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434. Federal Minister for Health and Women's Ordinance on the holdings of public pharmacies and the Anstaltsapotheken 2006
On the basis of § § 48, 62 (1) and 69a (2) of the German Medicines Act, Federal Law Gazette (BGBl). No 185/1983, as last amended by BGBl. I No 107/2005, shall be:
Scope
§ 1. (1) This Regulation shall apply to the establishments of public pharmacies and local pharmacies, unless it is a case of:
| 1. |
public pharmacies in which only |
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Medicinal products intended for direct delivery to the consumer or |
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the manufacture of individual products of medicinal products for users; or |
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| 2. |
Establishments in which only medicinal products which are intended for use in that hospital which operates this pharmacy must be manufactured. |
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(2) The provisions on medicinal products contained in this Regulation shall also apply to investigational medicinal products, unless there are any specific arrangements for investigational medicinal products.
Definitions
§ 2. (1) "Working area" means any room in which medicinal products are manufactured, placed on the market or controlled.
(2) 'starting material' means any substance or preparation of substances used for the manufacture of medicinal products.
(3) 'intermediate product' means any substance or preparation of substances which have to undergo one or more stages of production in order to become the bulk product.
(4) 'Bulkware' means any substance or preparation of substances which only have to be bottled or packaged in order to become the final product.
(5) "packaging material" means all components of the commercial packaging of medicinal products and all other containers and all the packing elements, including the package leaflets and all components, including the starting material, intermediate products, bulkware, end-of-life products, end-of-life products, and finished products shall be placed on the market, including the relevant markings. Materials which are not used as packaging material are used for the further packaging of commercial packages.
(6) "final product" means a medicinal product which has undergone all stages of manufacture but has not yet been released by a competent person in accordance with section 7 (6).
(7) "finished product" means a medicinal product which has undergone all phases of production and quality control and has been released by a competent person in accordance with § 7 (6).
(8) "Sachkundige Person", in conjunction with § 7, is a person in accordance with Article 48 of Directive 2001 /83/EC, as amended by Directives 2004 /24/EC and 2004 /27/EC, or in Article 52 of Directive 2001 /82/EC, as amended by Directive 2004 /28/EC, or Article 13 (2) of Directive 2001 /20/EC.
(9) "Manufacturer" means any person who is involved in activities for which an authorization pursuant to Article 40 (1) and (3) of Directive 2001 /83/EC, as amended by Directives 2004 /24/EC and 2004 /27/EC, or Article 44 (1) and (3) of the Directive 2001 /82/EC, as amended by Directive 2004 /28/EC, or Article 13 (1) of Directive 2001 /20/EC.
(10) 'Pharmaceutical quality assurance' means all the measures provided for in order to ensure that medicinal products or investigational medicinal products are of the quality required for the intended use.
(11) "investigational medicinal product" is a product according to § 2a (14) of the German Medicines Act.
(12) 'Good manufacturing practice' means the part of the pharmaceutical quality assurance system which ensures that medicinal products or investigational products are consistently produced and tested in accordance with quality standards corresponding to the intended use. In order to interpret the principles and guidelines of good manufacturing practice, the manufacturers and the Federal Office for Safety in Health Care have applied to the generally accepted scientific principles and requirements laid down in § 42 (1). 1 mentioned guidelines and annexes are to be obtained.
(13) 'Good distribution practice' is the part of the pharmaceutical quality assurance system which ensures that the distribution of medicinal products is consistent with quality standards which ensure the proper quality of the medicinal products during transport; and storage. In order to interpret these principles, pharmacy companies and the Federal Office for Health Safety have applied to the generally accepted scientific principles and requirements established by the European Commission. shall refer to the detailed guidelines published in accordance with Article 84 of Directive 2001 /83/EC, as amended by Directives 2004 /24/EC and 2004 /27/EC.
(14) "blinding" is the deliberate pretext of the information on the identity of a investigational medicinal product in accordance with the sponsor's instructions.
(15) "Unblinding" is the unveiling of the identity of a compound that has been blinded.
Good Manufacturing Practice, Good Sales Practice and Import
§ 3. (1) The manufacturer must ensure that the manufacturing operations are carried out in accordance with good manufacturing practice and the manufacturing authorisation. This also applies to medicinal products intended exclusively for export.
(2) In the case of medicinal products and investigational medicinal products imported from third countries, the importer shall ensure that they have been manufactured in accordance with standards established in accordance with the standards of good manufacturing practice laid down by the European Community are at least equivalent. In addition, the importer of medicinal products must ensure that the manufacturer of these medicinal products has a proper manufacturing authorisation. The importer of investigational medicinal products must ensure that the manufacturer of these investigational medicinal products is notified to and authorised by the competent authorities for this purpose.
(3) Pharmacy establishments which place medicinal products on the market or carry out a deposit function shall comply with the principles and guidelines of good distribution practices of medicinal products for human use.
Approval and clinical trial
§ 4. (1) The manufacturer must ensure that all processes for the production of medicinal products which require approval are in accordance with the information of the marketing authorisation application approved by the Federal Office for Safety in the Health Sector ,
(2) In the case of investigational medicinal products, the manufacturer must ensure that all operations are carried out in accordance with the information provided by the sponsor in the application approved by the Federal Office for Safety in the Health Sector in accordance with § 40 of the German Medicines Act (Medicinal Products Act) ,
(3) The manufacturer must regularly review its manufacturing processes taking into account the scientific and technical progress and the development of the investigational medicinal product. If a change to the registration documents or the content of the application is required in accordance with § 40 of the German Medicines Act (Medicines Act), an amendment must be submitted to the Federal Office for Safety in Health.
Pharmaceutical quality assurance system
§ 5. (1) Each pharmacy establishment must operate a functional pharmaceutical quality assurance system which provides for the active involvement of the management and staff of the various sectors concerned.
(2) Self-inspection is part of the pharmaceutical quality assurance system and must be carried out on a regular basis in order to monitor the application and observance of the rules of good manufacturing practice and good sales practices and to make proposals for any corrective measures that may be necessary. Records must be kept and kept by means of the self-inspection and the corrective measures subsequently taken.
(3) The pharmaceutical quality assurance system shall be guided by a person with the appropriate qualification, which is independent of manufacture.
Operational Organization, Staff
§ 6. (1) In order to achieve the objectives of the pharmaceutical quality assurance, each pharmacy establishment must have sufficient numbers of qualified and qualified staff.
(2) The tasks and responsibilities within the pharmacy establishment must be defined in an organisation scheme which must be carried out in pharmacies.
(3) The organisation scheme must clearly identify the assignment of all areas of responsibility and responsibility within the framework of production, quality control and warehousing.
(4) The tasks of the employees in a senior or responsible position, including the knowledgeable person responsible for the observance of good manufacturing practice, must be defined in job descriptions .
(5) The organisation scheme and job descriptions shall be approved in accordance with internal procedures.
(6) The staff referred to in paragraph 4 of this Article shall be given sufficient powers to enable them to fulfil their responsibilities.
(7) The staff must be trained continuously before the start of the activity and thereafter. The effectiveness of the training must be reviewed regularly. The training shall be based in particular on the theory and application of the pharmaceutical quality system, good distribution practices and, in the case of manufacturers of medicinal products, good manufacturing practice and, where appropriate, the special Requirements for the preparation of test specimens extend. The training measures must be documented. These documents shall be kept for a period of at least five years.
(8) Pharmacy establishments placing medicinal products on the market or carrying out a deposit function must have professional staff with regard to their product range, in particular a specially designated responsible person who has: successful completion of a degree in pharmacy in a contracting party of the European Economic Area or in Switzerland, and after successful completion of the degree course, a minimum of one year qualified activity in a or a number of undertakings in a Contracting Party to the European the economic area or in Switzerland to which a wholesale authorisation has been granted. This person shall ensure that a pharmaceutical quality assurance system is introduced and maintained.
Knowledgeable person
§ 7. (1) A knowledgeable person within the meaning of this Regulation shall:
| 1. |
in a Contracting Party of the European Economic Area or in Switzerland, a study of pharmacy, human, dental or veterinary medicine, chemistry or biology, or a training course of at least four years, recognised as equivalent, of theoretical and practical teaching in one of these fields of expertise, have successfully completed and |
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| 2. |
after successful completion of the course of studies or training referred to in Z 1, an activity of at least two years in one or more undertakings in a Contracting Party of the European Economic Area or in Switzerland, to which a authorisation to manufacture or control medicinal products has been granted, in the field of the qualitative analysis of medicinal products, the quantitative analysis of the active ingredients, and the tests and tests necessary to ensure that the medicinal products are used for the production or control of medicinal products. Quality of medicinal products must be ensured. |
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(2) The Federal Office for Health Security must demonstrate that the course of studies or the course of training referred to in paragraph 1 Z 1 has included theoretical and practical teaching in at least the following basic subjects and in which sufficient Knowledge is available:
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Experimental physics, |
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General and Inorganic Chemistry, |
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Organic chemistry, |
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Analytical chemistry, |
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Pharmaceutical chemistry including drug analysis, |
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General and applied (medical) biochemistry, |
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| g) |
Physiology, |
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| h) |
microbiology, |
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| i) |
Pharmacology, |
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| j) |
Pharmaceutical technology, |
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| k) |
toxicology, and |
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| l) |
Pharmacognosy (medical aspects). |
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(3) If, in the course of studies or training, according to paragraph 1, Z 1, the theoretical and practical teaching does not include individual subjects listed in paragraph 2, the lack of knowledge can also be completed after successfully completed studies, or The acquisition of the knowledge is to be proven beyond doubt. The scope of the theoretical and practical teaching in the individual subjects must correspond essentially to the course content and scope of the course in the course of the course of studies or training courses in accordance with paragraph 1 Z 1.
(4) A person who
| 1. |
in another Member State of the European Union, at the start of the application of Council Directive 75 /319/EEC on the approximation of laws, regulations and administrative provisions relating to proprietary medicinal products, OJ L 175, 5.7.1975, p. No. OJ L 147 of 9.6.1975 p.13 or Directive 81 /851/EEC on the approximation of the laws of the Member States relating to veterinary medicinal products, OJ L 136, 30.4.1981, p. No. L 317 of 6.11.1981 S.1 has exercised the activity of a competent person, or |
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| 2. |
in Austria before the 1. Jänner 1995 the activity of a control laboratory manager in accordance with the requirements of the Regulation on the scientific professional training and practical training of the head of a control laboratory, BGBl. No 405/1984, or |
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| 3. |
has a derogation pursuant to Section 93 of the Medicines Act, |
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| is authorised to carry out the activity of an expert person. |
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(5) A person who is after the 1. Jänner 1995 and before entry into force of this Regulation the activity of a control laboratory manager
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in accordance with the requirements of the Regulation on the training of scientific professionals and the practical training of the head of a control laboratory, BGBl. No 405/1984, or |
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| 2. |
in accordance with the requirements of the Regulation on the scientific vocational training and practical training of a person entrusted with the management of a control laboratory (KLVO 2005), BGBl. II No 480/2004, |
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| shall be entitled to carry out the activities of a competent person, provided that the qualifications referred to in paragraphs 1 to 3 above may be presented by 31 December 2007 at the latest. |
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(6) The competent person shall ensure that each batch of medicinal products in accordance with the provisions of the medicinal product legislation and in accordance with the requirements of the authorisation, and each batch of investigational medicinal products, shall be: The provisions of this Directive have been established and controlled in accordance with the information provided for the correct application for authorisation in accordance with Section 40 of the Medicines Act.
(7) The knowledgeable person shall release any batch of medicinal products and investigational medicinal products prior to sale or delivery within the European Economic Area or before export.
Premises
§ 8. (1) The working spaces must be suitable for the work to be carried out in pharmacy operations, in sufficient quantity and size, so that production, storage and storage of stocks corresponding to the state of the sciences, as well as the production of storage facilities, are available. Control of medicinal products is guaranteed. Access to the working rooms is restricted to authorized employees and to persons who have a corresponding explicit permission from the pharmacy's company.
(2) The working spaces shall be dedicated to a particular use. Work spaces must not be used in an undedicated way. The intended use of the individual working spaces shall be defined in a spatial plan plan which must be in operation.
(3) Working spaces shall be arranged or dedicated in such a way as to ensure an orderly, clear and smooth operation of all operations. In the case of a new direction or a conversion of a pharmacy operation, a risk analysis must be carried out within the framework of a design qualification. On the basis of this data, the rooms must be designed, designed and used in such a way that the risk of errors is minimal and the arrangement of the premises is adapted to the practical course of the processes.
(4) thorough cleaning and maintenance must be possible in order to avoid contamination, cross-contamination, confusion and, in general, any effect that impairs the quality of the product. Working spaces intended for use in manufacturing processes critical to the quality of the product must be checked with regard to their suitability and must be subject to qualification.
(5) The surfaces of the floors, walls and ceilings in the working spaces shall be durable, resistant, easy to clean and disinfect. Moreover, in the working spaces used for the manufacture of pharmaceuticals, the surfaces must be as smooth, seamless and free of cracks as possible.
(6) The lighting, heating, ventilation and air-conditioning of the working spaces shall be in accordance with the requirements of the operations to be carried out and the quality requirements of the medicinal products. If the air is recirculated for working spaces that are used for production, measures to prevent contamination or cross-contamination are to be taken.
(7) The working spaces shall be air-conditioned, if relevant with regard to product quality. Humidity and room temperature for the working spaces must be specified in a specification. Room temperature and humidity are to be measured and documented in the working rooms-if relevant with regard to product quality. A derogation from the specifications shall be examined to assess the influence of the deviation on the medicinal products in the working spaces and their quality, and the decision on disposal or re-use the medicinal product concerned must be recorded in a derogation protocol. The derogation protocol shall be completed by a person responsible for pharmaceutical quality assurance and shall be kept for a period of at least five years in pharmacies.
§ 9. (1) Working spaces in which steam, gas, strong odour development or the development of other pollutants can be unavoidable in the course of work must be equipped with a correspondingly dimensioned suction system.
(2) The extraction system referred to in paragraph 1 shall be installed in such a way that pollutants are detected as far as possible at the site of production. The derivation must be carried out in such a way that the air conditions in the pharmacy operation cannot be impaired. Suction and room ventilation must not be unfavorably influenced by each other.
§ 10. Rooms or containers in which animals are kept, in particular animal stables, shall not be directly linked to the working spaces. Appropriate facilities for animal husbandry, such as easy-to-clean and disinfecting cages, washable walls and floors, as well as a separate aeration and ventilation system from the other premises of the plant, must be provided. Quarantine possibility exists.
§ 11. (1) Separate spaces shall be provided for the manufacture, control and storage of medicinal products.
(2) Rooms in which medicinal products are manufactured must be designed and furnished in such a way as to ensure that:
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various production operations carried out in the same or adjacent premises shall be compatible with one another with regard to the nature of the medicinal products to be produced; and |
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the working and storage areas are arranged and dimensioned in such a way that: |
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the risk of confusion between different medicinal products or their components is halted, |
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mutual impurities are avoided and |
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the risk is halted that a manufacturing or control step is not carried out or is carried out improperly. |
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(3) Work operations within the spaces referred to in paragraph 1 shall be carried out in order to prevent contamination and confusion in specific areas of appropriate size, in particular for:
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entrance, identification, storage or quarantine and blocking of starting materials, packaging material, intermediate and end products during the sampling, testing and inspection by the control laboratory before release, |
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Storage of rejected starting materials, packaging material, intermediate products, end-and finished products, |
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Manufacture (each for pharmaceutical form and packaging), |
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Storage or quarantine of finished products, |
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Laboratory tests for quality control and |
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Office activities. |
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(4) For the
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Use of highly toxic or infectious substances or preparations of substances in the manufacture of medicinal products or |
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Application of biotechnical or genetic engineering methods |
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| , in accordance with the outcome of a risk analysis, provision should be made for separate working spaces, the equipment of which corresponds to the characteristics of |
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(5) The use of the premises referred to in paragraph 1 for the manufacture of other products as a medicinal product may only be carried out in accordance with an authorization granted in accordance with § 63 of the German Medicines Act and only in time separation from the manufacture of medicinal products.
(6) A transfer of working spaces to other establishments, as always, for the purpose of production, control or storage of medicinal products may only be carried out in accordance with a authorization granted in accordance with § 63 of the German Medicines Act. The granting of the authorization shall be granted to the pharmacy establishment which shall leave the working spaces. The responsibility for compliance with the provisions of this Regulation and, if necessary, on the occasion of the granting of the authorization, shall be borne by the establishment to which the working spaces are made available. It must also have an authorization in accordance with § 63 of the German Medicines Act and is subject to an inspection in accordance with § 67 of the German Medicines Act.
(7) A written agreement must be reached on the transfer of work spaces within the meaning of paragraph 6, which clearly establishes the duration and scope of the use.
(8) The agreement referred to in paragraph 7 shall be subject to constant suspension in the original or in the form of a copy, both in the operation to which the work spaces are made available and in the pharmacies holding it at the disposal of the undertaking. Upon request, the Federal Office for Health Security must prove the existence of the agreement.
(9) The manufacture (active substance manufacture, pharmaceutical form, primary packaging and, where appropriate, secondary packaging as a function of the outcome of a risk analysis) of penicillins and other strongly allergenic or highly effective medicinal products has in work spaces and installations which are separate from those used for other medicinal products. These working spaces shall be ventilated separately and shall be provided with their own locks for material and personnel.
(10) Manufacture (active substance manufacture, pharmaceutical form, primary packaging and, where appropriate, secondary packaging, depending on the outcome of a risk analysis) of medicinal products derived from infectious or potentially infectious starting material (organs, tissues, Cells, blood or blood components, bodily fluids) must be performed in work spaces and installations separate from those used for other medicinal products. These working spaces shall be ventilated separately and shall be provided with their own locks for material and personnel.
(11) In the case of a new direction or a conversion of clean rooms, air flow analyses carried out in the course of validation and qualification shall be recorded by video or other equivalent technical means and shall be carried out by the Federal Office for Security in the Health care on demand.
§ 12. In the case of working spaces for the production of sterile products, it must at least be specified that:
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the installation and use of the premises shall be carried out in such a way as to encourage the introduction, development and storage of microbial and particulate impurities; |
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by supplying filtered air, an overpressure is maintained in relation to the surrounding areas and there is a suitable automatic warning system for the reporting of disturbances in the air supply, |
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Ducts, pipelines and electrical installations are easily cleanable, no washbasins and processes in rooms of class A/B, which are used for the aseptic production of products, are available, in other clean rooms no direct connection between the washing basin and the machinery and the sewer system, and ground inlets are equipped to prevent the recontamination of the basins with a siphon or other shut-off device, |
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the various work processes in the preparation of the starting materials, the preparation of the product, the filling and sterilisation in separate areas and, where this is necessary for the safety of medicinal products, within the framework of the sterile area, |
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for aseptic production within the sterile area, a range of suitable cleanliness class to protect the sterile products produced there from any secondary microbial contamination is provided, |
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access to the working spaces in the sterile area only takes place by means of sluices intended for personnel or material which have to be equipped with appropriate facilities to prevent the introduction of germs; and |
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a temperature and humidity control is carried out. |
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§ 13. If the cleaning and sterilisation of the containers necessary for the manufacture of sterile products and other auxiliaries is carried out in pharmacy operations, the sterile area must have a washroom for the purpose of carrying out this work. has been set up accordingly. This room must not be directly accessible from the rooms of the sterile area.
Equipment
§ 14. (1) The equipment, such as machinery and instruments, as well as other operating and auxiliary equipment, must be suitable for the work to be carried out in pharmacy operations and must be present in sufficient quantities, so that a state of the art is required. the production, storage and storage of products, as well as control of the medicinal products. In the case of a new direction or a conversion of a pharmacy operation, a risk analysis must be carried out within the framework of a design qualification. On the basis of this data, the equipment must be designed, designed and used in such a way that the risk of errors is minimal and the arrangement of the equipment is adapted to the practical course of the processes.
(2) The equipment must be placed in such a way that it is easy to use when used, for cleaning purposes and for maintenance.
(3) Piping are to be marked with flow direction and content. Outflows are adequately large enough to prevent refluxes.
(4) No piece of equipment coming into contact with the product may interact with it in such a way that the product quality is adversely affected and thus a risk arises.
(5) Operating equipment, such as lubricants or coolants, shall not come into contact with medicinal products and packaging material.
(6) The equipment shall be kept clean and cleaned, calibrated and maintained at appropriate intervals. A maintenance and calibration programme shall be drawn up in writing. For the cleaning and maintenance of the equipment, including accessories and tools, written instructions are to be prepared. The instructions on maintenance, calibration, cleaning, hygiene measures and verifications shall be kept for five years in pharmacy operations. The instructions shall, in particular, take account of:
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Determination of responsibility for cleaning and maintenance, |
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Maintenance, cleaning and, where appropriate, hygiene plans, |
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a detailed description of the methods, equipment and materials used for the cleaning and maintenance procedures, as well as a description of the way in which the equipment is dismantled and assembled, to the extent that this is necessary for maintenance and maintenance of the equipment. cleaning is required, |
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the affixing and removal of batch markings of medicinal products on the equipment intended for manufacture; |
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Protection of clean equipment from contamination prior to use and |
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Check the purity of the equipment prior to use. |
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§ 15. (1) Provided that this is necessary for the safety of medicinal products, the equipment or parts thereof may only be used in a sterile condition. For risk analysis critical steps, written records of cleaning and maintenance work, as well as the use of the equipment intended for manufacture or control, are in individual device log books or through a different type of record chronologically with the date, time, product and batch name of each approach carried out and provided with the date and signature of the persons carrying out the recording.
(2) In the event that a lack of equipment may have an effect on the nature of the medicinal products, that part of the equipment which, as a result of the deficiency, may have a negative effect on the medicinal products, should be kept silent until such time as it is remedied; and to be labelled accordingly.
(3) In order to remedy the defect within the meaning of paragraph 2, records shall be kept which shall be kept in pharmacy at least until the end of five years after the removal of the defect.
(4) The equipment intended for the use of critical manufacturing or control operations in respect of product quality shall be subject to qualification and validation.
(5) Automatic, electronic equipment and computers and computer systems may only be used for the manufacture and quality control of medicinal products, provided that, where applicable, calibration, qualification and validation are carried out. . In addition, written records of up to five years after the decommissioning of the respective equipment or computer and EDP system shall be kept in pharmacy operations.
(6) The equipment required for risk analysis as critically defined production and control operations shall be marked with an unmistakable identification or coding system and shall be included in a list which shall be published in the Pharmacies must be stopped. This identification of the equipment shall be included in the production and/or To include control records for the clear identification of the equipment used and must be a part of the production report.
(7) A derogation and a lack of equipment and their effect on the quality of medicinal products must be examined, assessed and recorded in a protocol. The protocol must be completed by a person responsible for pharmaceutical quality assurance and must be kept for at least five years in pharmacies.
§ 16. (1) The scales, weight pieces and other measuring equipment used or made available for the manufacture and control of medicinal products must be in accordance with the measure and calibration law, BGBl. No 152/1950, as last amended by BGBl. I n ° 137/2004.
(2) According to the result of a risk analysis as critically defined measuring equipment which does not fall under the measure and calibration law, it must be appropriately qualified and calibrated. Qualifications, calibrations and justifications shall be kept in writing for at least five years in pharmacy operations.
(3) A deviation, a defect and a faulty calibration of the measuring devices and their effect on the quality of the medicinal product must be investigated, evaluated and recorded in a protocol. The protocol must be completed by a person responsible for pharmaceutical quality assurance and must be kept for at least five years in pharmacies.
§ 17. The equipment may only be used for the manufacture of other products other than medicinal products, if this does not affect the quality of the medicinal products.
Operating hygiene
§ 18. (1) It is necessary to ensure that medicinal products and packaging material are not adversely affected by external effects.
(2) The provision in accordance with paragraph 1 shall be carried out in accordance with a hygiene programme which, in accordance with the state of the art, meets the requirements for medicinal products to be produced, stored or controlled in pharmacies. The hygiene programme must be in pharmacy operation. The instructions shall be designed to prevent contamination of equipment, packaging materials and medicinal products.
(3) The hygiene programme shall at least contain:
| 1. |
Instructions for hygienic behaviour in the manufacture and storage of medicinal products, as well as information on the working clothes to be used, |
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Instructions on the cleaning and disinfection measures to be carried out, their frequency and the equipment and tools to be used, |
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where necessary, information on the permissible content of microbial and particulate pollutants in the atmosphere and instructions on the time intervals in which measurements are to be taken in this respect, |
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particulars of persons responsible for cleaning or disinfection and those responsible for the proper conduct of those activities; |
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instructions for combating an infestation with animals, in particular rodents and insects, including information on the authorising officers responsible for the fight against them and responsible for the proper conduct of those activities, In any case, written instructions must include the use of rodenticides, insecticides, fungicides, gassing agents, cleaners and disinfectants, and |
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| 6. |
Instructions for the disposal of waste, including information on the authorising officers responsible for disposal and responsible for the proper conduct of those activities. |
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(4) The measures implemented within the meaning of paragraph 3 (3) (3) and (5) shall keep records kept in pharmacy operations at least five years after the implementation of the measure concerned.
(5) The hygiene programme shall, in so far as it has to be borne in mind, be the person responsible for the manufacture, control or storage of medicinal products or packaging material and the persons referred to in paragraph 3 (3) (4) and (5) before the date of commencement of their In the event of any change in the hygiene programme and subsequently at least once a year, it should be shown that it is brought to the attention of the Commission.
(6) Waste water, waste and other residues in and out of the working spaces and their immediate surroundings must be disposed of in a safe and hygienic manner.
(7) Toilets and adequate washing facilities (cold and hot water, soap, disinfectant and disposable towels) must be easily accessible from the working rooms.
Quality control
§ 19. (1) In pharmacy establishments in which raw materials, intermediate products, bulk materials, packaging material or end products are manufactured or tested or approved in accordance with § 22 or in which analyses and tests are carried out in accordance with Article 26a of the German Medicines Act (Medicines Act) , a control laboratory shall be established. The control laboratory shall have sufficient staffing and appropriate facilities for the necessary examinations and tests of starting materials, packaging materials, intermediate products, bulk goods and end products. Responsibilities and procedures in the control laboratory must be in writing. The written instructions must be followed.
(2) Pharmacy establishments referred to in paragraph 1 shall have at least one competent person without interruption.
§ 20. (1) The management of the control laboratory shall be entrusted to a person who complies with the requirements of a regulation adopted pursuant to Section 70 (2) of the German Medicines Act (Medicines Act).
(2) The Head of the Control Laboratory shall be responsible for the proper conduct of the laboratory tests and releases and compliance with § § 21 to 24.
(3) The head of the control laboratory shall be independent in the technical assessment in the context of the tests to be carried out by the control laboratory from other organisational units of the pharmacy's establishment. It may also not be entrusted with tasks to be performed by other organisational units of the pharmacy operation; in particular, a personnel union of control laboratory head/control laboratory head and Manufacturer/Production Manager not allowed.
(4) A knowledgeable person is authorized to carry out the activity of a control laboratory manager, unless he/she acts as head of manufacture/production manager. A control laboratory manager may carry out the activity of an informed person if he/she meets the requirements of § 7.
§ 21. (1) The persons employed in the control laboratory shall carry out the necessary sampling either themselves or to delegate and monitor them to suitably trained personnel.
(2) The sampling of starting material, packaging material, intermediate products, bulk goods and end products must be carried out in each case on the basis of a sampling plan, which must be approved by the competent person. Each test method shall be validated, unless the method used is part of a relevant pharmacopoeia. The samples shall be examined by the control laboratory in accordance with the test procedure in accordance with § 23 (1).
(3) The persons referred to in paragraph 1 may not be used for activities relating to the production or storage of medicinal products or packaging material.
(4) Each delivery of medicinal products or packaging material shall be taken from representative samples in accordance with the sampling plan for examination by the control laboratory. Sampling has to be carried out in a specially designated area, whereby the containers are to be cleaned before taking the sample. The containers shall be opened, ordered and closed again in such a way as to prevent contamination or contamination of contents, surroundings, other medicinal products or packaging material. If necessary, sterile equipment or aseptic sampling techniques shall be used.
(5) Containers from which samples have been taken, and patterns shall be marked in such a way that patterns and containers are in each case clearly assigned.
(6) Where raw materials are susceptible to contamination by dirt, animals, microbial contamination or other harmful effects, it is necessary to consider such contamination on the basis of established rules.
§ 22. (1) In particular, the following tasks shall be assigned to the control laboratory, provided that they are to be carried out in pharmacy operations:
| 1. |
the development of quality standards and testing requirements; |
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| 2. |
Validation of tests, |
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| 3. |
Sampling, |
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| 4. |
Testing of raw material, bulk material, packaging material and end products, |
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| 5. |
Durability testing, |
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| 6. |
Release or rejection of raw material, bulk material, packaging material and end products, |
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| 7. |
review of medicinal products for which there is a lack of quality due to complaints outside pharmacy operations, |
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| 8. |
the determination of the quantity of the recovery patterns referred to in paragraphs 5 to 7, |
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| 9. |
Verification of the content of microbial and particulate impurities (§ 18 para. 3 Z 3), |
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| 10. |
Verification of manufacturing protocols to comply with the manufacturing rules, |
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| 11. |
Clarification of errors in the manufacture and control of medicinal products, |
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| 12. |
Preparation of sampling plans, |
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| 13. |
Establishment and evaluation or Inspection of in-process controls, |
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| 14. |
Investigation of deviations and compilation of deviation reports, |
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| 15. |
calibrations, |
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| 16. |
Stability studies, |
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| 17. |
Elaboration of acceptance criteria for sampling and testing and |
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| 18. |
Testing and standardisation of reference substances, reagents and standard solutions. |
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(2) The starting material, bulk material, packaging material and end products may not be supplied by the control laboratory to the next separate phase of manufacture or release by a competent person until after they have been released. Any deviation from written specifications, standards, sampling plans, test requirements or other types of laboratory control, as well as any deviation from laboratory results shall be investigated, substantiated and in writing. document. These documents must be signed by the control laboratory manager and by a person responsible in the pharmaceutical quality assurance system.
(3) If this is provided for in accordance with the instructions contained in the manufacturing instructions in accordance with § 30 (3) Z 8, the inspection, release or rejection of intermediate products within the meaning of paragraph 1 shall also be the responsibility of the control laboratory. In this case, the provisions of paragraph 2 shall apply mutatily to intermediate products.
(4) The control laboratory shall cooperate with the respective organisational units of the pharmacy establishment concerned, in particular in the case of the following tasks, provided that they are to be carried out in pharmacies:
| 1. |
Control of compliance with the regulations on storage (§ § 34 to 37), |
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| 2. |
Control of compliance with the rules on the cleaning of equipment (§ 15), |
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| 3. |
Control of compliance with the rules on cleaning and disinfection of work rooms and on general hygiene conditions (§ 18), |
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| 4. |
Validations of operating equipment, machinery, instruments, test equipment and procedures; and |
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| 5. |
Preparation of annual reports. |
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(5) From the packaging and starting material tested (excluding solvents, gases and water), recovery samples must be kept in a sufficient quantity at least two years after the release of the batch in the pharmacy establishment in order to be able to carry out the application in the marketing authorisation application be able to repeat twice as necessary for batch release. Restoring patterns whose durability is limited shall be kept at least until the end of a year at the end of the term. The storage of the reset patterns shall be carried out in accordance with the storage conditions within the meaning of section 35 (1).
(6) A recovery pattern of each batch of a finished product must be kept in a sufficient quantity for at least one year beyond the expiry date of the expiry date in the pharmacy establishment and shall be inspected visually for signs of spoidate at least once a year . This examination shall be documented in writing. In the event of suspicion of spouse, an investigation shall be initiated and the result should be documented. If a spouse is detected within the specified term, the Federal Office for Health Security has been shown to be able to communicate it. Furthermore, the examining pharmacy establishment shall have the effect of causing the concerned batch of medicinal product to be withdrawn from circulation.
(7) In the case of certain proprietary medicinal products which may be produced in individual cases or in small quantities or whose storage could cause particular problems, other provisions may be laid down within the scope of the authorization granted pursuant to § 63 of the German Medicines Act (Medicinal Products Act). about the reset patterns and their storage.
(8) Only the filling, packaging or marking of already released medicinal products which are not proprietary medicinal products must be filled, packaged or marked by the pharmacy establishment. Only the recovery patterns of the unfilled, unpacked or marked product must be Medicinal products are kept.
(9) In the case of investigational medicinal products, sufficient recovery patterns of each batch of a preparation in unpacked form and main components of the packaging of the individual batches of finished product must be completed at least two years after completion or formal demolition of the product. of the last clinical trial in which the batch was used, the longer period being applicable.
§ 23. (1) For each test to be carried out by the control laboratory, a test requirement corresponding to the respective state of the sciences must be available and must be available to all persons involved in the examination during their activities. The inspection procedure shall be approved by the control laboratory head and the competent person by signature.
(2) The test specification shall specify limit values within which the tested materials comply with the quality requirements. It is necessary to determine at which time intervals a further examination of the medicinal products or of the packaging material has to be carried out.
(3) Any amendment of a test specification shall be made by new edition. The previous test specification is to be drawn in when the new edition is issued, to be provided with the date of the out-of-force setting and to be marked as invalid.
(4) Out-of-force testing requirements shall be kept in pharmacy business for a period of five years, at least after the last test, in accordance with this test rule.
(5) Any examination of a medicinal product in accordance with the test procedure shall be validated. In pharmacies, a validation plan must be set up to be approved by the person knowledgeable. The validation plan shall be regularly updated.
(6) Detailed written instructions must be provided for the receipt, identification, storage, handling, sampling, testing and release or blocking of starting material, packaging material, intermediate products, bulk goods, end products and finished products. Pharmacies are up. These instructions shall be approved by the knowledgeable person.
§ 24. (1) Any control or audit carried out shall be documented without delay. Any release or rejection within the meaning of Section 22 (1) (6) or in connection with analyses and examinations pursuant to § 26a of the German Medicines Act (§ 26a of the German Medicines Act) can be used to produce a protocol which clearly shows the results of all the underlying reasons. to identify controls or checks and to include a summary assessment. The protocol has at least all information within the meaning of Section 5 (5) of the Pharmacopoitic Act, BGBl. No. 195/1980, as last amended by BGBl. I n ° 33/2002, and must be certified by the control laboratory head and, where necessary, by the competent person with signature.
(2) In the final control of end products prior to their release for the sale or distribution or for use in clinical trials, in addition to the analytical results, the production conditions, the results of the Inprocess controls, the inspection of the manufacturing documents and the conformity of the products with their specifications, including the final packaging, must be taken into account. In any event, the knowledgeable person shall certify before delivery for each batch of medicinal product produced, or any batch of medicinal products imported from a third country, in the minutes referred to in paragraph 1, and certify that: the rules on medicinal products have been complied with.
(3) In order to keep records of medicinal products for which a duration is fixed, they shall be kept at least until the end of one year after the end of the period in pharmacy. In the absence of a term, the records shall be kept for at least five years after they have been drawn up.
(4) Until the preparation of the Protocols, all the original data of the tests and checks, in particular laboratory records and working books, shall be kept in pharmacy operations.
(5) If a deviation is found in laboratory checks, this deviation shall be documented, examined and assessed. In the case of the investigations of the deviation, not only the concerned batch or the analysis concerned are the subject of the procedure, but also all relevant similar batches and investigations, which have been carried out under the same conditions. The report on the derogation shall be submitted by a person responsible for the quality assurance of pharmaceutical quality assurance. In addition, measures must be taken to prevent any deviation in the future.
§ 25. (1) With individual tasks of the control laboratory, with the exception of the release or rejection pursuant to Section 22 (1) Z 6 or in connection with analyses and examinations in accordance with § 26a of the German Medicines Act (Medicines Act), it is also possible to entrust non-operational facilities. There must be a written agreement between the contractor and the contracting authority, which clearly establishes the responsibilities of each side with regard to the duration and scope of the control and audit activities.
(2) The responsibility of the adjudicating entity for control and audit activities shall not be affected by the agreements referred to in paragraph 1. The contractor must have an authorisation in accordance with § 63 of the German Medicines Act (Medicines Act) or a corresponding authorisation of a competent authority of another Contracting Party of the European Economic Area and shall be subject to an inspection according to § 67 Medicinal Products Act or an inspection by a competent authority of another Contracting Party of the European Economic Area.
(3) The agreement referred to in paragraph 1 shall be kept permanently in the pharmacy establishment in the original or in the form of a copy. Upon request, the Federal Office for Health Security must prove the existence of the agreement.
(4) A contractor shall not disclose to third parties any work entrusted to it by contract without the written consent of the contracting authority.
(5) The head of the control laboratory and the competent person shall be responsible for ensuring that only such non-operational facilities are entrusted with the tasks of the control laboratory, the personnel and equipment of which shall be responsible for testing and equipping them. To expect control results that correspond to the state of the sciences.
(6) In relation to investigational medicinal products, the sponsor shall ensure that the contract laboratories comply with the requirements of the application approved by the Federal Office for Safety in Health Care in accordance with § 40 of the German Medicines Act (Medicines Act). In the case of imports from third countries, analytical tests of investigational medicinal products are not mandatory.
Manufacture of medicinal products
§ 26. (1) The manufacturer shall have continuous access to at least one person knowledgeable.
(2) For each pharmacy establishment in which medicinal products are manufactured, a head of manufacture/a head of production shall be ordered to be responsible for the proper manufacture of the medicinal products and for compliance with § § 27 to 33 of this Directive .
(3) The Head of Production/Production Manager shall:
| 1. |
in a Contracting Party of the European Economic Area or in Switzerland, a study programme in the fields of pharmacy, human, dental or veterinary medicine, chemistry or biology, or a course of study recognized as equivalent to have successfully completed at least four years, and |
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| 2. |
after successful completion of the course of studies or training referred to in Z 1, an activity of at least two years in the manufacture of medicinal products in one or more undertakings in one of the contracting parties to the European the economic area or in Switzerland, which has been granted an authorization to manufacture medicinal products. |
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(4) (3) does not apply to persons who are before the 1. Jänner worked as head of production/production manager in 1994.
(5) A personnel union of head of manufacture/production manager and control laboratory head/control laboratory head is not permitted.
(6) The knowledgeable person referred to in paragraph 1 shall be entitled to carry out the activity of a manufacturing manager, provided that he does not act as a control laboratory head. The Head of Production/The Head of Production may exercise the activity of an informed person if he/she meets the requirements of § 7.
§ 27. (1) During a manufacturing process, machinery, instruments and containers must be marked with information about the product contained therein or the end product to be produced and the batch designation.
(2) The individual manufacturing steps must be carried out in accordance with previously prepared instructions and process descriptions and in accordance with good manufacturing practice. Adequate and sufficient resources must be made available for the implementation of the in-process controls.
(3) The necessary technical and organisational measures need to be taken to avoid cross-contamination and confusion. In the case of test preparations, particular attention must be paid to the handling of the products during the course of and after completion of a blinding.
(4) In the case of medicinal products, any new manufacturing process and any substantial modification of an existing procedure must be validated. Critical phases of a manufacturing process must be regularly evaluated and, where appropriate, revalidated.
(5) In the case of investigational medicinal products, the manufacturing process as a whole shall be validated, provided that this is indicated, taking into account the product development phase. Critical process phases, such as sterilization, are to be validated. All steps for the design and development of a preparation process of a test preparation are to be fully documented.
§ 28. (1) Unless otherwise specified in paragraph 2, separate batches of a medicinal product or different medicinal products must be separated from each other, either spatially or temporally, with the same appearance or appearance which may give rise to confusion. produced.
(2) The simultaneous manufacture of various batches of a medicinal product or of different medicinal products of the same appearance or appearance which may give rise to confusion shall be permitted in the same room only if appropriate Measures such as the erection of partition walls and the implementation of appropriate physical and chemical controls during the production process are likely to hinder the risk of confusion.
(3) Product-critical purification methods identified as a result of a risk analysis are to be validated.
(4) Validations shall be made in accordance with the validation plan which must be carried out in pharmacy operations. The validation plan, which is to be updated regularly, must be approved by the competent person. Records must be kept and kept in the pharmacy establishment via the validations in accordance with paragraph 3 and section 27 (4) and (5).
§ 29. (1) For the manufacture of medicinal products,
| 1. |
starting material, |
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| 2. |
packaging material which may come into contact with medicinal products or which may affect their quality; and |
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| 3. |
printed or otherwise marked packaging material, on which the pressure is a part of the design of the finished product, |
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| only after approval by the control laboratory in accordance with § 22 (1) Z 6. |
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(2) The use of fibre-emitting filters shall be permitted only if it is not possible to produce the medicinal product without the use of such a filter. If the use of fiber-emitting filters is not to be avoided, an additional non-fiber-emitting filter of 0.22 μm or, if production-related unavoidable, 0.45 μm of maximum average pore width must subsequently be used. The filters used in the manufacture of medicinal products must not adversely affect the quality of the medicinal products.
(3) It is appropriate to monitor the weighing, measurement and subdivision operations of medicinal products. Any raw material, intermediate, bulk or packaging material provided for the manufacture shall be verified by a second person or shall be recorded by an automated procedure.
(4) The addition of starting material, intermediate product, bulk material or packaging material to a batch is always to be confirmed by a second person. Yields must be determined after completion of all appropriate phases of the preparation of a medicinal product. Such provisions shall be verifiably verified by a second person or shall be recorded by an automated procedure.
(5) Time limits or limit values are to be defined for the termination of each manufacturing step. A deviation from these time limits or limit values upwards and downwards is to be justified and documented by a person responsible within the framework of the pharmaceutical quality assurance.
(6) The packaging material for the production of batches must be checked for identity and conformity with the production instructions and accurate control of the correct labelling is to be carried out. If the control is carried out by a visual inspection by the staff, a second person must carry out a further check, regardless of whether or not an automated procedure is carried out.
§ 30. (1) For each medicinal product to be produced in pharmacy operations, a corresponding production rule must be laid down and, in so far as it has to be observed by them, all persons involved in the production must be permanently available during their activities. . The manufacturing instructions must be approved by the competent person and the manufacturer of the manufacturing process by signature.
(2) The manufacture of medicinal products shall be carried out in accordance with the manufacturing procedure.
(3) The production specification shall refer to a standard batch size or to the batch size provided in each case and shall contain at least the following information:
| 1. |
the name of the product to be produced; |
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| 2. |
as appropriate, pharmaceutical form, |
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| 3. |
the information on the starting material according to the nature and quantity of the components to be used, including any acceptable tolerance values; |
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| 4. |
information on the technical equipment to be used and, where appropriate, on the preparation thereof, |
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| 5. |
description of each step, including any precautions to be taken to ensure that the product is in perfect condition; |
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| 6. |
description of the product to be manufactured, with information on the dimensions and weights or volumes per unit, including the permissible deviations, |
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| 7. |
the expected yield and the permissible deviations, |
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| 8. |
Instructions on the stages of the manufacture of controls, the nature of the checks and instructions on the organisational unit of the pharmacy's operations to be carried out, |
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| 9. |
information on the nature, quantity and labelling of the packaging material; |
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| 10. |
instructions for cleaning the containers in which the product is placed on the market and of the closure systems thereof, |
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| 11. |
Instructions on storage of the product produced and |
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| 12. |
Date of validity. |
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(4) The modification of the production specification shall be effected by new edition. At the beginning of the new edition, the changes to the chapter, page, and line are to be specified. It is also necessary to specify the reasons for the changes in question. The previous production specification is to be drawn in when the new edition is issued and to be marked as invalid.
(5) Production rules shall be kept in pharmacies at least for a period of five years after the last manufacture in accordance with this production rule.
§ 31. (1) In the course of the manufacturing process, a production report shall be drawn up on each batch of a medicinal product produced in the pharmacy establishment.
(2) The production report shall contain at least the following information:
| 1. |
the name of the product obtained, |
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| 2. |
as appropriate, pharmaceutical form, |
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| 3. |
Batch number and size of the batch, |
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| 4. |
information on the starting material according to the type, quantity and, where appropriate, labelling of the components used, even if they are no longer contained in the finished product, the quantities actually used being to be compared with the desired values, |
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| 5. |
information to ensure that the protocols relating to the batch are found in pharmacy operations in accordance with section 24 (1) of the pharmacy operation; |
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| 6. |
Confirmation of the implementation of all checks prescribed in accordance with § 30 (3) Z 8 during the production process, which is accompanied by the date and signature of the person responsible for the respective control, including the results of such checks. checks, |
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| 7. |
With the date and signature of the person responsible for the respective manufacturing step, confirmation of the implementation of each production step and record of any individual steps taken in accordance with the manufacturing procedure. safety precautions and other observations and special incidents, |
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| 8. |
the actual yield achieved by comparison of the theoretical yield, |
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| 9. |
the number of packs received, broken down by pack size, and the indication of any residual quantity, |
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| 10. |
the date of completion of the production and signature confirmation by the manufacturer ' s manufacturing manager that all the manufacturing steps of the manufacturing method have been carried out in accordance with the procedure, and |
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| 11. |
Confirmation of the date and signature of the control laboratory manager and-where necessary-the competent person about the release or rejection of the batch. |
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(3) If a pharmaceutical preparation carried out in a pharmacy establishment consists solely of the individual filling of a medicinal product which has already been released and which is not a proprietary medicinal product, the preparation report may contain information pursuant to paragraph 2 (2) (4), (6) to (9) and 11.
(4) In the case of medicinal products for which a maturity is fixed, the production reports shall be kept at least until the end of one year at the end of the period in pharmacy. In the absence of a term, the production reports shall be kept for at least five years after they have been drawn up.
(5) If a deviation is detected in the manufacture of a medicinal product, this deviation shall be examined, assessed and documented. In the investigation of the deviation, not only the concerned batch or the analysis concerned are the subject matter of the procedure, but also all relevant similar batches and investigations, which have been carried out under the same conditions. The resulting deviation report shall be completed by a person responsible for the pharmaceutical quality assurance. Measures shall be taken to prevent any deviation in the future.
§ 32. (1) In pharmacy establishments which manufacture medicinal products or carry out a deposit function, protocols have to be carried out in accordance with Article 24 (1) on the release of batches of medicinal products which are not manufactured by themselves in pharmacies but are further processed or in the form of a Transport shall be brought to bear during the period laid down in section 24 (3). Production reports in accordance with § 31 and the recovery pattern in accordance with § 22 shall also be able to be procured without delay during the time of their storage obligation through manufacturing operations which have not been carried out during operation.
(2) Paragraph 1 shall apply mutatily to pharmacies taking over the sales activities of a manufacturer or a depositary.
(3) In the pharmacy establishment Protocols within the meaning of Section 24 (1) concerning the release of batches shall also be kept in the pharmacy establishment with regard to medicinal products with regard to which the sales activities are to be released by another Operation has been taken.
(4) For each medicinal product produced in pharmacy (in the case of allergens only from tribal solutions and homeopathic medicinal products only from primary tinctures), an annual report shall be drawn up once a year, containing at least the following information: has:
| 1. |
the name of the medicinal product, |
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| 2. |
number of batches produced, |
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| 3. |
Statistical analysis of all quality-determining characteristics (production and quality control), |
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| 4. |
Quality-relevant changes in starting material, packaging material, manufacturing processes, quality control, deviations and quality defects as well as supplier exchange, exchange of machines and equipment, |
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| 5. |
stability data, |
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| 6. |
Conclusions from the data evaluated under Z 2 to 4; and |
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| 7. |
Date and signature of the knowledgeable person. |
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(5) At least one batch per year of each medicinal product which is produced in a pharmacy establishment is to be supplied in a pharmacy establishment to a stability test. If the production is changed or if there is a change in the supplier, the starting material or the primary packaging material, then a stability test shall be carried out. The results are to be collected and evaluated. The results are to be assessed by a person responsible within the framework of the pharmaceutical quality assurance, dated and must be in the pharmacy establishment. For the stability tests, a written test programme is to be established, which includes sample size, test intervals, storage conditions, test methods and validation of the test methods. The assessment of the stability shall be based on the same container/closure system in which the medicinal product is marketed. Medicinal products to be reconstituted should be considered at the time of reconstitution as well as in terms of shelf life after reconstitution.
(6) In the case of certain medicinal products which may be produced on a case-by-case basis or in small quantities, or which could cause particular problems to be stored, other provisions may be laid down within the framework of the authorisation granted in accordance with § 63 of the German Medicines Act. the stability tests and their storage are being carried out.
§ 33. (1) Pharmacy establishments in which medicinal products are manufactured shall have a list of all the medicinal products produced. This list shall be used in particular to identify medicinal products which are carried out or awarded on behalf of the contract.
(2) A written agreement must be concluded between the contracting authority and the contractor, whether in the original or in the form of an original or in the form of a contract, on the award or take-over of wage contracts relating to the manufacture of medicinal products or any associated operation. Form of a copy must be placed in the pharmacy establishment. In the agreement, the responsibilities of each side must be clearly defined and compliance with the rules of good manufacturing practice by the contractor as well as the manner in which the knowledgeable person who is responsible for the release of each batch is responsible for compliance with its responsibilities. Upon request, the Federal Office for Health Security must prove the existence of the agreement.
(3) The liability of the adjudicating entity for medicinal products produced on the contract is not affected by the agreements referred to in paragraph 2. The contractor must have an operating licence in accordance with § 63 of the German Medicines Act or a corresponding authorisation of a competent authority of another Contracting Party of the European Economic Area and shall be subject to an inspection in accordance with § 67 of the Medicines Act or an inspection by a competent authority of another Party of the European Economic Area.
(4) A contractor shall not disclose to third parties any work entrusted to it by contract without the written consent of the contracting authority.
Storage and delivery
§ 34. (1) Starting material, intermediate products, bulk goods, packaging materials, end-and finished products are to be stored in a clear way. Confusion shall be maintained by appropriate measures, such as separate storage and conspicuous marking or electronic procedures. The storage has to be carried out in such a way that a corresponding cleaning is possible at any time in all areas, in particular below and downstream of the stored product. Untested medicinal products and packaging material which has not yet been tested shall be stored in quarantine.
(2) For all entrants and exits, documents must be kept in the form of purchasing or sales documents with the following minimum information during a period of five years:
| 1. |
Date, |
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| 2. |
the name of the medicinal product, |
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| 3. |
the previous or quantity delivered, |
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| 4. |
Name and address of the supplier or of the recipient, |
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| 5. |
Result of a visual inspection of the overpackaging and the correct delivery and |
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| 6. |
Batch number. |
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(3) All supplies of medicinal products must be accompanied by the following documents, which shall contain at least the following information:
| 1. |
Date, |
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| 2. |
the name and pharmaceutical form of the medicinal product, |
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| 3. |
quantity delivered, |
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| 4. |
the name and address of the supplier and of the consignee; and |
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| 5. |
Batch number. |
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(4) Pharmacy establishments which place medicinal products on the market shall not be obliged to:
| 1. |
the batch number referred to in paragraph 2 (2) (6) relating to medicinal products for human use, and |
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| 2. |
the batch number referred to in paragraph 3 Z 5 in respect of medicinal products for human and veterinary use |
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| , provided that batches within the scope of the monitoring of medicinal products can be called back without any uninterrupted records, even without these records. |
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(5) In written procedures, work operations may be defined which may affect the quality of medicinal products, in particular:
| 1. |
Acceptance and control of deliveries, |
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| 2. |
storage, |
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| 3. |
Cleaning and maintenance of the premises (including pest control), |
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| 4. |
Records of storage conditions (including temperature and humidity measurements), |
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| 5. |
the safety of stocks on the ground and on-the-spot shipments, |
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| 6. |
Removal from the sales warehouse, |
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| 7. |
records, including documentation of customer orders, |
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| 8. |
products returned, and |
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| 9. |
Recall plans. |
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| The descriptions of the procedures shall be dated and signed by the person responsible for the pharmaceutical quality assurance system. |
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(6) In-and out deliveries must be protected from weather conditions during loading and unloading. The goods receipt, the goods outlet and the storage area must be separated from each other by appropriate measures.
(7) In the event of acceptance, the deliveries shall be checked to determine whether the validated transport time and transport temperature have been complied with, the containers are undamaged and the delivery is in accordance with the order. Medicinal products for which special storage conditions apply must be immediately identified and immediately stored accordingly.
(8) Medicinal products shall be stored separately from other products. The storage temperature and-if relevant with regard to product quality-the air humidity must be measured and recorded at regular intervals. Medicinal products must be stored in such a way as to avoid contamination or cross-contamination and to exclude any impairment of quality.
(9) Medicinal products and packaging materials shall be transported in such a way that:
| a) |
the labelling is not lost, |
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| b) |
they do not contaminate or contaminate other products or materials, |
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| c) |
adequate precautions against leeway, damage and theft, |
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| d) |
they are not exposed to any undue heat, cold, light, humidity or any other harmful influence, or microbial infestation or infestation, and |
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| e) |
they are safe from access by unauthorised persons. |
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(10) Medicinal products which have to be stored at a controlled temperature shall be transported with appropriate validated arrangements.
(11) Fair and validated interim storage and validated transport are to be assessed in the event of changes in the need for revalidation. The evaluation carried out, the result of which and any corrective measures are to be carried out in a protocol. The Protocol shall be kept for a period of at least five years.
(12) If the transport activity is delegated to another company by a pharmacy establishment that produces medicinal products or carries out a deposit function, the provisions of paragraphs 1 to 11, section 35 (1) to (3), section 36 (1) and section 37 shall apply mutagenically.
§ 35. (1) Unless already indicated in the labelling of authorised proprietary medicinal products according to § 7 para. 2 Z 6 of the Medicinal Products Act, in the production provision according to § 30 (3) Z 11 or in the pharmacopoeia according to § 1 of the Pharmacopoeia Act, special Storage conditions are to be carried out, storage and transport must be carried out under conditions which correspond to the state of the art and which meet the quality of the products in accordance with the requirements of § 4 of the German Medicines Act .
(2) The vessels or containers for the acceptance of starting material, intermediate products, bulk goods and finished products must be made of a material corresponding to the specific nature of the product to be stored, and must not have any adverse effect on the product. the quality of the product. They are provided with a clearly visible, legible and durable label that clearly shows the content and status (quarantined, released, locked). The status can also be indicated by a validated IT-technical administration. Each batch of a medicinal product or packaging material must be clearly identified. This marking must be part of the documentation of production and quality control and of the delivery documents.
(3) If a starting material is transferred from the original container to another container, the new container shall, in any case, be marked with the following information, without prejudice to any further labelling requirements:
| 1. |
name of the substance or article code, |
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| 2. |
the entry or control number, |
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| 3. |
Weight or measure in the new container and |
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| 4. |
where applicable, the approach to which the substance has been provided, including the name of the preparation to be prepared and batch number. |
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(4) Packaging material must be taken over by written instructions, to be identified, stored, examined, examined and examined. Written records of these activities must be kept in pharmacy operations. Access to the storage area for packaging material shall be restricted to authorised persons. The issue and withdrawal of packaging material from the warehouse shall be regulated by means of a written instruction and written records shall be kept. A balance sheet of the respective consumption has to be made.
§ 36. (1) Working spaces which serve the purpose of storage shall be secured by means of appropriate arrangements to ensure that unauthorised persons are not allowed to enter the premises.
(2) Where the marketing activities of a pharmacy company which produces medicinal products or carry out a deposit function are taken over by another establishment, a written agreement must be reached on the duration and extent of the marketing of the products. Sales activity is clearly defined. In particular, the contracting authority shall be granted the right to carry out checks within the meaning of section 22 (4) in respect of the medicinal products sold on its behalf in the contractor's working premises. The contractor must have an operating licence in accordance with § 63 of the German Medicines Act and is subject to an inspection according to § 67 of the German Drug Law.
(3) The agreement referred to in paragraph 2 shall be kept in the original or in the form of a copy in pharmacies. Upon request, the Federal Office for Health Security must prove the existence of the agreement.
§ 37. (1) In the case of raw material, intermediate products, bulk materials, packaging materials, end products and finished products, which are placed in the working spaces serving for storage or are delivered from there, records shall be kept for which at least the following: Information must be included:
| 1. |
the type and quantity, |
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| 2. |
the date of the access and, if applicable, the departure, |
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| 3. |
as applicable, the batch number and |
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| 4. |
by whom the medicinal products have been taken over and if applicable to whom they have been delivered. |
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| These records shall be kept in pharmacy business at least until the end of five years after the last entry. |
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(2) With regard to the medicinal products referred to in paragraph 1, a clear allocation must be made possible by means of the marking or other appropriate measures, and to indicate whether they are released in accordance with § 7 (6) or § 22 Abs.1 Z 6 or whether the Decision on release or rejection has not yet been taken.
(3) Rejected medicinal products and recovered packaging material shall be labelled as such and stored separately. The disposal of rejected medicinal products and packaging material must be proven in writing.
Marketability of medicines, complaints, product recall and blindness in emergency situations
§ 38. (1) Medicinal products which may not be placed on the market in accordance with the Medicinal Products Act (non-marketable medicinal products) shall be immediately conspicuously designated as such and shall immediately be spun-off. All necessary measures must be taken to prevent erroneous further processing or placing on the market.
(2) Each pharmacy establishment shall be obliged to take back medicinal products which it has made available upon request for the purpose of harmless disposal, if:
| 1. |
the medicinal products are not marketable for reasons to be represented by the medicinal product; |
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| 2. |
the medicinal products may not be placed on the market or made available on the basis of an official order; or |
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| 3. |
the medicinal products should not be placed on the market or placed on the market, according to their will. |
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(3) withdrawn medicinal products which fall within the area of responsibility of a pharmacy establishment shall only be assigned to the sale of certain stocks if the medicinal products are
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are in the unopened original containers and in good condition, |
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| 2. |
transported, stored and handled without gaps under defined conditions, |
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| 3. |
still have a reasonable shelf life, and |
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| 4. |
have been reviewed and assessed by an authorized person. |
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| In this assessment, all the facts relevant to the safety of the medicinal product shall be considered. To the extent necessary, contact the marketing authorisation holder or the competent person of the manufacturer. The decision shall be documented in writing and shall be kept for at least five years. |
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(4) Written instructions describing a system for the reprocessing of batches that do not meet the standards or specifications and the steps to be taken to ensure that reworked batches with all the specified Standards, specifications, and characteristics are to be created and followed. Reprocessing shall not be carried out without the inspection and approval of the control laboratory head and the competent person.
(5) A re-use of medicinal products,
| 1. |
which have been improperly stored or transported, or |
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| 2. |
where there is a suspicion of improper storage or improper transport, or |
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| 3. |
where there is a suspicion of an undermixing or exchange of the goods, or |
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| 4. |
where there is a suspicion that their quality has otherwise been negatively affected, |
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| is prohibited. These medicinal products are demonstrably to be destroyed. |
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§ 39. (1) The procedure for the detection of any kind of medicinal product or any other defect in medicinal products must be laid down in written instructions which have to be placed in pharmacy operations.
(2) All the facts which have led to the determination of any conceivable or other defects, the results of the investigations carried out in connection with this, all notifications pursuant to § § 75a and 75b of the Medicines Act as well as the Measures must be documented.
(3) In the case of medicinal products, each pharmacy must have a system to systematically record, review and make effective systematic arrangements for the medicinal products to be recalled at any time. can be. The pharmacy establishment has to record and investigate any complaint of a defect. In addition to any defect that may result in a recall or an unusual restriction of distribution, the pharmacy has to inform the Federal Office for Health Security and, as far as possible, the Recipient States.
(4) In the case of investigational medicinal products, the manufacturer must systematically record, check and make effective systematic arrangements in cooperation with the sponsor, so that the investigational products can be recalled quickly at any time. The manufacturer has to investigate any defect that may result in a recall or an unusual restriction of distribution, and must inform the Federal Office for Safety in the health care sector.
(5) In the case of investigational medicinal products, all test sites must be determined and, as far as possible, the recipient states.
(6) In the case of investigational medicinal products for which an authorisation has been granted, the manufacturer of the investigational medicinal product, in cooperation with the sponsor, shall inform the marketing authorisation holder of any defects associated with the authorised medicinal product. could.
(7) The sponsor shall apply a procedure for the rapid de-blinding of blinded products, if this is necessary for the immediate withdrawal according to paragraph 4. The sponsor shall ensure that the identity of a linked product is unveiled only to the extent that it is required.
Labelling of investigational medicinal products
§ 40. (1) In the case of investigational medicinal products, labelling must be carried out in such a way as to ensure the protection of test participants and traceability, to enable identification of the product and of the test, and to ensure that the product is tested and the product is tested and the product is tested. the proper use of the investigational medicinal product is facilitated.
(2) The information required in the German language on the outer packaging of investigational medicinal products or, where no outer packaging is present, on the primary packaging shall be based on the generally accepted scientific evidence. Principles and requirements to be found in the guide and annexes mentioned in section 42 (1).
Documentation
§ 41. (1) Where no time limit is specified in this Regulation for the retention of records and reports, the documents shall be kept for a period of at least five years from the last date of the signature.
(2) Each manufacturer must have a documentation system based on specifications, manufacturing requirements, processing and packaging instructions, as well as procedural descriptions and protocols on the production operations carried out. operate. The documents must be clear, clear, error-free and up-to-date. In addition to the specific documents relating to the production of each batch, it is necessary to provide in writing beforehand rules for general manufacturing operations and production conditions.
(3) The totality of the documents referred to in paragraph 2 shall permit the tracing of the progress of each batch and of the changes made in the course of the development of a test preparation.
(4) In relation to medicinal products, batch-related documents must be kept for at least one year beyond the expiry date of the relevant batch or at least five years beyond the date of issue of the Protocol, in accordance with Article 24 (1), with the longer period shall apply.
(5) In the case of investigational medicinal products, the batch-related dossiers must be kept 15 years after the completion or formal termination of the last clinical trial in which the batch was applied, each of the longer periods being longer than the previous clinical test. Time period applies. The sponsor or, if not the same, the holder of the authorisation shall ensure that the documents required for the approval are kept in accordance with Annex I to Directive 2001 /83/EC, as amended in 2004 /24/EC and 2004 /27/EC, provided that this is necessary for subsequent authorisation.
(6) If data are not recorded in writing but with electronic, photographic or other data processing systems, the manufacturer must first validate the system by providing evidence that the data are available during the expected period of time. Retention period is saved correctly. The data stored with such systems must be made available at all times in a readable form and must be submitted to the Federal Office for Health Security on request. Electronically stored data must be protected against data loss or damage by means of measures such as duplication or back-up and transfer to another storage system. These measures must be comprehensible.
References to acts of the European Community
§ 42. (1) The European Commission's Guide to Good Manufacturing Practice for medicinal products and investigational medicinal products, together with annexes, is published in Volume IV of the Regulation on Medicinal Products in the European Community.
(2) This Regulation implements the following Directives of the European Community:
| 1. |
Commission Directive 91 /412/EEC of 23 July 1991 laying down the principles and guidelines of good manufacturing practice for veterinary medicinal products (OJ L 327, 31.12.1991, p. No. OJ L 228, 17.8.1991, p. 70); |
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| 2. |
Directive 2001 /20/EC of the European Parliament and of the Council of 4 April 2001 on the approximation of the laws, regulations and administrative provisions of the Member States relating to the application of good clinical practice in the conduct of clinical trials with Medicinal products for human use (OJ No. OJ L 121, 1.5.2001); |
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| 3. |
Directive 2001 /82/EC of the European Parliament and of the Council of 6 November 2001 establishing a Community code relating to veterinary medicinal products (OJ L 327, 30.12.2001, p. No. OJ L 311, 28.11.2001, p. 1); |
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| 4. |
Directive 2001 /83/EC of the European Parliament and of the Council of 6 November 2001 establishing a Community code relating to medicinal products for human use (OJ L 327, 30.12.2001, p. No. OJ L 311, 28.11.2001, p. 67); |
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| 5. |
Commission Directive 2003 /94/EC laying down the principles and guidelines of good manufacturing practice for medicinal products for human use and investigational medicinal products intended for human use (OJ L 327, 30.4.2003, p. No. OJ L 262, 14.10.2003, p. 22); |
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| 6. |
Directive 2004 /24/EC of the European Parliament and of the Council of 31 March 2004 amending Directive 2001 /83/EC on the Community code relating to medicinal products for human use as regards traditional herbal medicinal products (OJ L 327, 30.4.2004, p. No. OJ L 136, 30.4.2004); |
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| 7. |
Directive 2004 /27/EC of the European Parliament and of the Council of 31 March 2004 amending Directive 2001 /83/EC on the Community code relating to medicinal products for human use (OJ L 197, 21.7.2004, p. No. OJ L 136, 30.4.2004); |
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| 8. |
Directive 2004 /28/EC of the European Parliament and of the Council of 31 March 2004 amending Directive 2001 /82/EC on the establishment of a Community code for veterinary medicinal products (OJ L 327, 30.4.2004, p. L No 136 of 30 April 2004). |
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In-force pedals
§ 43. This Regulation shall enter into force 1. Jänner 2006 in force. With the entry into force of this Regulation, the Regulation relates to the holdings of certain public pharmacies and Anstaltsapotheken, BGBl. No 429/1986, except for force.
Smoke-Kallat
