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

Subscribe to a Global-Regulation Premium Membership Today!

Key Benefits:

Subscribe Now

Read the untranslated law here: http://www.gesetze-im-internet.de/amwhv/BJNR252310006.html

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 (drug and active ingredient manufacturing regulation - AMWHV) AMWHV Ausfertigung date: 03.11.2006 full quotation: "pharmaceuticals and active ingredient production regulation by November 3, 2006 (BGBl. I S. 2523), most recently by article 1 of the Decree of October 28, 2014 (BGBl. I p. 1655) has been changed" stand : Last amended by art. 1 V v. 28.10.2014 I 1655 for details on the stand number found in the menu see remarks footnote (+++ text detection from: 10.11.2006 +++) (+++ official note of the standard authority on EC law: implementation of EGRL 20/2001 (CELEX Nr: 301 L 0020) EWGRL 412/91 (CELEX Nr: 391 L 0412) EGRL 82/2001 (CELEX Nr: 301 L 0082) EGRL 83/2001 (CELEX Nr: 301 L 0083) EGRL 94/2003 (CELEX Nr: 303 L 0094) EGRL 33/2004 (CELEX Nr)) : 304 L 0033) EGRL 23/2004 (CELEX Nr: 304 L 0023) EGRL 61/2005 (CELEX number: 305 L 0061) EGRL 62/2005 (CELEX Nr: 305 L 0062) EWGRL 167/90 (CELEX Nr: 390 L 0167) +++) 1 V v. 3.11.2006 was the V article I 2523 of the ministries for health and food, agriculture and consumer protection in agreement with the Federal Ministry of Economics and technology, for the environment, nature conservation and nuclear safety , for health, and with the consent of the Federal Council adopted. It is according to article 6 clause 1 of this V on the 10.11.2006 entered into force.
This regulation is designed to implement - Directive 91/412/EEC of 23 July 1991 laying down the principles and guidelines of good manufacturing practice for veterinary medicinal products (OJ EC No. L 228, p. 70), - Directive 2001/20/EC of the European Parliament and of the Council of 4 April 2001 on the approximation of the laws, regulations and administrative provisions of the Member States relating to the implementation of good clinical practice in the conduct of clinical trials of medicinal products for human use (OJ EC No. L 121, p. 34), - Directive 2001/82/EC of the European Parliament and of the Council of the 6 November 2001 on the Community code relating to veterinary medicinal products (OJ EC No. L 311, p. 1), as amended by Directive 2004/28/EC of the European Parliament and of the Council of 31 March 2004 (OJ EU no. L 136, p. 58), - Directive 2001/83/EC of the European Parliament and of the Council of the 6 November 2001 on the Community code relating to medicinal products for human use (OJ EC No. L 311, p. 67), as last amended by Directive 2004/27/EC of the European Parliament and of the Council of 31 March 2004 (OJ EU no. L 136, p. 34), - Directive 2003/94/EC of 8 October 2003 laying down the principles and guidelines of good manufacturing practice for medicinal products and for investigational use in humans (OJ EU no. L 262, p. 22), Directive 2004/33/EC of 22 March 2004 implementing Directive 2002/98/EC of the European Parliament and of the Council as regards certain technical requirements for blood and blood components (OJ EU no. L 91, p. 25), - Directive 2004/23/EC of the European Parliament and of the Council of 31 March 2004 laying down standards of quality and safety for the donation, procurement, testing, processing, preservation, storage and distribution of human tissues and cells (OJ EU no. L 102 S. 48), - Directive 2005/61/EC of 30 September 2005 implementing Directive 2002/98/EC of the European Parliament and of the Council as regards the requirements for traceability and the reporting of serious adverse events and serious adverse reactions (OJ EU no. L 256 S. 32), - Directive 2005/62/EC of the Commission of 30 September 2005 implementing Directive 2002/98/EC of the European Parliament and of the Council as regards Community standards and specifications relating to a quality system for blood establishments (OJ EU no. L 256 S. 41), - Directive 90/167/EEC of the Council of 28 March 1990 laying down the conditions for the manufacture, placing on the market and use of medicated feedingstuffs in the Community (OJ EC No. L 92 p. 42).

Table of contents section 1 scope and definitions article 1 scope article 2 definitions section 2 General requirements section 3 quality management system, good manufacturing practice and good practice section 4 staff § 5 premises and equipment section 6 hygiene measures section 7 storage and transport section 8 animal husbandry section 9 activities on behalf of § 10 General documentation section 11 self inspections and supplier qualification section 3 medicines, other blood components, blood products and products of human origin section 12 personnel in senior and responsible position § 13 manufacturing § 14 examination § 15 marking article 16 release to the placing on the market of § 17 placing on the market and importation § 18 samples § 19 complaints and recall section 20 retention of documentation section 4 agents of non-human origin section 21 organizational structure section 22 production section 23 examination article 24 labelling section 25 release to the placing on the market of section 26 placing on the market and import of section 27 samples § 28 complaints and recall section 29 retention documentation section 5 special provisions article 30 supplementary regulations for medicated feedingstuffs § 31 supplementary provisions for blood establishments section 5a special provisions for removal, tissue establishments and tissue donor laboratories § 32 additional General requirements article 33 determination of donor suitability and required for obtaining laboratory analysis § 34
Extraction of tissue through the sampling device § 35 transporting to the handling or processing and reception at the tissue establishment § 36 handling or processing and storage by the tissue establishment § 37 examination of tissues and tissue preparations section 38 approved by the tissue establishment § 39 placing on the market, import and transport through the tissue establishment § 40 notification of serious adverse reactions and serious adverse events and callback section 41 retention documentation section 6 offences section 42 offences section 7 final provisions § 43 transitional provisions section 1 scope and definitions article 1 scope of application (1) this Regulation shall Application on farms and facilities, the medicinal products 1, 2. active substances which are intended for the manufacture of medicinal products and are the human or animal or microbial origin or manufactured resulting way, 2a.
Tissue within the meaning of § 1a No. 4 of the transplantation law as amended by the notice of September 4, 2007 (Federal Law Gazette I p. 2206), 3 to drug manufacturing certain substances of human origin, 4. other than the active substances referred to in paragraph 2, which are intended for the manufacture of medicinal products, or 5 other than those referred to in point 3 and to the manufacture of pharmaceutical products for use in people certain substances , as far as them that according to the regulations of appropriate good manufacturing practice according to the guidelines of the European Commission in accordance with article 47 (5) of Directive 2001/83/EC of the European Parliament and of the Council of the 6 November 2001 on the Community code relating to medicinal products for human use (OJ L 311 of 28.11.2001, p. 67), most recently by the policy 2011/62/EC (OJ L 174 of the 1.7.2011, p. 74) is changed, to make are (AIDS), professional produce, check, store, bring in the traffic, spend into or out of the scope of the medicines Act, introduce or run. You shall also apply to persons who professionally carry out these activities.
(1a) on extraction and tissue establishments and tissue donor laboratories section 3 of this regulation does not apply.
(2) the regulation is also applicable to 1 pharmacies, retail of medicines from pharmacies, persons who are doctors or entitled to the practice of medicine in humans, dentists, veterinarians, veterinary house pharmacies and pharmaceutical wholesale companies, insofar as they require a permission in accordance with section 13 or section 72 (1) of the medicines Act, and 2. pharmaceutical entrepreneur according to § 4 paragraph 18 of the medicines Act, 3. companies and organisations or persons , who act with active ingredients for the manufacture of medicinal products which are intended for use in humans.
(3) the requirements of this regulation do not apply to 1 substances according to the Homeopathic Pharmacopoeia, to the production of homeopathic preparations as raw materials are used, 2. active substances, the substances within the meaning of § 3 are number 1, 2 or 3 of the medicines Act, or contain, as far as the requirements of the EC GMP Guide are subject to, 3 (dropped out) 4 (dropped out) 5 (dropped out) 6 ingredients for Ektoparasitika to the application's animals as well as 7 active ingredients for medicines , which are intended exclusively for use in pet animals according to section 60 of the medicines Act and are approved for transport outside of pharmacies.
In the case of sentence 1 is by maintaining comparable standards and procedures to ensure that the quality of the production and testing is equivalent to the requirements set out in paragraphs 2 to 4.
(4) the regulation shall not apply to establishments and facilities, which require a permit according to § 72 para 2 of the medicines Act. The regulation does not apply to individuals and entities that collect medicines.
(5) this Regulation shall not apply to active ingredients, excipients and intermediates, which are intended solely for the purpose of spending in countries that are not Member States of the European Union or other parties to the agreement on the European economic area, and under customs supervision and without manufacturing steps in the meaning of article 46a, paragraph 1 of Directive 2001/83/EC or article 50a paragraph 1 of Directive 2001/82/EC of the European Parliament and of the Council of 6 November 2001 on the creation of Community code relating to veterinary medicinal products (OJ EC No. L 311, p. 1), as amended by Directive 2004/28/EC of the European Parliament and of the Council of 31 March 2004 (OJ EU no. L 136, p. 58), carried by the scope of the regulation or of control type I or II are placed under a customs warehousing or a free zone (transit).
(6) the provisions of the implementing Regulation (EU) No. 520 / 2012 of the Commission by June 19, 2012 on the implementation of Regulation (EC) No 726 / 2004 of the European Parliament and of the Council and Directive 2001/83/EC of the European Parliament and of the Council provided for pharmacovigilance activities (OJ L 159 of the 20.6.2012, p. 5) shall remain unaffected.

Article 2 definitions for the purposes of this regulation 1 are products of human origin for the drug manufacturing certain substances within the meaning of § 4 para 19 of the medicines Act, which origin are human, or substances within the meaning of § 3 No. 3 of the German medicines Act, are the human origin in processed or unprocessed state, except blood products within the meaning of section 2 No. 3 of the transfusion act as amended by the notice of August 28, 2007 (Federal Law Gazette I p. 2169) and other blood components , 2. auxiliary substance is any part of a medicinal product, with the exception of the active substance or of the packing material, 3rd is the EC-GMP Guide (BAnz. S. 6887) of the Guide to good manufacturing practice for medicinal products and investigational medicinal products including its annexes, with which the European Commission has published the detailed guidelines referred to in article 47 of Directive 2001/83/EC and article 51 of Directive 2001/82/EC and to the interpretation of the principles and guidelines of good manufacturing practice referred to in article 3 paragraph 2 of Directive 2003/94/EC of 8 October 2003 laying down the principles and guidelines of good manufacturing practice for medicinal products for human and for investigational use in humans (OJ EU no. L 262, p. 22) and in accordance with article 3 of Directive 91/412/EEC of 23 July 1991 laying down the principles and guidelines of good manufacturing practice for veterinary medicinal products (OJ EC No. L 228 p. 70) is used; the Federal Ministry of health shall publish the current version of the guide in German language in the Federal Gazette, 4. quality management system (QMS) is a system that includes quality assurance, good manufacturing practice, or the good practice including quality control and the periodic product quality checks, 5. specifications are specifications and requirements, raw materials or intermediates for medicinal or active ingredient manufacturing, active substances, medicinal products or tissue must comply they are used as a basis for assessing quality, 6 in-process controls are carried out checks during the manufacturing to monitor and, if necessary, adaptation of the process and to ensure that the product conforms to its specification, 7 are investigational medicinal products within the meaning of § 3 para 3 of the GCP regulation of 9 August 2004 (BGBl. I p. 2081), by the Decree of March 15, 2006 (BGBl. I S. 542) changed , 8's line of production or management quality control of the head or the head of the production or quality control within the meaning of article 14, paragraph 1 No. 2 of the medicines Act, 9 is blood establishment an establishment within the meaning of section 2 No. 2 of the transfusion law, which draws blood or blood components, tests, processes, features, packed, releases, stored, within the meaning of § 4 para 17 of the German medicines Act in the traffic brings , introduces, runs, or into or out of the scope of the German medicines Act spends, 10 te is an institution, which in section b paragraph 1 of the German medicines Act performs 20 c para 1 or § 72 listed activities or spends the tissues or tissue preparations from Member States of the European Union or other parties to the agreement on the European economic area into or out of the scope of the medicines Act or executing; If the tissue establishment WINS website, it is also a sampling device within the meaning of point 11; If the tissue establishment carries out also the necessary lab tests for obtaining, it is also a tissue donor laboratory within the meaning of point 13, 11 is to a facility that WINS certain tissues within the meaning of § 1a No. 4 of the transplantation law for use in humans including all measures that are intended to the tissue in a loading or processing capable State sampling device to identify preserved, unique and transport , 12 giving person is a person who a gift within the meaning of section 2 No. 1 is taken from the Act of transfusion or a tissue donation 13 tissue dispenser laboratory is a laboratory that performs the necessary lab tests for obtaining tissue, 14 job descriptions are written specifications about the specific duties, powers and responsibilities that were assigned to individual employees or employees of an establishment or facility of their respective lines , 15 standard operating procedure (SOP) is a written statement to the description of the individual steps of recurring operations (standard operating procedures), including the materials to be used and methods, 16 validation is providing documented proof allocated with high security, that a product that meets the predetermined specifications and quality attributes is made by a specific process or a standard operating procedures, 17 providing a documented proof of qualification , the high-security indicates that a specific piece of equipment or a specific condition for the manufacture of a product that meets the predetermined specifications and quality characteristics, is suitable, 18 critical manufacturing or testing procedures are procedures that can have a significant impact on the quality or safety of the products, and critical additives materials, which may have such an impact, 19 critical items of equipment or appliances are those , which can come in contact with the products or have a different impact on the quality or safety of the products.
Section 2 General requirements section 3 quality management system, good manufacturing practice and good practice (1) the establishments and institutions need a functioning quality management system (QMS) according to the nature and scope of the activities carried operate. The quality system must in the cases referred to in paragraph 2 the good manufacturing practice and include in the cases pursuant to paragraph 3 the good practice and envisage the active participation of the management of farms and facilities and the staff of each affected area. All areas involved in the creation, maintenance, and implementation of the quality system are adequate to equip with competent staff and suitable and sufficient premises and equipment. The quality system must be fully documented and controlled its functioning.
(2) on the interpretation of the principles of good manufacturing practice of part I of the EC-GMP Guide applies to pharmaceutical products, blood products within the meaning of section 2 No. 3 of the Act of transfusion and other blood components, as well as for products of human origin. On the interpretation of the principles of good manufacturing practice and good distribution practice, the part applies to active substances II of EC GMP Guide. To the interpretation of the principles and the risk assessment of to appropriate good manufacturing practice for materials they can be (5) of Directive 2001/83/EC, of the European Commission in accordance with article 47 note adopted guidelines. The Ministry of health makes known the current version of the guidelines in the Federal Gazette.
(3) paragraph 2 shall not apply to extraction and tissue establishments and tissue donor laboratories that carry out their activities according to the standards of good practice.

§ 4 staff
(1) the establishments and facilities must have competent and appropriately qualified personnel in sufficient numbers. The staff may be used only in accordance with his training and his knowledge and is to teach about the care offered in the respective activities proven to start and then continuously. The instruction must extend in particular on the theory and application of the concept of quality assurance and good manufacturing practice or in the cases of § 3 paragraph 3 of good professional practice, as well as on specific features of the product group, which is manufactured, tested or stored. The success of the training is to consider.
(2) the tasks of the staff Chief or person in charge, who are responsible for the observance of good manufacturing practice in the cases of § 3 para 2, or in the cases of § 3 paragraph 3 of good professional practice, must be defined in job descriptions. No gaps or unfounded overlaps must be between the responsibilities of the staff. The hierarchical relations are to be described in an organization chart. Organization charts and job descriptions shall be approved according to manufacturer's internal procedures. The employees referred to in sentence 1 are sufficient powers to grant, so that they can fulfil their responsibilities.

§ 5 premises and equipment (1) the premises must according to type, size, number and equipment for the intended purposes be suitable and so designed and used, that the risk of errors to the smallest possible size is restricted and avoided any effect that is affecting the quality of the product. The premises should be arranged so that the production in logically sequential steps can take according to the order of operations and, as far as for the quality of the product required, the cleanliness class of spaces.
(2) where the premises and their equipment used for manufacturing operations in products of sections 3 and 5, which are for the quality of vital importance, they must be checked for their suitability (qualifying).
(3) the premises must be in proper condition. You must be sufficiently lighted and have suitable climatic conditions. The premises are appropriate measures to protect against unauthorized access.
(4) the premises and their equipment must be thoroughly cleanable and are maintained to prevent contamination and cross-contamination and any adverse effect the quality of the product. Before any processing operation is to ensure that the work area and equipment are clean and free of all raw materials not required for the planned operations, products, product residues, documents and other materials.

Section 6 hygiene measures (1) premises and their equipment must be regularly cleaned and, if necessary, disinfected or sterilized. Want to do after a hygiene plan, in which in particular 1 the incidence of the measures, 2. carried out cleaning, disinfection or sterilization procedures and to use devices and tools, 3. if applicable, way of sampling for the review of the effectiveness of measures and 4. the persons entrusted with the supervision laid down. The effectiveness of cleaning and sterilization methods is to validate, so far as it requires the production process or the product.
(2) without prejudice to the hygiene plan referred to in paragraph 1 written sanitation programs must exist that are adapted to the activities to be conducted. You should include in particular provisions health, about hygienic behaviour and the clothing of the personnel.
(3) where animals are used for the production and testing of products to which this regulation refers, the hygienic requirements must be observed in their attitude.

§ 7 storage and transport are (1) raw materials, intermediate and finished products, and samples to store, that their quality is not adversely affected, and confusion be avoided. Critical parameters of the storage and transport must be controlled and recorded, to confirm compliance with the requirements. Sentence 1 shall apply accordingly for containers, outer wrapping, labeling material and, as far as used for package inserts. Special precautions to observe in printed packaging and labelling materials.
(2) the storage containers and the internal transport containers must be such that the quality of the content is not affected. You must be provided with clear inscriptions which uniquely identify the content. As far as no. 1 of the German medicines Act by the Federal Institute for drugs and medical devices are designed and published according to § 10 para 6, these are to use. The content is to identify, as far as this is necessary to avoid confusion with additional information. Access permission to the containers is to restrict measures on persons for authorized pursuant to sentence 1.
(3) paragraph 2 shall appropriate apply to containers for delivery of intermediate or end products. If shipped to products for further processing by other establishments outside the control of the manufacturer, their containers should be so closed that meantime done opening can be determined.
(4) the person responsible for the storage has to make sure that the products and materials are properly stored at regular intervals of.
(5) the procedure for the storage and transport are set in writing. As far as they can have an influence on the quality of raw materials and intermediate products for the manufacture of medicinal products or medicinal products, is the appropriateness of the procedure to prove.
(6) during transport to the delivery in the area of responsibility of the recipient to take care is that no unauthorized access and the quality of the products is not affected.

§ To control 8 animal husbandry (1) which is the State of health of animals which are kept for the production or testing of medicinal products or active substances by a veterinarian.
(2) If a quarantine is required prior to the use of animals, to accommodate them in a quarantine barn and monitoring by a veterinarian are. The quarantine period is at least three weeks for equine and other large animals at least four for monkeys for pets at least two weeks, for cattle, pigs, sheep and goats at least six weeks. The quarantine barn must be separated from the other stables. The persons responsible for the care and maintenance of animals housed in the quarantine barn without adequate measures, in particular to preventing transmission of infections, shall not be employed in other areas.
(3) only animals may be used for the manufacture and testing of products, to which this Regulation applies, which show no signs of communicable diseases according to the results of the Veterinary examination and not suffer diseases, which can adversely affect the production or testing.
(4) companies and institutions that keep the animals referred to in paragraph 1, have the animals by species separate records to lead, which contain at least particulars 1 origin and date of purchase, 2. race or tribe, 3. number, 4. marking, 5. beginning and end of the quarantine period, 6 result of veterinary studies, 7 species, date and duration of use and 8 fate of animals after use.
(5) facilities, where animals are kept, must be separated from other areas and a private entrance as well as their own ventilation systems.

§ 9 activities on behalf of (1) for any activity on behalf of, in particular the production, testing and placing on the market or any associated operation that is carried out on behalf of a written contract between client and contractor must exist. The Treaty must clearly defined the responsibilities of each side and in particular the observance of good manufacturing practice in the cases of § 3 para 2, or the good practice in the cases of § 3 paragraph 3 be regulated.
(2) the customer has to make sure that the contractor carries out the activity in accordance with the instructions and has a permit, insofar as this is required according to §§ 13 and 72 of the medicines Act.
(3) the contractor may awarded without its written consent to third parties further no work contract conferred on him by the principal. He must comply with the principles and guidelines of good manufacturing practice or good professional practice and in particular the prescribed manufacturing and testing instructions in case of contract manufacturing or order testing.

§ 10 General documentation
(1) companies and institutions must maintain a documentation system according to the respective activities. Documents must permit the tracing of the route and the placing of each batch and the changes made in the course of development of an investigational medicinal product. The documents must be clear and clearly, correctly and up to date. The initial contents of the registration may be illegible. No changes may be made, unaware of let if they in the original registration or later have been made. The documents must be accessible authorized persons only.
(2) be the records with electronic, photographic or made other data processing systems, is sufficient to validate the system. It must be at least ensured that the data for the duration of the retention period are available and can be made readable within a reasonable period of time. The stored data must be protected against loss and damage. If a system is used for automatic data processing or transmission, so whose name playback is sufficient instead of the handwritten signature of the responsible persons is ensured in an appropriate manner, that only authorised persons can make the confirmation about the proper execution of the respective activities.
(3) the records of the placing on the market are to arrange that they allow the immediate recall of the product.

Compliance with the provisions of this regulation to ensure § 11 self inspections and supplier qualification (1) self inspections are required regularly according to laid down in advance. About the self inspections and the corrective measures then taken, records must be kept and stored.
(2) the qualification of suppliers for raw materials and primary and secondary packaging materials used for the production of medicines, is carried in the QM system of manufacturing operation after writing a set procedure.
(3) the procedure must be referred to in paragraph 2, insofar as it's active ingredients for the pharmaceutical production, finding the proper production 1 provide the implementation of inspections of the manufacturer's site (audits) staff adequately trained to do this, the drug manufacturer; Instead its own audits of the pharmaceutical companies can access third party appropriate knowledge, provided that the requirements for the conduct of audits correspond to those of the own quality management system, and the checks include 2, that the manufacturer of the active substance for the manufacture of pharmaceutical products for use in humans, provided that it is established in a country, the Member State of the European Union or another Contracting State of the agreement on the European economic area , is registered with the competent authority.
Sentence 1 Nos. 1 and 2 also applies to importers and distributors, insofar as to active substances for the manufacture of medicinal products which are intended to be applied to the people.
(4) in order to ensure the suitability of auxiliary materials for the manufacture of medicinal products which are intended for use in humans, the procedure should be a formalized risk assessment by the drug manufacturer referred to in paragraph 2. The risk assessment must in particular the verification of compliance with the regulations of appropriate good manufacturing practice in the production of auxiliary materials, their origin and intended using, and any knowledge of events of the past include.
(5) the specifications of the medicinal products and active ingredients to reflect internally accepted manufacturers and suppliers.
(6) paragraphs of 2, 3 number 1 and paragraph 5 shall apply to other critical raw materials for the manufacture of the active substance according to.
Section 3 drugs, blood products and other blood components, as well as personnel in senior and responsible position (1) the responsibility of the competent person is products of human origin article 12 pursuant to § 19 of the German medicines Act in writing set. The tasks of the management of manufacturing and quality control management are to set in writing. Especially 1 ensuring that the products are properly manufactured and stored, 2. approval of production statement according to § 13 para 1 and ensure that is adhered to, 3. control of maintenance, the premises and the equipment for the production, 4. ensure that the necessary validation of the manufacturing process are carried out, and 5 ensure of the required initial and ongoing training of the staff belong to the tasks of the management of the production , which operates in the field of manufacturing.
Especially 1 approval or rejection of starting materials, packaging materials and intermediate products, 2. approval of specifications, instructions for sampling and testing instructions according to article 14, paragraph 1, as well as ensuring that they are complied, 3. ensure that all necessary tests have been carried out, 4. consent to the assignment, as well as monitoring the analysis laboratories, which act on behalf of, 5 control of maintenance are among the tasks of the line of quality control , the premises and equipment for performing the tests, 6 ensure that the necessary validation of test procedures are carried out, and 7 ensure of the required initial and continuous training of the staff, which has been operating in the field of testing.
The production line and the line of quality control must be independent of each other.
(2) in so far as the finished product be placed on the market, the areas of responsibility of phased plan officers are in addition in accordance with of article 63a of the medicines Act and information Commissioner in accordance with section 74a of the of the German medicines Act to set.
(3) a person who manufactures medicinal products or products of human origin or introduced without need a permission according to § 13 or section 72 of the medicines Act, has set people who are responsible for the manufacture, including sharing, storage and quality control.

§ Production (1) which are manufacturing operations with the exception of release under the responsibility of the management of the production according to pre-established written instructions and procedures (production order) making 13. You must be in accordance with good manufacturing practice, as well as the pharmaceutical standards.
(2) in the case of medicinal products which are authorised or registered, the manufacturing instruction must comply with the approval documents for the trial in which they appear on the application, the admissions or registration documents, investigational. At Blutstammzellzubereitungen, have been approved according to section 21a of the medicines Act, the manufacturing instruction must comply with the approval documents.
(3) for the production of medicines, only active ingredients and auxiliary substances within the meaning of article 2 are to use number 2 as source materials that have been manufactured in accordance with good manufacturing practice. Sentence 1 shall apply for the manufacture of investigational accordingly, with the requirements of the active ingredient to adjust at each stage of development of the investigational product. Only raw materials and medicinal products may be used, the quality of which has been determined and appropriately identified.
(3a) if finished medicinal products which carry a safety feature in the sense of article 10 paragraph 1 c of the medicines Act, by other manufacturers to be are packed, to ensure that the manufacturer prior to the partial or complete removal or coverage of the security features of the authenticity of the medicinal product. Security features may be replaced only by those that allow the checking for authenticity and integrity of the outer casing in equivalent ways. The primary packaging may not be opened.
(4) by spatial or temporal separation of the different production operations or by other appropriate technical or organisational measures precaution shall be taken to avoid cross contamination and mix-ups. In the manufacture of investigational, special precautions are in during and after the blinding in the meaning of § 3 paragraph 10 of GCP regulation to comply with.
(5) the procedures applied to the manufacture shall be validated according to the current state of science and technology. Critical phases of manufacturing processes shall be regularly revalidated. The manufacturing process is derogation from sentence 1 investigational as to validate whole, insofar as this is appropriate, taking into account the product development phase. critical process steps are always to validate. All steps for the design and the development of the manufacturing process for the investigational drug should be documented fully.
(6) it must be adequate and sufficient resources for the implementation of in-process controls available.
(7) the manufacture of each batch is performed in accordance with the statement of production referred to in paragraph 1 and completely recorded (production Protocol). Any deviation in the process and by establishing the specification shall be documented and thoroughly to investigate. As far as the product not in batches produced, set is 1 in accordance with.
(8) in the production log is to confirm that the batch according to production was produced by the management of the production with date and signature.

Section 14 (1) raw materials and finished products, and, if necessary, also intermediates are testing to check under the responsibility of the management of quality control according to pre-established written instructions and procedures (test instruction). The examination must be in accordance with good manufacturing practice, as well as the pharmaceutical standards. Sentences 1 and 2 shall apply mutatis mutandis to containers, outer wrapping, packaging and labelling materials and package inserts.
(2) in the case of medicinal products which are authorised or registered, the testing procedure must comply with the approval documents for the trial in which they appear on the application, the admissions or registration documents, investigational. At Blutstammzellzubereitungen, have been approved according to section 21a of the medicines Act, the testing procedure must comply with the approval documents.
(3) the methods used for testing shall be validated according to the current state of science and technology. Critical test methods must regularly be evaluated if they are still valid and, if necessary, be revalidated.
(4) the audit is performed in accordance with the inspection instruction referred to in paragraph 1 and completely recorded (test report). Any deviation in the process and by establishing the specification shall be documented and thoroughly to investigate. The line of quality control has to confirm that conducted the test according to the test instructions and the product has the required quality in the test log with date and signature.
(5) was found the required quality, the products are appropriately marked to make; temporal limitation of durability is to specify the end date.
(6) raw materials, intermediate and finished products, which do not meet the quality requirements, are to make clearly identifiable as such and to secrete. On future action is to decide by authorized personnel. The measures must be documented.

Article 15 labelling (1) medicinal products which are intended for use in humans and are no medicinal or investigational, may be brought within the scope of the German medicines Act only in the traffic, if their containers and, if used, the outer casings are marked according to § 10 para 1 No. 1, 2, 4, 6 and 9 of the German medicines Act in legible font, in German and in a lasting way.
(2) finished pharmaceutical products, which are medicinal products within the meaning of § 2 para 2 No. 1a, 2 or 3 of the medicines Act, may be placed only on the market, if your containers and, if used, their outer casings are marked according to sec. 10 of the German medicines Act. The information on the dosage form, the active ingredients and the waiting time can be omitted. These medicines are on the container or, if used on the outer packaging or a leaflet in addition to specify 1 the application areas, 2. contra-indications, 3. the side effects, 4 the interactions with other means.
(3) finished product no. 4 of the German medicines Act are medicinal products within the meaning of section 2, paragraph 2, may be brought only in the traffic, if their containers and, insofar as used their outer packages according to § 10 para 1, 2, 6, 8 and 9 of the German medicines Act are marked. The description of the pharmaceutical form can be omitted. The active ingredients are medicinal products within the meaning of § 2 para 2 qualitative and quantitative to specify when no. 4 of the medicines Act, insofar as they are characteristic for the function of the medicinal product. The finished product consists of several parts, so are on the container and, where used, to specify the batch designation of the individual parts on the outer packaging. The indication of the active ingredients is not possible according to type and quantity on the container from lack of space it is on the outer packaging or, where this lack of space is not possible in one to make the container enclosed information sheet.
(4) for medicines, the authorisation or registration not requiring the indication of the registration number or registration number is omitted.
(5) the products of human origin are on their containers and, if used to label their outer wrappings in legible writing in German or English language and in a lasting way at least as follows: 1. the name or business name and address of the manufacturer of the product and that has as far as different, of the manufacturer, the bottled product, racked, repackaged or to marked, 2. name or identification code of the product , connected with the note "human sources" and, as far as possible and true to its purity, the reference to a pharmacopoeia as well as the international abbreviation for the World Health Organization, if applicable 3., content by weight or by volume; biological units or other data of the value are scientifically in use, they should be use, 4. the finished product batch name or, as far as the product not in batch is made, the date of manufacture and, where appropriate, also of the filled, decanted, repackaged, or to designated product, 5. expiry date or subsequent test date and 6 special transport or storage conditions, as far as for maintaining the quality of the product required.
In justified cases the competent authority may permit exceptions on the labelling.

§ 16 sharing a batch to the placing on the market must release to the placing on the market (1) by the person in charge according to § 14 of the German medicines Act, which is familiar only to written procedures pre-established by you and procedures referred to in paragraph 2 with the product and with the procedures used in its manufacture and testing or 3 sentence 2 are carried out.
(2) who can share the production Protocol take place only if 1 and the test report signed 2. in addition to analytical results, essential information are how the production conditions and the results of in-process controls were taken into account, 3. confirms the conformity of the products with their specifications, including final packaging, validation of the manufacturing and test documentation and 4th at approved or registered the accordance with the documentation for the approval for the drugs the accordance with the admissions or registration documents and investigational clinical trial in which they will be applied, exists.
(3) as far as medical liquified are decanted according to § 13 para 3 of the medicines Act, is to release only the shipping container of the tank vehicle prior to the placing on the market by way of derogation from paragraph 2. The documentation for the filling of the final container is subsequently immediately to present the line of production and the person in charge, and to confirm them in writing. The responsibility of the competent person defined in section 19 of the medicines Act remain unaffected.
(4) if the production or quality control is carried out in several stages, if necessary, also at different locations or at different manufacturers or from the complete manufacturing with the exception of the share to other companies and institutions, the qualified person that according to § 14 of the German medicines Act can attract the confirmations made by other knowledgeable people about the part manufacturing steps or tests within a quality system approved by her to the decision on the release of the batch of the finished product. It is overall responsible for the release to the placing on the market of the batch. Sentence 1 shall apply accordingly for confirmations that are presented by knowledgeable persons under article 48 of Directive 2001/83/EC or article 52 of Directive 2001/82/EC.
(5) in the cases of paragraph 4, the competent person has according to § 14 of the German medicines Act through personal acknowledgement or confirmation other sufficiently competent and appropriate people to convince that the manufacturer able to produce in accordance with good manufacturing practice and in accordance with the manufacturing and inspection instruction and check. The production shall be proven in a country which is not member of the European Union or another Contracting State of the agreement on the European economic area, according to standards which are at least equivalent to the standards of good manufacturing practice laid down by the European Union. The manufacturer must be authorised to carry out the respective activity according to national regulation.
(6) the qualified person can get according to § 14 of the German medicines Act in cases of short-term prevention, in particular due to illness or vacation, represented only by persons who have the expertise according to § 15 of the German medicines Act can have.
(7) the holder of a permit has to section 13 or section 72 of the German medicines act according to § 14 of the German medicines Act to enable the qualified person performing their tasks and to provide all necessary means to you.

§ 17 import and placing on the market medicinal products (1), other blood components, blood products and products of human origin, which have been manufactured and tested in the scope of the medicines Act, may be brought only in the traffic, when they were released in accordance with section 16. As far as the drugs, blood products and other blood components and products of human origin in the scope of the German medicines Act were spent or introduced, the release must be only according to section 16 to the placing on the market, if conducted the production in a plant, it is authorized under the relevant national law, and the audit was carried out according to § 14 within the scope of the medicines Act. Testing should capture all other checks in addition to the complete qualitative and quantitative analysis, particularly of the active ingredients, which are necessary to ensure the quality of each product. Sentence 2 shall not apply for investigational medicinal products.
(2) in the case of an introduction from a Member State of the European Union or another Contracting State to the agreement on the European economic area within the scope of the German medicines Act may be waived by the examination referred to in paragraph 1, if carried out the audit in the Member State or of the other Contracting State under the applicable legislation and were accompanied by the control reports signed by the qualified person.
(3) in the case of an importation from countries, not Member States of the European Union or other parties to the agreement on the European economic area are, can be apart of the examination referred to in paragraph 1, if the conditions laid down in section 72a, sentence 1 No. 1 of the German medicines Act, with blood products that are not medicines and products of human origin also to section 72a sentence 1 meets No. 2 of the German medicines Act or the examination in another Member State of the European Union was conducted and appropriate inspection reports have been delivered.
(4) if the investigational medicinal products manufactured in a country, the non-Member States of the European Union or another Contracting State of the agreement on the European economic area is and exists for an authorisation for the placing on the market in the country of origin, to be used in a clinical trial as comparison preparations, the qualified person is responsible for that each production batch has undergone all necessary verifications according to § 14 of the German medicines Act , the quality of the preparations in accordance with the approval documents for the trial in which they appear to apply to confirm. Sentence 1 shall apply even if according to § 14 of the German medicines Act No records are available of the competent person, certifying that each production batch has been manufactured according to standards which are at least equivalent to the standards of good manufacturing practice laid down by the European Union.
(5) the qualified person has according to § 14 of the German medicines Act to certify compliance with the provisions of the medicines Act and this regulation before the batch on the market in accordance with section 19, sentence 2 of the German medicines Act in a continuous register or a comparable document for each production batch intended for this. If batches are then called back, this is noted in the register or a comparable document.
(6) unless otherwise permitted by law, medicinal plants and facilities may be delivered, that a permit according to § 13, § 52a or § 72 of the medicines Act or are authorised for sale to the final consumer or to other bodies or persons who may obtain medicinal pursuant to § 47 of the medicines Act. Sentence 1 shall apply accordingly for enterprises, which are 2001/83/EC or a permit 65 of Directive 2001/82/EC in a permit pursuant to article 40 or a permit pursuant to article 77 of the directive pursuant to article 44 or a permit pursuant to article. Sufficient documents include the deliveries, emerge from which in particular the date of delivery, the name and quantity of the medicinal product and name and address of the supplier and the recipient. The batch number of the corresponding medicinal product must be specified in the case of delivery to companies and institutions that have according to set 1 or set 2 has a permit or a permit, in addition. In addition must be confirmed, indicating the issuing authority and date of issue, that the supplier has a permit according to § 13, § 52a or § 72 of the medicines Act. The obligation to the additional indication of the batch number is also 1 distribution of medicinal products to hospitals and hospital-serving pharmacies for the purposes of the supply of hospitals, 2. in the case of blood preparations, Sera from human blood and preparations from other substances of human origin as well as genetically manufactured blood components that replace missing components of blood, even if delivery of plants and facilities for sale to the final consumer , 3. in the case of submission of the application in animals of certain prescription medicines as well as 4th in the case of medicinal products, must wear the security features within the meaning of § 10 paragraph 1 c of the medicines Act.

§ 18 samples (1) who has qualified person responsible for the release according to § 16 according to § 14 of the German medicines Act to ensure that samples are maintained of each batch of finished medicinal in sufficient quantities for the purpose of necessary analytical follow-up testing and proof of identification including the package insert for at least a year after of the expiry date. If the operation of the release shall not at the same time is the pharmaceutical entrepreneur, or if more than a company specialized in the manufacture of a batch is involved, the responsibility for the returning point pattern stock within the meaning of § 9 is to regulate by contract. For the case of a closure of the operation, in which occurs the body pattern transfer, the pharmaceutical entrepreneur to plan has, that the samples be kept during the whole storage period pursuant to sentence 1. If a batch in two or more stages is finally packaged, in principle at least a samples per cycle is to be kept. Parallel imported or parallel distributed medicines, sentence 4 shall apply only if their secondary packaging for the purpose of amending the labelling or the package leaflet is opened. For medicinal products, the production of which is carried out for individual cases or in small quantities or when their storage poses a specific problem, the competent authority may allow exceptions through the samples and their storage.
(2) who has qualified person responsible for the release according to § 16 according to § 14 of the German medicines Act to ensure that samples at least two years after the release of medicines manufactured using these raw materials kept by each batch of starting materials used for the production of medicines a shorter shelf life be specified unless it is in the registration documents. Sentence 1 does not apply to extraction solvents, gases and water. Paragraph 1 shall apply set 6.
(3) by way of derogation from paragraph 1 has for the release according to § 16 to ensure qualified person responsible according to § 14 of the German medicines Act of investigational and their labelling and printed packaging materials sufficient samples of each production batch at least two years to retain after the completion or discontinuation of the last clinical trial in which the concerned batch was used. If unspecified the GCP regulation in accompanying documents pursuant to section 5, the pattern of these accompanying documents for each batch shall be kept.
(4) the storage of samples of finished medicinal pursuant to paragraph 1 must be in the scope of the medicines Act. Sentence 1 may be waived if the samples in a Member State of the European Union or in another Contracting State to the agreement on the European economic area are stored.

Section 19 complaints and recall (1) the or the phased plan representative is responsible for ensuring that collected all known messages about drug risks after writing a set procedure, and systematically recorded all complaints. It is immediately to arrange an immediate check of the messages and then to assess whether a drug risk exists, it is as serious and which risk measures are available. The measures are to coordinate and to bring the person in charge, so that they can, if necessary, take the measures necessary on their part, especially if it could be a quality problem according to § 14 of the German medicines Act. The effectiveness of the procedure is to check regularly.
(2) or the phased plan representative has the competent authority of any defect that could lead to a recall or abnormal restriction on sales to inform without delay and also to inform, in which States the drug is spent or executed. In addition, the Authority also on suspicion of a drug or active ingredient counterfeiting is to promptly inform; medicinal products intended for use in people, is also the holder of the authorisation to teach.
(3) or the Chief of the phased plan has to comply with the obligations existing under the medicines Act, insofar as they relate to drug risks. The reporting obligations according to § 14 of the GCP regulation remain unaffected.
(4) the provisions of paragraph 1 shall apply accordingly for investigational medicinal products. The or the phased plan representative is responsible for ensuring that in cooperation with the sponsor complaints systematically recorded, be reviewed and effective systematic arrangements for a further use of the investigational product can be prevented, if necessary. Any defect that could result in a recall or abnormal restriction on sales, is to document and to investigate and to inform the competent authority without delay and also share with the investigational product was shipped to what bodies within or outside the scope of the medicines Act. If the investigational product is an approved drug, the or the phased plan representative in cooperation should inform the marketing authorisation holder of any defect with the sponsor who can relate to the approved drug in conjunction.
(5) on the content of the messages, the type of check and the findings obtained in this way, the outcome of the assessment, the co-ordinated measures and has the notifications to keep records of or the phased plan representative.
(6) the phased plan representative should be independent of the sales and distribution units and can be represented only by persons, which have the expertise after section 63a paragraph 1 sentence 1 of the German medicines Act, and must be resident in the scope of the medicines Act or in another Member State of the European Union and active.
(7) If a pharmaceutical company listed products on the market brings other than in section 63a para 1 sentence 1 of the German medicines Act, he has to hire a person with the duties of the phased plan representative. The appropriately authorized person is responsible for the compliance with the obligations to the paragraphs 1 to 5.
(8) the pharmaceutical entrepreneur has to ensure that all incoming in the operation messages about drug risks and complaints, as well as information necessary for the evaluation of the risk-benefit of a pharmaceutical product immediately instructed person or the phased plan representative or under paragraph 7 sentence 1 according to be communicated.

Article 20 storage of documentation (1) all records of acquiring, manufacturing including sharing, testing, storage, the movement into or out of the scope of the medicines Act, imports or exports, the placing on the market including delivery, as well as records of the animal husbandry and records the or of the phased plan representative or according to § 19 paragraph 7, sentence 1 according to designated person are fully and at least until one year after the expiration date , but not less than five years to be kept. Must be kept in a suitable range of areas covered by the permission in accordance with section 13 or section 72 of the medicines Act. Access to the records pursuant to sentence 1 is to restrict through appropriate measures on persons authorized to do so. For the case of a closure of the manufacturer or the test operation of the retention of documentation pursuant to sentence 1 shall the pharmaceutical entrepreneur to plan has that documentation is kept throughout the storage period.
(2) by way of derogation from paragraph 1 records with figures 1 to identify the establishment, 2. to identify the giving person, are the tax and 7 the name or the company of the recipient in readable form in a suitable storage medium 3 about the name of the medicinal product, 4 to the batch number, 5. obtaining the donation (year, month, day), 6 the date blood preparations, Sera from human blood and genetically manufactured plasma proteins for treating hemostasis disorders for the purposes of traceability at least 30 years and other records of the donation collection and the associated measures in accordance with section 11, paragraph 1, of the transfusion Act to maintain at least 15 years or to save. The information must be deleted if the retention or storage is no longer necessary. The records are kept longer than 30 years or stored, they are anonymous.
(3) (dropped out) (4) paragraph 1 shall apply for investigational with the proviso that the documents to be kept at least five years after completion or discontinuation of the last clinical trial in which the concerned batch was used, are.
Section 4 active ingredients of non-human origin section 21 organizational structure (1) the quality system pursuant to section 3 must in particular the organizational structure as well as the procedures, processes and all activities include, which are necessary in order to ensure that the active ingredient meets the intended specifications for quality and purity. It must have at least one quality assurance unit, which is independent of the production. The quality assurance unit must be involved in all quality-related matters.
(2) where active substances are manufactured or imported subject to permission according to § 13 or section 72 of the medicines Act, article 12, paragraph 1 shall apply.
(3) a person who manufactures active substances or introducing, without need a permission according to § 13 or section 72 of the medicines Act, has accordingly set the persons entitled to the share of intermediate products and active ingredients.

§ Production (1) which are manufacturing operations including in-process controls carried out according to pre-established written instructions and procedures (production order) and in accordance with the good manufacturing practice 22.
(2) in the active ingredient production subject to permission according to § 13 of the German medicines Act, the line of production is responsible for the approval of production statement, insofar as not sharing is concerned. In other companies and institutions, it is the quality assurance unit.
(3) it only output or intermediate may be used, the quality of which has been determined and appropriately identified.
(4) by spatial or temporal separation of the different production operations or by other appropriate technical or organisational measures precaution shall be taken to avoid cross contamination and mix-ups.
(5) the methods used for the production are, as far as these are critical for the quality or purity of the active substance, to validate the current state of science and technology. Critical phases of manufacturing processes are regularly to revalidate.
(6) the manufacture of each batch including their packaging is performed in accordance with the statement of production referred to in paragraph 1 and completely recorded (production Protocol). Any deviation in the process and by establishing in the specification are to document and evaluate; critical deviations must be investigated. As far as the active ingredient in batches produced, sentences 1 and 2 shall apply mutatis mutandis.
(7) in the production log is the production date and signature to confirm that the batch according to production was manufactured in plants and facilities, which are subject to permission according to § 13 of the German medicines Act, by the Board. In other farms and facilities, one or more relevant persons are set, which are responsible for checking the logs for completeness and accuracy.

Section 23 (1) raw materials, intermediates and active ingredients are testing to examine according to pre-established written instructions and procedures (test instruction), and in accordance with good manufacturing practice. Sentence 1 shall apply accordingly for containers, packaging and labelling material of the active ingredients.
(2) for active substances, their making a permission of the German medicines Act is required according to § 13, the line of quality control is responsible for the approval of the inspection instruction. In other companies and institutions, it is the quality assurance unit.
(3) the procedures applied for the examination shall be validated insofar as they are not listed in a Pharmacopoeia or a comparable set of rules according to the current state of science and technology. Critical test methods must regularly be evaluated if they are still valid and, if necessary, be revalidated.
(4) the audit is performed in accordance with the inspection instruction referred to in paragraph 1 and completely recorded (test report). Any deviation in the process and by establishing the specification shall be documented and thoroughly to investigate.
(5) in companies and institutions, requiring a permit according to § 13 of the German medicines Act, the management of quality control in the test log with date and signature shall confirm that conducted the test according to the test instructions and the product is of the required quality. Corresponding responsibilities are set in other companies and institutions.
(6) was the required quality is detected, the active ingredients are appropriately marked to make; temporal limitation of durability is to specify the end date. If shown, also a verification date can be specified instead of the expiration date.
(7) raw materials, intermediates and active ingredients, which do not meet the quality requirements, are to make clearly identifiable as such and to secrete. On future action is to decide by authorized personnel. The measures must be documented.

§ Labelling (1) which is identification of intermediates and active ingredients making 24 according to pre-established written instructions and procedures and in accordance with good manufacturing practice. The management of the production is responsible for the approval of the statement and procedure active ingredient production subject to permission according to § 13 of the German medicines Act. In other companies and institutions, it is the quality assurance unit.
(2) intermediates and active ingredients are before their placing on the market on their containers and, if used to label their outer wrappings well legible and permanent manner at least as follows: 1. name company and also the address of the manufacturer, 2. name or identification code of the product, as far as possible, its purity; where applicable, reference to a pharmacopoeia and - if applicable - international short term of the World Health Organization, 3. content by weight or by volume; biological units or other data of the value are scientifically in use, they should be using, 4. batch number or, as far as the intermediate or the active ingredient in batches produced the manufacture date, 5. expiry date or subsequent test date, 6 special transport or storage conditions required for maintaining the quality of the active substance or substance as far as, 7 on genetically derived active ingredients genetically modified the description of the one used in the manufacture micro-organism or the cell line and 8 substances of microbial origin indication , that it is an active ingredient of microbial origin, and substances of animal origin to the production used the term animal species.
(3) if the intermediate or the active ingredient subsequently by an establishment other than the original manufacturer is was, racked, repackaged, to marked or released in addition of the name or the company and address of this establishment as well as the new batch number on the container and, unless used to specify the outer packaging of intermediate or of the active substance. The values are in German language unless it is brought to the intermediate or the active ingredient in the scope of the German medicines Act in the traffic. Further details shall be permitted insofar as they do not contradict the German data. Sentences 1 to 3 shall not apply if it is activities in individual cases that are required due to demonstrable damage to the original container or its packaging. An activity within the meaning of sentence 4 is not considered to be manufacturing step. The process is to document and to submit at the request of the competent authority.

Article 25 the release to the placing on the market must release to the placing on the market (1) only according to pre-established written procedures and procedures according to paragraph 3 or paragraph 4 sentence 1 of persons be made who are familiar with the products and with the procedures employed for their manufacture and testing.
(2) in companies and institutions, which are subject to the license requirements for section 13 or section 72 of the medicines Act, the qualified person is responsible for the release of those products that trigger the approval obligation according to § 14 of the German medicines Act; Article 16, paragraph 1 and 4 to 7 finds appropriate application. In addition, the quality assurance unit for sharing is responsible; Persons entitled to the share are set in writing.
(3) the release must be only referred to in paragraph 1, if the production and test protocols are signed, in addition to analytical results were considered as the production conditions and the results of in-process controls and validation of the manufacturing and test documents the conformity of the products with their specifications confirmed essential information.
(4) in the case of intermediate products and active substances, which are only filled to, bottled, packaged or labelled, the share referred to in paragraph 1 may be only, if 1 at least the identity of these products was established and exists in a duly signed test report 2 about the transfer, filling, packing and marking a duly signed production Protocol, 3 all quality or registration-related information required by the original manufacturer and, if applicable , another manufacturer of the active ingredients or intermediates including the certificates of analysis there are 4. sufficient knowledge of the original manufacturer, and, if applicable, are another manufacturer and its quality management system and 5. traceability is guaranteed to the original manufacturer of the product.
If the intermediates or active substances in primary containers are filled other than the original material or packaged, is to check the expiration date specified by the original manufacturer or the subsequent test date on the basis of additional stability data and, if necessary, to adapt. Intermediates and active ingredients, which are exclusively released the release allowed only pursuant to paragraph 1, if the requirements of sentence 1 No. 3 to 5 are met.

Article 26 import and placing on the market (1) active ingredients or intermediates, which were manufactured and tested within the scope of the medicines Act or which have been spent or introduced in the scope of the medicines Act, may be brought only in the traffic, when they were released in accordance with § 25. § § 72 and 72a para 1 and 2 of the German medicines Act remain unaffected.
(2) any quality or registration-related information, including the certificates of analysis and of the name or the company and the address of the original manufacturer are to inform the recipient of the substance or intermediate. As far as essential, particularly security-related information about the active ingredient or the metabolites from the receiver will receive, these are the active substance or intermediate manufacturer to forward without delay.

§ 27 (1) retain samples from every batch of active ingredient are properly marked pattern in a suitable container, and in sufficient quantities to be kept. Sentence 1 shall apply also in cases of exclusive filling to filling, packing and marking. For agents, the production of which is carried out for individual cases or in small quantities or when their storage poses a specific problem, the competent authority may allow exceptions through the samples and their storage.
(2) where a date has been set for the active ingredient, the patterns are at least one year after of the expiry date referred to in paragraph 1, but at least three years after the full distribution of the batch, to be kept.
(3) samples are to be kept at least three years after the full distribution of the batch, of active substances for which a subsequent test date was set instead of the expiration date referred to in paragraph 1.

§ 28 complaints and recall (1) are all quality-related complaints in plants and facilities that produce active substances within the scope of the medicines Act or spend within the scope of the law or introduce to document, to examine and evaluate the quality assurance unit after writing a set procedure. Also the original manufacturer of the complaints is as necessary to inform.
(2) If a suspicion that it is a serious deficiency, is the need for a callback after writing a set procedure to check. The conditions under which a product recall in consideration is to draw as well as the recall process itself are to be defined in writing. In the event of a serious or life-threatening situation are, to inform immediately the competent authority and the concerned Drugmakers or other recipient, the active ingredient was delivered to the.
(3) over the content of messages, the type of check and the findings, the outcome of the assessment, the measures and the notifications are records to lead.

§ 29 retention of documentation
(1) all records relating to the purchase, a year after of the expiry date, but not less than five years to keep the production including the import or export, and the placing on the market of including delivery, as well as animal husbandry and the records under section 28 release, the laboratory controls, the storage, the movement into or out of the scope of the medicines Act, are fully and at least.
(2) by way of derogation from paragraph 1 the records for active substances for which instead of the expiration date a subsequent test date was set, or at least three years the full placing of the charge by the manufacturer, to be kept.
(3) spent for the purposes of traceability of produced within the scope of the medicines Act or into or out of the scope of the Act, or within the scope of the law introduced or carried out active ingredients or intermediates are in addition to all certificates of analysis, including those of the original manufacturer, to preserve documents that have least information about: 1. the name of the active substance or intermediate, including the batch name of the original manufacturer , and, if applicable, another manufacturer, 2. the name or business name and the address of the original manufacturer, and, where appropriate, another manufacturer, 3. the transport and sales, 4. the name or business name and the address of the recipient.
Section 5 special provisions article 30 supplementary regulations for medicated feedingstuffs (1), for the manufacture of medicated feedingstuffs may only feed be used which correspond to the feed regulations and contain no Anticoccidial.
(2) section 3 is paragraph 2 shall apply, that the resulting according the scientific specifics of medicated feedingstuffs are to be considered. The manufacturer has to ensure that the medicated feedingstuff contains no avoidable after the State of the art contamination with pharmacologically active substances and the drug premix in prescribed quantities and homogeneous and stable distribution contains and is delivered correctly. The carriage shall only take in tankers or similar containers, if these are suitable and prior to each further use according to the generally accepted rules of technology so were cleaned, to avoid an unwanted interference or contamination of the medicated feedingstuffs. Medicated feedingstuffs are carried in tankers or similar containers, it is sufficient if after the pursuant to sections 10 and 11 of the medicines Act and the information required pursuant to paragraph 4 carried, for the pet owners accompanying transport are included.
(3) section 14 applies on medicated feedingstuffs with the proviso that the testing can be done at random. This, at least the examination of uniformity and the examination on contamination with pharmacologically active substances is making. From scrutiny beyond can seen when no evidence has shown, justify the doubts on the proper nature of the medicated feedingstuffs. When the drug premix used in the manufacture of medicated feedingstuffs to be aside from scrutiny beyond the sensory testing, no evidence showed, justify the doubts on the proper nature of the drug premix. With regard to the examination of the compound feed used, the feed-legal regulations apply.
(4) without prejudice to other provisions on the labelling, medicated feedingstuffs may be placed on the market only if they, as well as with the indication are provided to which percentage determines to meet food needs are characterized by the visible word "medicated feedingstuffs".
(5) by way of derogation from section 16 a responsible person who has sufficient training and knowledge, can share in cases of short-term prevention instead of the person in charge according to § 14 of the German medicines Act provisionally medicated feedingstuffs for the placing on the market. This preliminary release is the person in charge, which is responsible for sharing in this case in addition to the appointed person to present and to confirm this in writing subsequently. The qualified person has according to § 17 para 5 making the entry immediately after the confirmation.
(6) by way of derogation from § 18 para 1 patterns keep at least six months after of the expiry date of each batch. They are well legible and permanent way with the date of manufacture, to mark the label of the drug premix, as well as the batch number.
(7) the veterinary prescription required for the delivery of medicated feedingstuffs must be in four copies (original and three copies), the pattern of Appendix 1 of the Ordinance on veterinary pharmacies of House as amended by the notice of 27 March 1996 (BGBl. I p. 554), most recently by article 2 of the Decree of November 3, 2006 (BGBl. I S. 2523) is changed, in the amended , will be presented. The template of a fax of the prescription is to furnish the original of the prescribing veterinarian without delay is permitted. The manufacturer has the prescription before dispensing the medicated feedingstuffs with information to be entered by him to supplement. He has time allocated from the time of submission of the medicated feed five years to keep the remaining his originals and to submit without delay the competent authority upon request or to hand over.
(8) by way of derogation from paragraph 7 of the medicated feedingstuffs may be handed to a keeper based in another Member State of the European Union or another Contracting State to the agreement on the European economic area only upon presentation of a veterinary prescription, which complies with the requirements of the country of destination. Where the legislation of the country of destination, a companion certificate in the form required by the country of destination is the medicated feedingstuff be accompanied.

Article 31 supplementary provisions for blood establishments (1) the quality system pursuant to § 3 para 1 must in accordance with the in the annex of to Directive 2005/62/EC of the Commission of 30 September 2005 implementing Directive 2002/98/EC of the European Parliament and of the Council as regards Community standards and specifications relating to a quality system for blood establishments (OJ L 256 of the 1 October 2005, p. 41) be set up in the currently valid version of listed standards and in particular 1 ensure that all critical processes and standard operating procedures are defined in appropriate standard operating procedures, 2. adequate procedures to recall and traceability according to paragraph 4 sentence 3 and blood preparations in the meaning of Directive 2002/98/EC of the European Parliament and of the Council of 27 January 2003 laying down quality and safety standards for the production , Testing, processing, storage and distribution of human blood and blood components and amending Directive 2001/83/EC (OJ L 33 of the 8.2.2003, p. 30) as well as according to § 21a include paragraph 1 sentence 3 of the German medicines Act to report serious adverse events, serious adverse reactions and their suspected cases, 3. ensure that use products or relevant to the safety of the products and the back tracking process documents of an institution, which finished its activity in other institutions which have a permit within the meaning of § 13 of the German medicines Act , be passed, 4 by a person responsible for quality assurance are supported, that is responsible and in all quality-related issues should be included, if not the management of the production or the line of quality control is responsible for the approval of all quality-related documents, and 5. the management of farms and facilities regularly for efficiency are reviewed and adjusted, if necessary.
The person responsible for quality assurance can be identical with the person in charge according to § 14 of the German medicines Act, insofar as this is not at the same time line of production. As far as blood products or other blood components from blood establishments are involved in countries which are not Member States of the European Union or the other Contracting States of the European economic area, must the qualified person re according to § 14 of the medicines Act, ensure that a QM-system have these blood establishments using is set up according to the standards, which are at least equivalent to the standards set by the European Union.
(2) job descriptions for all staff are by way of derogation from article 4, paragraph 2, sentence 1 in blood establishments to hold, its Tätigkeiten can have effects on the quality of blood preparations.
(3) the General requirements for premises and equipment in § 5 are also on temporary or movable facilities are located outside, but under the control of the blood establishment (mobile site), to apply. The special features of the premises, including mobile sites, depending on the respective activities. In particular the area for the purpose of determining of the suitability and fitness of giving people must ensure a sufficient confidentiality 1 and separated from the donation processing areas, 2. allow donations area the safe removal, as well as a required treatment of the giving person, the laboratory area of the range for the determination of the fitness and suitability of the giving person and from the field for the processing of donations split off 3 and only authorised to be accessible , 4th in the storage area, a separate storage ensure products with varying status or of products which were produced according to specific criteria, and precautions taken in the event of failure of the equipment or the energy supply, 5 separate areas for waste disposal of potentially infectious materials exist.
(4) the statement of production must have details according to § 13 ABS. 1 giving personal and to the donation, as well as the associated documentation. She must at least provisions to be observed for each donation, contain in accordance with annex II of to Directive 2004/33/EC of 22 March 2004 implementing Directive 2002/98/EC of the European Parliament and of the Council as regards certain technical requirements for blood and blood components (OJ 1 information of potentially shady or shady person or from this unsustainable information after L 91 of the 30.3.2004, p. 25), by the implementing directive 2011/38/EC (OJ L 97 of the 12.4.2011, p. 28) has been changed, in the applicable version, 2. fashion a reliable identification of the giving person in determining their eligibility and suitability for use as well as prior to the sample and donation collection, 3. determination of the fitness and suitability of the giving person according to the suitability laid down in annex III to Directive 2004/33/EC and exclusion criteria , 4. collection of contributions and, if applicable, their processing, including the determination of the period up to the processing, 5. requirements for the donations, processing and final product containers, 6 marking of papers and containers, including donor-specific numbers or identification codes of donors and 7 conditions of storage and transportation of blood preparations or other blood components pursuant to annex IV of to Directive 2004/33/EC.
Without prejudice to article 13, paragraph 7, the production Protocol must ensure full traceability intermediates between donation and giving person, and it won and blood preparations including the for the extraction and processing used sterile one-time systems and their batch labels as well as the devices used and the test results obtained from the sample, regardless of the intended use of the donations. The donation collection and processing is adequate to monitor microbiologically. In addition, for the extraction of autologous donations, the generally recognised State of medical science and technology shall apply.
(5) the testing procedure according to § 14 para 1 must take account of the peculiarities of donated blood and blood preparations and in particular that 1 is the collection of laboratory specimens in appropriate, donor-specific numbers or identification codes marked containers at the time of the donation, the laboratory samples prior to testing is properly stored and testing within a given period making set, 2. each donor on the occasion of each donation to the State of science and technology at least on hepatitis B , Hepatitis C and human immune deficiency virus (HIV) is to test, 3. in addition the AB0 group, as far as it is not about plasma for fractionation are, and in the case of preparations of erythrocytes the Rhesus formula or in the case of preparations of platelets, the RH D group at each donation to determine is, 4 blood group serological investigations also technique for testing specific groups of donors are and the blood preparations, the quality requirements must meet 5 pursuant to annex V of to Directive 2004/33/EC.
Deviate from the specifications, especially in a repeatedly reactive or positive test result to set results 1 number 2 promptly to enlighten and to take appropriate action to confirm the results and to the exclusion of the use of the products concerned. For the testing of autologous donations, the generally recognised State of medical science and technology shall apply in addition.
(6) for the testing of donations and the donor samples, only laboratory reagents and other materials from in-House accepted suppliers may be used. The laboratory reagents must be suitable for their purposes and released prior to their use by a qualified person. The quality of the test procedure is regularly through participation in a formal system of performance test to check.
(7) during all stages of production the respective status of the product and the traceability to the giving person must emerge from the labelling clearly, as far as this is not ensured by other measures.
(8) preparations of fresh plasma and blood cells need as far as need not the approval according to § 21 para 2 No. 1a of the medicines Act, according to § 10 para paragraph 8a of the medicines Act correspond to the marking. Autologous donations must be identified clearly as such.
(9) prior to the release according to § 16 products are administratively and physically shared products be stored separately. Autologous donations must be stored separately. Products that deviate from the specifications, may not be released. If a product based on the test results can not be released is to make sure that all of the same and, where applicable, identifies products obtained earlier donations-giving person and are secreted. the measures must be documented. Second half-sentence set 4 finds appropriate application if subsequent knowledge of faulty, infectious or potentially infectious products be obtained, which were already placed on the market.
(10) by way of derogation from § 16 can make in cases of short-term prevention, and if this is an urgent need for medical reasons, a responsible person who has sufficient training and knowledge, temporarily release the blood preparations for immediate use in people for the placing on the market and the entry instead of the person in charge according to § 14 of the German medicines act according to § 17 para 5. This preliminary release and the preliminary entry according to § 17 para 5 are the person in charge, which is responsible for sharing in this case in addition to the appointed person to present and to confirm this in writing.
(11) section 18 shall not apply to preparations of blood cells or plasma, fresh. The qualified person has according to § 14 of the German medicines act as to keep samples follow-up sample of donors in sufficient quantities for the purpose of necessary analytical follow-up testing.
(12) without prejudice to section of the 19th century, the or the phased plan representative for this is responsible that collected all reports of serious adverse reactions after writing a set procedure, be assessed and reported to the competent federal authority or the competent authority according to article 63i paragraph 2 or paragraph 3 of the German medicines Act. Sentence 1 applies also to suspected cases of such reactions. While 1 must contain the initial meld all necessary information, in particular to the identification of the blood establishment, giving person, and the donation to the filing date and the donation, transfusion date, to the nature of the suspected reaction in accordance with annex II of Directive 2005/61/EC of 30 September 2005 implementing Directive 2002/98/EC of the European Parliament and of the Council as regards the requirements on the traceability and the reporting of serious adverse events and serious adverse reactions (OJ L 256 of the 1 October 2005, p. 32) in its up-to-date version; She must indicate also the degree of probability of a relationship between administration of blood preparation and the receiver response (allocation level), 2 are defined the initial meld, once you have sufficient evidence for this; in particular, it is to specify whether to confirm the initial meld and their mapping level in terms of the probability of a link, or whether and, where appropriate, how to report a change in the classification of the first is; also the clinical course in the receiver is so far known to specify. At the assignment level to distinguish in particular, whether a connection is excluded, unlikely, possible, probable, or safe or can not be evaluated.
The modalities, in particular to the technical specifications and formats of the declarations to the competent federal authority, can be controlled in a notice to the competent federal authority.
(13) paragraph 12 sentence 1 to 3 shall apply mutatis mutandis adverse events: 1 the initial meld must all necessary information include, in particular, whether product error, faulty equipment or human error, and whether the error in the production, processing, testing, storage, transport, the placing on the market or any other activity or with materials that were used in the production, testing or processing that occurred.
2. the first message is to define, as soon as sufficient evidence for this. In particular, is to analyze the root cause and to report on corrective measures taken.
Section 5a special provisions for removal and tissue establishments and tissue donor laboratories § 32 additional General requirements (1) the quality system pursuant to § 3 para 1 must for tissue establishments under the responsibility of the responsible person according to § 20 c of the German medicines Act in particular 1 ensure that all work processes, which affect the quality and safety of tissues and tissue preparations, as well as the standard operating procedures in the appropriate standard operating procedures are set, carried out under controlled conditions, and documented , 2. make sure that the equipment used, the working environment and the suitable conditions for the working or processing, as well as the storage of tissues and tissue preparations and regularly inspected 3. adequate procedures to the singling out and dealing with discarded tissues or tissue preparations and waste disposal include, 4. include sufficient procedures to traceability and the immediate notification of serious adverse events, serious adverse reactions and their suspected cases , 5. make sure that use tissue and tissue preparations or relevant to their safety or the back tracking process documents from a facility that terminates its operation, are passed to other facilities, provided a permit within the meaning of § 20 c of the medicines Act, and 6 regularly in terms of continuous and systematic improvements verified and adjusted.
If tissues or tissue preparations are obtained from institutions in countries which are not Member States of the European Union or the other Contracting States of the European economic area, must the person re pursuant to § 20 c of the medicines Act, ensure that a quality system have this equipment is set up according to the standards, which are at least equivalent to the standards set by the European Union. By way of derogation from section 3, subsection 1, sentence 1-collecting device and tissue donor laboratories must have adapted to its activities, a system of quality assurance according to the principles of good technical practice. Thus, in particular the compliance with the requirements set out in paragraphs 1, 3 and 4 must be ensured.
(2) the agreement must in particular details about the donor selection criteria and the tissue biopsy and the tissue donor laboratory pursuant to § 9 para 1 of a tissue establishment with the sampling device and, as far as the carried used, other laboratories, laboratory tests and exams, as well as the required documentation pursuant to this regulation and include § 3 and § 6 of the TPG tissue regulation. Sentence 1 shall apply accordingly for the procedures for immediate reporting of suspected cases of serious adverse reactions and serious adverse events. The contracts are to lead in the worked or processed tissue establishment a full list and to submit at the request of the competent authority.
(3) without prejudice to the section 10 must be at least made sure the documentation system of a tissue establishment, that 1 the secure identification of every donation and every tissue resulting or each tissue preparation resulting in each processing phase is possible and all steps are traceable to 2 for each critical activity the appropriate materials and equipment, as well as the executive staff can be identified, 3. the tissues or tissue preparations only for the working or processing propagated or released to the placing on the market , if they have complied with all the requirements in the respective specifications, 4. the records are reliable and only documents are used that have been approved by authorized persons, and the accidental use of outdated versions of a document will be prevented by appropriate measures.
The documentation system must be checked periodically by the responsible person according to § 20 c of the German medicines Act on timeliness and efficiency.
(4) the self inspections are according to § 11 para 1 in tissue establishments at least once every two years for trained and competent persons carry out, section 11 subsection 2 does not apply.

§ Assessment of donor suitability and required for the production of laboratory tests (1) are the determination of donor suitability in the sampling device and necessary for the production of laboratory tests in the fabric dispenser laboratory according to pre-established standard operating procedures in accordance with good professional practice making 33. In particular, the requirements are according to the articles 3 to 6 of TPG tissue regulation to be observed.
(2) the standard operating procedures must comply with the approval documents in tissue preparations have been approved according to section 21a of the medicines Act, referred to in paragraph 1.
(3) the procedures for the laboratory tests shall be validated according to the State of science and technology. Critical test methods must regularly be evaluated if they are still valid and, if necessary, be revalidated. The quality of the test methods referred to in sentence 2 can be checked through regular participation in a formal system of performance test. All reagents and other materials in-House accepted supplier may be used for laboratory examination. The laboratory reagents must be suitable for their purposes and released prior to their use by a qualified person.
(4) laboratory tests are carried out in accordance with the standard operating procedures referred to in paragraph 1 (test instruction) and completely recorded (test report). The person responsible for the laboratory results in the tissue donor laboratory shall confirm that carried out the laboratory tests according to the instructions of the test and the test results are correct in the test log with date and signature.

§ 34 extraction of tissue through the sampling device (1) section 4 is for collecting device no application. Staff, which takes the fabric, must have successfully completed training prior to the execution of this activity according to predefined program, whose creation was a clinical team which specializes in the tissue to be taken and according to § 13 of the German medicines Act involved also the respective maintenance or processing tissue establishment or the holder of a permit in the case of section 20B paragraph 2 of the medicines Act. The training must include dealing with the medical devices for tissue sampling.
(2) sections 5 and 6 apply for collection facilities with the proviso, that the premises and equipment, as well as the hygiene measures must be suitable to protect the properties of the tissue, which are necessary for its use and minimize the risk of microbial contamination during sampling: sterile medical devices must be 1 for the tissue removal. As far as medical devices be reapplied, whose preparation must be made according to § 4 section 2 of the medical devices operator Ordinance.
2. the removal from living donors must be in an environment that is adapted to the extent and the degree of risk of the intervention. The rooms are basically suitable, if these are used for a comparable medical treatment in accordance with the usual requirements including the hygiene measures.
3. the removal of donation from deceased donors to be in clean rooms, where the removal area with sterile towels will be covered.
4. If the tissue biopsy covered spaces must be by personnel seconded from the sampling device (mobile teams) outside of the permission in accordance with section 20 b of the German medicines Act and the possibility of withdrawal by mobile teams is basically provided in the permit, find the numbers 1 and 3 apply.
(3) the tissue removal including all measures that are intended to get the tissue in a loading or processing capable State, to identify and to transport, is carried out according to previously created standard operating procedure (removal instruction) in compliance with the requirements of § 2 of the TPG tissue regulation and in accordance with good professional practice.
(4) in the case of tissue preparations have been approved according to section 21a of the medicines Act, the collection statement must match the approval documents pursuant to paragraph 3.
(5) the collection statement must contain at least the following provisions pursuant to paragraph 3: 1 to verify the identity and determine the eligibility of donors, 2. for collection of donations and the samples for laboratory examination, as well as to dealing with the removed material, including a) the equipment to be used, b) of the procedure for the removal and to prevent a bacterial or other contamination during the withdrawal, as well as, if necessary, further measures to minimize contamination of the tissue , c) to the State of the removal place, as far as this outside the areas covered by the licence is located, and where necessary, to be complied conditions, as well as for deceased donors to the documentation of the period between the death and the removal of the donation, 3. requirements on the donations and sample containers, as well as on the used storage and transport solutions and other products and materials, with the donations in touch come and can have an impact on their quality and safety , 4. to mark the donations and the samples according to paragraph 6, 5. conditions an intermediate storage of donations or the samples to their transport to the treatment or processing or for laboratory testing, which is capable of whose characteristics and biological functions to get.
The procurement procedures must be reasonable the giving person and the nature of the donation, which preserve necessary properties of the tissue for their use and minimize the risk of microbial contamination of the donation.
(6) the tissue donations are to be provided at the time of their removal at least with the following information: 1 type of donation and specifying to the traceability of the donor / donor at the sampling device, which is consistent with data protection, as well as identification of the donor as a donor, when the donor organs for the purposes of the transfer have been taken, 2nd day and, if possible, time of collection , 3. warning of a possible hazard, 4. If present, type of used accessories, 5. for autologous donations note "only for autologous use" and directed donations the data to the receiver.
If the information can be provided pursuant to sentence 1 No. 2 to 5 not on the container, they are in a list accompanying document, which is attached to the container. The labelling of samples for laboratory examination must in particular the association with the giving person be undoubtedly possible and information about the place and time of the sampling.
(7) the tissue sampling and sampling are performed in accordance with the statement of withdrawal pursuant to paragraph 3 and without prejudice to the medical documentation obligations according to § 8 d para 2 of the transplantation law completely recorded (sample report). The sampling report shall contain at least the following information: 1. name and address of the tissue establishment; received the tissue
2. donor identification with information on family name, first name, gender, date of birth and living donors address or, if approved, the allocation number assigned by the sampling device for the donors of tissue, as well as identification of the donor as a donor, when the donor; taken from organs for the purpose of transmission
3. Description and identification code of the removed tissue;
4. family name, first name and address of the doctor responsible for the sampling;
5th day, time and place of collection and the nature and way of sampling and a possible interim storage;
6. for deceased donors at death, description of the conditions under which the body; preserves If a cooling system is conducted, time of commencement and end of cooling;
7 identification/batch number of the used storage and transport solutions.
Any deviation in the process and by establishing the specification shall be documented and thoroughly to investigate. Incidents occurred during the removal may also be documented including the affiliated carried out investigations. The person responsible for the removal has to confirm that the withdrawal according to the sampling instruction has been carried and the tissue for the treatment, processing or, are released conservation or retention within the meaning of § 8 d paragraph 1 sentence 2 No. 4 of the transplantation law in the procurement report with date and signature. The removal report is the tissue establishment, that the removed tissue and - or processed, to submit. The requirements on the donor file pursuant to section 5 of the TPG tissue Regulation shall remain unaffected.

§ 35 transport to the handling or processing and reception at the tissue establishment (1) is the transport carried out after previously created standard operating procedures. The procedure must be appropriate to the donation and protect the properties of tissues, which are required for their use, as well as minimize the risk of microbial contamination of the donation. It must set the type of the transport container and the labelling referred to in paragraph 2, the entering of any samples and the sampling report according to § 34 paragraph 7 on the maintenance or processing tissue establishment.
(2) without prejudice to article 7, paragraph 3, the containers for the transport of tissue to the working or processing with at least the following information shall be provided: 1. "caution" and "tissues and cells", 2. addresses and telephone numbers of the sampling device and the tissue establishment which is to get the tissues or tissue preparations for the working or processing, and the names of the respective contact persons, 3. date and time of the start of transportation , relevant transport and storage conditions, 4. precautions and instructions for handling and use.
(3) the reception at the tissue establishment to the working or processing of tissues including the related documentation and samples from the sampling equipment is carried out after previously created standard operating procedures. The procedure must in particular checking 1. integrity of the packaging, 2. identification, 3. compliance with the conditions of transport as well as 4 of the supplied documentation and, insofar as applicable, supplied samples capture. The fabrics are in quarantine to keep, until it was decided about their usefulness. As far as they do not meet the requirements, they are discarding. Accept or reject incoming tissue must be documented. The tissue collected from a donor, where also institutions for the purposes of the transfer have been taken the Te the co-ordination body according to article 11, paragraph 1, of the transplantation law shall immediately inform the donor identification according to § 34 paragraph 7 sentence 2 number 2; This is to specify whether the accepted tissue has been accepted or rejected.

§ Must be informed under section 20 c of the medicinal products act on the legal and ethical relationship of joining 36 handling or processing and storage by the tissue establishment (1) without prejudice to article 4, paragraph 1 the personnel under the responsibility of the person responsible. By way of derogation from article 4, paragraph 2, sentence 1, job descriptions for all staff are to hold.
(2) the premises and equipment for section 5 and the hygiene measures according to § 6 must be suitable, to protect the properties of the tissue, which are necessary for its use and minimize the risk of microbial contamination during treatment or processing: 1 as far as the tissue are exposed during their working or processing of the environment, must be done in an environment with fixed air quality and cleanliness. The effectiveness of these measures is to validate and monitor.
2. If the tissues undergo no inactivation or sterilization procedures referred to in point 1, an air purity for bacterial count and number of particles according to class A, the definition of the EC-GMP Guide, annex 1 is during the working or processing (notice of 12 March 2008, BAnz.) P. 1217), with a background environment appropriate for the working or processing of the tissue, at least class D of annex 1 of the Guide corresponding in particulate and microbial count, required. The environment may be derogated from the requirements, if a) a validated method for inactivation of bacteria or the final sterilization is applied or b) demonstrated that exposure to an environment of the class has A harmful impact on the required properties of the fabric, or c) is shown that with the way the use of tissues of the recipient, or the recipient a significantly lower risk of transmission of bacterial or fungal infection on the receiver or the Recipient is accompanied by tissue transplantation, or d) it is not technically possible, perform the required procedure in a class A environment.
It is to demonstrate and document that the required quality and safety of the tissues or tissue preparation is achieved with the selected area, at least, taking into account the purpose of the provision, the type of use and the immune status of the recipient or the recipient.
(3) all critical equipment and devices are according to pre-established standard operating procedures, which set also measures in case of any malfunction, to qualify and to undergo regular inspections. You are to wait before according to the instructions of the manufacturer. Equipment with a critical measuring function are to calibrate. To test the installation and before use to release are new and repaired equipment. The activities carried out are to be documented.
(4) the working or processing, including possible inactivation measures, labelling and packaging, is according to a pre-established standard operating procedures (working or processing instruction), which lays down critical additives perform in accordance with good professional practice.
(5) in the case of tissue preparations have been approved according to section 21a of the medicines Act, the working or processing instruction must match the approval documents pursuant to paragraph 4.
(6) the working or processing must be regularly assessed in order to ensure that they continue to achieve the desired results. Critical handling or processing procedures, including possible inactivation measures are to validate the current state of science and technology and may the tissues or tissue preparations not clinically ineffective or harmful, will leave for the recipient.
(7) during all working or processing stages identification and the status of the tissue or tissue preparation and traceability to the giving person must emerge from the labelling, insofar as this is not ensured by other measures. If it is an autologous or directed tissue preparation, this shall be indicated. Tissues or tissue preparations are of giving persons who were tested positive for infections or their lab test results are not yet available, to label.
(8) without prejudice to the requirements of § 10 paragraph 8b of the German medicines Act to tissue and tissue preparations before their placing on the market with following information and information on the outer container and, if used, fitted on the outer packages or in an accompanying document: 1. Description and, where necessary, mass of tissue morphology and functional data, 2. results of laboratory studies required for the extraction, 3 date of the levy , 4 storage recommendations, 5. instructions on how to open the container, the packaging and, if necessary, to handle, 6 expiry date after opening or after the above handling, 7 if applicable, following the occurrence of potentially harmful residues.
In addition, instructions for reporting serious adverse reactions or serious adverse events according to § 40 is for the receiver of the tissues or tissue preparations to add.
(9) the working or processing is carried out according to the statement pursuant to paragraph 4 and completely recorded (working or processing log). Any deviation in the process and by establishing the specification shall be documented and thoroughly to investigate. The person responsible for the working or processing has to confirm that the working or processing according to the instruction has been carried in the log with date and signature. The working or processing log must ensure full traceability between the donation as well as intermediate result obtained, giving person and products including the materials used and their batch designations, as well as the respective test results as far as this impact on the quality and safety of the tissues or tissue preparations.
(10) without prejudice to § 7 storage must be according to previously created standard operating procedure under controlled conditions and be suitable to maintain the quality of tissues and tissue preparations. The maximum storage time is set for each type of storage conditions. Prior to the release according to § 38 the tissue and tissue preparations are physically or administratively in quarantine and shared tissues and tissue preparations be stored separately. If tissues or tissue preparations have been discarded, these are to separately store to avoid mix-ups and cross-contamination.

§ 37 examination of tissues and tissue preparations (1) is to test compliance with the defined specification perform according to the previously-created standard operating procedures (test instruction) in accordance with good professional practice. Article 33, paragraph 3 shall apply mutatis mutandis.
(2) in the case of tissue preparations have been approved according to section 21a of the medicines Act, the testing procedure must correspond to the documents relating to the approval.
(3) the audit is performed in accordance with the inspection instruction referred to in paragraph 1 and completely recorded. Any deviation in the process and by the provisions of the specification shall be documented and thoroughly to investigate. The person responsible for the test is to confirm that was carried out the test in accordance with the inspection instruction and the results are correct in the test log with date and signature.

§ 38 release by the tissue establishment (1) the release of tissues or tissue preparations may be operated by the person responsible under section 20 c of the medicines Act and only be carried out by their previously approved standard operating procedures. The procedures must prevent the accidental release of tissues or tissue preparations if the conditions referred to in paragraph 2 are not fulfilled.
(2) the share may occur only if the verification of all required documents has confirmed compliance of the tissues or tissue preparations with their specifications, including final packaging, and tissue preparations, which are subject to approval according to section 21a of the medicines Act, compliance with the approval documents.
(3) which can person responsible under section 20 c of the German medicines Act represented only by persons who have the expertise to article 20 to have c par. 3 of the medicines Act. Must be drawn from the records clearly, who has carried out the release.
(4) the person in charge must make a risk assessment for such tissue and tissue preparations according to § 20 c of the medicines Act, have not yet delivered after their release and their expiration date has not expired, if subsequent findings have resulted in a change of extraction, treatment or processing or testing procedures or the donor selection criteria or the laboratory examination procedures with the aim of improving quality. The tissue and tissue preparations may be delivered only after positive conclusion of the risk assessment and written confirmation of the release. The risk assessment must be documented. Already delivered tissue and tissue preparations may only be redeemed in the stock, when they were assessed and considered in accordance with the specification in writing prescribed procedures.

§ 39 placing on the market, import and transport by the tissue establishment (1) tissue and tissue preparations are allowed only in the traffic, when they were released in accordance with section 38.
(2) in the case of a removal of the tissue preparations from a Member State of the European Union or another Contracting State to the agreement on the European economic area within the scope of the German medicines Act must the person re sure according to § 20 c of the German medicines act before releasing according to § 38 in particular that the conditions are fulfilled according to section 21a, paragraph 9, of the medicines Act.
(3) when an importation of tissues or tissue preparations from countries which are not Member States of the European Union or other parties to the agreement on the European economic area, must the person re sure according to § 20 c of the German medicines Act prior to the release according to § 38 in particular that the conditions are fulfilled according to § 72 (b) paragraphs 1 and 2 of the medicines Act. § 32 para 1 sentence 2 shall remain unaffected.
(4) the transport is carried out a predetermined standard operating procedures according to. The procedure must be appropriate tissue or tissue preparation and protect the properties of the tissue or tissue preparation, which are required for their use and minimize the risk of microbial contamination of tissues or tissue preparation.
(5) without prejudice to article 7, paragraph 3, the transport containers containing at least the following information shall be provided: 1. "caution" and "tissues and cells", 2. identification of the tissue establishment which be - or processed has the tissues or tissue preparations, as well as establishing the tissues or tissue preparations should receive relevant including their addresses and telephone numbers, as well as 3. transport and storage conditions as well as, if necessary, additional precautions and instructions for handling.

Article 40 notification of serious adverse reactions and serious adverse events and callback
(1) without prejudice to article 13c of the transplantation law there in record is 3 No. in collecting device in the sense of section 20B paragraph 1 of the German medicines Act 1 person responsible that the relevant standard operating procedure for tissue establishments according to previously created through all known serious adverse reactions within the meaning of § 63i, paragraph 7 of the German medicines Act and corresponding suspected cases, affecting the quality and safety of the tissues or tissue preparations or on these can be traced back , immediately be informed. Paragraph 3 sentence 2 shall apply accordingly.
(2) paragraph 1 shall apply accordingly for collecting device and tissue donor laboratories in the event of serious incidents in the sense of § 63i, paragraph 6 of the German medicines Act and corresponding suspected cases have occurred in connection with the extraction or the necessary lab tests for obtaining. Paragraph 3 sentence 2 shall apply accordingly.
(3) in tissue establishments, the person in charge is responsible that all known reports of serious adverse reactions are collected and evaluated according to paragraph 1 after previously created standard operating procedures under section 20 c of the German medicines Act for this. The messages are the competent federal authority or the competent authority in accordance with article 63i, paragraph 2 or 3 of the medicinal products Act and, as far as the donors of tissue is also organ donor to provide the NSS without delay pursuant to section 11 of the transplantation law. Sentence 1 applies also to suspected cases of such reactions. While 1 must contain all necessary information the initial meld, in particular for identifying removal - and the tissue establishment, the tissue donor laboratories, giving person and the donation, the filing date and the date of the donation collection and the suspected reaction to the kind of tissues involved in the suspected reaction or tissue preparation and the suspected reaction, as well as the likelihood of a link between administration of tissue or tissue preparation and the response of the receiver , 2. the initial message be spelled out once you have sufficient evidence for this; in particular, it is to specify whether the initial message is to confirm, or whether and, where appropriate, how to report a change in the classification of the first; as far as known, are also the clinical course of the recipient or the recipient and any further conclusions to specify, including any corrective actions and measures have been taken in relation to other affected, supplied for use in human tissue and tissue preparations.
(4) paragraph 3 shall set 1 to 3 on serious incidents referred to in paragraph 63i paragraph 6 of the German medicines Act mutatis mutandis. It must: 1 initial all necessary information contained, in particular for identifying removal - and the tissue establishment, the tissue donor laboratories, the affected donation, the filing date and the date of the fatal incident, whether defects in the tissue or tissue preparation, faulty equipment or human error, and whether the error in the recovery, laboratory testing required for obtaining , transport to the worked or processed tissue establishment, the working or processing, testing, release, storage, transport, the placing on the market or any other activity has occurred the 2 initial be spelled out, as soon as sufficient evidence for this. In particular, is to analyze the root cause and to report on corrective measures taken.
(5) the person in charge is responsible for that tissue and tissue preparations that the paragraphs 1 to 4 are affected or might be affected, messages can be identified, separated and recalled according to § 20 c of the medicines Act. Has to assess the need for a callback after writing a set procedure and to coordinate the necessary actions within a predetermined time and promptly to inform the competent authority of each callback and also to inform the tissues or tissue preparations were delivered to what facilities and what action it has taken in relation to other potentially affected tissue and tissue preparations. The effectiveness of the procedure is to check regularly.
(6) the modalities, in particular to the technical specifications and formats of the notifications under paragraphs 3 and 4 of the competent federal authority, can be controlled in a notice to the competent federal authority.
(7) over the content of messages, the type of check and the findings obtained in this way, the outcome of the assessment, the co-ordinated actions and notifications, as well as dealing with returned tissue or the person in charge has tissue preparations according to section 20 c of the German medicines Act will keep a record. Sentence 1 shall apply paragraph 1 sentence for persons according to § 20 3 No. 1 of the German medicines Act in accordance with.

Section 41 storage of documentation (1) for the retention of records of obtaining, laboratory testing, loading or processing, testing, release, storage, the movement into or out of the scope of the medicines Act, the import or export, placing on the market including delivery and the final destination of tissues or tissue preparation, as well as records of the person responsible for section 20 c of the German medicines Act § 15 of the transplantation law applies.
(2) the storage needs without prejudice to § 14 of the transplantation law in an adequate range of the permission in accordance with section 20 (b) or section 20c of the German medicines act performed covered spaces. Access to the records referred to in paragraph 1 is to restrict through appropriate measures on persons authorized to do so.
(3) in the case of a closure of the removal or tissue establishments or the tissue donor laboratories, where the retention of documentation is carried out pursuant to paragraph 1, the pharmaceutical entrepreneur to plan has that documentation is kept throughout the storage period.
Section 6 No. 31 of the German medicines Act is section 42 offences offences any person within the meaning of article 97, paragraph 2, who intentionally or negligently 1 contrary to § 13 paragraph 3a security features partially or fully removed or covered, without to be convinced by the authenticity of the medicinal product or by such replaced that allow the checking for authenticity and integrity of the outer casing in equivalent manner , 2. contrary to article 16, paragraph 1 or article 25, paragraph 1 a batch or an active ingredient of non-human origin to the placing on the market releases, 3. contrary to section 17, subsection 1, sentence 1 or § 26 para 1 sentence 1 brings a there called a product without a prior release circulation, 4. contrary to § 18 1 sentence 1 or paragraph 2 sentence 1 does not ensure that a there named samples will be kept , 5. contrary to § 18 para 3 sentence 1 does not ensure that a there called a pattern is stored, 5a.
contrary to article 19, paragraph 2 the competent authority or the marketing authorisation holder does not or not timely informed, 6 contrary to § 30 paragraph 1 used a feed, 7 violates article 30 par. 4 brings a medicated feedingstuffs on the market, 8 contrary to section 30, paragraph 7, sentence 3 not, incorrectly, incompletely or not in time adds a prescription or 9 contrary to section 30, paragraph 7, sentence 4 retained the original not or at least five years or not or not timely submit and not or not timely issued.
Section 7 final provisions § 43 transitional arrangements, this Regulation shall not apply to active substances, which are stored at the time of entry into force of this regulation within the scope of the medicines Act or involved due to an existing contractual obligation and running until November 9, 2008 in States outside the European Union or the European economic area.