Regulation On The Application Of Good Manufacturing Practice In The Production Of Medicines And Drugs And About The Application Of Good 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 professional practice in the manufacture of products of human origin (medicinal products and drugs). Active Ingredient Manufacturing Ordinance-AMWHV)

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AMWHV

Date of delivery: 03.11.2006

Full quote:

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

:Last modified by Art. 1 V v. 28.10.2014 I 1655

For details, see Notes

Footnote

(+ + + Text evidence from: 10.11.2006 + + +)
(+ + + Amcial). Notification of the norm provider to EC law:
Implementation of the
EGRL 20/2001 (CELEX Nr: 301L0020)
EWGRL 412/91 (CELEX Nr: 391L0412)
EGRL 82/2001 (CELEX Nr: 301L0082)
EGRL 83/2001 (CELEX NO: 301L0083)
EGRL 94/2003 (CELEX NO: 303L0094)
EGRL 33/2004 (CELEX NO: 304L0033)
EGRL 23/2004 (CELEX No: 304L0023)
EGRL 61/2005 (CELEX) No: 305L0061)
EGRL 62/2005 (CELEX Nr: 305L0062)
EWGRL 167/90 (CELEX Nr: 390L0167) + + +)

The V has been referred to as Article 1 of the V v. 3.11.2006 I 2523 from the Federal Ministries of Health and Food, Agriculture and Consumer Protection in agreement with the Federal Ministries of Economy and Technology, for the Environment, Nature Conservation and Nuclear Safety, for Health and with Approved by the Federal Council. She's gem. Article 6, first sentence, of this V entered into force on 10 November 2006.
This Regulation is intended to implement the
-
Commission Directive 91 /412/EEC of 23 November 2006. 1 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 70),
-
Directive 2001 /20/EC of the European Parliament and of the Council of 4. 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 on medicinal products for human use (OJ L 327, 30.4.2001, EC No 34),
-
Directive 2001 /82/EC of the European Parliament and of the Council of 6 June 2001. November 2001 on the Community code relating to veterinary medicinal products (OJ L 327, 28.12.2001, p. EC No 1), as amended by Directive 2004 /28/EC of the European Parliament and of the Council of 31 December 2001, 1 March 2004 (OJ L 327, EU No 58),
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Directive 2001 /83/EC of the European Parliament and of the Council of 6 June 2001. November 2001 on the Community code relating to medicinal products for human use (OJ L 327, 28.12.2001, p. EC No 67), as last amended by Directive 2004 /27/EC of the European Parliament and of the Council of 31 December 2001 on the European Parliament and of the Council of the European Communities 1 March 2004 (OJ L 327, EU No 34),
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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 22),
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Commission Directive 2004 /33/EC of 22 June 2002 on the implementation of the European Commission's 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 25),
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Directive 2004 /23/EC of the European Parliament and of the Council of 31 December 2001. March 2004 on setting standards of quality and safety for the donation, procurement, testing, processing, preservation, storage and distribution of human tissues and cells (OJ L 327, 28.3.2004, p. EU No 48),
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Commission Directive 2005 /61/EC of 30 June 2000. 1 September 2005 on the implementation of Directive 2002/98/EC of the European Parliament and of the Council as regards requirements for traceability and reporting of serious incidents and serious adverse reactions (OJ L 327, 30.12.2005, p. EU No 32),
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Commission Directive 2005 /62/EC of 30 June 2002. 1 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, 30.12.2005, p. EU No 41),
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Council Directive 90 /167/EEC of 28 June 1992, p. The Commission adopted a proposal for a resolution on the conditions for the production, placing on the market and use of medicated feedingstuffs in the Community (OJ L 327, 31.12.1990, p. EC No L 92 p. 42).
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content overview

Section 1
Scope and definitions
§ 1 Scope
§ 2Definitions
Section 2
General Requirements
§ 3 Quality Management System, Good Manufacturing Practice and Good Professional Practice
§ 4Personal
§ 5Operating rooms and equipment
§ 6Hygienic Measures
§ 7Storage and transport
§ 8Animal husbandry
§ 9Work on work order
§ 10General documentation
§ 11Self Inspections and Supplier Qualification
Section 3
Medicines, blood products and other blood components, as well as products of human origin
§ 12Personnel in senior and in responsible position
§ 13 Manufacture
§ 14Review
§ 15 Labeling
§ 16Release to Marketing
§ 17 Placing on the market and imports
§ 18Hold pattern
§ 19 Beanies and recall
§ 20documentation retention
Section 4
Active substances of non-human origin
§ 21Organization structure
§ 22Manufacturing
§ 23Review
§ 24Labeling
§ 25Release to market
§ 26Placing on the market and importation
§ 27reset pattern
§ 28Beanies and Recall
§ 29Retention of documentation
Section 5
Special Rules
§ 30 Supplementary regulations for medicated feedingstuffs
§ 31Supplementary Regulations for Blood Dispensing Devices
Section 5a
Special provisions for removal and tissue equipment, and for tissue dispenser laboratories
§ 32Supplemental general requirements
§ 33 Determination of the suitability of the donor and the laboratory tests required for the collection
§ 34Extraction of tissue by the Removal device
§ 35Transport for working or processing and receiving in tissue equipment
§ 36Processing and processing of tissue by tissue equipment
§ 37Fabric examination and tissue preparations
§ 38Release by tissue device
§ 39 Placing on the market, importation and transport by tissue equipment
§ 40Reporting of serious adverse reactions and serious incidents and recall
§ 41Documentation retention
 
Section 6
Violations
§ 42 Administrative Offences
Section 7
Final Provisions
§ 43Transitional

Section 1
Scope and definitions

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§ 1 Scope of application

(1) This Regulation shall apply to establishments and facilities that are
1.
Medicines,
2.
Active substances intended for the manufacture of medicinal products that are human or animal or microbial origin or which are produced by genetic engineering ,
2a.
tissues within the meaning of § 1a No. 4 of the Transplantation Act, as amended by the 4. September 2007 (BGBl. 2206),
3.
certain substances of human origin for the manufacture of medicinal products,
4.
other than the active substances referred to in paragraph 2 that are intended for the manufacture of pharmaceuticals, or
5.
other substances other than those mentioned in point 3 and intended for the manufacture of medicinal products for human use, provided that they are subject to the regulations of a reasonable good Manufacturing practice in accordance with the guidelines laid down by the European Commission in accordance with Article 47 (5) of Directive 2001 /83/EC of the European Parliament and of the Council of 6 June 2001 on the implementation of the November 2001 on the Community code relating to medicinal products for human use (OJ L 327, 28.12.2001, p. 67), as last amended by Directive 2011 /62/EU (OJ L 311, 28.11.2011, p. 74), which are to be manufactured, tested, stored, placed on the market, or in or out of the scope of the Medicines Act, are (auxiliary substances),
. 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-pendulum-labours.(2) The Regulation shall also apply to
1.
Pharmacies, retail trade in medicinal products outside of Pharmacies, persons who are doctors or otherwise have the power to exercise the medicine in humans, dentists, veterinarians, veterinarians ' pharmacies and wholesalers of medicinal products, insofar as they are authorised under § 13 or § 72 (1) of the Drug law requires, and
2.
pharmaceutical companies according to § 4 (18) of the Medicines Act,
3.
Companies and establishments or persons acting with active substances for the manufacture of medicinal products intended for use in humans.
(3) The requirements this Regulation shall not apply to
1.
Substances according to the homeopathic pharmacopoeia which are intended for the manufacture of Homeopathic preparations are used as starting materials,
2.
Active substances which are substances within the meaning of § 3 (1), (2) or (3) of the Medicines Act, or as far as they are not subject to the requirements of the EC GMP guide,
3.
(omitted)
4.
(omitted)
5.
(omitted)
6.
Active substances for ectoparasitics for use in animals as well as
7.
Active substances for medicines that are are intended exclusively for use in pet animals according to § 60 of the German Medicines Act and are approved for circulation outside of pharmacies.
In the case of sentence 1, compliance with comparable standards and procedures shall be ensure that the quality of production and testing is equivalent to the requirements laid down in Sections 2 to 4.(4) The Regulation shall not apply 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 shall not apply to active substances, excipients and intermediates solely for the purpose of being placed in countries other than the Member States of the European Union or other States Parties to the Convention on the The European Economic Area (EEA) is, and is intended to be, under customs supervision and without manufacturing steps within the meaning of Article 46a (1) of Directive 2001 /83/EC or Article 50a (1) of Directive 2001 /82/EC of the European Economic Area (EC) Parliament and the Council of 6 November 2001 on the Community code relating to veterinary medicinal products (OJ L 327, 28.12.2001, p. EC No 1), as amended by Directive 2004 /28/EC of the European Parliament and of the Council of 31 December 2001, 1 March 2004 (OJ L 327, 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 Implementing 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 136, 31.7.2001, p. 5) shall remain unaffected. Non-official table of contents

§ 2 Definitions

For the purposes of this Regulation < dl style="font-weight:normal; font-style:normal; text-decoration:none; ">
1.
products of human origin for the manufacture of pharmaceutical products are certain active substances within the meaning of § 4 Article 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 of human origin, in the processed or unprocessed state, with the exception of blood products within the meaning of § 2 No. 3 of the Transfusion Act, as amended by the 28. August 2007 (BGBl. 2169) and other blood components,
2.
is an excipient of any component of a medicinal product, with the exception of the active substance or the active substance. 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 thereof. 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 2003, 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 June 1991, 1 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 70); the Federal Ministry of Health is aware of the current version of the guide in German in the Federal Gazette,
4.
Quality management system (QM system) a system that includes quality assurance, good manufacturing practice or good professional practice, including quality control and periodic product quality checks ,
5.
are specifications of specifications and requirements to which starting materials or intermediate products for the preparation of medicinal products or active substances, active substances, medicines or tissues; they serve as the basis of the quality assessment,
6.
Inprocess controls are performed during manufacture. Checks to monitor and, if necessary, adjust the process and ensure that the product is in compliance with its specification
7.
Investigational 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 June 2008. March 2006 (BGBl. I p. 542),
8.
is the management of the production or management of the quality control of the conductors or the head of the production or quality control in the Article 14 (1) No. 2 of the German Medicines Act,
9.
Blood donation facility is a body within the meaning of § 2 No. 2 of the Transfusion Act, the blood or Bleeding, testing, processing, marking, packaging, release, storage, placing on the market within the meaning of § 4 (17) of the Medicinal Products Act, introducing, executing, carrying out or entering into or out of the scope of the Medicines Act
10.
tissue establishment is a body that carries out the activities listed in § 20c (1) or § 72b (1) of the Medicines Act or the tissues or tissue preparations from Member States of the European Union or of other States Parties to the Agreement on the European Economic Area in or out of the scope of the Medicines Act, provided that: Tissue establishment shall also recover tissue, it shall also be a removal device within the meaning of point 11; provided that the tissue establishment also carries out the laboratory tests required for the extraction, it shall also be a tissue laboratory in the sense of Number 13,
11.
means a device that acquires specific tissues for use in humans within the meaning of Section 1a (4) of the Transplantation Act, , including any measures intended to maintain, identify and transport the fabric in a working or processing condition,
12.
is a person who donates a donation within the meaning of § 2 No. 1 of the Transfusion Act or a tissue donation
13.
is a tissue laboratory laboratory that carries out the laboratory tests required for tissue engineering,
14.
are job descriptions written in writing about the specific tasks, responsibilities and responsibilities of the individual employees or employees of an operating or device assigned to their respective lines,
15.
is a standard operating statement (SOP), a written statement to describe The individual steps of recurrent operations (standard working methods), including the materials and methods to be used,
16.
is validation of the Providing a documented proof that proves to be high-security that a specific process or standard working method produces a product that provides the previously defined specifications and quality characteristics. ,
17.
Qualification is the provision of a documented proof that proves to be high-security that a specific item of equipment or a specific item of equipment is required to be able to specific environmental condition for the manufacture of a product that corresponds to the specifications and quality characteristics set out above,
18.
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.
are critical equipment or devices that come into contact with the products or 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. The QM system shall, in the cases referred to in paragraph 2, 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 shall provide for the areas concerned. 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 be checked for its functional capability.(2) The interpretation of the principles of good manufacturing practice applies to medicinal products, blood products within the meaning of § 2 No. 3 of the Transfusion Act and other blood components as well as to 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.(3) Paragraph 2 shall not apply to the collection and tissue establishments and tissue or tissue establishments which carry out their activities in accordance with the standards of good professional practice. Non-official table of contents

§ 4 staff

(1) The establishments and facilities must provide qualified and properly qualified personnel in adequate number. 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 an ongoing basis. The instruction must cover, in particular, the theory and application of the concept of quality assurance and good manufacturing practice, or in the cases of Section 3 (3) of Good Professional Practice, as well as the specific features of the product group, which is manufactured, tested or stored. The success of the training must be examined.(2) The duties of the employees in the executive 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 good professional practice, must be carried out in Job descriptions are set. 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. Non-official table of contents

§ 5 Operating rooms and equipment

(1) The operating rooms must be in accordance with the type, size, number and equipment for the shall be suitable and designed and used in such a way as to reduce the risk of errors to the smallest possible extent and to avoid any effect which would impair the quality of the product. The operating rooms should be arranged in such a way that the production can take place 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) Where the operating rooms and their equipment for manufacturing operations are used for 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 structural condition. They must be sufficiently illuminated and have suitable climatic conditions. The premises shall be protected by appropriate measures against the access of unauthorised persons.(4) The operating rooms and their equipment must be thoroughly cleaned and maintained in order to avoid contamination and cross-contamination as well as any effect impairing the quality of the product. 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) premises and their equipment must be cleaned regularly and, where necessary, shall be disinfected or sterilized. It is to be followed by 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 devices and aids to be used,
3.
if applicable, the sampling method used to verify the effectiveness of the measures and
4.
the people who are responsible for supervision
. The effectiveness of purification and sterilization procedures shall be validated to the extent that 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 for the activities to be carried out. In particular, they should contain provisions on health, hygiene behaviour and protective clothing for the staff.(3) Where animals are used for the manufacture and testing of products to which this Regulation relates, the hygiene requirements must be respected in their keeping. Non-official table of contents

§ 7 Storage and transport

(1) Starting materials, intermediate and end products, and reset patterns shall be stored in such a way that: their quality is not adversely affected and 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 as to ensure that the quality of the contents is not impaired. 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 intended 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 in an interim manner.(4) The person responsible for the storage has to be convinced at regular intervals that the products and materials are stored properly.(5) The procedures for storage and transport shall be laid down in writing. To the extent that 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 demonstrated.(6) During transport to the point of transfer to the recipient's area of responsibility, care must be taken to ensure that no unauthorised access has been granted and that the quality of the products is not impaired. Non-official table of contents

§ 8 Animal husbandry

(1) The state of health of animals used for the manufacture or testing of medicinal products, or Active substances must be kept under constant control by a veterinarian.(2) Where a quarantine is required prior to the use of the animals, they shall be placed in a quarantine stall 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 single-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 team 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 in the manufacture and testing of products to which this Regulation applies may be used. Diseases which may adversely affect production or testing are affected.(4) establishments and establishments which keep animals referred to in paragraph 1 shall keep separate records of animals by animal species containing at least information on the animals referred to in point (1). style="font-weight:normal; font-style:normal; text-decoration:none; ">
1.
Purchase date and date,
2.
race or tribe,
3.
number,
4.
Labeling,
5.
Start and end of quarantine period,
6.
Result of the veterinary examinations,
7.
Type, date and duration of use and
8.
The animals remain after use.
(5) Rooms in which animals are kept must be separated from other areas and must be separated from each other by means of their own Entrance as well as own ventilation systems. Non-official table of contents

§ 9 Activities on behalf

(1) For each activity on the work order, in particular the manufacture, testing, and the The placing on the market or any associated operation carried out on behalf of the contract must consist of a written contract 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 adjudicating entity 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 continue to award any work entrusted to him by the Client to third parties without his written consent. In the case 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. Non-official table of contents

§ 10 General documentation

(1) Holes and facilities must have a documentation system according to 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 investigational medicinal product. 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. Persons who can confirm the proper execution of the respective activities.(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. Non-official table of contents

§ 11 Self-inspections and Supplier Qualification

(1) In order to comply with the provisions of this Regulation , self-inspections must be carried out on a regular basis in accordance with a pre-defined programme. 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 used for the manufacture of medicinal products shall be within the framework of the QM system of the processing operation, in accordance with a written procedure. on the market.(3) The procedure referred to in paragraph 2 shall, in so far as it concerns active substances for the manufacture of medicinal products, to establish proper production
1.
The implementation of the manufacturer's on-site inspections (audits) by providing enough trained staff of the drug manufacturer; instead of your own audit, the Pharmaceutical manufacturers rely on appropriate knowledge of third parties, provided that the requirements for carrying out the audits correspond to those of its own QM system, and
2.
the reviews include that the manufacturer of the active substance for the manufacture of medicinal products for use in humans, provided that the latter is established in a country, the Member State the European Union or any other State Party to the Agreement on the European Economic Area, is registered with the competent authority.
Sentence 1 (1) and (2) shall also apply to importers and distributors, in so far as they are active substances for the manufacture of medicinal products intended for use in human beings.(4) In order to ensure the suitability of the excipients for the manufacture 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 incidents of the past.(5) The specifications of the medicinal products and active substances shall reflect the manufacturers and suppliers who are accepted by the company.(6) Paragraphs 2, 3 (1) and (5) shall apply to other critical starting materials for the preparation of active substances.

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 The responsibility of the competent person must 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 line of manufacture include, in particular,
1.
Ensure that the products are manufactured and stored properly,
2.
Approval of the manufacturing instruction in accordance with § 13 para. 1 and ensuring that these are complied with
3.
Control of maintenance, premises, and equipment for manufacture,
4.
Ensuring that the necessary validations of the manufacturing process are performed and
5.
ensuring the necessary initial and continuous training of the staff working in the field of manufacture.
Quality control includes, in particular,
1.
Approval or rejection of starting materials, Packaging material and intermediate products,
2.
Approval of specifications, instructions for sampling and test instructions in accordance with § 14 para. 1 as well as assuring, that they are being kept,
3.
To ensure that all required checks have been performed
4.
Consent to apply and monitor the analysis laboratories that work on the work order
5.
Control of maintenance, premises, and equipment for carrying out the tests,
6.
Ensuring that the necessary validations of the test procedures are performed and
7.
ensuring the necessary initial and continuous training of the staff working in the field of testing.
The management of the production and management of the Quality control must be independent of each other.(2) Insofar as ready-to-use medicinal products are placed on the market, the areas of responsibility of the phased planner are in addition to the provisions of Section 63a of the German Medicines Act and of Information Officillor in accordance with § 74a of the German Medicines Act Pharmaceutical legislation.(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 must lay down persons who are responsible for the production, including release, for storage and responsible for quality control. Non-official table of contents

§ 13 Manufacture

(1) The manufacturing operations are subject to the responsibility of the management of the Manufacture according to previous written instructions and procedural descriptions (production instruction). They must be in accordance with good manufacturing practice and the accepted pharmaceutical rules.(2) In the case of medicinal products which are authorised or registered, the manufacturing instruction must be subject to the approval or registration documents and, in the case of investigational medicinal products, to the approval dossier for the clinical examination in which they are to be used, . In the case of blood stem cell preparations, which have been approved in accordance with § 21a of the Medicines Act, the manufacturing instruction must comply with the approval documents.(3) For the manufacture of medicinal products, only active substances and excipients within the meaning of Section 2 (2) shall 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) To the extent that ready-to-use medicinal products bearing a safety feature within the meaning of Article 10 (1c) of the Medicines Act are to be repackaged by another manufacturer, the manufacturer shall have himself before the partial or complete removal, or To satisfy the safety features of the authenticity of the medicinal product. 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) The spatial or temporal separation of the individual manufacturing processes or by other appropriate technical or organizational measures shall ensure that cross-contamination and confusion are 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 shall be validated according to the respective state 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 in so 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 the development of the preparation process for the test preparation are to be fully documented.(6) adequate and sufficient resources must be made available for the implementation of 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. In so far as the product is not produced in batches, the first sentence shall apply accordingly.(8) The production protocol shall confirm from the date and signature of the production line that the batch has been produced in accordance with the manufacturing instruction. Non-official table of contents

§ 14 Review

(1) Starting materials and end products, as well as intermediate products, if necessary, are under responsibility check 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. Sentences 1 and 2 shall apply to containers, outer envelopes, packaging and labelling materials and package leaflets.(2) In the case of medicinal products which are approved or registered, the test instruction must comply with the approval or registration documents and, in the case of investigational medicinal products, the approval dossier for the clinical examination in which they are to be used. In the case of blood stem cell preparations, which have been approved in accordance with § 21a of the Medicines Act, the test instruction must comply with the approval documents.(3) The methods used for testing shall be validated according to the respective state of science and technology. Critical test procedures must be regularly evaluated to determine whether they are still valid and, if necessary, revalidated.(4) The test shall be carried out in accordance with the test instruction referred to in paragraph 1 and shall be recorded in full (test protocol). 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 determined, the products shall be marked accordingly; the end date shall be indicated if the shelf life is limited in time.(6) Starting materials, intermediate and end products which do not meet the quality requirements 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. Non-official table of contents

§ 15 Labelling

(1) Medicinal products that are intended for use in humans and are not ready for use in manufacture. Test specimens may only be placed on the market within the scope of the Medicines Act if their containers and, if used, the outer envelopes in accordance with § 10 (1) No. 1, 2, 4, 6 and 9 of the Medicines Act are to be placed in a legible Writing, in German language and in a permanent way.(2) Ready-made medicinal products which are medicinal products within the meaning of Article 2 (2) (1a), (2) or (3) of the Medicines Act may only be placed on the market if their containers and, where used, their outer envelopes according to § 10 of the Pharmaceutical legislation. The information on the dosage form, the active substances and the waiting time can be omitted. In the case of these medicinal products, on the container or, where used, on the outer packaging or in a package leaflet, in addition,
1.
the application areas,
2.
the counter-views,
3.
the side effects,
4.
the interactions with other means.
(3) ready-to-use medicines, which Medicinal products within the meaning of Section 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 para. 1, 2, 6, 8 and 9 of the Medicines Act ). 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 approval or registration, the registration number or registration number shall be omitted.(5) Products of human origin shall be marked on their containers and, if used, their outer envelopes in legible letters in German or English, and in a permanent manner at least as follows:
1.
the name or company and address of the manufacturer of the product and, if different, of the manufacturer, The product is filled, refilled, repacked or remarked,
2.
Name or identification code of the product, connected to the reference " human Origin " and, where possible and applicable, its degree of purity, reference to a pharmacopoeia, and the international abbreviation of the World Health Organization,
3.
where applicable, weight or space content; if biological units or other information are scientifically common, then these are too ,
4.
The batch name of the finished product or, if the product is not produced in batches, the date of manufacture and, where applicable, additional Also, the completed, refilled, repackaged or remarked product,
5.
expiration date or after-test date and
6.
special transport or storage conditions to the extent necessary to maintain the quality of the product.
In justified cases, the competent authority may make exceptions on the labelling. Non-official table of contents

§ 16 Release to be placed on the market

(1) The release of a batch for placing on the market may be made by the knowledgeable person. in accordance with § 14 of the Medicinal Products Act, which is familiar with the product and with the procedures used for its production and testing, only in accordance with written instructions and procedural descriptions referred to in paragraph 2 or 3 previously prepared Set 2.(2) Release must be done only if
1.
is the production log and the audit log is correct. ,
2.
In addition to the analytical results, essential information such as the manufacturing conditions and the results of the in-process controls ,
3.
the verification of the manufacturing and testing documents conformity of the products with their specifications, including the Final packaging, confirmed and
4.
in the case of authorised or registered medicinal products, compliance with the approval or registration documents and in the case of
(3) Insofar as liquefied medical gases are refilled in accordance with Section 13 (3) of the German Medicines Act, the test specimens shall be treated in accordance with the requirements of Article 13 (3) of the Medicinal Products Act. by way of derogation from paragraph 2, only the delivery container of the tanker shall be released prior to placing on the market. 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) Where production or quality control is carried out in several stages, including, where appropriate, at different locations or at different manufacturers, or the complete manufacture, with the exception of release in other establishments, and In accordance with Article 14 of the German Medicines Act, the competent person may, in accordance with § 14 of the Medicinal Products Act, confirmations made by other knowledgeable persons about the stages of manufacture or testing within a quality system recognised by the person responsible for the treatment of refer to the decision 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 be deemed to apply to confirmations submitted by knowledgeable persons under 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 knowledgeable person shall, in accordance with Article 14 of the Medicinal Products Act, be satisfied by personal knowledge or by confirmation of other sufficiently knowledgeable and appropriate persons that the manufacturer must: the situation is to be established and tested in accordance with good manufacturing practice and 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 authorised to carry out the activity in question pursuant to national legislation.(6) In cases of short-term prevention, in particular by illness or holidays, the knowledgeable person according to § 14 of the German Medicinal Products Act can only be represented by persons who are aware of the expertise in accordance with § 15 of the German Medicines Act (Medicinal Products Act) .(7) The holder of a licence in accordance with § 13 or § 72 of the German Medicines Act shall enable the competent person to carry out its task in accordance with § 14 of the German Medicines Act and, in particular, to make available to it all necessary means. . Non-official table of contents

§ 17 Placing on the market and importation

(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 have been 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 within the scope of the Medicinal Products Act, the examination referred to in paragraph 1 may be waited. where 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 have been annexed.(3) In the case of imports from countries which are not Member States of the European Union or other States Parties to the Agreement on the European Economic Area, the examination referred to in paragraph 1 may be waited if the conditions laid down in paragraph 1 are fulfilled. 72a, first sentence 1 of the Medicinal Products Act, in the case of blood products which are not medicinal products and where products of human origin are also satisfied in accordance with Section 72a Sentence 1 (2) of the Medicinal Products Act, or the examination already in another Member State of the The European Union has been carried out and appropriate monitoring reports have been sent.(4) Insofar as investigational medicinal products manufactured 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 and for which a marketing authorisation is granted in the In the case of a clinical trial, the country of origin is to be used as a comparative product, the competent person, in accordance with § 14 of the German Medicines Act, has the responsibility to ensure that each production batch is subject to all necessary tests in order to confirm the quality of the preparations in accordance with the approval documents for the clinical examination in which they are to be applied. 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 manufactured in accordance with standards established by the European Union Standards of good manufacturing practice shall be at least equivalent.(5) In accordance with § 19 sentence 2 of the Medicines Act, the knowledgeable person according to § 14 of the German Medicines Act has, in an ongoing register or a comparable document provided for this purpose, compliance with the regulations for each batch of medicinal products. of the Medicines Act and of this 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-made medicinal products may only be supplied to establishments and facilities which have a permit pursuant to § 13, § 52a or § 72 of the Medicines Act or to be handed over to the End-users are authorized or to other entities or persons who may refer to medicinal products in accordance with § 47 of the Medicines Act. 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 an authorisation pursuant to 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 add the batch designation also applies to
1.
when delivering Medicinal products to hospital pharmacies and pharmacies supplying hospital for the purpose of supplying hospitals,
2.
in the case of blood preparations, sera human blood and preparations of other substances of human origin, as well as genetically engineered blood components which replace missing blood components, including in the case of supply to establishments and facilities for delivery to the Final consumer,
3.
when the medicinal product is used for use in animals, as well as
4.
in the case of medicines that have to carry security features within the meaning of § 10 paragraph 1c of the Medicines Act.
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§ 18 reset pattern

(1) The competent person responsible for release according to § 16 of the German Medicines Act has to ensure that: a sufficient quantity for the recovery of each batch of a finished product for the purpose of an analytical detection, if necessary, and for the detection of the labelling, including the package leaflet, at least one year on the Expiry of the expiry date shall be kept. If the operation in which the release takes place is not at the same time the pharmaceutical contractor, 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 contractually to be regulated. 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 medicinal products is causing particular problems, the competent authority may allow derogations on the samples and their storage.(2) The competent person responsible for the release in accordance with § 16 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 the date of the release of the medicinal product. release of the medicinal products produced using these starting materials, unless a shorter shelf life is indicated in the registration documents. The first sentence shall not apply to solvents, gases and water. The first sentence of paragraph 1 shall be applicable.(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 sufficient material is available from test specimens as well as their identification and printed packaging materials. Samples of each production batch shall be kept for at least two years after 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 patterns of a finished medicinal product as referred to in paragraph 1 shall take place within 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. Non-official table of contents

§ 19 Complaints and recall

(1) The or the step plan representative is responsible for the fact that everyone is aware of collected reports on the risk of medicinal products are collected in accordance with a written procedure and any 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 on a regular basis.(2) The graduated planner or planner shall inform the competent authority without delay of any defect which might result in a recall or unusual restriction of the distribution, and shall also inform the competent authority of the States in which it is Medicinal product has been spent or has been 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 shall also be informed.(3) The stepped-plan officer must comply with the obligation to notify obligations under the Medicines Act to the extent that they relate to medicinal product risks. The reporting obligations under § 14 of the GCP Regulation shall remain unaffected.(4) Paragraph 1 shall apply by analogy to investigational medicinal products. 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 preparations 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 the 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 or planner must, in cooperation with the sponsor, 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 step-planning officer or records records.(6) The stepped-plan officer (s) shall be independent of the sales or distribution units and may only be represented by persons who have the expertise referred to in Article 63a (1), first sentence, of the Medicines Act, and must be present in the The scope of the Medicines Act or in another Member State of the European Union shall be established and active.(7) Where 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/she shall have a corresponding person with the performance of the duties of the phased plan officer or . The person responsible shall be responsible for compliance with the obligations referred to in paragraphs 1 to 5.(8) The pharmaceutical operator shall ensure that all notifications of medicinal products and complaints received during the holding and information for the assessment of the risk-benefit balance of a medicinal product are immediately followed by: or shall be communicated to the stepped planner or to the person responsible under paragraph 7, sentence 1. unofficial table of contents

§ 20 retention of documentation

(1) All records relating to the acquisition, production, including release, the examination, storage, transfer into or out of 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 or the staff of the stepped planner or the person responsible under the first sentence of § 19 (7) sentence 1 shall be kept fully and at least up to one year after 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. shall be withheld.(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.
to identify the donation facility,
2.
to identify the person who spends,
3.
about the name of the medicine,
4.
to the batch label,
5.
to obtain the donation (year, month, day),
6.
to the date of the submission and
7.
about the recipient's name or company
in readable form in keep or store for at least 15 years a suitable storage medium for at least 30 years and the other records relating to the collection of donations and the associated measures pursuant to Section 11 (1) of the Transfusion Act. 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) (1) shall apply to investigational medicinal products subject to the condition that the dossier must be kept at least five years after the end of the last clinical trial in which the batch was applied, and that the documents must be kept at least five years after the end of the test. name="BJNR252310006BJNG000400000 " />

Section 4
Non-Human Active Ingredients

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§ 21 Organizational 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. It must have at least one quality assurance unit that is independent of production. The quality assurance unit shall be included in all quality-related matters.(2) To the extent that active substances are manufactured or imported which are subject to the approval requirement in accordance with § 13 or § 72 of the German Medicines Act (Medicinal Products Act), § 12 para. 1 shall apply.(3) Any person who produces or introduces active substances without a permission in accordance with § 13 or § 72 of the German Medicines Act shall determine the persons entitled to release intermediate products and active substances accordingly. Non-official table of contents

§ 22 Manufacture

(1) The manufacturing operations, including in-process controls, are after previously created carry out written instructions and procedural descriptions (production instruction) and in accordance with good manufacturing practice.(2) In the case of the active substance manufacture which is subject to authorisation in accordance with § 13 of the German Medicines Act, the management of the production is responsible for the approval of the production instruction, unless the release is concerned. In other establishments and facilities, it is the quality assurance unit.(3) Only starting or intermediate products may be used whose quality has been determined and indicated accordingly.(4) The spatial or temporal separation of the individual manufacturing processes or by other appropriate technical or organizational measures shall ensure that cross-contamination and confusion are avoided.(5) The methods used for the preparation are to be validated according to the respective state of science and technology, insofar as these are critical for the quality or purity of the active substance. Critical phases of a manufacturing process must be revalidated on a regular basis.(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 (production 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 rates 1 and 2 shall apply accordingly.(7) In the production protocol, in establishments and facilities which are subject to the approval requirement in accordance with § 13 of the Medicines Act, it is to be confirmed by the management of the production with the date and signature that the batch according to the Manufacturing instruction has been manufactured. 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. Non-official table of contents

§ 23 Review

(1) Starting materials, intermediate products and active substances are after written instructions and have been prepared previously. Test procedures (test instruction) and in accordance with good manufacturing practice. The first sentence shall be applicable to containers, packaging materials and labelling material for the active substances.(2) In the case of active substances whose production requires permission in accordance with § 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 procedures used for the examination shall be validated according to the respective state of science and technology in so far as they are not listed in a pharmacopoeia or a similar set of rules. Critical test procedures must be regularly evaluated to determine whether they are still valid and, if necessary, revalidated.(4) The test shall be carried out in accordance with the test instruction referred to in paragraph 1 and shall be recorded in full (test protocol). All deviations in the process and from the specification in the specification are to be documented and thoroughly investigated.(5) In establishments and facilities which require a permit pursuant to § 13 of the Medicines Act, the management of the quality control in the test log must confirm with the date and signature that the test according to the test instruction has been carried out and the product has the required quality. In other establishments and facilities, appropriate responsibilities shall be laid down.(6) If the required quality has been established, the active substances must be indicated accordingly; the end date shall be indicated if the shelf life is limited in time. If displayed, a verification date can also be specified instead of the expiration 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. Non-official table of contents

§ 24 Labelling

(1) The identification of the intermediate products and active substances shall be made after prior written Carry out instructions and procedural descriptions and in accordance with good manufacturing practice. In the case of the production of the active substance, which is subject to authorization in accordance with § 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 labelled prior to their placing on the market on their containers and, where used, their outer envelopes in a legible font and in a durable manner at least as follows: style="font-weight:normal; font-style:normal; text-decoration:none; ">
1.
name or company and additional address of the manufacturer,
2.
Name or identification code of the product, as far as possible of its degree of purity; if applicable, reference to a pharmacopoeia and-if available-international Short description of the World Health Organization,
3.
Content by weight or volume of space; are biological units or other information on the weight , use them,
4.
batch name or, if the intermediate or active substance is not produced in batches, the product is to be used in batches, Date of manufacture,
5.
expiration date or after-test date,
6.
special transport-or Storage conditions, where 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 or cell line and
8.
in the case of active substances of microbial origin, indicating that it is a The active substance of microbial origin, and in the case of active substances of animal origin, is the name of the animal species used for the production.
(3) Where the intermediate product or the active substance is subsequently operated by a different establishment other than that of the original manufacturer has been refilled, repackaged, marked or released, the name or company name and address of this holding, as well as the new batch name on the container and, where used, the outer packaging of the intermediate product or of the 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. Non-official table of contents

§ 25 Release to be placed on the market

(1) The release for placing on the market may only be made after previously written written Instructions and procedural descriptions referred to in paragraph 3 or 4, first sentence, of persons familiar with the products and with the procedures used for their production and testing shall be made.(2) In establishments and facilities which are subject to the authorisation requirement in accordance with § 13 or § 72 of the German Medicines Act, the competent person is responsible according to § 14 of the Medicines Act for the release of those products which are the To trigger a licence, § 16 (1) and (4) to (7) shall apply. In addition, the quality assurance unit shall be responsible for the release; the persons entitled to release shall be determined in writing.(3) The release referred to in paragraph 1 may only take place if the manufacturing protocol and the test protocol are duly signed, in addition to the analytical results, essential information such as the manufacturing conditions and the results. The inspection of the manufacturing and testing documents has confirmed 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 detected and has a properly signed-in audit log,
2.
has a properly signed production log on refill, bottling, packaging, and identification,
3.
all necessary quality or registration-related information from the original manufacturer and, if applicable, other manufacturers of the active substances or intermediates including the analytical certificates,
4.
sufficient knowledge of the original manufacturer and, where applicable, other manufacturers and their quality management system, and
5.
ensuring traceability to the original manufacturer of the product.
If the intermediate products or Active substances in primary containers other than the original material are either filled or packed, the expiry date specified by the original manufacturer or the date of post-test shall be verified on the basis of additional stability data; and if necessary, to 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 of the first sentence of 1 (3) to (5) are met. Non-official table of contents

§ 26 Placing on the market and imports

(1) Active substances or intermediates that are 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 Section 25. § § 72 and 72a (1) and (2) of the Medicines Act remain unaffected.(2) All quality or authorisation-related information, including the analytical certificates and the name or company and the address of the original manufacturer, shall be communicated to 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. Non-official table of contents

§ 27 Hold pattern

(1) Each batch of active substances has a properly marked pattern in a suitable container and to store them 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) Where a expiry date has been established for the active substance, the samples referred to in paragraph 1 shall be kept for at least one year on the expiry date of the expiry date, but at least three years beyond the full distribution of the batch.(3) In the case of active substances for which a post-test date has been established instead of the expiry date, samples shall be kept for at least three years beyond the full distribution of the batch in accordance with paragraph 1. Non-official table of contents

§ 28 Beanies and recall

(1) All quality-related complaints are in establishments and facilities that are Manufacture or import active substances within the scope of the Medicines Act, or in the scope of the law, to document, examine and to document the quality assurance unit in accordance with the procedures laid down in writing. assess. Where necessary, the original manufacturer must also be informed of the complaints.(2) If there is a suspicion that this is a serious defect, it is necessary to examine the need for a recall in accordance with the procedures laid down in writing. 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 manufacturer of medicinal products concerned or any other recipient to which the active substance has been supplied shall be informed without delay.(3) The content of the notifications, the nature of the review and the findings obtained, the outcome of the evaluation, the measures and the notifications shall be kept records. Non-official table of contents

§ 29 retention of documentation

(1) All records relating to the acquisition, production, including release, laboratory checks, storage, transfer to or from the scope of the pharmaceutical law, 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.By way of derogation from paragraph 1, in the case of active substances for which the date of expiry of the expiry date has been established, records shall be kept for at least three years beyond the manufacturer's complete placing on the market of the batch.(3) For the purpose of traceability of the active substances produced or brought into or out of the scope of the law in the scope of the Medicines Act, or of active substances introduced or exported into the scope of the law or intermediate products shall be kept in addition to all analytical certificates, including those of the original manufacturer, which 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 the company and address of the original manufacturer, and, where applicable, further Manufacturer,
3.
the transport and distribution,
4.
the name or the company and the address the recipient.

Section 5
Special Regulations

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§ 30 Supplementary rules 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 a coccidiostat may be used.(2) § 3 (2) shall apply with the proviso that the specific characteristics of medicated feedingstuffs following the state of science must be taken into consideration. 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. Accompanying documents are included.(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. With regard to the examination of the compound feedingstuffs used, the provisions of the futtermittellegislation shall apply.(4) Without prejudice to other provisions relating to labelling, medicated feedingstuffs may be placed on the market only if they are identified by the clearly visible word "medicated feedingstuffs" and provided with an indication of: what percentage they are intended to meet the demand for feed.(5) By way of derogation from § 16, in cases of short-term prevention instead of the knowledgeable person in accordance with § 14 of the German Medicines Act, a person responsible for providing adequate training and knowledge may provisionally apply medicated feedingstuffs for the Release on the market. This provisional release is subsequently to be submitted to the knowledgeable person who, in this case, also bears responsibility for the release, in addition to the person responsible, and to confirm this in writing. The competent 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 prescription required for the delivery of medicated feedingstuffs must be made in four copies (original and three copies), which are the model of Annex 1 to the Regulation on veterinary medicinal products in the version of the Notice of 27 March March 1996 (BGBl. 554), as last amended by Article 2 of the Regulation of 3 June 2000. November 2006 (BGBl. 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 information to be submitted by him. He shall keep the originals remaining with him in an orderly manner from the date of delivery of the medicated feedingstuffs for five years and shall, on request, submit or hand him out without delay to the competent authority.(8) By way of derogation from paragraph 7, the medicated feedingstuff 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 upon presentation of a veterinary prescription, which complies 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. Non-official table of contents

§ 31 Supplementary regulations for blood donation facilities

(1) The QM system according to § 3 (1) shall be required in accordance with the provisions of the Annex Commission Directive 2005 /62/EC of 30 May 2005 1 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, 30.12.2005, p. 41), as amended by the applicable version, and in particular
1.
ensure that all critical work flows and default work procedures are set in appropriate default work instructions,
2.
sufficient procedures for recall and traceability in accordance with 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 the 27. 1 January 2003 setting standards of quality and safety for the collection, testing, processing, storage and distribution of human blood and blood components and amending Directive 2001 /83/EC (OJ L 327, 28.3.2001, p. 30) and Article 21a (1), third sentence, of the Medicines Act for the reporting of serious incidents, serious adverse reactions and their suspected cases,
3.
ensure that usable products or products and the traceability process are relevant documents from a facility that is operating ended, handed over to other entities that have a permit within the meaning of Section 13 of the Medicines Act,
4.
through a quality assurance shall be assisted, in particular responsible for the approval of all quality-related documents, and shall be included in all quality-related matters, unless the management of the production or management of the Quality control is responsible, as well as
5.
regularly checked for efficiency by the management of the 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 the person is not at the same time a director of manufacture. 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 the person according to § 14 of the German Medicines Act that these blood establishments have a QM system that is set up in accordance with standards that are at least equivalent to the standards set by the European Union.(2) By way of derogation from the first sentence of Article 4 (2), job descriptions shall be provided in blood establishments for the entire staff whose activities may have an effect on the quality of the blood preparations.(3) The general requirements for operating rooms and equipment in § 5 shall also apply to temporary or mobile devices located outside but under the control of the blood donation facility (mobile location). The particularities of the operating rooms, including mobile locations, depend on the respective activities. In particular,
1.
must be the area for determining the suitability and suitability of the spender Ensure sufficient confidentiality and be separated from the donation processing areas,
2.
the donation area for safe removal as well as a where appropriate, the necessary treatment of the person to be donated,
3.
the laboratory area of the area for the determination of the suitability and suitability of the donating person as well as from the area for the donation processing separated and only authorized to be accessible,
4.
in the storage area a separate storage of products with different status or products manufactured in accordance with specific criteria, and that precautions are taken in the event of failure of equipment or energy supply,
5.
Separated areas for waste disposal of potentially infectious materials.
(4) The manufacturing instruction in accordance with § 13 para. 1 must have details on the to donate and to donate as well as the documentation related thereto. It must contain at least the stipulations that are to be observed at each donation over the
1.
Information of the potentially donating or donating person or of the information to be kept according to the conditions laid down in Annex II to Commission Directive 2004 /33/EC of 22 June 2004. 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. 25), as set out in the Implementing Directive 2011 /38/EU (OJ L 158, 30.4.2011, p. 28), as amended,
2.
A safe identification of the donating person in the case of a statement of the person who is to be identified. 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 conditions laid down in Annex III the eligibility and exclusion criteria laid down in Directive 2004 /33/EC,
4.
Pickup of the donations and, where applicable, their further processing, including the Determination of the period until further processing,
5.
Request for donations, processing and end product containers,
6.
Labeling of documents and containers, including donor-specific numbers or identification codes of the 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 § 13 (7) the production protocol must ensure full traceability between the person donating the donation and the donation and the intermediate products and preparations obtained therefrom, including those used for extraction and processing sterile one-off 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 specificities of the blood donations and blood preparations and in particular, stipulate that
1.
the laboratory samples are taken in suitable containers marked with donor-specific numbers or identification codes at the time of the donation, before the laboratory samples are taken the test is properly stored and the test is to be carried out within a given period of time,
2.
each donor on the occasion of each donation according to the state of the art of science and technology at least for hepatitis B, hepatitis C and human immunodeficiency virus (HIV) is to be tested,
3.
additionally the AB0 group, unless it is not for fractionation, and in the case of erythrocyte preparations, the rhesus formula or, in the case of platelet preparations, the Rh-D group is to be determined at each donation,
4.
in blood group serological studies, procedures are also to be used to test specific donor groups and
5.
the blood preparations must comply with the quality requirements set out in Annex V to Directive 2004 /33/EC.
in the case of a repeatedly reactive or positive test result as set out in the first sentence of the first sentence of paragraph 2, it shall be clarified immediately and appropriate measures shall be taken to confirm the results and to exclude the use of the products concerned. 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 from suppliers accepted by the company may be used for the examination of the donations and the donor samples. 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 shall be reviewed regularly by participation in a formal performance test system.(7) During all stages of production, the labelling of the product's status and the traceability to the person to be donated must be clearly indicated, unless other measures are taken to ensure that such traceability is carried out.(8) Preparations from fresh plasma and blood cells must, in so far as they do not require approval in accordance with Section 21 (2) (1a) of the Medicinal Products Act, the labelling in accordance with § 10 paragraph. Article 8 (8a) of the Medicines Act. Individual blood donations must be clearly identified as such.(9) Prior to the release in accordance with § 16, the products shall be stored separately in administrative terms and physically 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. The second half-sentence of the second 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 of short-term prevention and if this is urgently required for medical reasons, instead of the knowledgeable person in accordance with § 14 of the German Medicines Act, an authorised person who is sufficiently competent to do so shall be able to Training and knowledge, the blood preparations for direct use in humans are provisionally released for placing on the market and make the entry according to § 17 paragraph 5. This provisional release and the provisional entry in accordance with 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. are confirmed.(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 as a recovery pattern.(12) Without prejudice to § 19, the step-planning officer shall be responsible for collecting, evaluating and evaluating all reports of serious adverse reactions in accordance with a written procedure, and for the competent authority of the Federal Government or of the competent authority. the competent authority shall be notified in accordance with Section 63i (2) or (3) of the Medicines Act. Sentence 1 shall also apply to suspected cases of such reactions. where
1.
must contain all the necessary information, in particular to identify the the blood donation establishment, the person concerned and the donation, the date of notification and the donation, the date of transfusion, the type of suspected reaction, as set out in Annex II to Commission Directive 2005 /61/EC of 30 June 2005. 1 September 2005 on the implementation of Directive 2002/98/EC of the European Parliament and of the Council as regards requirements for traceability and reporting of serious incidents and serious adverse reactions (OJ L 327, 30.12.2005, p. 32), as amended; it must also 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 will be specified as soon as sufficient evidence is available, in particular whether the initial notification and its allocation level will be The likelihood of a relationship to be confirmed or whether and where appropriate in which way 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 more detailed information, in particular on the technical specifications and format of the reports to the competent authority of the federal authority, can be regulated in a notice issued by the competent federal authority.(13) Paragraph 12, sentences 1 to 3, shall apply mutatily to serious incidents:
1.
The initial notification shall be: 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, placing on the market or in a other activities or in the case of materials used in the collection, testing or processing.
2.
The initial notification shall be specified, as soon as sufficient evidence is available. In particular, the main cause is to be analysed and to report on corrective measures taken.

Section 5a
Special provisions for removal and tissue establishments as well as for Tissue Penderlabs

Non-official table of contents

§ 32 Supplementary general requirements

(1) The QM system according to § 3 para. 1 must be 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 that affect the quality and safety of tissues and tissue preparations, as well as the standard working methods in appropriate Standard operating instructions are set, carried out under controlled conditions, and documented,
2.
ensure that the equipment used, the work environment, as well as the conditions for working or processing, and storage of tissues and tissue preparations, and are regularly controlled,
3.
sufficient procedures for the removal and handling of discarded fabrics or tissue preparations and for waste disposal,
4.
sufficient traceability procedures as well as prompt reporting of serious incidents, serious adverse reactions and suspected cases of suspected adverse reactions
5.
ensure that tissues and tissue preparations that are capable of use or for their safety or the tracing process are relevant an institution that terminates its activities to other entities that have a permit within the meaning of § 20c of the Medicines Act, and
6.
regularly reviewed with regard to continuous and systematic improvements and, if necessary, adjusted.
If tissue or tissue preparations are Entities in countries which are not Member States of the European Union or other Contracting States on the European Economic Area must reassure themselves of the person responsible under Section 20c of the Medicines Act, that these bodies have a quality system which is set up 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, compliance with the requirements set out in points 1, 3 and 4 must be guaranteed.(2) The contract in accordance with § 9 (1) of a tissue establishment with the removal device shall in particular require details of the donor selection criteria and the tissue removal and with the tissue dispenser laboratory and, where used, other laboratories which shall: Laboratory tests and tests to be carried out, as well as 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 listed in a full list in the working 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 device shall at least ensure that
1.
the secure identification of each donation and any tissue or tissue preparation resulting from it is possible in every processing phase and all Steps understandable,
2.
for each critical activity, the corresponding materials and equipment as well as the executive staff will be identified
3.
The tissues or tissue preparations can only be passed on for working or processing, or released for placing on the market if they are all Requirements in the respective specifications have been met,
4.
the records are reliable and only documents that are authorized by it are used. Persons authorised and the accidental use of overhauled versions of a document is prevented by appropriate measures.
The documentation system must be provided by the responsible person in accordance with § 20c of the Medicines Act are regularly checked for up-to-dateness and efficiency.(4) The self-inspections pursuant to § 11 (1) shall be carried out in tissue establishments at least every two years by persons trained and competent for this purpose, Section 11 (2) shall not apply. Non-official table of contents

§ 33 Determination of the suitability of the donation and laboratory tests required for the collection

(1) The determination of the Donor suitability in the removal equipment and the laboratory tests required for the extraction in the tissue laboratory laboratory shall be carried out in accordance with the good professional practice according to previously established standard operating instructions. In particular, the requirements according to § § 3 to 6 of the TPG tissue regulation must be observed.(2) The standard work instructions referred to in paragraph 1 shall comply with the approval documents in the case of tissue preparations which have been approved in accordance with Article 21a of the Medicines Act.(3) The methods used for laboratory tests shall be validated according to the state of science 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 from suppliers accepted by the company may be used for laboratory testing. The laboratory reagents shall be suitable for their purposes and shall be released prior to their 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 shall be fully recorded (test protocol). 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 . Non-official table of contents

§ 34 Extraction of tissue by the removal device

(1) § 4 does not apply to removal devices. 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, and 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 the medical devices for tissue removal.(2) § § 5 and 6 shall apply to removal facilities, subject to the condition that the premises and equipment as well as the hygiene measures must be suitable to protect the properties of the tissue required for its use and minimize the risk of microbial contamination during removal:
1.
For the Tissue removal is to be used for sterile medical devices. To the extent that medical devices are used again, their treatment must be carried out in accordance with § 4 (2) of the Medical Devices Ordinance.
2.
The removal of living organisms Donors must be located in an environment that is 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 hygiene measures, including hygiene measures.
3.
The dispensing of deceased donors is to be done in clean rooms where the removal area is covered with sterile cloths.
4.
If the tissue removal is done by personnel (mobile teams) posted by the withdrawal facility outside of the rooms covered by the permission in accordance with § 20b of the Medicines Act (3) The removal of tissue, including any measures intended to do so, shall be subject to the conditions laid down in paragraphs 1 and 3.
in a working or working condition, to be obtained, marked and transported in accordance with the requirements of § 2 of the TPG tissue ordinance and in compliance with the requirements of § 2 of the TPG tissue regulation and in accordance with the standard operating instructions (removal instructions) To comply with the good professional practice.(4) In the case of tissue preparations which have been approved in accordance with Article 21a of the Medicines Act, the removal instruction provided for in paragraph 3 shall be in accordance with the approval documents.(5) The removal instruction referred to in paragraph 3 shall contain at least the following rules:
1.
for review the identity and determination of the suitability of the donor,
2.
for the collection of the donations and the samples for the laboratory examination, as well as for the handling of the material taken from the laboratory, including
a)
of the equipment to be used,
b)
the procedure for the removal and prevention of bacterial or other contamination during removal, as well as, if necessary, further measures to minimize the risk of Tissue contamination,
c)
to indicate the place of withdrawal, to the extent that it is outside the premises covered by the permit, and where necessary the conditions to be met, and in the case of deceased donors, to document the period between the date of death and the removal of the donation
3.
Requirements for the donation and sample containers as well as for the storage and transport solutions used and other products and materials that come into contact with the donations and have an impact on their quality and safety ,
4.
to identify the donations and the samples referred to in paragraph 6,
5.
on conditions an intermediate storage of the donations or samples up to their transport for working or processing or for laboratory examination, which is suitable for obtaining their characteristics and biological functions.
The removal procedure must be completed The person and the type of donation shall be appropriate, preserve the properties of the tissues required for their use, and minimise the risk of microbial contamination of the donation.(6) The tissue spends shall be provided at least with the following information at the time of their removal:
1.
Type of donation and traceability of the donor/donor at the removal device, which is compatible with the data protection, as well as the donor's labelling as Organ donor, if organs have been removed from the donor for the purpose of transmission,
2.
day and, if possible, time of removal,
3.
warning of potential hazard,
4.
if available, type of use Additions,
5.
for autologous donations the indication "Only for autologous use" and in the case of directed donations the information about the recipient.
If the data according to sentence 1 No 2 to 5 may not be placed on the container, they shall be listed in an accompanying document which shall be attached to the container. From the labelling of the samples for the laboratory examination, the assignment to the donating person must, in particular, be possible without any doubt and information about the place and time of the sampling must be given.(7) The removal of tissue and the sampling shall be carried out in accordance with the withdrawal instructions provided for in paragraph 3 and shall be fully recorded (removal report), without prejudice to the medical documentation requirements of § 8d (2) of the Transplantation Act. The withdrawal report must contain at least the following information:
1.
Name and address of the Tissue device intended to obtain the tissue;
2.
donor identity including family name, first name, gender, day of birth, and living donors address or, as far as it is granted, the allocation number assigned by the tissue dispenser for the tissue dispenser and the donor's identification as an organ donor, if organs have been removed from the donor for the purpose of the transfer;
3.
Description and Labeling code of the extracted tissue;
4.
Family name, first name and address of the Doctor responsible for removal;
5.
Day, time and place of withdrawal as well as the manner of removal and any possible removal of the product from the product. Intermediate storage;
6.
in the case of deceased donors, time of death, description of the conditions under which the corpse is kept; provided that a cooling is performed the date of the beginning and end of the cooling;
7.
Identification/batch number of the storage and transport solutions used.
All deviations in the The process and 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 Transplantation Act. 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. Non-official table of contents

§ 35 Transport for processing and processing in tissue equipment

(1) Transport is after advance created default work instruction. The method must be appropriate to 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 shall determine the type of transport container and its labelling as referred to in paragraph 2, the transfer of any samples and the withdrawal report in accordance with section 34 (7) to the working or processing tissue equipment.(2) Without prejudice to Article 7 (3), the containers for the transport of the fabric for processing or processing shall be provided with at least the following information:
1.
"Caution" and "tissues and cells",
2.
addresses and telephone numbers of the removal device and the tissue device, which are used for processing the tissue or tissue preparations for working or processing , as well as the names of each contact person,
3.
Transport start date and time, relevant transport and storage conditions,
4.
Precautions and instructions for use and handling.
(3) The receipt in the tissue device for the processing of the tissues, including the The relevant documents and samples from the removal equipment shall be carried out in accordance with the standard operating instructions previously created. The procedure must in particular check the
1.
integrity of the packaging,
2.
Labeling,
3.
Compliance with transport conditions, and
4.
the supplied documentation and, where applicable, samples included
. The tissues shall be held in quarantine until a decision has been taken on their use. Insofar as they do not meet the requirements, they are to be discarded. The acceptance or rejection of the tissue is to be documented. If 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. Non-official table of contents

§ 36 Processing and storage by tissue establishment

(1) Without prejudice to § 4 (1), the staff shall be required to: Responsibility of the responsible person according to § 20c of the Medicines Act is informed of the legal and ethical relationship of his activity. By way of derogation from § 4 (2) sentence 1, job descriptions are to be held for the entire staff.(2) The premises and equipment referred to in § 5 and the hygiene measures referred to in § 6 shall be capable of protecting the properties of the tissue which are necessary for its use and the risk of microbial contamination during the operation.
1.
As far as the tissues are used during their working or processing , this must be carried out in an environment with a defined air quality and cleanliness. The effectiveness of these measures shall be validated and monitored.
2.
Insofar as the tissues referred to in point 1 are not subject to inactivation or sterilisation procedures. , during working or processing, a degree of air purity for the number of bacteria and the number of particles corresponding to class A of the definition of the EC-GMP guide, 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. Requests to the environment can be deviated if
a)
is a validated procedure for the Inactivation of germs or for end sterilization, or
b)
it is demonstrated that exposure to an environment of class A is harmful Effects on the required properties of the tissue, or
c)
it is demonstrated that the use of the tissues in the recipient or in the case of the tissue is detected by the tissue. the recipient is at a significantly lower risk of transmission of a bacterial or fungal infection to the recipient or the recipient than in the tissue transplant, or
d)
It is not technically possible to perform the required procedure in a Class A environment.
It is necessary to demonstrate and document that the the required quality and safety of the tissue or tissue preparation shall be achieved, at least taking into account the purpose of destination, the type of use and the immune status of the recipient or the recipient.(3) All critical equipment and equipment shall be qualified as well as regular inspections in accordance with previously established standard operating instructions, which shall also determine measures in the event of possible malfunctions. 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 based on a previously prepared standard working instruction (instructions or processing instructions), which also establishes 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 processing instructions or processing instructions referred to in paragraph 4 must comply with the approval documents.(6) The working or processing procedures shall be regularly assessed in order 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, identification and status of the tissue or tissue preparation as well as traceability to the person to be donated must be derived from the marking, as far as this is not carried out by others. Measures shall be ensured. 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 Article 10 (8b) of the Medicines Act, tissues and tissue preparations must, before they are placed on the market, provide the following information and information on the outer container and, where used, on the outer container. Wrapped or accompanied in an accompanying document:
1.
Description and, if necessary, Dimensions of the tissue, morphology and functional data,
2.
Results of the laboratory tests required for the extraction,
3.
Date of submission,
4.
Storage recommendations,
5.
How to open the container, the packaging, and, if necessary, handling,
6.
expiration date after opening or after pre-set handling,
7.
as applicable, presence
In addition, instructions for the reporting of serious adverse reactions or serious incidents in accordance with § 40 shall be attached to the recipients of tissues or tissue preparations.(9) The working or processing shall be carried out in accordance with the instructions provided for in paragraph 4 and shall be recorded in full (processing and processing minutes). 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 ensure the quality and safety of the tissues or tissue preparations in each case.(10) Without prejudice to § 7, the storage must be carried out in accordance with previously established standard operating instructions under controlled conditions and shall be suitable for maintaining the quality of the tissues and 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. Non-official table of contents

§ 37 Examination of tissue and tissue preparations

(1) The verification of compliance with the specified specification shall be based on: pre-created standard work instruction (test instruction) in accordance with the good professional practice. Section 33 (3) shall apply accordingly.(2) In the case of tissue preparations which have been approved in accordance with Article 21a of the Medicines Act, the test instruction must comply with the documents relating to the approval.(3) The test shall be carried out in accordance with the test instruction referred to in paragraph 1 and shall be recorded in full. 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. Non-official table of contents

§ 38 Release by tissue establishment

(1) The release of tissue or tissue preparations may only be released from the responsible person in accordance with § 20c of the German Medicines Act and only by means of a standard working instruction previously approved. The procedure shall 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 made if the verification of all necessary documents has confirmed the conformity of the tissues or tissue preparations with their specifications, including the final packaging, and in the case of tissue preparations, which are subject to the approval requirement in accordance with § 21a of the Medicines Act, which is in accordance with the approval documents.(3) The responsible person in accordance with § 20c of the Medicines Act can only be represented by persons who have the expertise in accordance with § 20c (3) of the Medicines Act. It must be clear from the records who carried out the release.(4) The responsible person in accordance with § 20c of the Medicines Act must carry out a risk assessment for such tissues and tissue preparations which have not yet been delivered after they have been released and whose expiry date has not yet expired, if subsequent findings have resulted in a change in the profit, working or processing or testing procedures or the donor selection criteria or the laboratory examination procedures with the aim of improving the quality of the products. Tissue and tissue preparations may be delivered only 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. Non-official table of contents

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

(1) tissues and tissue preparations may only be used in shall be placed on the market if they have been released in accordance with Article 38.(2) When the tissue preparations from a Member State of the European Union or another State Party to the Agreement on the European Economic Area are brought into the scope of the Medicines Act, the responsible person in accordance with § 20c of the German Medicines Act before release pursuant to § 38, in particular reassure that the conditions are fulfilled in accordance with § 21a (9) of the Medicines Act.(3) In the case of an import 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 responsible person shall be subject to the provisions of § 20c Before release in accordance with § 38 of the German Medicines Act, in particular, reassure that the requirements of § 72b (1) and (2) of the Medicines Act are fulfilled. The second sentence of Section 32 (1) remains unaffected.(4) The transport shall be carried out in accordance with the standard operating instructions previously defined. 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 of the tissue preparation.(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 identifier of the fabric device that has been used or processed by the fabric or tissue preparations, as well as the device to be used to obtain the tissue or tissue preparations, including its addresses and telephone numbers, as well as
3.
relevant transport and storage conditions, as well as, if necessary, further precautions and Instructions for handling.
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§ 40 Notification of serious adverse reactions and serious incidents

(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 are responsible for the treatment of the tissue in question. after previously established standard working instruction on all serious adverse reactions referred to in § 63i (7) of the Medicines Act and corresponding suspected cases, which are the quality and safety of the tissues or Tissue preparations may be influenced or returned to the tissue preparations, and immediately informed. The second sentence of paragraph 3 shall apply accordingly.(2) Paragraph 1 shall apply to the collection and tissue collection laboratories in the event of serious incidents within the meaning of Section 63i (6) of the Medicinal Products Act and related suspected cases in connection with the extraction of tissue. or the laboratory tests required for the collection. The second sentence of paragraph 3 shall apply accordingly.(3) In tissue establishments, the responsible person is responsible, in accordance with § 20c of the German Medicines Act, for the fact that all known reports of serious adverse reactions referred to in paragraph 1 are made after prior Standard work instruction is collected and evaluated. The reports shall be submitted to the competent authority or to the competent authority in accordance with Section 63i (2) or (3) of the Medicines Act and, in so far as the tissue donor is also organ donor, the coordinating body in accordance with § 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.
must contain all the necessary information, in particular to identify the Sampling and tissue equipment, tissue donor laboratory, the person concerned and the donation, the date of registration and the date of the recovery of the donation and the suspected reaction, on the nature of the tissues involved in the suspected reaction or tissue preparation and the suspected reaction, as well as the degree of probability of a relationship between the administration of the tissue or the tissue preparation and the recipient reaction,
2.
the initial notification will be specified as soon as sufficient evidence is available; in particular, it must be stated whether the initial notification is to be confirmed or whether and where appropriate in which If a change of the first classification is to be reported, the clinical course of the recipient or the recipient and any further conclusions, including any corrective measures, shall be indicated to the extent that they are known. and measures taken with regard to other tissues and tissue preparations intended for use in human beings.
(4) Paragraph 3, subparagraphs 1 to 3, shall apply to serious incidents within the meaning of Article 63i (6) of the Pharmaceutical law applicable. Where:
1.
The initial notification must contain all the necessary information, in particular to identify the Removal and tissue equipment, tissue donor laboratory, affected donation, reporting date and date of serious incident, whether it is a defect in tissue or tissue preparation, defective equipment or human failure, and whether the fault in the extraction, the laboratory examination required for the extraction, the transport to be used for processing or processing, the processing, testing, release, storage, transport, ,
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 is responsible for the fact that tissue and tissue preparations, which are Reports referred to in paragraphs 1 to 4 may be or may be affected, identified, separated and recalled. It shall, in accordance with a written procedure, assess the need for a recall and coordinate the necessary measures within pre-determined periods, and shall inform the competent authority of any recall without delay, and in so doing 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 on a regular basis.(6) The closer details, in particular to the technical specifications and formats of the reports referred to in paragraphs 3 and 4 to the competent federal authority, may be regulated in a notice issued by the competent federal authority.(7) 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, and the handling of returned tissue or tissue preparations. the responsible person shall keep records in accordance with § 20c of the Medicines Act. Sentence 1 shall apply to persons in accordance with Section 20b (1) sentence 3 No. 1 of the Medicines Act. Non-official table of contents

§ 41 retention of documentation

(1) For the retention of records of the collection, laboratory examination, or or processing, testing, release, storage, transfer into or out of the scope of the pharmaceutical law, import or export, placing on the market, including delivery and final determination of the tissue or the tissue preparation as well as records of the responsible person pursuant to § 20c of the Medicines Act shall apply to § 15 of the Transplantation Act.(2) The storage must be without prejudice to § 14 of the Transplant Act in a suitable area of the rooms covered by the permission 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 authorised to do so.(3) In the event of the closure of the removal or tissue establishments or the tissue establishments laboratories in which the documentation referred to in paragraph 1 is kept, the pharmaceutical contractor shall ensure that the documentation is provided during the total retention period.

Section 6
Administrative Offences

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§ 42 Administrative Offences

unlawful within the meaning of Section 97 (2) No. 31 of the Medicines Act, who intentionally or negligently
1.
contrary to § 13, paragraph 3a, security features partially or completely removed or covered, without to be convinced of the authenticity of the medicinal product or to replace it with those which do not allow the authenticity and integrity of the outer packaging to be checked in an equivalent manner,
2.
contrary to § 16 para. 1 or § 25 para. 1, release a batch or an active substance of non-human origin for placing on the market,
3.
contrary to § 17 para. 1 sentence 1 or § 26 para. 1 sentence 1 a product referred to there without prior release put on the market,
4.
contrary to § 18 para. 1 sentence 1 or para. 2 sentence 1, it does not ensure that a reset pattern is kept there,
5.
contrary to § 18, paragraph 3, sentence 1, not ensuring that a named pattern is kept,
5a.
contrary to § 19, paragraph 2, the competent authority or the marketing authorisation holder is not informed or not informed in good time,
6.
contrary to § 30 para. 1 a compound feedingstuff is used,
7.
contrary to § 30 para. 4 a medicated feedingstuff on the market,
8.
contrary to § 30 (7) sentence 3, a prescription shall not, not correct, not complete or not completed in time, or
9.
contrary to § 30, paragraph 7, sentence 4, the original not or not at least five years stored or not or not presented in time and not or not in time

Section 7
Final Provisions

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§ 43 Transitional arrangements

This Regulation shall not apply to active substances which are stored within the scope of the Medicines Act at the date of entry into force of this Regulation, or which are based on an existing contractual obligation and the up to the 9. The European Union and the European Economic Area will be implemented in countries outside the European Union or the European Economic Area in November 2008