personnel in a senior and responsible position

(1) The area of responsibility of the knowledgeable person is to be determined in writing in accordance with § 19 of the German Medicines Act. The tasks of the management of the production and the management of quality control must also be defined in writing. The tasks of the management of the production shall include in particular:
1.
Ensure that the products are manufactured and stored in accordance with the rules,
2.
approval of the manufacturing instruction in accordance with section 13 (1) and ensuring that it is complied with,
3.
Control of maintenance, premises and equipment for manufacture,
4.
to ensure that the necessary validations of the manufacturing processes are carried out, and
5.
To ensure the necessary initial and continuous training of personnel working in the field of manufacture.
The tasks of the management of quality control shall include in particular:
1.
Approval or rejection of raw materials, packaging materials and intermediate products,
2.
approval of specifications, instructions for sampling and test instructions in accordance with § 14 (1), and ensuring that they are complied with,
3.
ensuring that all the necessary tests have been carried out,
4.
Consent to the commissioning and monitoring of analytical laboratories acting on behalf of the
5.
control of the maintenance, premises and equipment for carrying out the tests;
6.
ensuring that the necessary validations of the test procedures are carried out, and
7.
To ensure the necessary initial and continuous training of the staff working in the field of testing.
The management of the production and the management of the quality control must be independent of each other. (2) Insofar as ready-to-use drugs are placed on the market, the areas of responsibility of the phased planners are in addition to the requirements of § 63a of the Medicines Act and of information officers in accordance with § 74a of the Medicines Act. (3) Anyone who produces or introduces medicinal products or products of human origin without a permit pursuant to § 13 or § 72 of the German Medicines Act (§ 13) of the German Medicines Act ( To require pharmaceutical law, it is necessary to establish persons who are responsible for the production of including the release, storage and quality control. Unofficial table of contents

§ 13 Manufacture

(1) The production processes shall be carried out with the exception of release under the responsibility of the management of the production according to prior written instructions and procedural descriptions (production instruction). They must be carried out in accordance with good manufacturing practice and the accepted pharmaceutical rules. (2) In the case of medicinal products which are registered or registered, the manufacturing instruction shall be subject to the approval or approval of the marketing authorisation. Registration documents, in the case of investigational medicinal products, comply with the approval documents for the clinical examination in which they are to be applied. In the case of blood stem cell preparations, which have been approved in accordance with § 21a of the Medicines Act, the production instruction must comply with the approval documents. (3) Only active substances and auxiliary substances in the sense of § are used for the production of medicaments. 2, to be used as starting materials which have been manufactured in accordance with good manufacturing practice. The first sentence is applicable to the preparation of test preparations, the requirements for the active substance being adapted to the respective development stage of the test preparation. Only starting materials and medicinal products must be used, the quality of which has been determined and indicated accordingly. (3a) Insofar as ready-to-use medicinal products, which are a safety feature within the meaning of Article 10 (1c) of the Medicines Act to be repackaged by another manufacturer, the manufacturer has to be convinced of the authenticity of the medicinal product prior to the partial or complete removal or overlap of the safety features. The security features may only be replaced by those which, in an equivalent manner, allow the verification of the authenticity and integrity of the outer packaging. The primary packaging must not be opened. (4) Due to the spatial or temporal separation of the individual manufacturing processes or by other appropriate technical or organizational measures, it is necessary to make provision for cross-contamination and confusion is avoided. In the production of test specimens, special precautions must also be taken during and after blinding within the meaning of § 3 (10) of the GCP Regulation. (5) The methods used for the production are according to the respective state of the art. of science and technology. Critical phases of a manufacturing process must be regularly revalidated. By way of derogation from the first sentence, in the case of test specimens, the manufacturing process as a whole shall be validated as far as this is indicated, taking into account the product development phase; critical process steps shall always be validated. All steps for the design and development of the preparation process for the test preparation must be fully documented. (6) adequate and sufficient resources must be made available for carrying out the in-process controls. (7) The production of each batch shall be carried out in accordance with the manufacturing instruction referred to in paragraph 1 and shall be recorded in full (production protocol). All deviations in the process and from the specification of the specification are to be documented and thoroughly investigated. To the extent that the product is not produced in batches, the first sentence shall apply. (8) The production protocol shall confirm from the management of the production with the date and signature that the batch is manufactured in accordance with the manufacturing instructions. . Unofficial table of contents

Section 14 Examination

(1) Starting materials and end products as well as, if necessary, intermediate products shall be considered under the responsibility of the management of quality control after prior written instructions and procedural descriptions (test instruction). The test must be carried out in accordance with good manufacturing practice and the recognised pharmaceutical regulations. Phrases 1 and 2 shall apply to containers, outer wrapping, packaging and labelling materials and package leaflets. (2) In the case of medicinal products which are registered or registered, the test instruction shall be subject to the authorisation or registration of the product. Registration documents, in the case of investigational medicinal products, comply with the approval documents for the clinical examination in which they are to be applied. In the case of blood stem cell preparations which have been approved in accordance with § 21a of the Medicinal Products Act, the test instruction must comply with the approval documents. (3) The procedures used for the examination are according to the respective state of science and Technology to validate. Critical test procedures must be regularly evaluated to determine whether they are still valid and, if necessary, revalidated. (4) The test must be carried out in accordance with the test instruction referred to in paragraph 1 and to be fully recorded. (audit trail). All deviations in the process and from the specification in the specification are to be documented and thoroughly investigated. The quality control management has to confirm in the test log with the date and signature that the test has been carried out in accordance with the test instruction and that the product has the required quality. (5) If the required quality has been completed, the required quality of the test must be completed. (6) Starting materials, intermediate and end products which do not meet the quality requirements are considered to be of the highest quality, and if the quality of the products is to be marked, the end date must be indicated. to be identified and to be able to be identified. The other measures shall be taken by staff authorised to do so. The measures must be documented. Unofficial table of contents

§ 15 Labelling

(1) Medicinal products intended for use in humans and not manufactured medicinal products or investigational medicinal products may be placed on the market only if their containers and, where used, are used, the products of the 1, 2, 4, 6 and 9 of the Medicinal Products Act are marked in good legible writing, in German and in a permanent manner. (2) Ready-to-use medicinal products, which are medicinal products within the meaning of § 2 (2) (2) (1a), (2) or (3) of the Medicines Act, may only be placed on the market if their containers are and, where used, their outer envelopes are identified in accordance with § 10 of the Medicines Act. The information on the dosage form, the active substances and the waiting time can be omitted. In the case of these medicinal products, additional information shall be given on the container or, where used, on the outer packaging or on the package leaflet.
1.
the fields of application,
2.
the contra-indications,
3.
the side effects,
4.
the interactions with other means.
(3) Ready-made medicinal products which are medicinal products within the meaning of Article 2 (2) (4) of the Medicines Act may only be placed on the market if their containers and, where used, their outer envelopes according to § 10 (1), (2), (6), (8) and (9) of the Pharmaceutical legislation. The information on the dosage form can be omitted. The active substances must be stated in the form of medicinal products within the meaning of Article 2 (2) (4) of the German Medicines Act as far as they are characteristic of the function of the medicinal product. Where the finished medicinal product is composed of several parts, the batch names of the individual parts shall be indicated on the container and, where used, on the outer casing. If the indication of the active substances by type and quantity on the container is not possible due to lack of space, it shall be placed on the outer packaging or, if this is not possible due to lack of space, in an information sheet attached to the container. (4) In the case of medicinal products which do not require registration or registration, the registration number or registration number shall be omitted. (5) Products of human origin shall be on their containers and, where used, their external products. Envelopes in a legible font in German or English language and on to at least be labelled as follows:
1.
the name or company and address of the manufacturer of the product and, where different, the manufacturer who has filled, repacked, repacked or remarked the product,
2.
the name or identification code of the product, linked to the reference of "human origin" and, where possible and applicable, of its degree of purity, the reference to a pharmacopoeia and the international short term of the World Health Organization,
3.
where applicable, weight or volume content; if biological units or other information on the weight are scientifically common, they shall be used,
4.
batch name of the finished product or, if the product is not produced in batches, the date of manufacture and, where applicable, in addition also the completed, repacked, repackaged or re-marked product,
5.
Expiry date or post-test date and
6.
special conditions of transport or storage, to the extent necessary to maintain the quality of the product.
In duly substantiated cases, the competent authority may allow derogations to be made on the labelling. Unofficial table of contents

Section 16 Release on placing on the market

(1) The release of a batch for placing on the market may only be released by the competent person according to § 14 of the Medicinal Products Act, which is familiar with the product and with the procedures used for its production and testing, only after having previously been (2) The release may be effected only if:
1.
the production protocol and the audit protocol are duly signed,
2.
In addition to the analytical results, essential information such as the manufacturing conditions and the results of the in-process controls have been taken into account,
3.
the verification of the manufacturing and testing documentation has confirmed the conformity of the products with their specifications, including the final packaging, and
4.
in the case of authorised or registered medicinal products, compliance with the approval or registration documents and, in the case of investigational medicinal products, conformity with the clinical examination documentation, in which they are used , is available.
(3) By way of derogation from paragraph 2, only the delivery container of the tanker vehicle before placing on the market shall be released to the extent that liquefied medical gases are refilled in accordance with Section 13 (3) of the Medicines Act. The documentation for the filling of the final container shall be submitted retrospectively to the management of the production and the knowledgeable person retrospectively and shall be confirmed in writing by the person responsible for the preparation. The area of responsibility of the knowledgeable person as defined in § 19 of the German Medicines Act remains unaffected. (4) Insofar as the production or quality control is carried out in several stages, including where appropriate in different places or at different stages. different manufacturers or the complete manufacture with the exception of release takes place in other establishments and facilities, the knowledgeable person can, according to § 14 of the German Medicines Act, those of other knowledgeable persons Confirmations concerning the stages of the stages or tests carried out within a Use their approved quality system to decide on the release of the finished product batch. It is personally responsible for the release to place the batch on the market as a whole. The first sentence shall apply mutagenally to confirmations submitted by knowledgeable persons referred to in Article 48 of Directive 2001 /83/EC or Article 52 of Directive 2001 /82/EC. (5) In the cases referred to in paragraph 4, the competent person referred to in Article 14 of the above to persuade the Medicines Act, by personal knowledge or by confirmation of other sufficiently knowledgeable and appropriate persons, that the manufacturer is in a position to comply with good manufacturing practice; and to be prepared and tested in accordance with the manufacturing and testing instructions. Production must be demonstrated in a country which is not a Member State of the European Union or other State Party to the Agreement on the European Economic Area, in accordance with the standards laid down by the European Union Standards of good manufacturing practice shall be at least equivalent. The manufacturer must be empowered to carry out the relevant activities according to national legislation. (6) In cases of short-term prevention, in particular illness or holidays, the competent person in accordance with § 14 of the German Medicines Act (Medicines Act) may be entitled to: (7) The holder of a licence pursuant to § 13 or § 72 of the German Medicines Act (Medicinal Products Act) has the competent person in accordance with § 14 of the German Medicines Act (Medicines Act). to enable it to carry out its task and, in particular, to ensure that to make funds available. Unofficial table of contents

Section 17 placing on the market and imports

(1) Medicinal products, blood products and other blood components, as well as products of human origin which have been manufactured and tested within the scope of the Medicines Act, may only be placed on the market if they are released in accordance with § 16 . To the extent that the medicinal products, blood products and other blood components and products of human origin have been introduced or introduced into the scope of the Medicines Act, the release pursuant to § 16 for placing on the market may only be effected if: the production has been carried out in a holding which is authorised to do so under the respective national law, and the examination in accordance with § 14 has been carried out within the scope of the Medicines Act. In addition to the full qualitative and quantitative analysis, in particular of the active substances, the test shall also cover all other verifications necessary to ensure the quality of the product concerned. Sentence 2 shall not apply to investigational medicinal products. (2) In the case of a movement from a Member State of the European Union or of another State Party to the Agreement on the European Economic Area, the scope of the Medicines Act may be covered by the provisions of the The examination referred to in paragraph 1 shall be waited if the examination is carried out in the Member State or in the other Contracting State in accordance with the legislation in force there and the inspection reports signed by the competent person are attached. (3) In the case of imports from non-Member States of the European Union, Union or other States Parties to the Agreement on the European Economic Area may be waied from the examination referred to in paragraph 1 if the conditions laid down in Article 72a, first sentence, of the Medicinal Products Act, in the case of blood products which do not contain any Medicinal products are, and in the case of products of human origin, also complied with in accordance with Section 72a, first sentence, No. 2 of the Medicines Act, or the examination has already been carried out in another Member State of the European Union and the relevant control reports (4) Insofar as investigational medicinal products manufactured in a country have been produced, the is not a Member State of the European Union or of any other State Party to the Agreement on the European Economic Area and for which a marketing authorisation is available in the country of origin, in a clinical trial as In accordance with § 14 of the Medicines Act, the competent person shall bear the responsibility for the fact that each production batch has undergone all the necessary tests to ensure the quality of the preparations according to the approval documents for the clinical trial in which they are to be applied; are confirmed. The first sentence shall also apply if, according to Article 14 of the Medicines Act, the competent person is not available to confirm that any production batch has been produced in accordance with the standards laid down by the European Union (5) The knowledgeable person in accordance with § 14 of the Medicines Act has, in accordance with § 19 sentence 2 of the Medicinal Products Act, in an ongoing register or a comparable comparable Document for each batch of medicinal products to comply with the requirements of the Pharmaceutical legislation and the present Regulation before the batch is placed on the market. If batches are then recalled, this is to be noted in the register or a comparable document. (6) As far as nothing else is permitted by law, ready-to-use medicinal products may only be used in establishments and facilities. , which have a permit pursuant to § 13, § 52a or § 72 of the Medicines Act or are authorized to submit to the final consumer or to other entities or persons who are authorised pursuant to § 47 of the Medicinal Products Act (Medicines Act) shall be permitted. Sentence 1 shall apply mutatily to establishments holding a permit referred to in Article 40 or a permit referred to in Article 77 of Directive 2001 /83/EC or a permit referred to in Article 44 or a permit referred to in Article 65 of Directive 2001 /82/EC . The supplies shall be accompanied by sufficient documentation, in particular the date of delivery, the name and quantity of the medicinal product, and the name and address of the supplier and the consignee. In the case of delivery to establishments and establishments which have a permit or permit in accordance with the first or second sentence of the second sentence, the batch name of the medicinal product must also be indicated. In addition, stating the issuing authority and the date of the exhibition, it must be confirmed that the supplier has a permit according to § 13, § 52a or § 72 of the Medicines Act. The obligation to provide additional details of the batch designation shall also apply:
1.
in the supply of medicinal products to hospital pharmacies and pharmacies providing hospital care for the purposes of supplying hospitals,
2.
in the case of blood preparations, sera from human blood and preparations of other substances of human origin and of genetically engineered blood components which replace missing blood components, including in the case of supply to holdings, and equipment to be delivered to the final consumer,
3.
in the case of medicinal products subject to medical prescription intended for use in animals, and
4.
in the case of medicinal products which have to carry safety features within the meaning of Article 10 (1c) of the Medicines Act.
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§ 18 Return pattern

(1) The competent person responsible for the release in accordance with § 16 of the German Medicines Act shall ensure that a sufficient quantity of a medicinal product for the purpose of a medicinal product for the purpose of a medicinal product for the purpose of a medicinal product is available for the purposes of the release. shall be kept for at least one year beyond the expiry date of the expiry date, in order to demonstrate the necessary analytical re-testing and the identification of the labelling, including the package leaflet. If the holding in which the release takes place is not the pharmaceutical contractor at the same time, or if more than one operation is involved in the manufacture of a batch, the responsibility for the return pattern storage is in the sense of the § 9 to be contractually agreed. In the event of a closure of the holding in which the return pattern storage is carried out, the pharmaceutical contractor shall ensure that the reset patterns are held in accordance with the first sentence during the entire retention period. If a batch is finally packed in two or more operations, in principle at least one reset pattern per packaging process must be kept. In the case of medicinal products imported or sold in parallel, sentence 4 shall apply only if the secondary packaging thereof is opened for the purpose of amending the labelling or the package leaflet. In the case of medicinal products for which the production is carried out on a case-by-case basis or in small quantities, or where the storage of such medicinal products presents particular problems, the competent authority may authorise the use of the samples and their storage. (2) The rules for the release according to § 16 responsible person in accordance with § 14 of the German Medicines Act shall ensure that the recovery pattern of each batch of starting materials used for the manufacture of medicinal products shall be at least two years after release of the raw materials used for the manufacture of the medicinal product. these starting materials are kept, unless: in the registration documents a shorter shelf life is indicated. The first sentence shall not apply to solvents, gases and water. Paragraph 1, sentence 6 shall apply. (3) By way of derogation from paragraph 1, the competent person responsible for the release in accordance with § 16 shall ensure, in accordance with § 14 of the German Medicines Act, that investigational medicinal products as well as their identification and/or labelling requirements are printed packaging materials shall be kept in sufficient samples of each batch for at least two years after the completion or termination of the last clinical trial in which the batch concerned was applied. As far as information is given in accompanying documents in accordance with § 5 of the GCP Regulation, the samples of these accompanying documents shall also be kept for each batch. (4) The retention of the restoring samples of a finished medicinal product as referred to in paragraph 1 shall be kept in the the scope of the Medicines Act. The provisions of the first sentence may be waited if the recovery patterns are stored in a Member State of the European Union or in another State Party to the Agreement on the European Economic Area. Unofficial table of contents

Section 19 Complaints and recall

(1) The stepped planner shall be responsible for the fact that all known reports on the risk of medicinal products are collected in accordance with procedures established in writing, and that all complaints are systematically recorded. In doing so, the immediate review of the notifications shall be made without delay and shall then be evaluated as to whether there is a risk of a medicinal product, the severity of the risk, and the measures to be taken in order to prevent risks. The necessary measures must be coordinated and brought to the attention of the knowledgeable person in accordance with Article 14 of the Medicines Act, so that it may, if necessary, take the necessary measures, in particular if it is a matter of Quality problem could be a problem. The effectiveness of the procedures shall be reviewed regularly. (2) The stepped-plan officer shall immediately be responsible for any defect which might result in a recall or an unusual restriction on the distribution of the product. and also inform the States in which the medicinal product has been brought or exported. In addition, the Authority shall also be immediately informed of any suspicion of falsification of medicinal products or of active substance; in the case of medicinal products intended for use in humans, the holder of the authorisation must also be informed. (3) The or the Graduated Planner has to comply with the notification obligations under the Medicines Act to the extent that they concern drug risks. The reporting obligations under § 14 of the GCP Regulation shall remain unaffected. (4) Paragraph 1 shall apply for investigational products accordingly. The stepped planner is responsible for the systematic recording, review and effective systematic arrangements in cooperation with the sponsor, in order to ensure that the application of the Test specimens can be prevented, if necessary. Any defect which might result in a recall or an unusual restriction on distribution must be documented and examined and the competent authority shall be informed without delay and shall also inform the competent authority of which: Inspection bodies within or outside the scope of the Medicines Act have been extradited to the investigational medicinal product. If the investigational medicinal product is an authorised medicinal product, the stepped planner, in cooperation with the sponsor, must inform the marketing authorisation holder of any deficiency that may be associated with the authorised medicinal product. (5) The content of the notifications, the nature of the review and the findings obtained, the outcome of the evaluation, the coordinated actions and the notifications shall keep the level-planning officer's records or records. (6) The or the stepped planner is to be appointed by the sales or distribution units be independent and can only be represented by persons who have the expertise referred to in Article 63a (1), first sentence, of the Medicines Act, and must be within the scope of the Medicines Act or in another Member State of the (7) As far as a marketing authorisation holder places on the market other products other than those referred to in § 63a (1) sentence 1 of the Medicinal Products Act, he has a corresponding person with the perception of the task of the phased planner or of the phased planner. The person responsible shall be responsible for compliance with the obligations laid down in paragraphs 1 to 5. (8) The pharmaceutical operator shall ensure that all notifications concerning the risk of medicinal products in the holding are carried out and Complaints and information for the assessment of the risk-benefit balance of a medicinal product shall be immediately communicated to the or the phased planner or to the person responsible under the first sentence of paragraph 7. Unofficial table of contents

§ 20 Storage of documentation

(1) All records relating to the acquisition, manufacture, including release, testing, storage, transfer to or from the scope of the pharmaceutical law, the import or export, the placing on the market, including: the extradition and records of the animal husbandry and records of the graduated planner or of the person responsible for the management pursuant to section 19 (7) sentence 1 shall be complete and at least until one year after the expiry of the expiry date, but not less than five years. Storage must be carried out in a suitable area of the rooms covered by the permission in accordance with § 13 or § 72 of the Medicines Act. The right to access the records referred to in the first sentence shall be restricted by appropriate measures on persons authorised to do so. In the event of a closure of the manufacturer's or test facility, in which the documentation is kept in accordance with the first sentence, the pharmaceutical contractor shall ensure that the documentation is kept during the entire storage period. (2) By way of derogation from paragraph 1, in the case of blood preparations, sera from human blood and genetically engineered plasma proteins for the treatment of haemostasis disorders for the purpose of traceability records with information
1.
for the identification of the donation facility,
2.
to identify the person to be donated,
3.
on the name of the medicinal product,
4.
to the batch name,
5.
to obtain the donation (year, month, day),
6.
on the date of delivery and
7.
of the name or company of the recipient
in legible form in a suitable storage medium for at least 30 years and the other records relating to the collection of donations and the associated measures, in accordance with Article 11 (1) of the Transfusion Act, to be kept for at least 15 years or to . The information must be deleted if the retention or storage is no longer required. If the records are kept or stored for more than 30 years, they are to be anonymized. (3) (omitted) (4) Paragraph 1 applies to investigational medicinal products subject to the proviso that the documents shall be at least five years after the completion or cancellation of the last documents. The clinical trial in which the batch was used should be kept.

Section 4
Active substances not of human origin

Unofficial table of contents

Section 21 Organisational structure

(1) The QM system according to § 3 must include in particular the organizational structure as well as the procedures, processes and all activities necessary to ensure that the active substance is the intended specifications for quality and purity. is fulfilled. It must have at least one quality assurance unit that is independent of production. The quality assurance unit must be included in all quality-related matters. (2) Insofar as active substances are manufactured or imported which are subject to the approval requirement in accordance with § 13 or § 72 of the German Medicines Act (Medicines Act) § 12 para. 1 Application. (3) Any person who produces or introduces active substances without a permission in accordance with § 13 or § 72 of the Medicines Act must determine the persons entitled to release intermediate products and active substances accordingly. Unofficial table of contents

Section 22 Manufacture

(1) The manufacturing operations, including in-process controls, must be carried out in accordance with written instructions and procedures (manufacturing instruction) and in accordance with good manufacturing practice. (2) According to § 13 of the German Medicines Act, the production line is responsible for the approval of the production instruction, unless the release is affected. In other establishments and facilities, it is the quality assurance unit. (3) Only starting or intermediate products must be used whose quality has been determined and appropriately marked. (4) By spatial or temporal The separation of the individual manufacturing processes or other appropriate technical or organisational measures must be taken to ensure that cross-contamination and confusion are avoided. (5) The methods used for the manufacture of the products are: as far as this is critical for the quality or purity of the active substance are to be validated according to the respective state of science and technology. Critical phases of a manufacturing process shall be regularly revalidated. (6) The production of each batch, including its packaging, shall be carried out in accordance with the manufacturing instruction referred to in paragraph 1 and shall be recorded in full. (Manufacturing protocol). All deviations in the process and from the specification in the specification are to be documented and evaluated; critical deviations are to be investigated. In so far as the active substance is not produced in batches, the first and second sentences apply. (7) In the production protocol, in establishments and facilities subject to the approval requirement in accordance with § 13 of the German Medicines Act (Medicines Act), the management of the active substance shall be subject to the following conditions: Manufacture with the date and signature to confirm that the batch has been produced in accordance with the manufacturing instruction. In other establishments and facilities, one or more persons responsible for checking the protocols shall be responsible for the completeness and accuracy of the records. Unofficial table of contents

Section 23 Examination

(1) Starting materials, intermediate products and active substances shall be tested in accordance with written instructions and procedures (test instruction) and in accordance with good manufacturing practice. The first sentence shall apply to containers, packaging materials and labelling material of the active substances. (2) In the case of active substances whose manufacture requires a permit pursuant to § 13 of the Medicines Act, the management of the quality control shall be responsible for the Approval of the test instruction. In other establishments and facilities, it is the quality assurance unit. (3) The methods used for the examination must be validated according to the state of science and technology, provided that they are not in a pharmacopoeia or in a pharmacopoeia. comparable rules. Critical test procedures must be regularly evaluated to determine whether they are still valid and, if necessary, revalidated. (4) The test must be carried out in accordance with the test instruction referred to in paragraph 1 and to be fully recorded. (audit trail). All deviations in the process and from the specification in the specification are to be documented and thoroughly investigated. (5) In companies and institutions that require a permit pursuant to § 13 of the German Medicines Act (Medicines Act), the management of the Quality control in the test log with the date and signature to confirm that the test has been carried out in accordance with the test instruction and that the product is of the required quality. In other establishments and facilities corresponding responsibilities are to be determined. (6) If the required quality has been established, the active substances must be identified accordingly; in the case of a time limitation of the shelf life, the end date shall be . If appropriate, a verification date can also be specified instead of the expiry date. (7) Starting materials, intermediate products and active substances which do not meet the requirements for quality are to be identified as such and are to be conserved. The other measures shall be taken by staff authorised to do so. The measures must be documented. Unofficial table of contents

Section 24 Labelling

(1) The labelling of intermediate products and active substances shall be carried out in accordance with prior written instructions and procedures, and in accordance with good manufacturing practice. In the case of the production of the active substance, which is subject to authorization pursuant to § 13 of the German Medicines Act, the management of the production is responsible for the approval of the instruction and the In other establishments and facilities, it is the quality assurance unit. (2) intermediates and active substances shall be placed on their containers before they are placed on the market and, where used, their outer envelopes in legible and legible letters and on to at least be labelled as follows:
1.
name or company and additional address of the manufacturer,
2.
the name or identification code of the product, as far as possible also of its degree of purity; where applicable, reference to a pharmacopoeia and, where available, the international short name of the World Health Organization,
3.
Contents by weight or volume of space; biological units or other information on the weight are scientifically common, they shall be used,
4.
the name of the batch or, in so far as the intermediate or active substance is not produced in batches, the date of manufacture,
5.
Expiry date or date of after-test,
6.
special conditions of transport or storage, if necessary for the maintenance of the quality of the active substance or substance,
7.
in the case of active substances obtained by genetic engineering, the name of the genetically modified micro-organism used in the production or the cell line; and
8.
in the case of active substances of microbial origin, the indication that it is an active substance of microbial origin and, in the case of active substances of animal origin, the name of the animal species used for the manufacture of active substances of animal origin.
(3) If the intermediate product or the active substance has subsequently been refilled, repackaged, re-labelled or released from a holding other than the original manufacturer, the name or company name and address of this holding shall be added to the product. as well as the new batch designation on the container and, where used, the outer packaging of the intermediate product or active substance. The information shall be provided in German, provided that the intermediate product or the active substance is placed on the market within the scope of the Medicines Act. Further information shall be permitted provided that it does not contradict the German data. The provisions of sentences 1 to 3 shall not apply, provided that they are carried out on a case-by-case basis and which are necessary on the basis of evidence of damage to the original container or its packaging. An activity within the meaning of the fourth sentence shall not be considered as a production step. The process shall be documented and shall be submitted at the request of the competent authority. Unofficial table of contents

Section 25 Release on placing on the market

(1) The release for placing on the market may only be carried out in accordance with written instructions and descriptions of the procedures referred to in paragraph 3 or 4, sentence 1, by persons who use the products and with the products for their production and (2) In establishments and facilities subject to the authorisation requirement in accordance with § 13 or § 72 of the German Medicines Act (Medicines Act), the competent person shall be responsible for the Release of those products that trigger authorisations; § 16 (1) and (4) to (7) appropriate application. In addition, the quality assurance unit shall be responsible for the release; the persons entitled to release it shall be determined in writing. (3) The release referred to in paragraph 1 may only take place if the production protocol and the audit trail have been duly signed, in addition to the analytical results, have taken into account essential information such as the manufacturing conditions and the results of the in-process controls, and the review of the manufacturing and Test documents confirm the conformity of the products with their specifications (4) In the case of intermediate products and active substances which are exclusively filled, bottled, packaged or labelled, the release referred to in paragraph 1 may only take place if:
1.
at least the identity of these products has been identified and there is a duly signed audit trail,
2.
a duly signed production protocol is available for the refilling, filling, packaging and identification of the label,
3.
all necessary quality or authorisation-related information is available from the original manufacturer and, where applicable, other manufacturers of the active substances or intermediate products, including the analytical certificates,
4.
have sufficient knowledge of the original manufacturer and, where applicable, other manufacturers and their quality management system, and
5.
the traceability to the original manufacturer of the product is guaranteed.
If the intermediate products or active substances are filled or packed in primary containers other than the original material, the expiry date specified by the original manufacturer or the last-date test date shall be based on additional stability data. check and, if necessary, adjust accordingly. In the case of intermediate products and active substances which are released exclusively, the release referred to in paragraph 1 may only take place if the requirements set out in the first sentence of the third sentence of paragraph 1 are fulfilled. Unofficial table of contents

Section 26 Marketing and imports

(1) Active substances or intermediates which have been manufactured and tested within the scope of the Medicines Act or which have been brought into or imported into the scope of the Medicines Act may only be placed on the market, if they have been released in accordance with § 25. § § 72 and 72a (1) and (2) of the German Medicines Act remain unaffected. (2) All quality or authorisation-related information, including the analysis certificates and the name or the company and the address of the original manufacturer, shall be without prejudice to the To inform the recipient of the active substance or intermediate product. Where essential, in particular safety-relevant information about the active substance or the intermediate products are obtained from the recipient, these shall be forwarded immediately to the active substance or intermediate product manufacturer. Unofficial table of contents

§ 27 Reset pattern

(1) Each batch of active substances shall store duly marked samples in a suitable container and in a sufficient quantity. The first sentence shall also apply in the cases of exclusive refilling, filling, packaging and labelling. In the case of active substances which are produced on a case-by-case basis or in small quantities, or which cause particular problems to be stored, the competent authority may allow derogations to be made on the samples and their storage. (2) Insofar as the active substance is used for the active substance If the expiry date has been established, the samples referred to in paragraph 1 shall be kept for at least one year beyond the expiry date, but at least three years beyond the full distribution of the batch. (3) For active substances, for which the samples shall be replaced by If the date of expiry of the expiry date has been set, the samples referred to in paragraph 1 shall be at least for three years, beyond the full distribution of the batch. Unofficial table of contents

Section 28 Complaints and recall

(1) All quality-related complaints are in establishments and facilities that manufacture active substances within the scope of the Medicines Act, or which are to be introduced or introduced into the scope of the law, by the quality assurance unit to document, investigate and evaluate the procedure in writing. Where necessary, the original manufacturer must also be informed about the complaints. (2) If there is a suspicion that this is a serious defect, the need for a recall is to be made in writing. Procedures to be examined. The conditions under which a product recall is to be taken into consideration and the recall procedure itself must be laid down in writing. In the event of a serious or life-threatening situation, the competent authority and the manufacturers of medicinal products concerned or other recipients to which the active substance has been supplied shall be immediately informed. (3) Reports, the nature of the review and the findings obtained, the result of the evaluation, the measures and the notifications shall be kept records. Unofficial table of contents

§ 29 Storage of documentation

(1) All records relating to the acquisition, manufacture, including release, laboratory checks, storage, transfer to or from the scope of the Medicines Act, the import or export and the placing on the market , including extradition and the keeping of animals and records in accordance with § 28 shall be kept in full and at least one year beyond the expiry of the expiry date, but not less than five years. (2) Notwithstanding paragraph 1 are the records of active substances for which, instead of the decay date, a (3) For the purpose of traceability of the products manufactured in accordance with the provisions of the Medicines Act, or in accordance with the provisions of the Directive, the following dates have been set for the purpose of traceability of the batch. the active substances or intermediates imported or exported from the scope of the Act are in addition to all analytical certificates, including those of the Original manufacturer to keep records that have at least information on:
1.
the name of the active substance or intermediate product, including the batch name of the original manufacturer, and, where applicable, other manufacturers,
2.
the name or business name and address of the original manufacturer, and, where applicable, other manufacturers,
3.
transport and distribution,
4.
the name or company and address of the consignee.

Section 5
Special provisions

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§ 30 Supplementary provisions for medicated feedingstuffs

(1) For the manufacture of medicated feedingstuffs, only compound feedingstuffs which comply with the provisions of the futures legislation and do not contain any coccidiostat may be used. (2) § 3 (2) shall apply with the proviso that the following shall apply: to take account of the state of the scientific nature of medicated feedingstuffs. The manufacturer must ensure that the medicated feedingstuff does not contain any contamination with pharmacologically active substances that can be avoided according to the state of the art, and that the pre-mix of medicinal products in prescribed quantities and in homogenous and stable distribution and properly delivered. Carriage may be carried out in tankers or similar containers only if they are suitable and have been cleaned prior to any re-use in accordance with the generally accepted rules of technology in such a way as to prevent undesirable effects on the transport of such containers. Contamination of the medicated feedingstuff is avoided. When feeding medicinal products are transported in tankers or similar containers, it is sufficient if the information required under Articles 10 and 11 of the Medicines Act and the information required pursuant to paragraph 4 in the case of the animal keeper is intended for the animal keeper. (3) § 14 shall apply to medicated feedingstuffs, subject to the proviso that the test may be carried out at random. At least the test of homogeneity and the test for contamination with pharmacologically active substances must be carried out. A further examination may be carried out if there is no evidence that there is any doubt as to the flawless nature of the medicated feedingstuff. In the case of the pre-mix used for the manufacture of the medicated feedingstuff, a test beyond the sensory test may be waited if there are no indications that there is a doubt as to the correct the nature of the premix of medicinal products. In respect of the examination of the compound feedingstuffs used, the provisions relating to animal feed shall apply. (4) Without prejudice to other provisions on labelling, medicated feedingstuffs may be placed on the market only if they are placed on the market by the (5) By way of derogation from § 16, in cases of short-term prevention, it may be possible to replace the expert person in accordance with § 14 of the German Medicines Act (Medicines Act) Person who has sufficient training and knowledge to release medicated feedingstuffs provisionally for placing on the market. This provisional release shall be subsequently submitted to the knowledgeable person who, in this case, also bears responsibility for the release, in addition to the person responsible for the release, and to confirm this in writing. The knowledgeable person shall carry out the entry in accordance with Section 17 (5) immediately following the confirmation. (6) By way of derogation from Section 18 (1), samples of each batch must be kept for at least six months beyond the expiry date of the expiry date. . They shall be marked in good legible writing and in a durable manner with the date of manufacture, the name of the premix of medicinal products and the batch number. (7) The veterinary medicinal products required for the delivery of medicated feedingstuffs The prescription must be four copies (original and three copies), which are the model of Appendix 1 to the Regulation on veterinary medicinal products in the version of the Notice of 27 March 1996 (BGBl. 554), as last amended by Article 2 of the Regulation of 3 November 2006 (BGBl I). 2523), which are in accordance with the current version. A copy of a copy of the prescription shall be permitted, the original of which shall be immediately followed by the prescribing veterinarian. The manufacturer must supplement the prescription prior to the delivery of the medicated feedingstuff by the particulars to be submitted by the manufacturer. He shall keep the originals which remain with him in an orderly manner from the date of delivery of the medicated feedingstuffs for five years and shall, on request, be notified or handed over to the competent authority without delay. (8) By way of derogation from paragraph 7 the medicated feedingstuffs may be sent to an animal holder established in another Member State of the European Union or another State Party to the Agreement on the European Economic Area, only after presentation of a veterinary prescription, in accordance with the rules of the country of destination. Where the rules of the country of destination so provide, the medicated feedingstuffs must be accompanied by an accompanying certificate in the form required by the country of destination. Unofficial table of contents

Section 31 Supplementary provisions for blood establishments

(1) The QM system referred to in Article 3 (1) shall be subject to the conditions laid down in the Annex to Commission Directive 2005 /62/EC of 30 September 2005 on the implementation of Directive 2002/98/EC of the European Parliament and of the Council as regards the Community Standards and specifications for a quality system for blood establishments (OJ L 196, 27.7.2001, p. 41), as amended in the current version, and in particular:
1.
ensure that all critical work processes and standard work procedures are defined in appropriate standard operating procedures,
2.
adequate procedures for the recall and traceability referred to in the third sentence of paragraph 4 and in the case of blood preparations as defined in Directive 2002/98/EC of the European Parliament and of the Council of 27 January 2003 setting out quality and quality standards for the Safety standards for the collection, testing, processing, storage and distribution of human blood and blood components and amending Directive 2001 /83/EC (OJ L 197, 21.7.2001, p. 30) and Article 21a (1), third sentence, of the Medicines Act, which provide for the reporting of serious incidents, serious adverse reactions and suspected cases of suspected adverse reactions,
3.
ensure that products that are capable of being used or for the safety of products and the traceability process are accompanied by documents from a body which terminates their activities to other bodies which are subject to a permit referred to in Article 13 of this Regulation of the Medicines Act,
4.
supported by a person responsible for quality assurance, who is responsible, in particular, for the approval of all quality-related documents and is to be included in all quality-related matters, unless the management is responsible for: the production or management of quality control, and
5.
are regularly checked for efficiency by the management of establishments and facilities and, if necessary, adjusted.
The person responsible for quality assurance may be identical with the competent person in accordance with § 14 of the German Medicines Act, provided that this person is not at the same time a director of the production. In so far as blood products or other blood components from blood establishments are obtained in countries not Member States of the European Union or other Contracting States on the European Economic Area, the competent authorities must: Reassure person under § 14 of the German Medicines Act that these blood establishments have a QM system which is set up according to standards at least equivalent to those laid down by the European Union. (2) By way of derogation from § 4 (2) sentence 1, blood establishments shall be subject to the following conditions: to provide job descriptions for all personnel whose activities can have an impact on the quality of the blood preparations. (3) The general requirements for premises and equipment in § 5 are also temporary or Movable devices located outside but under the control of the blood donation facility (mobile site), shall be used. The particularities of the operating rooms, including mobile locations, depend on the respective activities. In particular,
1.
ensure sufficient confidentiality in the field for determining the suitability and suitability of the persons to be donated and be separated from the donation processing areas,
2.
enable the donation area to be removed safely and, where appropriate, to treat the person who has been donated;
3.
the laboratory sector shall be separated from the area for the determination of the suitability and suitability of the donating person and from the area for the processing of donations, and shall be accessible only to the authorities,
4.
in the storage area, a separate storage of products of different status or of products manufactured in accordance with specific criteria shall be ensured and arrangements shall be made in the event of failure of the equipment or of the products energy supply,
5.
separated areas for the waste disposal of potentially infectious materials.
(4) The production instruction in accordance with § 13 para. 1 shall have details of the person to be donated and the donation as well as the documentation relating to it. It shall contain at least the provisions to be complied with at each donation.
1.
Information of the potentially donating or donating person or of the information to be kept informed in accordance with Annex II to Commission Directive 2004 /33/EC of 22 March 2004 implementing Directive 2002/98/EC of the European Parliament and of the Council of 22 March 2004 on the implementation of Directive 2002 /33/EC Parliament and Council with regard to certain technical requirements for blood and blood components (OJ L 136, 31.7.2006, p 25), as set out in the Implementing Directive 2011 /38/EU (OJ L 158, 30.4.2011, p. OJ L 97, 12.4.2011, p. 28), as amended,
2.
the identification of the person to be donated in the determination of their suitability and suitability as well as prior to sampling and donation,
3.
Determination of the suitability and suitability of the donating person in accordance with the eligibility and exclusion criteria laid down in Annex III to Directive 2004 /33/EC,
4.
removal of the donations and, where applicable, their further processing, including the determination of the period until further processing,
5.
Requirements for the donations, processing and end product containers,
6.
Identification of documents and containers, including donor-specific numbers or identification codes of donors, and
7.
Conditions of storage and transport of the blood preparations or other blood components in accordance with Annex IV to Directive 2004 /33/EC.
Without prejudice to Article 13 (7), the manufacturing protocol must ensure full traceability between the person and the donation, as well as intermediate products and blood preparations obtained therefrom, including those for the production and the production of Processing of sterile disposable systems and their batch designations, as well as the equipment used and the test results obtained from the sample, irrespective of the intended use of the donations. The collection and processing process is to be monitored appropriately microbiologically. In addition, the generally accepted state of medical science and technology is used for the production of own blood donations. (5) The test instruction in accordance with § 14 para. 1 must take into account the peculiarities of the blood donations and the blood preparations. and in particular to lay down that
1.
the laboratory samples shall be taken in appropriate containers marked with donor-specific numbers or identification codes at the time of donation, the laboratory samples shall be stored properly prior to the test and the test shall be carried out within for a given period of time,
2.
Each donor must be tested for at least hepatitis B, hepatitis C and human immunodeficiency virus (HIV) on the occasion of each donation according to the state of science and technology;
3.
in addition, the AB0 group, in so far as it is not plasma fractionation, and, in the case of erythrocyte preparations, the rhesus formula or, in the case of platelets preparations, the Rh-D group is to be observed at each donation,
4.
in the case of blood group serological studies, procedures should also be provided for the testing of specific donor groups; and
5.
the blood preparations must comply with the quality requirements laid down in Annex V to Directive 2004 /33/EC.
Results differing from the specifications, in particular in the case of a repeated reactive or positive test result in accordance with the first sentence of the first sentence of the first sentence, shall be clarified and appropriate measures shall be taken to confirm the results and to exclude them from the Use of the products concerned to be taken. In addition, the generally accepted state of medical science and technology is used for the examination of own blood donations. (6) Only laboratory reagents and other materials may be used for the examination of the donations and the donor samples. -to-be-accepted suppliers. The laboratory reagents shall be suitable for their purposes and shall be released prior to their use by a qualified person. The quality of the test procedures must be checked regularly by taking part in a formal performance test system. (7) During all stages of production, the status of the product and the traceability of the product must be determined from the labelling of the product. (8) Preparations from fresh plasma and blood cells must, in so far as they do not require approval pursuant to Article 21 (2) (1a) of the Medicinal Products Act, must be made clear the marking in accordance with § 10 Abs. Article 8 (8a) of the Medicines Act. Individual blood donations must be clearly identified as such. (9) Prior to the release according to § 16, the products are to be stored administratively and physically separately from released products. Individual blood donations must be stored separately. Products that deviate from the specifications may not be released. If a product cannot be released on the basis of the test results, it shall be ensured that all products obtained from the same person and, where applicable, from previous donations of that person, will be identified and segregated; the measures are to be documented. Sentence 4 of the second half-sentence shall apply if subsequent knowledge of defective, infectious or potentially infectious products is obtained which has already been placed on the market. (10) By way of derogation from § 16, in cases where: short-term prevention and, if necessary for medical reasons, instead of the knowledgeable person in accordance with § 14 of the German Medicines Act, a person responsible for adequate training and knowledge, who has sufficient training and knowledge to Blood preparations for direct use in humans provisionally for the Release on the market and make the entry in accordance with § 17 (5). This provisional release and the provisional entry pursuant to section 17 (5) shall be submitted subsequently to the knowledgeable person who, in this case, shall also be responsible for the release, in addition to the person responsible, and shall be informed by the person responsible for the release in writing. (11) § 18 shall not apply to preparations of blood cells or fresh plasma. The knowledgeable person according to § 14 of the German Medicines Act has to keep the donor in sufficient quantity for the purpose of any necessary analytical re-testing. (12) Without prejudice to § 19 the step-planning representative shall be responsible for collecting, evaluating and evaluating all reports of serious adverse reactions in accordance with the procedures laid down in writing, and of the competent authority or authority pursuant to Section 63i (2) or (3) of the Medicinal Products Act are reported. Sentence 1 shall also apply to suspected cases of such reactions. Where:
1.
the initial notification shall contain all the necessary information, in particular for the identification of the blood donation establishment, the person concerned and the donation, the date of notification and the donation, the date of transfusion, the nature of the suspected reaction Annex II to Commission Directive 2005 /61/EC of 30 September 2005 on the implementation of Directive 2002/98/EC of the European Parliament and of the Council as regards traceability requirements and the reporting of serious products Incidents and serious adverse reactions (OJ C 327, 30.4.2004, p. 32), as amended; it also needs to indicate the degree of probability of a link between the administration of the blood preparation and the recipient reaction (allocation level),
2.
the initial notification shall be specified as soon as sufficient evidence is available for it; in particular, it shall be indicated whether the initial notification and its allocation stage are to be confirmed with regard to the likelihood of a link or whether, and where appropriate, the manner in which a change in the first classification is to be reported; as far as is known, the clinical course of the recipient must also be indicated. In particular, the allocation level should be distinguished as to whether a connection is excluded, unlikely, possible, probable or safe, or cannot be evaluated.
The detailed details, in particular the technical specifications and formats of the notifications to the competent federal authority, may be regulated in a notice issued by the competent federal authority. (13) Paragraph 12, sentence 1 to 3, shall apply. as appropriate for serious incidents:
1.
The initial notification shall contain all the necessary information, in particular whether it concerns product defects, defective equipment or human error, and whether the error occurred during the extraction, processing, testing, storage, transport, the or any other activity or materials used in the collection, testing or processing of such materials.
2.
The initial notification shall be specified as soon as sufficient evidence is available for it. In particular, the main cause is to be analysed and to report on corrective measures taken.

Section 5a
Special requirements for removal and tissue establishments and for tissue laboratory laboratories

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Section 32 Supplementary general requirements

(1) The QM system in accordance with § 3 para. 1 shall be required for tissue establishments under the responsibility of the responsible person in accordance with § 20c of the Medicines Act, in particular:
1.
ensure that all work processes affecting the quality and safety of tissues and tissue preparations, as well as the standard working procedures, are carried out in appropriate standard operating procedures, carried out under controlled conditions, and is documented,
2.
ensure that the equipment used, the working environment and the conditions for working or processing and storage of tissues and tissue preparations are and are regularly monitored,
3.
include adequate procedures for the disposal and handling of discarded tissue or tissue preparations and waste disposal,
4.
include sufficient traceability procedures and the prompt reporting of serious incidents, serious adverse reactions and suspected cases of suspected adverse reactions,
5.
ensure that usable tissues and tissue preparations, or for their safety or the tracing process, documents relevant to a body that terminates its activities to other bodies subject to a permit in the According to § 20c of the Medicines Act, they are handed over and
6.
shall be reviewed regularly with a view to continuous and systematic improvements and, if necessary, adjusted.
If tissue or tissue preparations are obtained from facilities in countries which are not Member States of the European Union or other Contracting States on the European Economic Area, the person responsible shall, according to § 20c of the European Union, be responsible for: Pharmaceutical law reassure that these facilities have a quality system established in accordance with standards at least equivalent to those laid down by the European Union. By way of derogation from the first sentence of Article 3 (1), removal equipment and tissue derlabs must have a system of quality assurance adapted to their activities in accordance with the principles of good professional practice. In particular, it is necessary to ensure compliance with the requirements set out in points 1, 3 and 4. (2) The contract in accordance with § 9 (1) of a tissue establishment with the removal device shall in particular have to be provided with details of the Donor selection criteria and tissue sampling and with the tissue laboratory laboratory and, where used, other laboratories, the laboratory tests and tests to be carried out, and the documentation required under this Regulation and in accordance with § 3 or § 6 of the TPG tissue regulation. The first sentence shall apply mutagenic to the procedures for the immediate notification of suspected cases of serious adverse reactions and serious incidents. The contracts shall be placed in a complete list in the processing or processing tissue establishment and shall be presented at the request of the competent authority. (3) Without prejudice to § 10, the documentation system of a tissue establishment shall at least: ensuring that
1.
the safe identification of each donation and any tissue resulting from it, or any tissue preparation resulting from it, is possible at every stage of the processing, and can be understood by all the steps,
2.
for each critical activity, the appropriate materials and equipment as well as the performing personnel can be identified,
3.
the tissues or tissue preparations are only passed on for processing or processing or released for placing on the market if they have complied with all the requirements laid down in the relevant specifications,
4.
the records shall be reliable and shall only be used for documents authorised by authorised persons, and the accidental use of overhauled versions of a document shall be prevented by appropriate measures.
The documentation system must be regularly checked for timeliness and efficiency by the responsible person in accordance with § 20c of the Medicines Act. (4) The self-inspections according to § 11 para. 1 are at least every two years in tissue establishments. to be carried out by qualified and competent persons, Section 11 (2) shall not apply. Unofficial table of contents

Section 33 Determination of the suitability of the donor and the laboratory tests required for the collection

(1) The determination of the suitability of the donor in the removal equipment and the laboratory tests required for the extraction in the tissue laboratory laboratory are, according to previously prepared standard operating instructions, in accordance with the good technical Practice. In particular, the requirements of § § 3 to 6 of the TPG tissue regulation must be taken into account. (2) The standard work instructions referred to in paragraph 1 must be approved in the case of tissue preparations which have been approved in accordance with Article 21a of the German Medicines Act (TPG). (3) The methods used for laboratory testing shall be validated according to the state of the art and technology. Critical test procedures must be regularly evaluated to determine whether they are still valid and, if necessary, revalidated. The quality of the test procedures referred to in the second sentence shall be reviewed by regular participation in a formal performance test system. Only reagents and other materials accepted by the company shall be used for laboratory testing. The laboratory reagents shall be suitable for their purposes and shall be released before use by a qualified person. (4) The laboratory tests shall be carried out in accordance with the standard operating instructions referred to in paragraph 1 (test instruction). and to log in full (audit trail). The person responsible for the laboratory results in the tissue laboratory laboratory shall confirm in the test log with the date and signature that the laboratory tests have been carried out in accordance with the test instruction and that the test results are correct . Unofficial table of contents

Section 34 Extraction of tissue by the removal device

(1) § 4 shall not apply to removal equipment. The staff who take off the tissue must have successfully completed a training course according to a given programme prior to carrying out this activity. A clinical team specialising in the tissue to be removed has to be drawn up in the course of this training. and in the case of Section 20b (2) of the Medicines Act, the respective working or processing tissue establishment or the holder of a permit pursuant to Section 13 of the Medicines Act was also involved. The training must also include the handling of medical devices for the removal of tissue. (2) § § 5 and 6 shall apply to take-off devices with the proviso that the operating rooms and equipment as well as the hygiene measures may be suitable , to protect the properties of the tissue required for its use and minimise the risk of microbial contamination during the removal process:
1.
For the removal of tissue, sterile medical devices must be used. To the extent that medical devices are used again, their treatment must be carried out in accordance with § 4 (2) of the Medical Devices Act.
2.
The withdrawal of live donors shall be carried out in an environment adapted to the extent and degree of risk of the interventions. In principle, the rooms are considered suitable if they are used for comparable medical treatment in compliance with the requirements of the hygiene regulations, including the hygiene measures.
3.
Dispensing with deceased donors should be done in clean rooms, where the removal area is covered with sterile cloths.
4.
If the removal of tissue by personnel posted by the withdrawal facility (mobile teams) must be carried out outside the premises covered by the licence pursuant to § 20b of the Medicines Act, and the possibility of removal by mobile teams , in principle, paragraphs 1 and 3 shall apply mutatily to the authorization.
(3) The removal of tissue, including any measures intended to preserve, label and transport the tissue in a working or processing condition, shall be carried out in accordance with previously established standard operating instructions. (4) In the case of tissue preparations which have been approved in accordance with § 21a of the German Medicines Act (Medicinal Products Act), the following must be carried out in accordance with the requirements of § 2 of the TPG tissue regulation. Withdrawal instructions provided for in paragraph 3 correspond to the approval documents. (5) The The removal instructions referred to in paragraph 3 shall contain at least the following rules:
1.
on the verification of identity and the determination of the suitability of the donor,
2.
for the collection of the donations and the samples for the laboratory examination and for the handling of the material taken, including
a)
the equipment to be used,
b)
the procedure for the removal and prevention of bacterial or other contamination during the removal, and, if necessary, further measures to minimise the contamination of the tissues;
c)
for the indication of the place of withdrawal, insofar as it is outside the premises covered by the permit, and, where necessary, conditions to be met, and in the case of deceased donors, for the documentation of the period between the entry of the death and the Withdrawal of donation,
3.
requirements for the donation and sample containers as well as the storage and transport solutions used and other products and materials that come into contact with the donations and which have an impact on their quality and safety ,
4.
for the labelling of the donations and the samples referred to in paragraph 6,
5.
on conditions of interim storage of the donations or of the samples up to their transport for working or processing, or for laboratory examination, which is suitable for obtaining their characteristics and biological functions.
The sampling procedure must be appropriate to the person to be donated and to the species of donation, to preserve the properties of the tissues required for their use, and to minimise the risk of microbial contamination of the donation. (6) The Tissue donations shall be provided at least with the following information at the time of their removal:
1.
Type of donation and indication of the donor's traceability in the case of the withdrawal facility, which is compatible with data protection, and the identification of the donor as an organ donor, if the donor is responsible for the transfer of organs for the purpose of transmission have been taken,
2.
Day and, where possible, time of withdrawal,
3.
Warning of potential hazard potential,
4.
if available, type of additives used,
5.
in the case of autologous donations, the indication "Only for autologous use" and in the case of directed donations, the information on the recipient.
Where the information referred to in the first sentence of the first sentence of 1 (2) to (5) cannot be made on the container, they shall be listed in an accompanying document which shall be annexed to the container. In particular, the identification of the samples for the laboratory examination must be possible without any doubt as to the assignment of the person to be donated and shall indicate the place and time of the sampling. (7) The tissue sampling and sampling shall be carried out in accordance with the To carry out the removal instructions in accordance with paragraph 3 and to record in full (removal report) without prejudice to the medical documentation requirements according to § 8d (2) of the Transplantation Act. The withdrawal report shall contain at least the following information:
1.
the name and address of the tissue equipment to be obtained from the tissue;
2.
Donor identity with details of the surname, first name, sex, day of birth and in the case of live donors address or, as far as is recognized, the assignment number assigned by the tissue dispenser for the tissue dispenser as well as the donor's identification as an organ donor, if organs have been removed from the donor for the purpose of transmission;
3.
description and identification code of the removed tissue;
4.
Family name, first name and address of the doctor responsible for the removal;
5.
the date, time and place of collection and the manner in which the collection and any interim storage may be carried out;
6.
in the case of deceased donors, the date of death, the description of the conditions under which the body is kept; provided that cooling is carried out, the time of commencement and the end of the cooling process;
7.
Identification/batch number of the storage and transport solutions used.
All deviations in the process and from the specification of the specification are to be documented and thoroughly investigated. Any incidents that have occurred during the removal process may also be documented, including the investigations which have been carried out. The person responsible for the removal has to confirm in the withdrawal report with the date and signature that the removal has been carried out in accordance with the removal instructions and that the tissues for processing, working or processing are carried out, Conservation or preservation within the meaning of Section 8d (1) sentence 2 No. 4 of the Transplant Act is released. The removal report shall be transmitted to the tissue device which processes or processes the extracted tissue. The requirements for the donor file in accordance with § 5 of the TPG tissue regulation remain unaffected. Unofficial table of contents

§ 35 Transport for processing and processing in the tissue establishment

(1) The transport must be carried out after the standard operating instruction has been created. The method must be appropriate for the donation and must protect the properties of the tissues required for their use, as well as minimise the risk of microbial contamination of the donation. It is necessary to determine the type of transport container and its marking in accordance with paragraph 2, the transfer of any samples as well as the removal report according to § 34, paragraph 7, to the processing or processing tissue establishment. (2) Without prejudice to § 7 (3), the following shall be determined: At least the following particulars shall be provided for the transport of the fabric for working or processing:
1.
"Caution" and "tissues and cells",
2.
the addresses and telephone numbers of the withdrawal device and the tissue establishment which is to receive the tissue or tissue preparations for processing or processing, as well as the names of the relevant contact persons,
3.
the date and time of the start of transport, relevant transport and storage conditions,
4.
Precautions and instructions for handling and use.
(3) The reception in the tissue equipment for the processing or processing of the tissue, including the accompanying documents and samples from the removal means, must be carried out after the standard operating instruction has been produced beforehand. The procedure shall, in particular, include the review of
1.
the integrity of the packaging,
2.
Marking,
3.
Compliance with transport conditions and
4.
the documentation provided and, where applicable, samples supplied
collect. The tissues shall be kept in quarantine until a decision has been taken on their use. To the extent that they do not meet the requirements, they must be discarded. The acceptance or rejection of the tissue is to be documented. Where the tissue has been removed from a donor in which organs have also been removed for the purpose of transmission, the tissue establishment shall immediately inform the coordinating body of the transplant law in accordance with Article 11 (1) of the Transplantation Act. Donor identity in accordance with Article 34 (7), second sentence, point 2, indicating whether or not the received tissue has been accepted or rejected. Unofficial table of contents

§ 36 Processing and storage of the tissue by the tissue establishment

(1) Without prejudice to § 4 (1), the personnel under the responsibility of the responsible person must be informed in accordance with § 20c of the Medicines Act concerning the legal and ethical relationship of his activity. By way of derogation from § 4 (2) sentence 1, job descriptions shall be provided for all personnel. (2) The operating rooms and equipment according to § 5 and the hygiene measures in accordance with § 6 must be suitable to protect the properties of the fabric, which are necessary for their use and minimise the risk of microbial contamination during working or processing:
1.
To the extent that the tissues are exposed to the environment during their working or processing, this must be done in an environment with a defined air quality and cleanliness. The effectiveness of these measures shall be validated and monitored.
2.
In so far as the tissues referred to in point 1 are not subjected to an inactivation or sterilisation process, the degree of air purity for the number of germs and the number of particles corresponding to class A of the EC-GMP guideline shall be the degree of air purity during the working or processing operation, Annex 1 (Notice of 12 March 2008, BAnz. 1217), with a background environment suitable for the working or processing of the tissue, which corresponds to at least Class D of Annex I of the Guide in relation to the number of particles and germs. Requirements for the environment may be deviated if:
a)
a validated procedure for the inactivation of germs or for end sterilisation is used; or
b)
it is demonstrated that exposure to a Class A environment has adverse effects on the required properties of the tissues; or
c)
it is demonstrated that the use of tissues in the recipient or the recipient entails a significantly lower risk of transmission of a bacterial or fungal infection to the recipient or to the recipient than in the case of the recipient. the tissue transplant, or
d)
it is technically not possible to carry out the required procedure in a class A environment.
It shall be demonstrated and documented that the required quality and safety of the tissue or tissue preparation is achieved with the chosen environment, at least taking into account the purpose of the intended purpose, the nature of the use and the nature of the use, and the immune status of the recipient or the recipient. (3) All critical equipment and equipment shall be qualified according to previously established standard operating instructions, which shall also determine measures in the event of possible malfunctions, and shall be regular To carry out inspections. They are to be preventable according to the instructions of the manufacturer. Equipment with a critical measuring function shall be calibrated. New and repaired equipment must be tested during installation and be released prior to use. The activities carried out shall be documented. (4) The working or processing, including any inactivation measures as well as the marking and packaging, shall be carried out in accordance with a previously prepared standard operating instruction (Be- or processing instruction), which also specifies critical additives, in accordance with good professional practice. (5) In the case of tissue preparations which have been approved in accordance with Article 21a of the Medicines Act, the working or processing instructions must be carried out in accordance with the requirements of the German Medicines Act. the processing instructions referred to in paragraph 4 correspond to the approval documents. (6) The Processing procedures shall be regularly assessed to ensure that they continue to achieve the desired results. Critical working or processing procedures, including any inactivation measures, shall be validated according to the state of science and technology, and the tissues or tissue preparations shall not be clinically ineffective or harmful. for the recipients. (7) During all stages of processing or processing, the identification and status of the tissue or tissue preparation as well as the traceability to the person to be donated must be derived from the marking, insofar as this is not ensured by other measures. If it is an autologous or directed tissue preparation, this should also be indicated. Tissue or tissue preparations of donating persons who have been tested positive for infections or whose laboratory examination results are not yet available shall be labelled accordingly. (8) Without prejudice to the requirements of § 10 (8b) of the Medicines Act, tissues and tissue preparations must, before they are placed on the market, be accompanied by the following information and information on the outer container and, where used, on the outer wrapping or in an accompanying document:
1.
description and, where necessary, dimensions of the tissue, morphology and functional data,
2.
the results of the laboratory tests required for the collection,
3.
the date of delivery,
4.
Inventory recommendations,
5.
Instructions for opening the container, the packaging and, where necessary, handling,
6.
Expiry date after opening or after the specified handling,
7.
where applicable, the presence of potentially harmful residues.
In addition, the recipients of tissue or tissue preparations shall be accompanied by guidance for the reporting of serious adverse reactions or serious incidents in accordance with § 40. (9) The working or processing shall be carried out in accordance with the To carry out and to log in full the instructions provided for in paragraph 4 (processing or processing protocol). All deviations in the process and from the specification of the specification are to be documented and thoroughly investigated. The person responsible for the processing or processing shall confirm in the record with the date and signature that the working or processing has been carried out in accordance with the instruction. The working or processing protocol must be fully traceable between the donor and the donation, as well as the intermediate and final products obtained therefrom, including the materials used and their batch designations, and (10) Without prejudice to § 7, the storage must be carried out in accordance with the standard operating instructions which have been previously produced, under the following conditions: controlled conditions and be suitable, the quality of the tissues and to maintain tissue preparations. The maximum storage period shall be fixed for each type of storage condition. Before release in accordance with § 38, the tissues and tissue preparations shall be stored administratively or physically in quarantine and by released tissues and tissue preparations separately. If tissue or tissue preparations have been discarded, they shall be stored separately in order to avoid confusion and cross-contamination. Unofficial table of contents

Section 37 Examination of tissue and tissue preparations

(1) The verification of compliance with the specified specification shall be carried out in accordance with the good professional practice according to previously established standard work instruction (test instruction). (2) In the case of tissue preparations which have been approved in accordance with § 21a of the German Medicines Act, the test instruction must comply with the documents relating to the approval. (3) The examination shall be in accordance with the test instruction referred to in paragraph 1 and to log it completely. All deviations in the process and from the specifications of the specification are to be documented and thoroughly investigated. The person responsible for the examination shall confirm in the audit trail with the date and signature that the examination has been carried out in accordance with the test instruction and that the results are correct. Unofficial table of contents

§ 38 Release by tissue establishment

(1) The release of tissue or tissue preparations may only be carried out by the responsible person in accordance with § 20c of the German Medicines Act and only on the basis of a standard working instruction previously approved by the person responsible. The procedure must prevent accidental release of the tissue or tissue preparations if the conditions laid down in paragraph 2 are not met. (2) The release may only be carried out if the verification of all the documents required for that purpose is to be carried out. Conformity of the tissues or tissue preparations with their specifications, including the final packaging, has been confirmed and in the case of tissue preparations subject to the authorisation requirement in accordance with Article 21a of the Medicinal Products Act, the conformity of the tissue or tissue preparations according to § 21a of the with the approval documents. (3) The person responsible Pursuant to § 20c of the Medicines Act, only persons who have the expertise in accordance with Section 20c (3) of the Medicines Act may be represented. The records must clearly show who carried out the release. (4) The responsible person in accordance with § 20c of the German Medicines Act must carry out a risk assessment for such tissues and tissue preparations which, after they have been released, still have to be have not been extradited and the expiry date of which has not yet expired, if subsequent findings on a change in the profit, working or processing or the test procedures or the donor selection criteria or the Laboratory examination procedures with the aim of improving quality. Tissues and tissue preparations may only be delivered after the positive conclusion of the risk assessment and written confirmation of release. The risk assessment shall be documented. Tissue and tissue preparations already delivered may only be returned to the stock if they have been assessed in accordance with the procedure laid down in writing and have been classified as being consistent with the specification. Unofficial table of contents

Section 39 placing on the market, importation and transport by tissue equipment

(1) tissues and tissue preparations may only be placed on the market if they have been released in accordance with Section 38. (2) In the event of a movement of tissue preparations from a Member State of the European Union or another State Party to the Agreement on the European Economic Area within the scope of the Medicines Act the responsible person must, in accordance with § 20c of the German Medicinal Products Act, reassure himself, before the release pursuant to § 38, that the conditions for Article 21a (9) of the German Medicines Act (Medicinal Products Act) is fulfilled. (3) On imports of tissue or tissue preparations from countries which are not Member States of the European Union or other States Parties to the Agreement on the European Economic Area, the person responsible shall, in accordance with Article 20c of the Medicinal Products Act, be present before the Release in accordance with § 38, in particular, reassure that the requirements of § 72b (1) and (2) of the Medicines Act are fulfilled. Section 32 (1) sentence 2 shall remain unaffected. (4) The transport shall be carried out according to a previously defined standard operating instruction. The method must be appropriate to the tissue or tissue preparation and to protect the properties of the tissue or tissue preparation required for its use, as well as the risk of microbial contamination of the tissue or tissue; or (5) Without prejudice to Article 7 (3), the transport containers shall be provided with at least the following information:
1.
"Caution" and "tissues and cells",
2.
the identification of the tissue device which has been used or processed by the tissue or tissue preparations, and the device to be used for the tissue or tissue preparations, including their addresses and telephone numbers, and
3.
relevant transport and storage conditions and, if necessary, other precautionary measures and instructions for handling.
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Section 40 Notification of serious adverse reactions and serious incidents and recall

(1) Without prejudice to § 13c of the Transplant Act, the person referred to in the third sentence of sentence 3 of the German Medicines Act shall be responsible for the fact that the tissue establishments concerned shall be responsible for the treatment of the tissue establishments referred to in the first sentence of Standard working instruction on all serious adverse reactions referred to in § 63i (7) of the German Medicines Act and corresponding suspected cases, which are responsible for the quality and safety of tissues or tissues. Tissue preparations may be influenced or returned to the tissue preparations immediately in Knowledge is to be made. The second sentence of paragraph 3 shall apply. (2) Paragraph 1 shall apply mutatily to the collection and tissue collection laboratories in the event of serious incidents within the meaning of Section 63i (6) of the Medicines Act and related suspected cases; which have been carried out in connection with the extraction or the laboratory tests required for the collection. (3) In tissue establishments, the responsible person is responsible, in accordance with § 20c of the German Medicines Act, for all known reports of serious adverse reactions referred to in paragraph 1 of this Article to be published in accordance with the provisions of paragraph 1 of this Article. standard work instruction previously created and evaluated. The reports shall be submitted to the competent authority or competent authority in accordance with Section 63i (2) or (3) of the German Medicines Act and, in so far as the tissue donor is also organ donor, the coordinating body according to § 11 of the German Medicines Act (Bundesoberbehörde). Transplant Act shall be transmitted immediately. Sentence 1 shall also apply to suspected cases of such reactions. Where:
1.
the initial notification shall contain all the necessary information, in particular for the identification of the collection and tissue establishment, the tissue donor laboratory, the person concerned and the donation, the date of registration and the date of the acquisition of the donation. and the suspected response, the nature of the tissue or tissue preparation involved in the suspected response and the suspected reaction, and the degree of probability of a relationship between the administration of the tissue or the tissue or the tissue. Tissue preparation and the recipient reaction,
2.
the initial notification shall be specified as soon as sufficient evidence is available for it; in particular, it shall be indicated whether the initial notification is to be confirmed or whether, and if so, the manner in which a change in the first classification is to be reported; to the extent that: , it shall also indicate the clinical course of the recipient or the recipient and any further conclusions, including any corrective measures and measures relating to the use of such products, for use in the case of the recipient or the recipient. tissue and tissue preparations supplied to humans.
(4) Paragraph 3, sentences 1 to 3, shall apply to serious incidents within the meaning of Article 63i (6) of the Medicines Act. The following must be:
1.
the initial notification shall contain all the necessary information, in particular for the identification of the removal and tissue equipment, the tissue donor laboratory, the donation concerned, the date of notification and the date of the serious incident, whether or not it is Defects in tissue or tissue preparation, defective equipment or human error, and whether the defect in the extraction, the laboratory examination required for the extraction, the transport for the processing or processing of the tissue, Tissue equipment, working or processing, testing, release, storage, the transport, placing on the market or any other activity has occurred;
2.
the initial notification will be specified as soon as sufficient evidence is available for it. In particular, the main cause is to be analysed and to report on corrective measures taken.
(5) The responsible person in accordance with § 20c of the Medicines Act shall be responsible for the identification of tissue and tissue preparations affected or likely to be affected by reports referred to in paragraphs 1 to 4, and can be recalled. It shall, in accordance with a written procedure, assess the need for a recall and shall coordinate the necessary measures within pre-determined periods and shall inform the competent authority of any recall without delay. and also to indicate to which facilities the tissues or tissue preparations have been delivered and what measures it has taken with regard to other tissues and tissue preparations that may be affected. The effectiveness of the procedures shall be reviewed regularly. (6) The details, in particular the technical specifications and formats of the notifications referred to in paragraphs 3 and 4, shall be made available to the competent federal authority in a (7) On the content of the reports, the nature of the review and the lessons learned, the outcome of the evaluation, the coordinated actions and the notifications, as well as the Handling of returned tissue or tissue preparations has the responsible Person according to § 20c of the Medicines Act records. Sentence 1 shall apply to persons in accordance with Section 20b (1) sentence 3 No. 1 of the Medicines Act. Unofficial table of contents

§ 41 Storage of documentation

(1) For the storage of records relating to the collection, laboratory inspection, working or processing, testing, release, storage, transfer into or out of the scope of the Medicines Act, the import or export, the Placing on the market, including delivery and final determination of tissue or tissue preparation, as well as records of the responsible person according to § 20c of the Medicinal Products Act, § 15 of the Transplantation Act Application. (2) The retention must be without prejudice to § 14 of the transplant law in a suitable area of the rooms covered by the authorisation in accordance with § 20b or § 20c of the Medicines Act. Access to the records referred to in paragraph 1 shall be restricted by means of appropriate measures on persons authorized to do so. (3) In the event of closure of the removal or tissue establishments or tissue or tissue establishments laboratories in which the In the case of the documentation referred to in paragraph 1, the pharmaceutical operator shall ensure that the documentation is kept during the entire retention period.

Section 6
Irregularities

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§ 42 Administrative Offences

Contrary to the provisions of Section 97 (2) (31) of the Medicinal Products Act, who intentionally or negligently acts
1.
, contrary to Article 13 (3a), certain security features are partially or completely removed or covered without first convincing themselves of the authenticity of the medicinal product or replacing it with those which do not in an equivalent manner make the verification of authenticity and allow for the integrity of the outer packaging,
2.
, contrary to Article 16 (1) or section 25 (1), release a charge or active substance of non-human origin for placing on the market,
3.
, contrary to the first sentence of Article 17 (1) or the first sentence of Article 26 (1), a product referred to there is placed on the market without prior release,
4.
Contrary to the first sentence of Article 18 (1) or the first sentence of paragraph 2, the first sentence of the first sentence of the second sentence shall not ensure that a
5.
Contrary to Section 18 (3) sentence 1, it does not ensure that a model referred to therein is kept,
5a.
the competent authority or the holder of the authorisation shall not, or not be informed in due time, in accordance with Article 19 (2
6.
the use of compound feedingstuffs, contrary to Article 30 (1),
7.
Contrary to Article 30 (4), a medicated feedingstuffs is placed on the market,
8.
contrary to § 30 (7) sentence 3, a prescription shall not, not correct, be completed in full or not in good time, or
9.
Contrary to § 30 (7) sentence 4, the original shall not be retained or not, or shall not be presented in due time, or shall not be handed over in good time, or shall not be stored in good time.

Section 7
Final provisions

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Section 43 Transitional regime

This Regulation shall not apply to active substances which, at the date of entry into force of this Regulation, are stored within the scope of the Medicines Act or are referred to by virtue of an existing contractual obligation, and which are subject to the 9 November 2008 shall be carried out in countries outside the European Union or the European Economic Area.