Decree of the Ministry of Health and the Ministry of Agriculture No. 296 / 2000 Coll.
Decree of the Ministry of Health and the Ministry of Agriculture establishing good manufacturing practice, good distribution practice and closer conditions for authorising the production and distribution of medicinal products, including medicated feedingstuffs
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Order
Effective from 28.08.2000
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296
DECLARATION
Ministry of Health and Ministry of Agriculture
of 16 August 2000
establishing good manufacturing practice, good distribution practice and closer conditions for authorising the production and distribution of medicinal products, including medicated feed
The Ministry of Health and the Ministry of Agriculture, pursuant to § 75 (2) (a) of Act No. 79 / 1997 Coll., on Medicines, and on amendments and additions to certain related laws, as amended by Act No. 149 / 2000 Coll., hereinafter referred to as "the Act ':
Preliminary provisions
(1) According to this decree,
(a) the production, distribution and quality control of medicinal products and medicinal substances;
(b) imports of medicinal products and active substances from third countries; and
(c) control of the activities referred to in points (a) and (b).
(2) The Order lays down the particulars of the application for
(a) authorisation of manufacture of medicinal products, or amendment of authorisation of manufacture of medicinal products;
(b) authorisation for imports of medicinal products from third countries; and
(c) the authorisation of the distribution of medicinal products or the modification of the authorisation of the distribution of medicinal products, including medicated feed and veterinary autogenic vaccines.
(3) Furthermore, the Decree lays down detailed conditions for authorising the operation of control laboratories.
For the purposes of this decree:
(a) contamination by biological, microbiological, chemical or physical contamination of material intended for the manufacture of medicinal products and medicinal products at each stage of production (hereinafter referred to as "material");
(b) a prescription for a medicinal product, a document containing the name of the medicinal product, its description, the quantity of each material intended for the manufacture of the medicinal product, the batch size and the prescribed yield of the medicinal product,
(c) an instruction document describing the process of own manufacture of the medicinal product (technology), the equipment intended for such manufacture and packaging, the procedures for carrying out the ongoing production controls and the values to be achieved during such checks;
(d) by standard operating procedure, a document setting out the repetitive activities in the manufacture and distribution of medicinal products, with the exception of the procedures provided for in the instructions;
(e) the specification of a document containing detailed requirements to be complied with by materials and packaging of medicinal products;
(f) validation of documented verification that the manufacturing and control procedures for pharmaceuticals normally meet the requirements laid down in the manufacturing regulations, instructions, specifications and documentation submitted in the framework of the marketing authorisation procedure (3) for a particular medicinal product;
(g) the qualification of the verification that the equipment or premises used in the manufacture and control of the quality of the medicinal products meet the requirements laid down in the specifications by default;
(h) ensuring the quality of all measures taken to ensure the quality of the medicines required for their intended use.
ADMINISTRATIVE PRODUCTION PRACTICE
Principles
(1) The following conditions are met to ensure the standard manufacture of the medicinal product:
(a) a summary of the requirements referred to in paragraphs 4 to 10 is established and systematically applied throughout the production process, where appropriate, specifying the guidelines, the State Institute for Drug Control and the Institute for State Control of Veterinary Bioprafts and Medicines in its information medium, 4)
(b) the establishment and compliance with good manufacturing practice in the design and development of medicines;
(c) records are made of activities arising from the requirements referred to in (a);
(d) internal procedures have been established to approve the organisational structure and the workload of staff;
(e) the conditions for the control activity.
(2) The manufacturer shall establish and maintain an effective quality assurance system in which staff of the departments involved in the quality assurance system are actively involved.
(3) The manufacturer shall carry out continuous internal checks to verify the implementation and compliance with good manufacturing practice and to propose the necessary corrective measures. It shall keep and retain records of such checks and document corrective actions taken on their basis.
Staff requirements
(1) The number of eligible workers (5) and the requirements for their qualification are established in such a way as to correspond to the type and extent of medicinal products manufactured and to the quality assurance needs at each manufacturing site.
(2) Other requirements for manufacturers that concern workers (6) in the manufacture of pharmaceuticals are:
(a) the establishment of the organisational structure and workload of staff, including the definition of responsibilities and powers related to the quality assurance of medicinal products and the relationship between subordinate and superior staff and qualified persons;
(b) ensuring the competence and equipment for the qualified person, the staff responsible for the manufacture of the medicines themselves, the staff responsible for the control of the medicines, the staff responsible for the quality assurance system and the staff responsible for the issue in the establishment of the transfusion service required for the performance of their duties;
(c) laying down conditions in the field of hygiene to prevent contamination of materials and packaging of medicinal products which include the health status of workers, their hygiene and clothing;
(d) carrying out initial and ongoing training and training of staff, focusing on the type and extent of activity in the manufacture of pharmaceuticals and on the theoretical knowledge and practical application of the quality assurance system and good manufacturing practice.
Spaces and equipment
(1) The premises and facilities intended for the manufacture of medicinal products are located, designed and constructed in such a way as to correspond to the type and extent of the medicinal products produced. These premises and facilities shall be maintained and controlled to ensure the required quality of the medicines.
(2) Production facilities are organised and interconnected in such a way that their use
(a) allow for the gradual continuity of the individual production activities;
(b) ensure easy cleaning and maintenance;
in order to minimise the risk of errors, to avoid contamination and confusion of medicinal products or any other adverse effects on their quality.
(3) The premises and facilities which may affect their quality in the manufacture of medicinal products must be qualified and checked for compliance with the requirements laid down in standard operating procedures.
Documentation
(1) The manufacturer shall develop and maintain a documentation system consisting of production regulations, instructions, specifications, standard operating procedures and records of repeated operations.
(2) The production rules, instructions, specifications and standard operating procedures must be understood and kept up to date.
(3) Documents governing generally the conditions of manufacture and the conditions of manufacture of the batch of the medicinal product shall be drawn up before the start of manufacture. Documents and records relating to the manufacture of a batch of medicinal products shall be drawn up in such a way as to permit monitoring of the production of the lot and shall be kept for at least 1 year after the expiry of the lot, but not less than 5 years after the written consent referred to in Article 8 (5) has been given.
(4) The content of the record shall be kept permanently legible and protected from damage or deterioration or loss. Electronic, photographic or other recording and processing systems, where they replace written documents, shall be validated to demonstrate that data are available for the period prescribed for their preservation.
Own production
(1) Technical and organisational measures are always carried out before and during the manufacture of the batch of the medicinal product to prevent contamination and confusion of the medicinal product.
(2) Only materials and packaging which conform to the specified specifications are used for the manufacture of medicines.
(3) Individual manufacturing activities, ongoing production checks and validation are carried out according to pre-established production rules, instructions, specifications, standard operating procedures, documentation submitted under registration control (2) and manufacturing authorities.7)
(4) The condition for the newly introduced manufacture of medicines is its validation; a similar validation condition is required for the manufacture of medicinal products if changes have occurred during the validation process which may affect the quality of the medicinal products. Validation of manufacturing activities essential to the quality assurance of medicinal products must be repeated regularly.
Quality control
(1) The quality control unit [§ 41b (c) of the Act] has one or more laboratories, which are equipped with a sufficient number of eligible staff and facilities for laboratory control of starting materials, packaging materials, intermediate products and final products.
(2) Individual quality control activities, including validation of procedures, shall be carried out according to pre-established specifications, standard operational procedures, documentation submitted under the marketing authorisation procedure (3) and manufacturing authorities.7)
(3) When checking the quality of the batch of the medicinal product before its release into distribution, the evaluation shall be carried out on:
(a) the results of quality checks prescribed for the manufactured medicinal product;
(b) details of the production conditions, including the results of the checks during the production process;
(c) the results of the checks carried out on the documentation of the own manufacture of the medicinal product;
(d) the appearance of the packaging of the final product;
(e) the conformity of the controlled data referred to in points (a) to (d) with the medicinal product registration dossier data.
For medicinal products not manufactured in batches, quality control shall be evaluated in accordance with points (a) to (d) before their release for distribution or supply.
(4) Each batch of the medicinal product shall be sampled; these samples shall be kept for at least 1 year after the expiry date of the lot of the medicinal product from which they were taken.
(5) From materials intended for the manufacture of medicinal products, except solvents, gases or water, samples shall be kept for at least 2 years after the release of the manufactured batch of medicinal products; that period may be shortened if the stability of the starting substance specified in its specification is shorter.
(6) The samples referred to in paragraphs 4 and 5 shall be kept for any use by the State Institute for the Control of Medicinal Products, if any, if it is for a medicinal product for human use or the Institute for State Control of Veterinary Bioprafts and Medicines, if it is for a veterinary medicinal product. In the case of medicaments manufactured individually or those which are difficult to store, conditions of storage and sampling different from those laid down in paragraphs 4 and 5 may be established following prior consultation with the manufacturer and with the State Institute for the Control of Veterinary Bioprafts and Medicines.
(7) The provisions of paragraphs 4, 5 and 6 do not apply to transfusion preparations and to raw materials or intermediate products of blood and its constituents for further production.
Contract production and control of pharmaceuticals
(1) The contract on the manufacture of pharmaceuticals or on laboratory control of pharmaceuticals (9) is concluded in writing between the manufacturer of pharmaceuticals and the external manufacturer of pharmaceuticals or a control laboratory and defines the obligations and responsibilities of the contracting parties, in particular for the observance of good manufacturing practice, and the manner in which the qualified person responsible for placing the batch of medicinal products into distribution fulfils his responsibility. If one of the Contracting Parties to the Transfusion Service Facility, this contract shall include the obligations and responsibilities of the Contracting Parties and the manner in which the liability of the qualified person is defined.
(2) An external manufacturer or control laboratory may provide for an agreed activity with another person only with the written consent of the manufacturer.
Complaint and recall of medicines
The establishment and application of a system for the registration and assessment of complaints and complaints concerning the quality, safety and efficacy of medicinal products shall be part of good manufacturing practice, including measures enabling the withdrawal of a batch of medicinal products from circulation without delay if necessary.
CORRECT PRODUCTION PRACTICE IN TRANSFUSE SERVICES EQUIPMENT
Good manufacturing practice means requirements for the production of blood transfusions and raw materials or components thereof, in particular the production of blood and its components, their processing, labelling, control, storage, packaging, transport, delivery and documentation in these activities. Good manufacturing practice in a transfusion service facility also means requirements for the intake, storage and supply of blood products and blood derivatives. Unless otherwise provided for in Section 2, the transmission service facility shall proceed under the conditions of good manufacturing practice set out in Section 1.
Principles
(1) Prior to the start of the output of the new transfusion product and the new raw material or intermediate product from blood or its constituents for further production, before the start of the new activity and when the change in activity which may affect the quality of the transfusion product and the raw material or intermediate product from blood or intermediate product from blood is validated in the framework of the testing operation of the proposed processes or changes in processes, verify that the standard requirements laid down by the documentation [§ 2 (b), (c), (d) and (e)] and the specifications of transfusions and raw materials or intermediate products from blood or its constituents for further production are reached and demonstrate that the transfusing the raw material or intermediate product which passes for further production meet the quality requirements.
(2) In carrying out the various activities of the transfusion service facility
(a) indicates the collection, laboratory samples produced during the collection and processing of blood products, transfusions and raw materials or intermediate products of blood or its constituents for further production, and all records thereof, in order to avoid confusion and ensure accurate records of both the donor and the recipient of the individual samples, transfusions and raw materials or blood or its constituents for further production;
(b) select materials, apparatus and equipment which satisfy the conditions of the quality and specification assurance system (Sections 2 (d) and 2 (e)) and which cannot adversely affect the quality of transfusion preparations and raw materials or intermediate products from blood or its constituents for further production, and use them in accordance with the manufacturer's instructions.
Space
The transfusion services are carried out in separate separate premises
(a) blood and donor blood collection;
(b) processing of the blood collected and its components;
(c) the storage of unreleased blood and blood components, the marking and release of transfusions for supply and raw materials or intermediate products from blood or its constituents for further production; a separate part of the premises referred to in point (b) may also be used for such purposes, where appropriate;
(d) laboratory activities;
(e) storage and supply of transfusion products made available for medicinal uses and raw materials or intermediate products from blood or blood components made available for further production.
Documentation
(1) The written procedures of the establishments shall consist, in addition to the documentation referred to in Article 2 (b), (c), (d) and (e), of specifications of transfusion products and raw materials or intermediate products of blood or its constituents for further production in accordance with paragraph 2.
(2) The specification of transfusion preparations and raw materials or intermediate products from blood or its constituents for further production contains summary data on:
(a) the formation, packaging, characteristics, composition and contents of the package;
(b) marking,
(c) storage and transport conditions and the period of application;
(d) quality checks, sampling procedures and frequency of checks, the results of the checks carried out, including criteria for their evaluation;
(e) tolerances for quantitatively measurable data;
(f) proper administration, therapeutic indications and contraindications and of adverse effects in transfusion products and the purpose of using the raw material or intermediate product from blood or its constituents for further production.
(3) Transfusion service facilities provide and store donor data, 11) which include:
(a) the name, surname, address and donor identification number;
(b) the questionnaire and the donor statement, where the donor provides data on himself and on his or her health at each collection, except for autologous;
(c) informed consent of the donor to the collection and laboratory examination of his blood;
(d) records of donor medical assessment and sampling.
(4) The activities leading to the formation of the transfusion product and the raw material or intermediate product from blood or its constituents for further production, the intake and supply of the transfusion product, the supply of raw material or intermediate product from blood or its constituents for further production shall be recorded in a manner that allows the donor and the recipient of the blood product and the raw material or intermediate product from blood or its components for further production, and the return of all processes from the collection of the donor to the supply of the transfusion product or intermediate product from blood or its components for further production.
(5) For cleaning, maintenance and use of instruments and measuring equipment, calibration and verification, written procedures shall be developed, including instructions from the instrument manufacturer and measuring equipment. There shall be records of cleaning, maintenance, use, calibration and verification.
(6) All provisions and records determining and documenting the course of production, quality checks, release of blood products and raw material or intermediate products from blood or its constituents for further production, supply of blood products, supply of raw material or intermediate products from blood or its constituents for further production and quality assurance in accordance with the specifications laid down in Section 14 (2) of the blood product or intermediate products from blood or its constituents for further production shall be kept for at least 10 years.
Own production
(1) Transfusion service facilities
(a) assessment of donor medical fitness for different types of sampling, including autologous sampling;
(b) blood collection, blood collection in the premises of the transfusion service facilities, including autologous sampling;
(c) blood samples carried out outside the permanent premises of the transfusions service facility ("blood collection at exit");
(d) the receipt of blood collected and its components from other establishments of the blood service (hereinafter referred to as the "supplied blood") and the quality assurance check of the blood delivered and its components at the place of operation of another establishment of the blood service;
(e) processing at the place of collection or delivery of blood or its constituents simultaneously into one or more transfusion preparations and raw material or intermediate product for further production according to a predetermined procedure;
(f) specialised activities, in particular the irradiation of transfusion preparations and the preparation of cryopreserved cell concentrate;
(g) marking and storage of blood collected, intermediate products and final transfusion preparations and raw materials or intermediate products of blood or its constituents for further production, including transport thereof, in accordance with the storage conditions laid down in the specifications (§ 14 (2)).
(2) In deciding on donor medical fitness to be taken, the health status, test results and donor history shall be assessed in order to avoid damage to donor health by collecting or damaging the health of the recipient of the medicinal product derived from blood or blood components of the donor; a doctor is responsible for assessing donor medical fitness.
(3) A separate space and conditions for providing health information and, where appropriate, for the risk behaviour of the donor, shall be provided for the donor for interview and assessment of the donor's eligibility for procurement.
(4) Blood collection during exit and transport of blood from another blood establishment shall also ensure that the blood collected during transport is stored in accordance with a validated procedure according to the production instructions (§ 6 (1)).
(5) The sampling and processing shall be carried out to avoid contamination or precipitate formation in the sampling kit. It shall be carried out in a closed, sterile system, with the exception of injection at start of collection, or by another validated and equally safe procedure to prevent contamination during the process.
(6) The equipment of the transfusion service shall indicate on the label of each transfusion product which it releases for delivery and on the label of each raw material or intermediate product from blood or its constituents which it releases for further production,
(a) the identification number of the transfusion product or, where applicable, the raw material or intermediate product of blood or its constituents for further production, which includes the identification code of the transfusion service facility, the last two digits of the year of collection, the registration number of the collection and the identification of the individual parts for the split collection;
(b) the name of the transfusion preparation or, where appropriate, the raw material or intermediate product;
(c) the name, registered office and identification code of the establishments of the transfusion service;
(d) the quantity (volume and content of the active ingredients), the anticoagulant or stabilising solution used, as appropriate, the conditions required for storage;
(e) the date of collection.
The data referred to in points (a), (b) and (e) shall also be characterised by a barcode for the transfusion preparation.
(7) In addition to the information referred to in paragraph 6, the establishments shall indicate the transfusion service on the label of the transfusion product which they release for delivery,
(a) the date and, in the case of the shelf life of the transfusion product within 48 hours, the exact time by which the transfusion product is applicable to the person being treated;
(b) blood type of system AB0 (A, B, 0, AB),
(c) symbol D of system Rh [Rh (D) positive, Rh (D) negative],
(d) in the case of plasma for clinical use, a satisfactory result of repeated donor testing after plasma quarantine; the duration of the quarantine shall be determined by a time interval corresponding to the interval during which, in the case of a healthy person, the result of the laboratory examination referred to in Article 18 (1) (b) is changed from negative to positive in case of infection;
(e) if it is an autologous transfusion, a clear indication of AUTOTRANSFUZE and the name, surname and identification number of the person who is both donor and recipient of the transfusion.
The data referred to in points (b) and (c) shall also be marked by a barcode.
(8) For autologous transfusion products, separate storage from transfusion products and raw materials or intermediate products from blood or its components released for supply or for further production is required.
(9) Pending the preparation for administration to a person treated with a transfusions facility, the transfusions shall be protected against pollution and damage and ensure compliance with the storage conditions as specified in the specification (Section 14 (2)); the raw material or intermediate product of blood or its components shall be secured against pollution and damage by the contract processor until the time of delivery for further production and the storage conditions specified in the specification are met (Section 14 (2)), including the continuous registration of the storage conditions achieved.
Release of blood or its components for further production
(1) Any transfusion product and raw material or intermediate product from blood or its constituents, marked with a label, may be released for release or for further production only after the written consent of the qualified person has been given; the person confirms by his signature that the results of the quality checks, production conditions, documentation, appearance and labelling of the finished product are in conformity with the specified specification (Section 14 (2)) and the principles laid down in this Decree.
(2) With its identification code, the transfusion service facility shall identify all transfusion preparations and raw materials or intermediate products from blood or its constituents for further production which it has released for supply or for further production.
Receipt and supply of blood products and blood derivatives
(1) Transfusion service facilities shall be issued by the medical institution to: 12)
(a) own-production transfusions which they release for delivery after labelling (Sections 15 (6) and (7)), indicating their identification code, name and registered office;
(b) transfusions provided by the transfusions service facility;
(c) blood derivatives supplied by their distributor at the request of the issuing body of the blood service only on condition that the blood supply of the blood service complies with the requirement. 13)
(2) When receiving the transfusion products and blood derivatives supplied, the accuracy and completeness of the documentation supplied, the appearance and integrity of the packaging, the completeness of the label data and their conformity with the documentation provided and the conditions of storage during transport shall be checked. Blood derivatives shall also be checked for batch release protocols for distribution.
(3) Transfusion products are issued on the basis of a request. 14) When requiring a transfusion product for a person being treated and requesting a pre-transfusion examination, a marked blood sample shall be provided and the diagnosis data, previous transfusions and reactions to transfusions, births and abortions, antibodies detected shall be provided on demand. If the data on the request are illegible or incomplete, or if the sample for the pre-transfusion examination has not been identified by the name, surname, consignee identification number and date of collection, the transfusion shall not be issued. In the event of a danger of delay, the product shall be issued after the necessary data for the issue have been established without delay.
(4) A transfusion product issued for a person being treated is accompanied by accompanying documentation which allows verification
(a) the name and address of the issuing establishment of the transfusion service;
(b) identification of the medical establishment receiving the transfusion product;
(c) the identification number, the name of the transfusion product and the particulars referred to in Article 15 (7) (a), (b), (c) and (e);
(d) data on the quantity of the transfusion preparation characterising the content of the active ingredient;
(e) the date of issue of the transfusion product and any transport requirements,
(f) the date of execution and the result of the pre-transfusion examination, if any, and the signature of the official who carried out the examination;
(g) the name, surname and identity number of the treated person.
(5) At the request of the customer of the transfusions product, the transfusions service facility shall provide a summary of the basic data on the transfusions product as specified by it (Section 14 (2)).
(6) The authorisation to issue 14a) blood products and blood derivatives is granted in writing by the head of the establishment of the transfusion service.
(7) A returned transfusion product and a returned raw material or intermediate product from blood or its constituents may be reissued or provided for production if:
(a) it is in the original package,
(b) has not been exposed to adverse effects on quality, safety and efficacy;
(c) has been assessed by a qualified person and found satisfactory in terms of quality, safety and efficacy.
Quality control
(1) The establishment of a transfusion service, within the scope of the activities it carries out, ensures quality control, which includes:
(a) for each collection, a laboratory examination of donor blood to assess donor medical fitness for sampling;
(b) for each collection, except for autologous sampling, tests to show signs of AIDS, hepatitis B, hepatitis C and syphilis infection;
(c) each collection, except for autologous sampling, blood type tests in the AB0 system, the Rh (D) character and the clinically significant irregular antibodies to erythrocytes; the result of blood type tests in the AB0 system shall be independently verified;
(d) for autologous sampling, the tests referred to in (b) and (c) shall be carried out at least once in each series of samples for the intended therapeutic performance;
(e) other immunohematology tests, further examination of signs of infection according to the specified specification (§ 14 (2)),
(f) for final products of control of volume or weight, active ingredients, undesirable constituents and performance indicators, safety and stability according to the specified specification (§ 14 (2)); where necessary, such checks shall also be carried out during production;
(g) for randomly selected blood samples and its components, continuous monitoring of the effectiveness of the disinfection of the site of venipuncture;
(h) at random microbiological checks of the surfaces in the premises where the bags are handled, taken and products in the bags without further packaging;
(i) checks of materials supplied for own production and quality control according to the specification [Section 2 (e)] prior to their use in the operation of the equipment of the transfusion service.
(2) Diagnostics authorised for use in the provision of health care are used for the compulsory testing of infectious diseases and immunohaematology [Sections 18 (1) (b) and (c)]. 15)
(3) The testing of infectious diseases shall be carried out in such a way as to ensure, with the re-reactive result of the sampling by the standard method used, that the transfusion product and the raw material or intermediate product derived from such collection are not released for supply or further production.
(4) A sample shall be retained from each sampling to examine signs of infectious diseases. If the sample is not used for testing where there is doubt as to the quality of the transfusion preparation and the raw material or intermediate product from blood or its constituents for further production (Section 20 (2)), it shall be kept for at least 1 year after the expiry date of the transfusion preparation and, in the case of raw material or intermediate product from blood or its constituents for further production, shall be kept for at least 2 years after delivery for further production.
(5) Checks on transfusion products shall be carried out to demonstrate that their quality is satisfactory throughout the period of application.
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Regulation Information
| Citation | Decree of the Ministry of Health and the Ministry of Agriculture No. 296 / 2000 Coll., establishing good manufacturing practice, good distribution practice and closer conditions for authorising the production and distribution of medicinal products, including medicated feed |
|---|---|
| Regulation Type | Order |
| Author | - |
| Collection | Code of Laws |
| Date of Promulgation | 28.08.2000 |
|---|---|
| Effective from | 28.08.2000 |
| Effective until | - |
| Status | Valid |
The regulation text is for informational purposes only.
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