Read the untranslated law here: https://www.vestnesis.lv/ta/id/134261
Cabinet of Ministers Regulations No 304 of 2006 in Riga 18 April (pr. No 22 21) rules for the production and control of medicinal products order about pharmaceutical officers qualification requirements and professional experience and the order in which pharmaceutical company of good manufacturing practice shall be issued a Certificate Issued in accordance with article 5 of the law on Pharmacy 3 and 13 and 52 of article i. General questions 1. determined the medicine production and control procedures for the medicine production officers qualifications and professional experience requirements as well as the order in which the pharmaceutical company to issue the certificate of good manufacturing practice.
2. These provisions apply to: 2.1. medicinal products for human use manufactured industrially or manufactured by a method that involves an industrial process;
2.2. for medicinal products manufactured in the Republic of Latvia and only intended for export to countries, not Member States of the European Union or European Free Trade Association (EFTA) countries which are signatories to the agreement on the European economic area (hereinafter referred to as the European economic area);
2.3. intermediate products;
2.4. homeopathic medicinal products;
2.5. herbal medicines that meet the traditional herbal medicinal products, the criteria laid down in the rules of registration of the medicinal product;
2.6. the manufacture of the investigational medicinal product;
2.7. the pharmacy made the medicine quality control.
3. These provisions shall not apply to: 3.1 radionuclides (radioactive isotopes) in the form of sealed sources.
3.2. the whole human blood, plasma or blood cells, except for plasma which is prepared industrially.
4. the meaning of these provisions: 4.1 the active substance is a substance or mixture of substances intended for use in the manufacture of the medicinal product and which in this case becomes the active ingredients of the medicinal product concerned;
4.2. packaging is a division of the finished product in a certain number of units;
4.3. the finished product is a medicinal product covered all stages of production, including packaging in the final packaging;
4.4. packaging is any operation, also filling and labelling to unpackaged products into finished products;
4.5. starting materials shall mean any substance used in the manufacture of medicinal products, except for the packaging materials;
4.6 qualification is the operation demonstrated and documented that the medicinal products used for the manufacture of any of the equipment is properly installed, work correctly and provide the expected results. Qualification is part of the validation, but the individual qualification stage did not mean the process validation;
4.7. good manufacturing practice is part of pharmaceutical quality assurance system, which guarantees that the product is constantly produced and inspected in accordance with the foreseen in the body use the appropriate quality requirements;
4.8. the series is a specific uniform (with certain tolerances) or intermediate quantity of medicines collected from a certain production process or in multiple processes. If is a continuous production, the series may be a production to a certain part. The series is given a certain amount or quantity produced during a given period;
4.9. specification is a detailed description of the requirements of the medicinal products used in the production process or the resulting products or materials;
4.10. an intermediate product is partially recycled material, including raw materials, subject to the subsequent stages of the manufacture of medicinal products (stages) before it becomes a bulk product;
4.11. validation is documented in the implementation of the program, which allows you to say with great conviction that the process, method or system that is used in the production of medicines or controlled, constant work, delivering results that meet the criteria set out above.
II. requirements for the production of medicines 5. Medication, including investigational medicinal products, may be produced in the specified form of the medicinal product, where, according to the pharmaceutical law, those rules and regulations that govern the special permit (license) the pharmaceutical activity, suspension of service, re-registering and cancellation procedures, the merchant has received the medicine government agency issued a special permit (license) for the manufacture of medicinal products/import (hereinafter referred to as the special permit (license) for the production of medicinal products).
6. Special permit (license) for the production of medicines requires both complete and partial production, as well as a variety of packing, packaging and product design process.
7. Special permit (license) for the production of medicinal products does not require that pharmacists pharmacy medicines manufactured and fast, as well as change the packaging or presentation of medicinal products intended for individual patient after medical treatment person's prescription (the magistral formula) or the hospital's written request, or medicinal products which are manufactured according to the pharmacopoeia monographs and which is intended for distribution to patients served by the pharmacy in question (the officinal formula).
8. the Person involved in the transaction, which requires a special permit (license) for the production of medicinal products (hereinafter referred to as the pharmaceutical manufacturer), ensure that the following requirements are met: 8.1 in the production and control of medicinal products employing the appropriate qualification of staff, providing production and control requirements in accordance with these rules;
8.2. use of registered medicinal products and investigational medicinal products in accordance with legislation on the distribution of medicinal products laid down in the good distribution practice;
8.3. the pharmaceutical law referred to in article 52 officers (hereinafter referred to as the qualified person) Exchange immediately (but not later than five days) shall inform the State Agency of medicines;
8.4. ensure medicine State agency officials any time of the day to visit all the premises of the manufacturer of the medicinal product;
8.5. ensure the qualified person to fulfil this provision in paragraph 10 and 11 obligations, for example, placing at its disposal all the necessary facilities;
8.6. the medicinal products comply with the principles and guidelines of good manufacturing practice and use of raw materials only active substances which have been manufactured in accordance with the active substance of good manufacturing practice guidelines. The production of active substances include both full and partial active substances manufactured or imported, as well as different types of packing, packaging and presentation of the activities carried out prior to their inclusion in the composition of the medicinal product, including the reuse packaging or labelling by the distributor of raw materials;
8.7. the production operations carried out in accordance with a special permit (license) for the manufacture of medicinal products;
8.8. medications that require a registration certificate, manufactured in accordance with the registration of the submitted data and documents. As regards investigational medicinal product shall ensure that all manufacturing operations are carried out in accordance with the information specified by the sponsor of the clinical trial of the medicinal product in the application for authorisation. Production methods to be used, taking into account scientific and technical progress and the development of the investigational medicinal product, regularly reviewed.
9. the manufacturer of the medicinal product shall ensure that they have permanently and continuously at his disposal at least one qualified person whose education and practical experience meet the rules set out in chapter III qualifications and professional experience requirements and which are primarily responsible for this provision in paragraph 10 and 11 of the said obligations. If the manufacturer of the medicinal product personally meet this provision in paragraph 13 of the said conditions, he can take the responsibility and to discharge the duties of the qualified person.
10. The qualified person shall, without prejudice to its relationship with a drug company, is responsible for ensuring that each series of medicinal products produced and controlled, subject to the requirements of this regulation and in accordance with the registration documentation for the method. If the investigational medicinal products are manufactured, the qualified person shall be responsible for ensuring that each drug is manufactured and tested in accordance with the principles and guidelines of good manufacturing practice, product specification documents and information that the sponsor has specified in the application to the State Agency of medicines for clinical trial authorisation.
11. in all cases, the qualified person (especially if the product sold) finished product certification, making exact records log or other equivalent provided for this purpose in the document and certify with signature that each series of medicines manufactured and controlled according to the provisions in this paragraph 10. After certain actions log or the relevant document and keep the company not less than five years since the last entry, providing the medicine State agency officials said access to the journal or document.
12. The illicit manufacture of narcotic drugs and psychotropic pharmaceutical respects the requirements of the law "on the illicit manufacture of narcotic drugs and psychotropic substances and to the legitimate movement of medicinal products order", "law on precursors" and the relevant legislation, which lays down the requirements for the illicit manufacture of narcotic drugs and psychotropic substances and drugs, as well as precursors for use of medicinal plants.
III. Qualified person qualifications and professional experience requirements 13. The qualified person shall meet the following qualifications and professional experience requirements:
13.1. the qualified person shall possess a diploma, certificate or other evidence of formal qualifications obtained by the University (University) study programme completion or after completion of a study programme in Latvia by law established recognised as equivalent by the University studies program, which includes at least four years of theoretical and practical study in one of the following sectors: science, medicine, pharmacy, veterinary medicine, chemistry, pharmaceutical chemistry and technology, biology. The minimum duration of the University course may be three and a half years, if followed by at least one year of theoretical and practical training, including at least six months training in a general type of Pharmacy and pass an exam at the end of which the corresponding University course requirements;
13.2. the rules referred to in paragraph 13.1 study program includes theoretical and practical studies, which are acquired at least the following study courses: 13.2.1. physics;
13.2.2. General and inorganic chemistry;
13.2.3. organic chemistry;
13.2.4. analytical chemistry;
13.2.5. pharmaceutical chemistry, including analysis of medicinal products;
13.2.6. General and medical biochemistry;
13.2.10. pharmaceutical technology;
13.2.12. pharmacognosy (plant and active substances of animal origin study of the composition and effects of the);
13.3. no less than two years practical experience in one or more undertakings which have a special permit (license) for the manufacture of medicinal products, in the activities of qualitative analysis of medicinal products, of quantitative analysis of active substances as well as the testing and checking necessary to ensure the quality of medicinal products. Practical experience may be less than one year, if the University studies of at least five years, and about a year and a half less, if studies of at least six years.
14. Study this rule 13.2. bottom subjects referred to in point a must be an amount to the person concerned to fulfil this provision in paragraph 10 and 11 under certain obligations by the qualified person.
15. If the diplomas, certificates or other formal qualifications do not meet the criteria laid down in that provision in paragraph 13.1, the State Agency of medicines shall require that the person concerned shall submit a certification issued by the University for this rule 13.2. the courses referred to in point.
IV. Good manufacturing practice principles and guidelines 16. Companies will establish and implement a quality assurance system for medicinal products containing all the organisational measures to ensure that medicinal products or investigational medicinal products meet the quality required for their intended use. Quality assurance system guarantees that: 16.1 the medicines posed and drawn up in accordance with the good manufacturing practice and good laboratory practice;
16.2. the production and control operations are clearly defined and complies with good manufacturing practice;
16.3. have a clear management responsibilities;
16.4. measures have been taken to correct the raw and packaging materials for the production, delivery and use;
16.5. is carried out all the necessary checks and any intermediate process of verification and validation;
16.6. the finished product correctly processed and inspected in accordance with established procedure;
10.4. the medicinal product sold or delivered only after the qualified person has certified that all medicines series is produced and tested according to the registration certificate and the rest of the rules relating to the manufacture, control and release;
16.8. There is agreement that, to the extent possible, the medication is stored, distributed and handled so as to maintain the quality of the product throughout the storage period;
10.5. a system of self checking or quality control procedures in accordance with regularly evaluate the quality system effectiveness and applicability.
17. the manufacturer of the medicinal product as regards personnel, ensure that the following requirements are met: 17.1. each site for the production and control of the producer have sufficient numbers of staff with the necessary qualifications and practical experience in order to ensure that the intended use of the medicinal product quality;
17.2. the managing and administrative staff the obligation laid down in the description of the job responsibilities. Personnel responsible for the application of good manufacturing practice and functional, is the qualified person, the head of the production department and the quality control Department. Staff relation hierarchy determines the Organization's structure diagram. Structure diagram and description of the tasks of the work shall be approved in accordance with the drug manufacturer's specific internal procedures;
17.3. this rule 17.2. staff referred to grant certain powers duties;
17.4. the staff provides initial and continuing training (the regular assessment of its practical usefulness), which include quality assurance and good manufacturing practice principles of theoretical and practical learning, as well as, if necessary, specific requirements for the manufacture of investigational medicinal products;
17.5. develop and observe hygiene programmes adapted to the activities to, especially by emphasizing the requirements relating to staff health, personal hygiene and clothing.
18. Premises and equipment in addition to those laid down in the laws and requirements of construction shall meet the following requirements: 18.1. premises and manufacturing equipment shall be located, designed, constructed, adapted and maintained to suit the operations to be undertaken;
18.2. premises and manufacturing equipment shall be located, constructed and used so as to minimise the risk of error and permit effective cleaning and maintenance (maintenance), to prevent the contamination of raw materials and medicinal products, cross-contamination (contamination of finished product with another material or product), and any adverse effect on the quality of the product;
18.3. the premises and equipment used for production operations, are suitably qualified and validated.
19. the manufacturer of the medicinal product shall establish and maintain a documentation system, which includes the specifications, manufacturing formulae and processing and packaging instructions processing instructions, specific to the production of medicinal products, directly or indirectly, related activities, and other measures of prudence descriptions (hereinafter procedure) and the Protocol relating to the various manufacturing operations performed. These documents are clear, error-free, and are regularly updated. Available predefined procedures, as well as a specific set of documents, which reflect the series production process and quality control process (hereinafter referred to as the serial number). This set of documents provides traceability of medicinal products, each serial production history, the changes that are made to the investigational medicinal product during development, the dissemination of information about the series, as well as other significant circumstances that affect the quality of the finished product (hereinafter referred to as the series documentation).
20. a series of documentation on products stored for at least a year after a series of drug expiration date or at least five years after this provision referred to in paragraph 11 of the final certification, taking into account the longer period.
21. a series of documentation of investigational medicinal product to be kept for at least five years after the last clinical trial completion or formal discontinuation of the series which was used. The sponsor or the holder of the registration certificate (the owner), if not the same person, is responsible for the maintenance of the series needed for the subsequent registration of the medicinal product in accordance with the legislation on medicinal products vajiem in normat.
22. If the documentation is not presented in the series writing, but uses the electro-electronic check, photographic or other data processing system, the manufacturer of the medicinal product the first validation of the system, to ensure that the data will be stored in the storage period. Data stored in these systems are easily available and understandable, and, on request, provide the State Agency of medicines. Electronically stored data against data loss or corruption protects them copying, duplicating or sending to a different storage system, as well as maintain the audit trail.
23. the manufacturing process of the medicinal product shall meet the following requirements: 23.1. activities carried out according to the approved instructions, procedures and good manufacturing practice requirements;
23.2. the control of the production process, ensure appropriate resources;
23.3. all production process deviations and product defects shall be documented and thoroughly investigated;
23.4. in technical and organisational measures to prevent drugs and mutual pollution of raw materials and mixing. For investigational medicinal products, with particular attention to the processing of the product coding methods (deliberate concealment of the identity of an investigational medicinal product in accordance with the instructions of the sponsor) during use and after its use;
14.6. any new production processes or major changes in the production process in a fixed order validated. The critical stage of the manufacturing process shall be regularly repeated to validate;
14.7. as regards investigational medicinal product provides validation of the manufacturing process as a whole, so far as is necessary, taking into account the stage of product development. At least the critical process, such as sterilization, validation. Fully documented all of creation and production process development stage.
24. Quality control shall meet the following requirements: 24.1. medicines manufacturer shall establish and maintain a quality control Department, which is headed by a person with the appropriate qualifications (defined in the job description) and is independent of production;
24.2. the quality control Department Manager have at its disposal one or more quality control laboratories appropriately staffed and equipment to be able to make the necessary raw materials, packaging materials and intermediate and finished products;
24.3. medicines can be used for the quality control laboratory, with which the contract was concluded, if these rules are met the conditions referred to in paragraph 27;
15.2. with regard to the investigational medicinal product, the sponsor shall ensure that the laboratory to which the conclusion of the contract, comply with the submission (submitted to the State Agency of medicines of the medicines in the clinical trial for receiving initiation) specified requirements;
15.2. the last control of the finished product before release of medicines for sale or delivery, or for use in the clinical trials quality control Department in addition to the analytical results taken into account other relevant information, such as on the conditions of production, the production process of the results of the checks carried out, the production and inspection of documents, the final product and its compliance with the specifications of the packaging;
24.6. each series of finished products look gus kept for at least one year after the expiration date;
24.7. with regard to the investigational medicinal product-appropriate samples from each boxed product series and the main primary packaging components used in each of the final series, to be kept for at least two years after its last clinical trial completion or formal discontinuation of the lot which was used, taking into account the longer period;
15.4. starting materials used in the manufacture of medicinal products, other than solvents, gases and water, stored for not less than two years after product release. Sample storage time may be less if the period of stability laid down in the specifications is shorter;
15.5. the sample product and raw material storage site shall inform the State Agency of medicines, and its officials have the opportunity at any time to visit the respective areas;
24.10. where a medicinal product produces an individual order, small quantities of raw materials or medicinal products and sample storage, because of their characteristics, are cumbersome, by agreement with the State Agency of medicines can designate other sampling and storage conditions.
25. If any industry or activity or quality control carried out by another person (hereinafter referred to as the contractor), pharmaceutical manufacturer and contractor shall sign a written contract for a particular job. Identify the Treaty obligations of the parties, with particular emphasis on contractor's obligation to comply with the principles and guidelines of good manufacturing practice, as well as the manner in which the qualified person responsible for certifying each batch is to discharge his responsibilities.
26. the contractor shall ensure the following requirements are met: 26.1. If not received written authorisation by the manufacturer of the medicinal product, with a third party subcontract for work in accordance with the provisions of the agreement referred to in paragraph 25 of the entrusted contractor, do not switch;
26.2. the contractor that the original contract in the name of the manufacturer take part manufacturing operation, can only be the manufacturer of the medicinal product for which a special permit (license) for the manufacture of medicinal products;
26.3. the prescribed in these provisions comply with the principles and guidelines of good manufacturing practice, as well as the State Agency of medicines under control.
27. Before the conclusion of the contract for carrying out the quality control of medicinal products, the manufacturer shall ensure that the medicine State agency officials carry out a check and give an opinion on the compliance of laboratories of good manufacturing practice requirements.
28. the manufacturer of the medicinal product (if the investigational medicinal products are manufactured, in cooperation with the sponsor) provides the following requirements to take complaints, drug withdrawal and coded disclosure of identity of an investigational medicinal product (hereinafter referred to as unwrapping): 28.1. introduce for the medicinal product received complaint registration and examination system, as well as at the effective operation of the system, on the basis of which the existing distribution network products quickly and at any time, be removed from circulation. Drug company records all complaints on defects and investigate them. The manufacturer of the medicinal product in 24 hours after the fact finding, inform the State Agency of medicines of any defects or complaints, which could be the basis for the withdrawal from the market of the medicinal product or distribution limitation, extraordinary and, if possible, also indicate the countries of destination;
28.2. any withdrawal from the market of the medicinal products in accordance with the requirements laid down in the laws of distribution of medicinal products;
28.3. in cooperation with the sponsor establishes an investigational medicinal product complaint registration and examination system, as well as at the effective operation of the system, on the basis of which the existing distribution network for investigational medicinal products quickly and at any time, be removed from circulation. Investigational medicinal product manufacturer registers and investigates all complaints on defects and inform the State Agency of medicines for them, if the defect can be removed from the courtroom or out of round limit their distribution;
28.4. all investigational medicinal product related research sites identified and, to the extent possible indicate the countries of destination;
28.5. in the case of investigational medicinal products that have been registered with, investigational medicinal product manufacturer, in cooperation with the sponsor, inform the registration certificate holder (owner) of any defect that might apply to products that have been registered;
28.6. the sponsor shall make fast to unscramble the investigational medicinal product if the investigational medicinal product required immediate removal from circulation in accordance with the provisions of subparagraph. 17.6. The sponsor shall ensure that the identity of an investigational medicinal product magazines found only in so far as it is necessary.
29. Drug manufacturer provides repeat self-control, to monitor implementation of good manufacturing practice and observance, as well as to propose necessary corrective measures. Such self-control and then carry out the corrective actions shall be documented and shall be retained for not less than five years.
30. Good manufacturing practice principles and guidelines referred to in this chapter, as well as active substance the principles of good manufacturing practice for medicinal products, the manufacturer of interpretation having regard to the European Commission's guidance on medicinal products and investigational medicinal products good manufacturing practices (hereinafter referred to as the guidelines of the European Commission), the European Commission published the European Union regulatory framework for medicinal products document item 4. volume and Latvian language is published by the National Agency for Medicines home page on the internet (URwww.zva.gov.lv).
31. the manufacturer of the medicinal product, which is manufactured from human blood and plasma derived medicinal products, in the manufacture of these products supports the production process used and the whole cleaning process according to the validation to ensure the homogeneity of the series and all guaranteed to the extent permitted by the technology, security against infection with specific viruses. Drug manufacturer shall inform the State Agency of medicines of the methods that is used to reduce or eliminate pathogenic viruses that can be transmitted through such medicinal products. This medicine is used in the production of raw materials (human blood and plasma), with which it is not possible to transfer the infectious diseases and which are received from the national blood establishments and medical institutions for the preparation of blood units that human blood and blood components collection, testing, processing, storage and distribution takes place according to the laws of human blood and blood components collection, testing, processing, storage and distribution of the quality and safety standards.
V. of good manufacturing practice certificate procedure 32. in order to ensure that the manufacturer of the medicinal product followed these rules laid down in the principles of good manufacturing practice and the base of the stādn, the State Agency of medicines: 32.1. by special permit (license) for the production of medicinal products issued not less frequently than every three years, made repeated good manufacturing practice inspections (inspections). The State Agency of medicines shall agree with the drug manufacturer at the time when the test will be launched, and notify in writing not later than 10 working days before the start of the inspection;
32.2. If necessary, carry out checks for which has been announced, and in the case of samples tested by the national agency of Medicine laboratory or a laboratory that has the right to control drug;
32.3. If there is reasonable suspicion of non-compliance with the principles and guidelines of good manufacturing practice, shall be entitled to carry out inspections for which has been announced, for the raw materials used in the premises of the manufacturer of the substance or the holder of the registration certificate on the premises. Such inspections may also be carried out by another Member State of the European Union or the European economic area, the European Commission or the European Medicines Agency's request;
32.4. is entitled to take raw material testing (inspections), based on the manufacturer of the medicinal product during application.
33. The rules referred to in paragraph 32 of the testing of medicinal products authorises the competent national agency officials who are trained to take the good manufacturing practice requirements and the monitoring of, and control which has the following rights:
33.1. to check the drug or substance used for the raw materials and the production of all laboratories that use the drug manufacturer to determine whether the medications produced and controlled in accordance with good manufacturing practices and the registration documents submitted to the production and control methods. This also applies to contractor inspection, which with a drug company has concluded the provision referred to in paragraph 25 of the Treaty on certain stages of production or quality control;
33.2. sampling, also to make independent testing by the national agency of medicinal products in a laboratory or another laboratory, which has the power to take control of the quality of medicinal products. With drug testing-related costs shall be borne by the controlled person in accordance with the State Agency of medicines to the public provided by the paid service price list;
33.3. to examine all the test object's documentation, subject to the restrictions in relation to the description of the manufacturing method;
20.8. immunological preparations (vaccines, toxins, allergen products) in particular to check that the manufacturing processes used are properly validated and ensure the homogeneity of the series.
34. the manufacturer of the medicinal product during control provides drug national agency officials: 34.1. information about the control and finished product control and production of components at an intermediate state of the control in accordance with the registration dossier;
21.3. the immunological preparations and from human blood and plasma-derived medicinal products-all final copies of the certificates that are issued by the qualified person.
35. the National Agency for medicinal products authorised officials of the pharmaceutical company reviews take into account the Commission's overview of Community inspection and information exchange procedures. To interpret the principles and guidelines of good manufacturing practice for active substances, including the principles of good manufacturing practice, take into account the instructions of the European Commission.
36. the National Agency for medicinal products authorised officials within 10 working days after each of these regulations 32. the checks referred to in paragraph 1 shall draw up an inspection report in accordance with the provisions specified in annex 1 of the sample form. One copy of the message is sent to the manufacturer of the medicinal product, which is carried out a second, if necessary, shall forward to the authority that requested the verification. Where the producer of the investigational medicinal product, one copy of the inspection report shall also be sent to the sponsor, ensuring confidentiality. The State Agency of medicines of the investigational medicinal product manufacturer control message may be made available to the other Member States, the Ethics Committee or the European Medicines Agency after their reasoned request.
37. Expenses related to the pharmaceutical company's good manufacturing practice inspection and testing of samples shall be borne by the manufacturer of the medicinal product in accordance with the State Agency of medicines to the public provided by the paid service price list.
38. the State Agency of medicines on the basis of this provision, paragraph 36 of that report, in the month following the completion of the inspection shall take a decision on the issue of the certificate: 38.1. If examination of compliance with the established principles and guidelines of good manufacturing practice;
38.2. the temporary suspension of issue of the certificate, stating the reasons and the time frame in which to take the necessary measures. In determining this period should take into account that the final good manufacturing practices certificate issued shall not exceed 90 days from the provision referred to in paragraph 32 of the inspection;
38.3. the refusal to issue a certificate.
39. the State Agency of medicines shall adopt the decision on the refusal to issue a certificate, if the control report has found that: 39.1. production of medicines of the medicines in question at the place of production does not meet the rules set out in those accession the principles and guidelines of good manufacturing practice;
24.4. pharmaceutical company is not qualified;
39.3. the obligations made by the qualified person person whose qualifications and experience does not meet the requirements laid down in these provisions.
40. the State Agency of medicines shall, not later than five days after the adoption of the decision in writing notify the manufacturer of the medicinal product.
41. the State Agency of medicines: drug company issued a 41.1. good manufacturing practice compliance certificate (annex 2). This certificate shall be issued after the manufacturer of the medicinal product in accordance with the State Agency of medicines to the public provided by the paid list price is paid for the issue of the certificate;
41.2. If adopted this rule 38.3. referred to in decision, inform the Commission of the pharmaceutical activities of licensing, which according to the laws and regulations on special permit (license) the pharmaceutical activities, and the cancellation of the suspension arrangements shall take a decision on the special permission (license) for the manufacture of the medicinal product suspension to control report that issue;
41.3. electronically transmitted by the European Medicines Agency this rule 41.1. the certificate referred to in paragraph for inclusion in the database of the European Union;
25.7. the European Medicines Agency this rule 38.3. referred to information on the refusal to issue a certificate of admission to the European Union's database.
Vi. The Pharmacy made quality control of medicines In chapter 42. medicinal products set out in the quality control requirements apply to medicinal products prepared in a pharmacy in accordance with the recipe (the magistral formula) or the hospital's written request (the officinal formula).
43. Pharmacy Manager is responsible for the quality of medicines produced in pharmacies. Make and take control of the quality of these products must not be the same person.
44. The Pharmacy manufactured drugs is mandatory for the following controls: 44.1. According to this provision, paragraph 61 and 64 (presentation of the results in writing);
44.2. in accordance with the provisions of paragraph 66 and 67.-mineral medicinal product uniformity, mass, color, taste and smell, as well as the solution to determine the mechanical impurities (hereinafter organoleptic control);
27.5. According to this provision, 74, 75 and 76. point – the issue of drugs.
45. The Pharmacy manufactured medicinal products, if required (based on the instructions of the head of the pharmacy), out: 45.1. physical control, in accordance with the provisions of paragraph 68 and 69;
45.2. chemical control, in accordance with this provision, 71 and 72 70;
45.3. the control of the survey in accordance with this paragraph 73.
46. in order to carry out the quality control of medicinal products manufactured in the pharmacy is a specially equipped work space with analytical devices to be used in the work, hardware and equipment. Pharmacy Manager, taking into account the nature of the work of the pharmacy, analytical work in developing the necessary equipment, hardware and equipment list. This list is used in this provision of the annex 3. List into line with the State Agency of medicines.
47. The pharmacy manager pharmacy approved to use the concentrate and semi-finished stock list.
48. The pharmacy manager, on the persons whom the pharmacy perform the following duties: 48.1. the person who checks the purchased raw materials, as well as these rules 53, 54, 55, 56, 57, 58 and 59. the obligations laid down in paragraph 1;
48.2. the person who takes recipes and receive your medicines (hereinafter referred to as the receptār), as well as take that rule 61, 64, 74, 75, 76 and 77.. the obligations laid down in points;
48.3. the person who manufactures the medication and make that rule 62 and 63. the obligations laid down in paragraph 1;
30.1. the person who tested the drugs and take this rule 66, 67, 68, 69, 70, 71 and 72 point.
49. The Pharmacy uses measurement features that are calibrated and verified according to the regulations issued in accordance with the law "on a uniformity of measurements".
50. Pharmacy control results are recorded in a journal concerned (annex 4).
51. Before the first entry of this provision in paragraph 50 the journal page number, log cauršuj and approved by the Pharmacy and the pharmacy manager's signature. After the last recording in the journal pharmacy stores in one year.
52. the annual report on the quality control of medicinal products in pharmacies (annex 5) pharmacy medicine State Agency shall be submitted to the next February 1.
53. The Pharmacy Manager provides the raw materials intended for the manufacture of medicinal products, making control of the pharmacy. Control includes the following measures: 53.1. the quality of the raw materials of formal verification of validity;
53.2. packaging and marking the tightness check;
53.3. organoleptic control (if possible).
54. If in doubt or suspicion, pharmacy raw materials samples sent to the National Agency for medicines full chemical analysis. To question the final clarification of this raw material is placed in a quarantine area. If the analysis is the discovery of non-compliance with the quality requirements, the State Agency of medicines shall also notify the national pharmaceutical inspection.
55. the raw material stores according to the substance of the storage requirements laid down.
56. On the stāvtrauk, which stores materials, place the label indicating the name of the raw material, the production serial number, expiration date and the date of filling. If you store stāvtrauk these rules referred to in annex 6, strong exposure to substances on the label mentioned in this annex also indicates the highest one-time and daily. Stāvtrauk-the label says the name of the person, the name and signature of the iepildīj inputs. On the stāvtrauk for the source materials used for the manufacture of sterile medicinal forms are "Sterilaj-dosage forms".
57. Liquids stored in stāvtrauko, which is equipped with a calibrated pipettes in the ERS or pilināt that indicate a specific fluid drops per millilitre.
58. Stāvtrauk-refill only after the previous content of the use and handling of the container as instructed.
59. The population collected herbs in check after a drog pharmacy external signs, determining their identity, takes samples, and provides the following checks: 59.1. microscopic examination to determine their identity;
59.2. heavy metals (lead, cadmium);
59.3. qualitative and quantitative analysis (if necessary).
60. The Pharmacy all the recipes, which are made of grass, the recorded prescription log that are designed according to the provisions of annex 7. The medical authorities of the registration of the request constitutes a separate journal. Pharmacy prescription is stored in the log, and medical authorities request log on the current and previous year.
61. Receptār performs the following actions: 61.1. check type consistency prescription prescriptions composition;
61.2. testing recipes design compliance with laws and regulations that govern the prescription;
38.1. check the expiry date of the prescription;
61.4. check the recipe specified these rules referred to in annex 6, strong action single and daily compliance with the age of the patient;
61.5. checks in accordance with the laws and regulations that determine the prescription, do not exceed the specific quantity of the substance that can write to one of the recipes if prescriptions consists of ethyl alcohol, narcotic drugs and psychotropic substances recognized as mentioned in Latvia allowed the illicit manufacture of narcotic drugs and psychotropic substances and precursors in list II, and psychotropic substances referred to in Latvia allowed the illicit manufacture of narcotic drugs and psychotropic substances and precursors (iii) list;
61.6. assess composition of prescriptions from the chemical and physical compatibility point of view, to verify the effectiveness of medicines and mixing made fun & safety.
38.3. the calculation of the price of medicinal products;
38.4. the prescription filled in logs, issue receipt and completed the customer orally inform the customer about a time when you can get a finished product, indicating how long they should be removed;
Add the recipe to 61.9. receipt number and the recipe served for the manufacture of medicinal products.
62. A Person who manufactures the product, follow the instructions and recipes for the time to be made.
63. at the time of the manufacture of medicinal products or immediately after manufacture of the medicinal product, if you do not want the previous calculations, the person who made the grass fills the control token, indicating that the information referred to in annex 8.
64. a Person who manufactures the product, fill the control voucher along with the manufactured and tested products and recipe (request) served receptār. Receptār: 64.1. compare data and recipe control talon (request);
64.2. testing the correctness of calculations;
64.3. verify compliance with the packaging of the medicinal products constituting the components of the physical and chemical properties;
64.4. ensure that medicines produced and tested until the issue of the patient or medical authority would be stored according to their physical and chemical properties.
65. Control pharmacy store vouchers, three months after the filing. To control the pass is the persons who made the drug that made packaged medicines (if the product were iepakojus by a person other than the person that made), that tested the drug, as well as the signature of receptār. Control voucher shall also indicate the number of the analysis of the medicinal product.
66. the oral medicines for children checked each taste products and medicinal products for adults – random.
67. in order to determine the mechanical impurities ophthalmological solutions, performs organoleptic control, subject to the following requirements: 67.1. controls shall be carried out by filtering and draining the solution directly in the package;
67.2. controls shall be carried out in a dedicated work space, protected from the direct sunlight and equipped with a device for the detection of mechanical impurities solutions. It is acceptable to use a black and white screen that illuminated so that the light is shining eyes ruler;
67.3. controls shall be carried out with the solution by looking in the filled the unit against the white and black background that illuminated by Matt watt electric bulb 60 or 20 Watt fluorescent lamp. Colorful solutions uses 100 Watts and accordingly 30-watt bulb. The distance from the eyes to the transparent object must be between 25 to 30 cm, but the angle between the optical axis see-through and light direction should be approximately 90 °.
41.9. controlling the Visual acuity is 1.0 (if necessary, adjust it with optical devices);
67.5. transparent surface of the unit is clean and dry;
67.6. packing unit in the control area, inverted and screened against a black and white background. Then, without making sudden moves, it turns to its original state and once again screened against a black and white background;
67.7. If mechanical impurities, the solution found to repeatedly filter and control.
68. The physical checks shall be carried out at random, taking into account all types of medicines manufactured. Take physical control, check the total mass of the medicinal product or the volume of the individual dozējam unit weight and quantity, respecting the permissible deviations according to annex 9 of these regulations.
69. the concentration of the solution can be calculated using a formula that uses the refractometric termination factor.
70. in order to determine the drug substances constituting identity (qualitative analysis) and quantitative (quantitative analysis), chemical control.
71. Qualitative analysis: 71.1. purified water obtained from the pharmacy. Analysis is conducted every day, taking water from each container, or, if you use the pipeline, each place of examination of calcium, magnesium, hlorīdjon, and sulfātjon presence according to the requirements of the European Pharmacopoeia. The solution provided for newborns and eye drop preparation for water reducētājviel and also check for the presence of ammonium ions. Quarterly purified water pharmacy sends the State Agency of medicines of the full chemical analysis;
71.2. raw materials for the manufacture of the medicinal product by getting the room. The rules referred to in annex 6, strong exposure to substances, if in doubt or suspicion, receive a pharmacy.
72. the qualitative and quantitative analysis: 72.1. eye drops and eye ointment containing narcotic substances, tetrakaīn hydrochloride (dikaīn) or atropine sulphate;
72.2. medicines for newborns up to the age of one month;
72.3. hydrochloric acid solution for oral use, atropine sulphate, mercury dichloride and silver nitrate solution;
72.4. all concentrates and semi-finished products, including triturācij;
72.5. If the solution of ethyl alcohol diluted in determining the concentration of pharmacies in% vol with spirtometr or with a hydrometer or by density hydrometers, or using a pycnometer Pharmacopoeia table (if required-receive a pharmacy too);
72.6 at random all. manufactured medicinal products, with particular emphasis on medicines for children.
73. Random and if in doubt, the pharmacy may take the survey. The person who conducted the survey, called the first test after the constituents of the medicinal product, as the person who made the Hall, called all the ingredients and take it.
74. the issue of pharmacy medicines produced in the patient or medical authority, carry out the control.
75. the issue of drugs, receptār checks: 75.1. the receipt and label the information compliance with prescription (request);
75.2. recipes (demand) and the time of preparation of the medicinal product;
75.3. medicine labelling compliance with legislation on the labelling of medicinal products.
76. the issue of drugs, receptār to subscribe to recipes, indicating the date of issue of the medicinal product, and fills a prescription log.
77. the issue of drugs, receptār reminds the customer as medication use, indicating that the drug should not be used longer than the specified time, the doctor and the medicine recommends that you follow the expiration date and the storage conditions.
VII. monitoring and penalties prescribed in these provisions 78. pharmaceutical supervision requirements provide the State Agency of medicines, making this the rule referred to in paragraph 32 inspection (inspection). State Pharmacy Inspectorate monitored the pharmacy made the drug quality control requirements.
79. Member States of the European Union, European economic area, the European Commission or the European Medicines Agency at the request of the State Agency of medicines shall authorise the officials that provision referred to in paragraph 32 for carrying out checks at the companies located in third countries.
80. the State Agency of medicines shall examine whether the skilled person's qualifications comply with the requirements laid down in these rules, and shall be entitled to propose a manufacturer of medicinal products at the time suspended or be removed from Office by a qualified person if it does not comply with the provisions of paragraphs 10 and 11 of these duties.
81. the State Agency of medicines has the right to send the rule 36, paragraph control report national pharmaceutical inspection for a decision on the suspension of the manufacture of medicinal products, if found during the inspection and the inspection report indicated that: 81.1. production in facilities other than those referred to in the application for a special permit (license) for the manufacture of medicinal products;
81.2. produced medicinal product or form, other than those referred to in the application for a special permit (license) for the manufacture of medicinal products;
81.3. drug company does not ensure that the requirements laid down in point 8;
81.4. qualified person not carrying out this provision in paragraph 10 and 11 obligations;
81.5. drug company control does not produce this provision set out in paragraph 34 the data and documentation.
82. following these rules referred to in paragraph 81 of the national agency of Drug Control report, the national pharmaceutical inspection shall take a decision on the suspension of the activities of the enterprise in accordance with the law "About companies, institutions and organisations of the suspension of the order".
83. If the suspension of the manufacture of medicinal products is associated with offences surrounding the illicit manufacture of narcotic drugs and psychotropic substances and precursors in the use in the manufacture of medicinal products laid down by law "for the illicit manufacture of narcotic drugs and psychotropic substances and to the legitimate movement of medicinal products order" and "law on precursors", as well as the European Parliament and of the Council of 11 February 2004, by Regulation (EC) No 273/2004 on drug precursors, Council on 22 December 2004, Regulation (EC) No 111/2005 laying down rules for the supervision of trade in drug precursors between the community and third countries and the Commission of 27 July 2005, Regulation (EC) No 1277/2005 on the implementation of the provisions of European Parliament and Council Regulation (EC) No 273/2004 on drug precursors and for Council Regulation (EC) No 111/2005 laying down rules for the trade in drug precursors between the community and third countries supervision National pharmaceutical inspection, notify law enforcement authorities.
84. national pharmaceutical inspection not less frequently than quarterly inspections pharmacies that have been authorised for the manufacture of medicinal products in pharmacies.
85. If there is reasonable suspicion or doubt, national pharmaceutical inspection is entitled to get from the pharmacy, produced for purified water, used for the manufacture of medicinal products and semi-finished products, samples of concentrate and send them to the laboratory investigation, including microbiological testing. Testing costs controlled in accordance with the State Agency of medicines to the public provided by the paid service price list.
86. Taking samples of medicinal products quality control, national pharmaceutical inspection official shall draw up a sampling of legislation consistent with the laws that determine the order in which the market surveillance authorities shall require and receive product samples. Sampling, in addition to the Act specifies the following information: 86.1. a prescription or medical authority number;
86.3. the title, name and surname, which manufactured medicines;
86.4. it the person's title, first name and last name that tested medicines.
87. national pharmaceutical inspection passes the State Agency of medicines samples for inspection when you act on the transfer of expertise, in accordance with the regulations, arrangements for market surveillance authorities to request and receive product samples.
88. the State Agency of medicines shall carry out inspection of samples of a medicinal product submitted to organoleptic testing, physical testing and chemical testing, full qualitative and quantitative analysis.
89. the results of the control state agency of medicines shall prepare and submit to the national pharmaceutical inspection inspection findings, the test reports in accordance with the regulations, arrangements for market surveillance authorities to request and receive product samples.
90. A pharmacy after the State Agency of medicines shall provide any request of information related to the manufacture of medicinal products, quality control and documentation.
91. If the testing is found in pharmacies for medicinal products manufactured quality does not correspond to the approved technical standards documentation (such as Pharmacopoeia, technical regulations) requirements, the national pharmaceutical inspectorate shall inform in writing the pharmacy. Pharmacy manager identifies the quality of medicinal causes of non-compliance and implement measures to avoid and prevent such contraventions. The measures taken to the pharmacy manager shall inform the national pharmaceutical inspection. If the quality of the product is affected by the raw material quality, not a pharmacy manager shall ensure that withdrawn from these raw materials the pharmacy made medicine.
92. time of year again When irregularities are found which may affect the quality of the product produced, the national pharmaceutical inspectorate shall inform the Licensing Commission of the pharmaceutical activities.
93. the State Agency of medicines and the national pharmaceutical inspection according to the competency provides operational exchange of information to facilitate implementation of these provisions, as well as provide law enforcement institutions and the Ministry of information on the Health conditions of the diversion of illegal medicinal products.
94. The Ministry of health, State Agency of medicines, national pharmaceutical inspection and other institutions disclose information related to the drug manufacturer's trade secret and become known to them by ensuring compliance with these rules.
VIII. Closing questions 95. Be declared unenforceable: 95.1. Cabinet of Ministers of 12 December 2000, the provisions of no. 432 "production and control of medicinal products" (Latvian journal, 2000, 454./457.nr.; 2003, 114 no);
95.2. Cabinet of Ministers of 11 September 2001 Regulation No 396 "good manufacturing practice for medicinal products and for conformity assessment of good manufacturing practice certificate procedure of manufacturing companies" (Latvian journal, 2001, nr. 131, no. 167; 2003).
96. A Person filled with obligations by the qualified person before December 16, 2000, but whose qualifications and professional experience do not meet the requirements laid down in these provisions, shall be empowered to continue fulfilling the obligations referred to in the European Union and European economic area countries. With an investigational medicinal product related area such a person is entitled to continue their duties by the qualified person in the Republic of Latvia.
97. If a person has a diploma, certificate or other evidence of formal qualifications granted before December 16, 2000, finally University programs or course learning what Latvia recognized as equivalent to that referred to in paragraph 13, it can be performed by the qualified person if she is at least two years of work experience in one or more of the pharmaceutical companies, which have a special permit (license) for the manufacture of medicinal products, in the field that is awash with binding production monitoring, active substances on the qualitative and quantitative analysis, as well as the quality of the finished product for the required inspection by the qualified person of direct authority. If the person concerned, practical work experience more than 10 years, but the last two years she has been employed in medicine production monitoring, quality control of qualified persons direct authority, she must work for at least one year under the supervision of medicine production, quality control of qualified persons direct authority to obtain the right to work as a qualified person.
98. with regard to herbal medicines corresponding to traditional herbal medicinal products, the criteria established in the registration of the medicinal product, and which is on the market this provision enters into force, this provision must be introduced to 20 May 2011.
99. This provision is referred to in paragraph 5 of the special permission (license) for the manufacture of medicinal products/import, but no longer than up to 31 December 2006 the provisions referred to in point 6 of manufacturing activity are entitled to make merchants, which to this date of entry into force of the provisions have been issued a special permit (license) for the following pharmaceutical activities: 99.1. pharmaceutical company to open the (operation);
99.2. production of medicines in pharmacies;
99.3. for the production of medicinal products (repackaging and rewrapping) drug lieltirgotav.
100. the provisions shall enter into force by 1 July 2006.
Informative reference to European Union directives, the regulations include provisions resulting from: 1) of the European Parliament and of the Council of 4 April 2001, Directive 2001/20/EC on the approximation of the laws, regulations and administrative provisions of the Member States relating to the implementation of good clinical practice in the conduct of clinical trials on medicinal products for human use;
2) of the European Parliament and of the Council of 6 November 2001, Directive 2001/83/EC on the Community code relating to medicinal products for human use;
3) Commission of 8 October 2003 Directive 2003/94/EC laying down the principles of good manufacturing practice and the base of the stādn relating to medicinal products for human use and investigational medicinal products for human use (text with EEA relevance);
4) of the European Parliament and of the Council of 31 March 2004, Directive 2004/24/EC amending, as regards traditional herbal medicinal products, Directive 2001/83/EC on the Community code relating to medicinal products for human use;
5) of the European Parliament and of the Council of 31 March 2004, Directive 2004/27/EC amending Directive 2001/83/EC on the Community code relating to medicinal products for human use;
6) Commission of 8 April 2005 of Directive 2005/28/EC laying down the good clinical practice principles and detailed guidelines on investigational medicinal products for human use, as well as the requirements for authorisation of the manufacturing or importation of such products (text with EEA relevance).
Prime Minister a. Halloween Health Minister g. Smith Editorial Note: regulations shall enter into force by 1 July 2006.
Annex 1-9 ZIP 115 kb
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