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LEGAL ACTS OF THE REPUBLIC OF LATVIA
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The translation of this document is outdated.
Translation validity: 09.08.2008.–14.10.2013.
Amendments not included: 08.10.2013., 11.08.2015., 25.09.2018., 15.01.2019., 04.03.2021., 07.12.2021.
Text consolidated by Valsts valodas centrs (State Language Centre) with amending regulations of:

20 February 2007 [shall come into force on 24 February 2007];
4 August 2008 [shall come into force on 9 August 2008].

If a whole or part of a paragraph has been amended, the date of the amending regulation appears in square brackets at the end of the paragraph. If a whole paragraph or sub-paragraph has been deleted, the date of the deletion appears in square brackets beside the deleted paragraph or sub-paragraph.


Republic of Latvia

Cabinet
Regulation No. 304
Adopted 18 April 2006

Regulations Regarding the Procedures for the Manufacture and Control of Medicinal Products, the Requirements for the Qualification and Professional Experience of a Qualified Person and the Procedures for the Issuance of the Certificate of Good Manufacturing Practice to a Medicinal Products Manufacturing Undertaking

Issued pursuant to
Section 5, Clauses 3 and 13 and Section 52
of the Pharmaceutical Law

I. General Provisions

1. These Regulations prescribe the procedures for the manufacture and control of medicinal products, the requirements for the qualification and professional experience of a qualified person and the procedures for the issuance of the certificate of good manufacturing practice to a medicinal products manufacturing undertaking.

2. These Regulations apply to:

2.1. medicinal products for human use manufactured industrially or prepared using a method, which includes an industrial process;

2.2. medicinal products manufactured in the Republic of Latvia and intended only for export to the states other than the Member States of the European Union or the states of the European Free Trade Association (EFTA) and which have signed the European Economic Area agreement (hereinafter - European Economic Area states);

2.3. intermediate products,

2.4. homeopathic medicinal products;

2.5. herbal medicinal products, which comply with the criteria for traditional herbal medicinal products specified in regulations regarding the registration of medicinal products;

2.6. the manufacture of investigational medicinal products; and

2.7. the quality control of medicinal products prepared in a pharmacy.

3. These Regulations do not apply to:

3.1. radionuclides (radioactive isotopes) in the form of sealed radiation sources; and

3.2. whole blood, plasma or blood cells of human origin, except for industrially prepared plasma.

4. For the purpose of these Regulations:

4.1. an active substance is a substance or a mixture of substances intended for use in the manufacture of a medicinal product and which in such case becomes an active ingredient of the certain medicinal product;

4.2. dividing up is the dividing of finished medicinal products into a certain amount of units;

4.3. a finished product is a medicinal product to which all the stages of manufacture are applicable, including packaging in its final container;

4.4. packaging is any operation for turning a bulk product into a finished product, also filling and labelling;

4.5. a starting material is any substance used for the manufacture of medicinal products, except for the packaging material;

4.6. qualification is an operation by which it is confirmed and documented that any equipment used for the manufacture of medicinal products is appropriately installed, operates correctly and ensures the expected results. Qualification is a part of validation, but the performance of qualification of separate stages does not mean the process validation;

4.7. good manufacturing practice is a part of the quality assurance system, which ensures that medicinal products are consistently produced and controlled in accordance with the quality requirements appropriate to their intended use;

4.8. a batch is a defijned quantity of a homogenous (with specified tolerances) medicinal product or intermediate product that is obtained in a separate manufacturing process or in several processes. In case of continuous manufacture, a batch may be a certain part of an amount manufactured. A batch size is a certain specified amount or amounts manufactured during a specified period of time;

4.9. specification is a detailed description of the requirements for the products and materials used or obtained in the manufacturing process;

4.10. an intermediate product is a partly processed material, also a starting material, which is subject to the further manufacturing steps (stages) of a medicinal product before it becomes a bulk product; and

4.11. validation is a documented programme the implementation of which allows to affirm with great certainty that a certain process, method or system used in the manufacture or control of a medicinal product, works constantly, ensuring the results which comply with the previously specified criteria.

[4 August 2008]

II. Requirements for the Manufacture of Medicinal Products

5. Medicinal products, including investigational medicinal products, may be manufactured in a specified form of the medicinal products if a merchant has received the special permit (licence) (hereinafter - the special permit (licence) for the manufacture of medicinal products) issued by the State Agency of Medicines in accordance with the Pharmaceutical Law, these Regulations and regulatory enactments which determine the procedures for the issuing, suspension, re-registration and revocation of the special permit (licence) for pharmaceutical operation.

6. The special permit (licence) for the manufacture of medicinal products is required for the performance of both total and partial manufacturing process, as well as for different dividing up, packaging and presentation processes of a finished product.

7. The special permit (licence) for the manufacture of medicinal products shall not be required for a pharmacy in which a pharmacist prepares and divides up, as well as changes the packaging or presentation of medicinal products intended for individual patients on prescription by a medical practitioner (formula magistralis) or on a written request by a medical institution, or for medicinal products, which are manufactured according to the pharmacopoeia monographs and which are intended for distribution to the patients served by the relevant pharmacy (formula officinalis)

8. A person, which is involved in operations for the performance of which the special permit (licence) for the manufacture of medicinal products is required (hereinafter - a medicinal product manufacturer) shall ensure the fulfilment of the following requirements:

8.1. personnel with adequate qualifications are engaged in the manufacture and control of the medicinal products and such personnel ensure the compliance with the requirements for the manufacture and control in accordance with these Regulations;

8.2. disposes of the registered medicinal products and investigational medicinal products in accordance with the principles of good distribution practice specified in the regulatory enactments regarding the distribution of medicinal products;

8.3. immediately (but not later than within 5 working days) notifies the State Agency of Medicines in writing regarding the change of the responsible official referred to in Section 52 of the Pharmaceutical Law (hereinafter - a qualified person);

8.4. ensures a possibility for the officials of the State Agency of Medicines to visit all the premises of the medicinal product manufacturer;

8.5. ensures a possibility for a qualified person to fulfil the duties referred to in Paragraphs 10 and 11 of these Regulations, for example, by placing at his or her disposal all the necessary facilities;

8.6. complies with the principles and guidelines of good manufacturing practice and as starting materials uses only such active substances, which are manufactured in accordance with the guidelines of good manufacturing practice for active substances. The manufacture of active substances includes both total and partial manufacture or import of active substances, as well as different types of dividing up, packaging and presentation operations, which are performed before the inclusion thereof in the composition of the medicinal products, including re-packaging or re-labelling performed by the distributor of the starting materials;

8.7. manufacturing operations are performed in accordance with the conditions of the special permit (licence) for the manufacture of medicinal products; and

8.8. medicinal products, for which the registration certificate is required, are manufactured in accordance with the data and documents submitted for the registration of the medicinal products. In respect of investigational medicinal products ensures that all manufacturing operations are performed in accordance with the information, which the sponsor has indicated in the submission for the clinical trial of medicinal products permit. The manufacturing methods to be used, taking into account the scientific and technical progress and development of investigational medicinal products, shall be reviewed on a regular basis.

[4 August 2008]

9. A medicinal product manufacturer shall ensure that at least one qualified person, the education and practical experience of which complies with the qualification and professional requirements specified in Chapter III of these Regulations and which is mainly responsible for the fulfilment of the duties referred to in Paragraphs 10 and 11 of these Regulations, is at his or her disposal permanently and continuously. If the medicinal product manufacturer complies with the conditions referred to in Paragraph 13 of these Regulations, he or she himself or herself may take responsibility and fulfil the duties of a qualified person.

10. A qualified person, without prejudice to his or her relationship with the medicinal product manufacturer, shall be responsible for the compliance of the manufacture and control of each batch of the medicinal product with the requirements of these Regulations and with the methods indicated in the registration documentation of the medicinal product. If investigational medicinal products are manufactured, a qualified person shall be responsible for the compliance of the manufacture and verification of each batch of the medicinal products with the principles and guidelines of good manufacturing practice, the documents and information of the product specification that the sponsor has indicated in the submission to the State Agency of Medicines for the receipt of the permit for clinical trials.

11. A qualified person shall in all cases (especially, if the medicinal products are released for sale) certify the finished product, making accurate entries in the register or another equivalent document intended for such purpose and attesting with his or her signature that each batch of the medicinal product is manufactured and controlled in accordance with the requirements referred to in Paragraph 10 of these Regulations. After the specified operations the register or the relevant document shall be supplemented, and retained in the undertaking for at least 5 years since the last entry made, ensuring the accessibility to the referred to register or document for the officials of the State Agency of Medicines.

12. The requirements specified in the Law On Procedures for the Legal Trade of Narcotic and Psychotropic Substances and Medicinal Products, in the Law on Precursors and in the relevant regulatory enactments which determine the requirements for the use of narcotic and psychotropic substances and medicinal products, as well as precursors, in medicinal products manufacturing undertakings, shall be observed in the manufacture of narcotic and psychotropic medicinal products.

III. Qualification and Professional Experience Requirements for a Qualified Person

13. A qualified person shall meet the following qualification and professional experience requirements:

13.1. a qualified person shall possess a diploma, certificate or other evidence of the qualification awarded upon completion of the study programme of an institution of higher education (university), or completion of such programme which in accordance with the procedures specified in regulatory enactments is recognised as equal to the university study programme in Latvia and which includes at least four years of theoretical and practical studies in one of the following scientific disciplines: pharmacy, medicine, veterinary medicine, chemistry, pharmaceutical chemistry and technology, biology. The minimum duration of studies may be three and a half years if followed by the theoretical and practical studies of at least one year that include the training of at least six months in a general-type pharmacy, and at the end of which an examination is taken in conformity with the requirements specified in the university study programme;

13.2. the study programme referred to in Sub-paragraph 13.1 of these Regulations shall include the theoretical and practical studies in which at least the following study courses are acquired:

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 the analysis of medicinal products;

13.2.6. general and medical biochemistry;

13.2.7. physiology;

13.2.8. microbiology;

13.2.9. pharmacology;

13.2.10. pharmaceutical technology;

13.2.11. toxicology; and

13.2.12. pharmacognosy (the study of the composition of the active substances of plant and animal origin and the effects of the active substances); and

13.3. at least two years practical experience in one or several undertakings, which have the special permit (licence) for the manufacture of medicinal products in such areas as the qualitative analysis of medicinal products, the quantitative analysis of active substances, as well as testing and inspecting that are necessary to ensure the quality of medicinal products. The practical experience may be reduced by one year if the duration of studies at a university is at least 5 years, and by a year and a half if the duration of studies is at least 6 years.

14. Studies of the study courses referred to in Sub-paragraph 13.2 of these Regulations shall be in such proportion as to enable the relevant person to fulfil the obligations specified in Paragraphs 10 and 11 of these Regulations.

[4 August 2008]

15. If diplomas, certificates or other official evidences of the qualification do not conform to the criteria specified in Sub-paragraph 13.1 of these Regulations, the State Agency of Medicines shall request that the relevant person submits the certification issued by the institution of higher education regarding the completion of the study courses referred to in Sub-paragraph 13.2 of these Regulations.

IV. Principles and Guidelines of Good Manufacturing Practice

16. A medicinal products manufacturer shall develop and implement the quality assurance system, which includes a set of organisational measures, in order to ensure that the medicinal products or investigational medicinal products comply with such quality which is required for their intended use. The quality assurance system shall guarantee, that:

16.1. medicinal products are designed and developed in accordance with the requirements of good manufacturing practice and good laboratory practice;

16.2. manufacturing and control operations are clearly specified and comply with good manufacturing practice;

16.3. management responsiblities are clearly specified;

16.4. the arrangements for the manufacture, delivery and use of proper starting materials and packaging materials are made;

16.5. all the necessary inspections of intermediate products and all inspections and validations of the process are performed;

16.6. the finished products shall be processed and inspected properly in accordance with the specified procedure;

16.7. medicinal products are sold or supplied only after a qualified person has verified that all the batches of the medicinal products are manufactured and inspected in accordance with the registration certificate and other provisions which apply to the manufacture, control and release of medicinal products;

16.8. there is an arrangement that medicinal products in so far as it is possible are stored, distributed and handled in such a way as to maintain the quality of the medicinal products during all the time period of storage; and

16.9. the self-inspection system or the quality control procedure is developed in accordance with which the efficacy and applicability of the quality assurance system is assessed regularly.

17. A manufacturer of medicinal products shall ensure the compliance with the following requirements in respect of the personnel:

17.1. a sufficient number of employees with the required qualification and practical experience are at the manufacturer's disposal in each manufacturing and control site, in order to ensure the appropriate quality for the intended use of the medicinal products;

17.2. the duties of the managing and administrative personnel are specified in the job description. The principal personnel, which are responsible for the application and functioning of good manufacturing practice, are a qualified person, the head of the manufacturing unit and the head of the quality control unit. The hierarchical relationships of the personnel shall be determined in the organisation chart of the undertaking. The structure chart and job descriptions shall be approved in accordance with the internal procedures specified by the medicinal products manufacturer;

17.3. the personnel referred to in Sub-paragraph 17.2 of these Regulations shall be given certain authority for the performance of their duties;

17.4. the personnel shall be ensured with the initial and ongoing training (regularly evaluating the practical effectiveness thereof), which includes theory and application of the concepts of quality assurance and good manufacturing practice, as well as, if necessary, certain requirements for the manufacture of investigational medicinal products; and

17.5. shall develop and observe the hygiene programmes adjusted for the operations to be performed, especially emphasising the requirements, which apply to the health, personal hygiene and clothing of the personnel.

18. Premises and equipment shall, in addition to the construction requirements specified in regulatory enactments, comply with the following requirements:

18.1. premises and manufacturing equipment shall be located, designed, constructed, adapted and maintained to suit the intended operations;

18.2. premises and manufacturing equipment shall be laid out, designed and operated in such a way as to minimise the risk of error and to permit effective cleaning and maintenance in order to avoid contamination, cross contamination of medicinal products and starting materials (contamination of a material or a finished product with another material or product) and any adverse effect on the quality of the product; and

18.3. premises and equipment to be used for manufacturing operations shall be subjected to appropriate qualification and validation.

19. A medicinal product manufacturer shall develop and maintain a documentation system, which includes the specifications, manufacturing formulae, instructions for processing and packaging, instructions for the performance of certain operations directly or indirectly connected with the manufacture of medicinal products, descriptions of precautionary and other measures (hereinafter - procedures) and reports, which apply to various manufacturing operations performed. The documents referred to shall be clear, free from error and kept up to date. Pre-established procedures, as well as a set of specific documents, which reflect the course of the manufacturing process and quality control process of a batch (hereinafter - batch records), shall be accessible. That set of documents shall enable the traceability of the history of the manufacture of each batch, the changes introduced during the development of an investigational medicinal product, information regarding the distribution of a batch, as well as other important circumstances, which affect the quality of the finished product (hereinafter - batch documentation).

20. For a medicinal product, the batch documentation shall be retained for at least 1 year after the expiry date of the batch to which it relates or for at least 5 years after the certification of the finished product referred to in Paragraph 11 of these Regulations, whichever is the longer period.

21. For an investigational medicinal product, the batch documentation shall be retained for at least 5 years after the completion or formal discontinuation of the last clinical trial in which the batch was used. The sponsor or registration certificate holder (owner), if different, shall be responsible for ensuring that the batch records are retained, which are required for the subsequent registration in accordance with the regulatory enactments regarding the registration of medicinal products.

22. When electronic, photographic or other data processing systems are used instead of written documents, the medicinal product manufacturer shall first validate the systems by showing that the data will be stored during the anticipated period of storage. Data stored by those systems shall be made readily available in legible form and shall be provided to the State Agency of Medicines upon request. The electronically stored data shall be protected, by methods such as duplication or back-up and transfer on to another storage system, against loss or damage of data, and audit trails shall be maintained.

23. The manufacturing process of medicinal products shall comply with the following requirements:

23.1. production operations shall be carried out in accordance with pre-established instructions, procedures and with the requirements of good manufacturing practice

23.2. sufficient resources required shall be made available for the in-process control;

23.3. all process deviations and product defects shall be documented and thoroughly investigated;

23.4. appropriate technical or organisational measures shall be taken to avoid cross contamination and mix-ups of medicinal products and starting materials. In the case of investigational medicinal products, particular attention shall be paid to the handling of products during and after a blinding operation (the deliberate disguising of the identity of an investigational medicinal product in accordance with the instructions of the sponsor);

23.5. any new manufacture process or important modification of a manufacturing process shall be validated. The critical phases of manufacturing processes shall be regularly re-validated; and

23.6. for investigational medicinal products, the manufacturing process shall be validated in its entirety in so far as is appropriate, taking into account the stage of the product development. At least the critical process steps, such as sterilisation, shall be validated. All steps in the design and development of the manufacturing process shall be fully documented.

24. The quality control shall meet the following requirements:

24.1. a medicinal product manufacturer shall establish and maintain a quality control unit placed under the authority of a person who has the requisite qualification (specified in the job description) and is independent of production;

24.2. the head of the unit shall have at his or her disposal one or more quality control laboratories appropriately staffed and equipped to carry out the necessary examination of the starting materials, packaging materials and intermediate and finished products;

24.3. for the quality control of medicinal products, contract laboratories may be used if the conditions referred to in Paragraph 27 of these Regulations have been fulfilled;

24.4. for investigational medicinal products, the sponsor shall ensure that the contract laboratory complies with the requirements specified in the submission (submitted to the State Agency of medicines for the receipt of the permit for commencement of a clinical trial on the medicinal product);

24.5. during the final control of the finished product before its release for sale or distribution or for use in clinical trials, the quality control unit shall take into account, in addition to the analytical results, other essential information such as the manufacturing conditions, the results of the in-process controls, the examination of the manufacturing documents and the conformity of the finished product to its specifications and packaging;

24.6. samples of each batch of a finished medicinal product shall be retained for at least 1 year after the expiry date;

24.7. for an investigational medicinal product, sufficient samples of each batch of bulk formulated product and of key immediate packaging components used for each finished product batch shall be retained for at least 2 years after the completion or formal discontinuation of the last clinical trial in which the batch was used, whichever period is the longer;

24.8. samples of starting materials, other than solvents, gases or water, used in the manufacturing process shall be retained for at least 2 years after the release of the product. The storage period of the samples may be shortened if the period of stability of the material, as indicated in the relevant specification, is shorter;

24.9. the State Agency of Medicines shall be notified of the storage place of medicinal products and starting materials, and its officials shall be provided with a possibility to visit the relevant premises at any time; and

24.10. if medicinal products are manufactured for an individual order or in small quantities, or if the storage of the samples of medicinal products and starting materials is difficult because of their properties, other sampling and storing conditions may be specified upon agreement with the State Agency of Medicines.

25. If any manufacturing operation or operation linked thereto or quality control is carried out by another person (hereinafter - a contract acceptor), the medicinal product manufacturer and contract acceptor shall enter into a written contract regarding the performance of certain work. The contract shall clearly define the responsibilities of each party and shall define, in particular, the observance of principles and guidelines of good manufacturing practice to be followed by the contract acceptor and the manner in which the qualified person responsible for certifying each batch is to discharge his or her responsibilities.

26. A contract acceptor shall ensure the fulfilment of the following requirements:

26.1. shall not subcontract any of the work entrusted to him or her under the contract referred to in Paragraph 25 of these Regulations without a written permission from the medicinal product manufacturer;

26.2. a contract acceptor, who performs a part of the manufacturing operations under the contract on behalf of the initial manufacturer, may be only the medicinal product manufacturer, who has the special permit (licence) for the manufacture of medicinal products; and

26.3. shall comply with the principles and guidelines of good manufacturing practice, as well as submit to the inspections carried out by the State Agency of Medicines.

27. Prior to entering into an agreement regarding the performance of the quality control, a medicinal product manufacturer shall ensure that the officials of the State Agency of Medicines carry out the inspection and provide a statement of conformity regarding the compliance of the laboratory with the requirements of good manufacturing practice.

28. A medicinal product manufacturer shall (if investigational medicinal products are being produced - in co-operation with the sponsor) ensure the fulfilment of the following requirements in respect of complaints, recalling of the medicinal products and disclosure of the identity of the blinded investigational products (hereinafter - unblinding):

28.1. implement a system for recording and reviewing complaints received regarding the medicinal products together with an effective operation of such system on the basis of which the medicinal products, which have already entered the distribution network, may be recalled promptly and at any time. The medicinal product manufacturer shall record and investigate any complaint concerning a defect. The medicinal product manufacturer shall inform the State Agency of Medicines within 24 hours after the detection of the fact of any defect or complaint that could result in a recall or abnormal restriction on supply, and, in so far as it is possible, indicate also the countries of destination;

28.2. any recall of medicinal products shall be made in accordance with the requirements specified in the regulatory enactments regarding the distribution of medicinal products;

28.3. in co-operation with the sponsor implement the system for recording and reviewing complaints regarding the investigational medicinal products together with an effective operation of such system on the basis of which the medicinal products, which have already entered the distribution network, may be recalled promptly and at any time. The investigational medicinal products manufacturer shall record and investigate any complaint concerning defects of the medicinal products and shall inform the State Agency of Medicines of any defect that could result in a recall or abnormal restriction on supply of the medicinal products;

28.4. all trial sites related to the investigational medicinal products shall be identified and, in so far as it is possible, the countries of destination shall be indicated;

28.5. in respect of the investigational medicinal products, which have been registered, the manufacturer of the investigational medicinal product shall, in co-operation with the sponsor, inform the registration certificate holder (owner) of any defect that could be related to the registered medicinal product; and

28.6. the sponsor shall implement a procedure for the rapid unblinding of the investigational medicinal products, where this is necessary for a prompt recall in accordance with Sub-paragraph 28.3 of these Regulations. The sponsor shall ensure that the unblinding discloses the identity of the investigational medicinal products only in so far as it is necessary.

29. A medicinal product manufacturer shall conduct repeated self-inspections in order to supervise the implementation of and compliance with good manufacturing practice, as well as in order to propose any necessary corrective measures. Such self-inspections and any corrective actions subsequently taken shall be documented and the records shall be kept for at least 5 years.

30. For the interpretation of the principles and guidelines of good manufacturing practice referred to in this Chapter, as well as of the principles of good manufacturing practice for active substances, a medicinal product manufacturer shall take into account the detailed guidelines of the European Commission regarding good manufacturing practice of medicinal products and investigational medicinal products (hereinafter - the guidelines of the European Commission), published by the European Commission in the Volume 4 of the collection of Rules Governing Medicinal Products in the European Union and which have been published on the Internet home page of the State Agency of Medicines (www.zva.gov.lv).

31.A medicinal product manufacturer manufacturing medicinal products derived from human blood and plasma shall:

31.1. ensure that the manufacturing and purifying processes used in the manufacture of the medicinal products derived from human blood or human plasma are properly validated, in order to attain batch-to-batch consistency, and guarantee protection from contamination with specific viruses (hepatitis B surface antigen (HBs Ag), HIV 1 and HIV 2 antibodies (anti-HIV ½) hepatitis C virus antibody (anti-HCV));

31.2. notify the State Agency of Medicines of the methods used to reduce or eliminate pathogenic viruses liable to be transmitted by such medicinal products; and

31.3. use such statrting materials (human blood and plasma) for the manufacture of these medicinal products, received from such blood preparation institutions, where the collection, testing, processing, storage and distribution of human blood and blood components is carried out in accordance with the regulatory enactments regarding the quality and safety standards for collection, testing, processing, storage and distribution of the human blood and blood components and which are subjected to control of the Health Statistics and Medicinal Technologies State Agency. The place of obtaining human blood and plasma intended for manufacturing of medicinal products derived from human blood shall be subject to the control of the State Agency of Medicines.

[4 August 2008]

V. Procedures for the Issuance of the Good Manufacturing Practice Certificate

32. In order to ensure that a medicinal product manufacturer observes the good manufacturing practice principles and guidelines specified in these Regulations, the State Agency of Medicines shall:

32.1. after the issuance of the special permit (licence) for the manufacture of medicinal products perform the repeated inspections of good manufacturing practice at least once in 3 years. The State Agency of Medicines shall agree with the manufacturer of medicinal products regarding the time period when the inspection is to be started and notify thereof in writing not later than 10 working days prior to the inspection;

32.2. if necessary, perform unannounced inspections, and in the relevant case the samples shall be tested in the laboratory of the State Agency of Medicines or in a laboratory, which has the right to test medicinal products;

32.3. if there are substantiated suspicions regarding the non-compliance with the principles and guidelines of good manufacturing practice, be entitled to perform inspections, which have not been notified, in the premises of the manufacturer of substances used as starting materials or in the premises of the registration certificate holder. Such inspections may also be performed upon the request of another Member State of the European Union or European Economic Area State, the European Commission or European Medicines Agency; and

32.4. be entitled to perform an inspection of the manufacturer of starting materials, on the basis of an application by the manufacturer itself, if the manufacturer is registered in the Republic of Latvia.

[4 August 2008]

33. The State Agency of Medicines shall authorise competent officials for the performance of the inspection referred to in Paragraph 32 of these Regulations, which have been trained to perform the control and supervision of the observance of the requirements of good manufacturing practice and who have the following right:

33.1. to inspection medicinal products or substances used as starting materials manufacturing undertakings and all the laboratories which are used by the manufacturer of the medicinal products in order to determine whether the medicinal products are manufactured and controlled in accordance with good manufacturing practice and the manufacturing and control methods indicated in the documents submitted for the registration of the medicinal products. The referred to shall also apply to the inspection of contract acceptors, who have entered into the agreement referred to in Paragraph 25 of these Regulations with a medicinal product manufacturer regarding the performance of separate manufacturing stages or the quality control;

33.2. to take samples, also to perform the independent testing in the laboratory of the State Agency of Medicines or in another laboratory, which is entitled to perform the quality control of medicinal products. Expenses connected with the testing of medicinal products shall be covered by the person controlled in accordance with the public services pay rates provided by the State Agency of Medicinal Products;

33.3. to examine all the documentation of the object to be inspectioned, taking into account the restrictions in respect of the description of the manufacturing method; and

33.4. to inspection that the manufacturing processes used in the manufacture of immunological products (vaccines, toxins, allergenic products) are properly validated and attain batch-to-batch consistency.

34. A medicinal product manufacturer shall provide to the officials of the State Agency of Medicines the following data during the control:

34.1. information regarding the control of the finished medicinal products and control of the ingredients and control carried out at the intermediate stages of the manufacturing process in accordance with the documentation of the registration of the medicinal products; and

34.2. regarding the immunological products and medicinal products obtained from human blood and plasma - copies of the certificates of all the finished products issued by the qualified person.

35. The authorised officials of the State Agency of Medicines during the inspections of medicinal products manufacturing undertakings shall take into account the Compilation of Coomunity Procedures on Inspections and Exchange of Information published on behalf of the Eureopean Commission. In order to interpret the principles and guidelines of good manufacturing practice, also the principles of good manufacturing practice for active substances, the guidelines of the European Commission shall be taken into account.

36. The authorised officials of the State Agency of Medicines shall prepare the control report in accordance with the sample form indicated in Annex 1 to these Regulations within 10 working days after the inspection referred to in Paragraph 32 of these Regulations. One copy of the report shall be sent to the medicinal product manufacturer, where the inspection had been carried out, the other copy, if necessary, to the institution, which requested the performance of the inspection. If the manufacturer of investigational medicinal products is inspectioned, one copy of the control report shall be sent also to the sponsor, ensuring the observance of confidentiality. The State Agency of Medicines may make available the control report of the medicinal product manufacturer to other Member States, the Ethics Committee or the European Medicines Agency upon the justified request thereof.

37. Expenses related to the inspection of good manufacturing practice of a medicinal product manufacturing undertaking and the sample testing shall be covered by the medicinal product manufacturer in accordance with the public services pay rates provided by the State Agency of Medicinal Products.

38. The State Agency of Medicines shall, on the basis of the report referred to in Paragraph 36 of these Regulations, take the relevant decision within a month after the completion of the control:

38.1. regarding the issuance of the certificate, if the compliance with the principles and guidelines of good manufacturing practice has been determined during the inspection;

38.2. regarding the posponement of the issuance of the certificate, indicating the reasons and time period during which the necessary measures shall be carried out. In determining the period of time it shall be taken into account that the final time period for the issuance of the certificate of good manufacturing practice may not exceed 90 days after the carrying out the inspection referred to in Paragraph 32 of these Regulations; and

38.3. regarding the refusal to issue the certificate.

39. The State Agency of Medicines shall take a decision regarding the refusal to issue a certificate, if it is determined in the control report, that:

39.1. the manufacture of medicinal products at a certain manufacturing site does not comply with the principles and guidelines of good manufacturing practice specified in these Regulations;

39.2. there are no qualified person at the medicinal products manufacturing undertaking; and

39.3. the duties of a qualified person are carried out by a person, whose qualification and experience does not comply with the requirements specified in these Regulations.

40. The State Agency of Medicines shall not later than within 5 days after taking of the relevant decision to notify in writing the medicinal product manufacturer thereof.

41. The State Agency of Medicines shall:

41.1. issue the certificate of compliance with good manufacturing practice of the medicinal product manufacturer (Annex 2). The referred to certificate shall be issued after the medicinal product manufacturer has paid the fee specified regarding the issuance of the certificate in accordance with the public services pay rates provided by the State Agency of Medicines. If the good manufacturing practice conformity assessment is associated with travel, the medicinal product manufacturer shall cover the travel (transport) expenses of the official of the State Agency of Medicines to the undertaking and return, expenditures for the hotel (lodging), health insurance expenses and daily subsistence allowance in conformity with regulatory enactments regarding the procedures by which expenditures associated with official travel and employee work travel shall be compensated;

41.2. if the decision referred to in Sub-paragraph 38.3 of these Regulations has been taken, the Pharmaceutical Activity Licensing Commission shall be notified which in accordance with the regulatory enactments regarding the procedures for the issuance, suspension and revocation of the special permit for pharmaceutical activity takes a decision regarding the suspension of the operation of the special permit (licence) for the manufacture of medicinal products up to the rectification of deficiencies referred to in the control report;

41.3. electronically send the certificate referred to in Sub-paragraph 41.1 of these Regulations to the European Medicines Agency for the inclusion thereof in the database of the European Union; and

41.4. send the information referred to in Sub-paragraph 38.3 of these Regulations to the European Medicines Agency regarding the refusal to issue the certificate for the inclusion thereof in the database of the European Union.

[20 February 2007]

VI. Quality Control of Medicinal Products Prepared in a Pharmacy

42. The quality control requirements specified in this Chapter shall apply to medicinal products prepared in a pharmacy in accordance with a prescription (formula magistralis) or a written request of a medical treatment institution (formula officinalis).

43. The head of a pharmacy shall be liable for the quality of medicinal products prepared in the pharmacy. The same person may not prepare medicinal products and carry out the quality control of these medicinal products.

44. The following control shall be mandatory for medicinal products prepared in a pharmacy:

44.1. in accordance with Paragraphs 61 and 64 of these Regulations (by documenting the results in writing);

44.2. in accordance with Paragraphs 66 and 67 of these Regulations - the inspection of the aggregative state, uniformity of mass, colour, taste and odour of the medicinal products, as well as the inspection of solutions in order to specify particulate matter (hereinafter - the organoleptic control); and

44.3. in accordance with Paragraphs 74, 75 and 76 of these Regulations - when dispensing medicinal products.

45. For medicinal products prepared in a pharmacy, if necessary (on the basis of instructions of the head of the pharmacy), shall perform:

45.1. the physical control - in accordance with Paragraphs 68 and 69 of these Regulations;

45.2. the chemical control - in accordance with Paragraphs 70, 71 and 72 of these Regulations; and

45.3. the questioning control - in accordance with Paragraph 73 of these Regulations.

46. In order to perform the quality control of the medicinal products prepared, a specially equipped workplace with devices, apparatus and equipment used in analytical work shall be present in a pharmacy. The head of a pharmacy, taking into account the nature of the pharmacy work, shall develop the list of devices, apparatus and equipment required for the analytical work. In drawing up this list Annex 3 to these Regulations shall be used. The list shall be co-ordinated with the State Agency of Medicines.

47. The head of a pharmacy shall approve the list of the concentrates and semi-finished products nomenclature used in the pharmacy.

48. The head of a pharmacy shall approve the list of those persons that perform the following duties:

48.1. a person who inspects the starting materials purchased, as well as performs the duties specified in Paragraphs 53, 54, 55, 56, 57, 58 and 59 of these Regulations;

48.2. a person who accepts prescriptions and dispenses medicinal products (hereinafter - a dispensing chemist), as well as performs the duties specified in Paragraphs 61, 64, 74, 75, 76 and 77 of these Regulations;

48.3. a person who prepares medicinal products and performs the duties specified in Paragraphs 62 and 63 of these Regulations; and

48.4. a person who tests medicinal products and performs the duties specified in Paragraphs 66, 67, 68, 69, 70, 71 and 72 of these Regulations.

49. The measuring instruments calibrated and verified in accordance with the regulatory enactments issued pursuant to the Law on Uniformity of Measurements shall be used in a pharmacy.

50. The results of the control performed in a pharmacy shall be registered in the relevant register (Annex 4).

51. Before making the first entry in the register referred to in Paragraph 50 of these Regulations, the pages shall be numbered, the logbook shall be sewn through and approved with the seal of the pharmacy and the signature of the head of the pharmacy. The register shall be kept in the pharmacy for a year after making the last entry.

52. A pharmacy shall submit the annual report regarding the quality control of medicinal products in the pharmacy (Annex 5) to the State Agency of Medicines by 1 February of the next year.

53. The head of a pharmacy shall ensure incoming control of starting materials intended for the preparation of medicinal products in the pharmacy. The control shall include the following measures:

53.1. the inspection of the existence of the documents attesting to the quality of the starting materials;

53.2. the inspection of the leakproofness and labelling of the packaging; and

53.3. the organoleptic control (if possible).

54. If there are any doubts or suspicions, a pharmacy shall send the samples of starting materials to the State Agency of Medicines for the performance of the full chemical analysis. These starting materials shall be placed in the quarantine zone up to the final ascertaining of the matter. If in performing the analysis non-compliance with the quality requirements has been determined, the State Agency of Medicines shall notify thereof also the Health Inspectorate.

[4 August 2008]

55. Starting materials shall be stored in accordance with the storage requirements specified for the relevant substance.

56. On flat-bottomed vessels, in which starting materials are stored, a labelling shall be placed indicating the name, manufacturing batch number, expiry date and filling date of the starting materials. If the highly potent substances referred to in Annex 6 of these Regulations are being stored in a flat-bottomed vessel, the maximum single and daily doses referred to in this Annex shall be indicated on the labelling. The given name, surname and signature of that person, who has filled in the starting materials, shall be indicated on the labelling of the flat-bottomed vessel. the indication "Sterilajām zāļu formām" [For sterile pharmaceutical forms] shall be on the flat-bottomed vessels intended for starting materials, which are used for the preparation of sterile pharmaceutical forms.

57. Liquids shall be kept in the flat-bottomed vessels equipped with calibrated droppers or pipettes on which the number of drops of a certain liquid per one millilitre is indicated.

58. A flat-bottomed vessel shall be refilled only after the utilisation of the previous content thereof and the treatment of a container in accordance with the instruction.

59. Crude herbal medicinal plants collected by inhabitants shall be inspected in a pharmacy by the external features, specifying their identity, the samples shall be taken and the following inspections shall be ensured:

59.1. the microscopic inspection in order to specify the identity thereof;

59.2. the determination of heavy metals (lead, cadmium); and

59.3. the qualitative and quantitative analysis (if necessary).

60. All prescriptions by which medicinal products are prepared shall be registered in a pharmacy in the prescription register, which is drawn up in accordance with Annex 7 of these Regulations. For the registration of requests of medical treatment institutions a separate register shall be created. The prescription registers and registers of requests of medical treatment institutions shall be stored in the pharmacy for the current and previous year.

61. A dispensing chemist shall carry out the following operations:

61.1. inspect the compliance of the prescription type with the content of the medicinal product prescribed;

61.2. inspect the compliance of the drawing up of the prescription with the regulatory enactments determining the procedures for drawing up prescriptions;

61.3. inspect the term of validity of the prescription;

61.4. inspect the compliance of the single and daily doses of the powerfully acting substances referred to in Annex 6 of these Regulations, which are specified on the prescription, with the patient's age;

61.5. inspect whether in accordance with the regulatory enactments determining the procedures for drawing up prescriptions the amount of a certain substance is not exceeded, which is allowed to be prescribed on one prescription, if the composition of the prescribed medicinal product includes ethyl alcohol, narcotic and equivalent psychotropic substances referred to on the list II of narcotic and psychotropic substances and precursors permitted in Latvia, and psychotropic substances referred to on the list III of narcotic and psychotropic substances and precursors permitted in Latvia;

61.6. assess the composition of the prescribed medicinal products from the point of view of the chemical and psychical compatibility in order to ascertain that the medicinal products to be prepared are effective and safe;

61.7. calculate the price of the medicinal products;

61.8. fill in the prescription register, issue a completed receipt to the customer and inform the customer orally regarding the time, when he or she may receive the finished medicinal product, indicating the time up to which the medicinal product shall be taken out; and

61.9. attach the receipt number to the prescription and hand over the prescription for the preparation of the medicinal product.

62. A person, who prepares medicinal products, shall observe the instructions on the prescription and the time up to which the medicinal products are to be prepared.

63. During the preparation of medicinal products or immediately after the preparation of medicinal products, if it is not necessary to make calculations previously, the person, who prepares the medicinal products, shall fill in a control counterfoil in which the information referred to in Annex 8 to these Regulations shall be indicated.

64. The person, who prepares medicinal products, shall hand over a completed control counterfoil together with the prepared and inspected medicinal products and the prescription (request) to a dispensing chemist. A dispensing chemist shall:

64.1. compare the data on the control counterfoil and the prescription (request);

64.2. inspect the correctness of the calculations made;

64.3. inspect the suitability of the packaging of the medicinal products with the physical and chemical features of the ingredients included in the composition of the medicinal products; and

64.4. ensure that the prepared and inspected medicinal products are stored in accordance with their physical and chemical features up to the dispensing to the patient or medical treatment institution.

65. Control counterfoils shall be kept in a pharmacy for 3 months after completing thereof. The signatures of those persons, who have prepared the medicinal product, who have packed the medicinal product (if the medicinal product has been packed by a person other than the person who has prepared it) and who has inspected the medicinal product, as well as the signature of the dispensing chemist shall be on the control counterfoil. The analysis number of the medicinal product shall also be indicated on the control counterfoil.

66. For medicinal products to be used orally, which are intended for children, the taste shall be inspected for each preparation, but for medicinal products, which are intended for adults - randomly.

67. In order to specify particulate matter in ophthalmological solutions, the organoleptic control shall be carried out taking into account the following requirements:

67.1. the control shall be carried out after the filtration of the solution and filling in the direct packaging;

67.2. the control shall be performed in a specially arranged workplace, which is protected against the direct sun light and equipped with a device for the determination of mechanical impurities in solutions. It is allowed to use the white and black display which is illuminated in such a way that the light does not shine into the eyes of a controller;

67.3. the control shall be carried out by screening the packaging units filled with a solution against the white and black background, which is illuminated with a 60 watts mat bulb or a 20 watts fluorescent light bulb. For coloured solutions 100 watts and 30 watts bulbs shall be used respectively. The distance from the eyes to the screening object shall be from 25 to 30 cm, but the angle between the optical axis of screening and the light direction shall be around 900;

67.4. the visual acuity of the controller shall be 1.0 (if necessary it shall be corrected with optical devices);

67.5. the surface of the packaging unit to be screened shall be clean and dry;

67.6. the packaging unit shall be placed in the control area, turned upside down and screened against the black and white background. Then, avoiding sharp motions, it shall be turned back to the initial state and screened again against the black and white background; and

67.7. if mechanical impurities are detected, the solution shall be filtered and controlled again.

68. The physical control shall be carried out randomly taking into account all the types of the medicinal products prepared. In performing the physical control, the total weight and volume of the medicinal products, the weight and volume of the separate dosage units shall be inspected taking into account the permissible deviations in accordance with Annex 9 to these Regulations.

69. The concentration of a solution may be calculated using the formula in which the refractive index determined with a refractometer is used.

70. In order to determine the identity of the substances included in the composition of medicinal products (the qualitative analysis) and the amount thereof (the quantitative analysis), the chemical control shall be performed.

71. The qualitative analysis shall be carried out for:

71.1. the purified water obtained in a pharmacy. The analysis shall be performed once a day prior to preparation of medicinal products, taking the water from each container, or if a pipeline is used, at each workplace, inspecting the presence of calcium, magnesium, chloride ions and sulphate ions in accordance with the requirements of the European Pharmacopoeia. The presence of oxidisable substances and ammonium ions shall be also inspected in the water intended for the preparation of solutions and eye drops for newborn children. Once in a half year a pharmacy shall send the purified water to the State Agency of Medicines for carrying out the full chemical analysis; and

71.2. the starting materials upon the receipt thereof at the premises of the preparation. For the highly potent substances referred to in Annex 6 of these Regulations, if any doubts or suspicions have arisen - also upon the receipt in a pharmacy.

[4 August 2008]

72. The qualitative and quantitative analysis shall be performed for:

72.1. the eye drops and eye ointments containing narcotic substances, tetracaine hydrochloride (dicaine) or atropine sulphate;

72.2. the medicinal products intended for newborn children up to the age of 1 month;

72.3. the hydrochloric acid solution for internal use, atropine sulphate, mercury dichloride and silver nitrate solutions;

72.4. all concentrates and semi-finished products, including triturations;

72.5. the ethyl alcohol solution, if it is diluted in a pharmacy, determining the concentration in percentage by volume with an alcoholmeter or by density with an aerometer or a hydrometer, or a pycnometer, using the pharmacopoeia tables, if necessary - also upon the receipt in a pharmacy); and

72.6. all types of the prepared medicinal products randomly, paying special attention to the medicinal products intended for children.

73. The questioning control may be performed in a pharmacy randomly and in the case of doubts. A person who carries out the questioning control shall call the first ingredient of the medicinal product to be inspected, then the person, who has prepared the medicinal product, shall call all the ingredients taken and the amounts thereof.

74. When dispensing medicinal products prepared in a pharmacy to a patient or medical treatment institution, the control thereof shall be performed.

75. When dispensing medicinal products a dispensing chemist shall inspect the following:

75.1. the compliance of the information indicated on the receipt and the labelling with the prescription (request);

75.2. the time of submission of the prescription (request) and the time of the preparation of the medicinal product; and

75.3. the compliance of the labelling of the medicinal products with the regulatory enactments regarding the labelling of medicinal products.

76. When dispensing medicinal products a dispensing chemist shall sign on the prescription, indicating the date of dispensing of the medicinal products, and shall fill in the prescription register.

77. When dispensing medicinal products to a customer, a dispensing chemist shall remind how the medicinal products are to be used by indicating that the medicinal products may not be used for a longer period of time than is specified by the doctor, and recommend to observe the expiry date of the medicinal products and the storage indications.

VII. Supervision and Sanctions

78. The supervision of the requirements for the manufacture of medicinal products specified in these Regulations shall be ensured by the State Agency of Medicines, carrying out the inspections referred to in Paragraph 32 of these Regulations. The Health Inspectorate shall supervise the observance of the requirements for the quality control of medicinal products prepared in a pharmacy.

[4 August 2008]

79. Upon the request of the Member States of the European Union, the European Economic Area states, the European Commission or the European Medicines Agency, the State Agency of Medicines shall authorise officials for carrying out the inspections referred to in Paragraph 32 of these Regulations at the medicinal product manufacturer who is located in the third countries.

80. The State Agency of Medicines shall inspection whether the qualification of a qualified person meets the requirements set out in these Regulations, as well as is entitled to propose that the medicinal product manufacturer carries out a temporary suspension or dismissal from office of the qualified person if he or she fails to perform the duties referred to in Paragraphs 10 and 11 of these Regulations.

81. The State Agency of Medicines is entitled to send the control report referred to in Paragraph 36 of these Regulations to the Health Inspectorate for taking a decision regarding the suspension of the manufacture of medicinal products, if during the inspection it has been determined and in the control report it is indicated that:

81.1. the manufacturing is carried out in premises not referred to in the submission for the receipt of the special permit (licence) for the manufacture of medicinal products;

81.2. the manufacture of such medicinal products or dosage forms is being performed, which have not been referred to in the submission for the receipt of the special permit (licence) for the manufacture of medicinal products;

81.3. the medicinal product manufacturer does not ensure the compliance with the requirements specified in Paragraph 8 of these Regulations;

81.4. the qualified person does not perform the duties specified in Paragraphs 10 and 11 of these Regulations; and

81.5. the manufacturer of medicinal products does not present the data and documentation specified in Paragraph 34 of these Regulations.

[4 August 2008]

82. After the receipt of the control report of the State Agency of Medicines referred to in Paragraph 81 of these Regulations, the Health Inspectorate shall take a decision regarding the suspension of the production of medicinal products in accordance with the Pharmaceutical Law.

[4 August 2008]

83. If the suspension of the manufacture of medicinal products is connected with the violations regarding the utilisation of narcotic and psychotropic substances and precursors in the manufacture of medicinal products specified in the Law On Procedures for the Legal Trade of Narcotic and Psychotropic Substances and Medicinal Products and in the Law On Precursors, as well as in the Regulation (EC) No. 273/2004 of the European Parliament and of the Council of 11 February 2004 on drug precursors, Council Regulation (EC) No. 111/2005 of 22 December 2004 laying down rules for the monitoring of trade between the Community and third countries in drug precursors, Commission Regulation (EC) No. 1277/2005 of 27 July 2005 laying down implementing rules for Regulation (EC) No. 273/2004 of the European Parliament and of the Council on drug precursors and for Council Regulation (EC) No. 111/2005 laying down rules for the monitoring of trade between the Community and third countries in drug precursors, the Health Inspectorate shall notify the law enforcement institutions thereof.

[4 August 2008]

84. The Health Inspectorate shall at least once a year carry out the inspections in pharmacies owning a specific permit (a licence) for opening (operation) of a general-type pharmacy or for opening (operation) of a closed-type pharmacy with a condition of specific operation - preparation of medicinal products.

[4 August 2008]

85. If there are substantiated suspicions or doubts, the Health Inspectorate is entitled to take samples of the medicinal products prepared, the purified water obtained, the concentrates and semi-finished products to be used for the preparation of medicinal products in a pharmacy and send them to the laboratory for the examination, including the microbiological testing. Expenses of the testing shall be covered by the person controlled in accordance with the public services pay rates provided by the State Agency of Medicines.

[4 August 2008]

86. When taking samples of medicinal products for the quality control, the official of the Health Inspectorate shall draw up the sampling record in accordance with the regulatory enactments, which determine the procedures by which the market supervision institutions shall request and take samples of products. The document on the sampling shall contain the following additional information:

86.1. the number of the prescription or the request of the medical treatment institution;

86.2. the composition of the medicinal product;

86.3. the position, given name and surname of the person, who has prepared the medicinal product; and

86.4. the position, given name and surname of the person, who has inspected the medicinal product.

[4 August 2008]

87. The Health Inspectorate shall hand over the samples to the State Agency of Medicines for carrying out the expert-examination by drawing up the document regarding the handing over of the samples for the expert-examination in accordance with the regulatory enactments regarding the procedures, by which the market supervision institutions shall request and receive samples of products.

[4 August 2008]

88. The State Agency of Medicines shall carry out the organoleptic testing, physical testing and full chemical testing - the qualitative and quantitative analysis - of the samples of the medicinal products submitted for the expert-examination.

89. The State Agency of Medicines shall prepare and submit the opinion of the expert-examination regarding the control results - the testing report - to the Health Inspectorate in accordance with the regulatory enactments regarding the procedures by which the market supervision institutions shall request and receive samples of products.

[4 August 2008]

90. A pharmacy shall, upon the request of the State Agency of Medicines, provide any information connected with the preparation, quality control and documentation of the medicinal products.

91. If it is determined during the testing of samples that the quality of the medicinal products prepared in a pharmacy does not comply with the requirements specified in the documentation of the technical norms (for example, in the pharmacopoeia, technical rules), the Health Inspectorate shall notify the pharmacy thereof in writing in a time period of three days. The head of the pharmacy shall identify the reasons for non-compliance of the quality of the medicinal products and implement measures in order to prevent and not to allow such violations in future, as well as shall, within a time period of one month, notify in writing the Health Inspectorate regarding the measures performed. If the quality of the medicinal products has been affected by inappropriate quality of the starting materials, the head of pharmacy shall ensure that the medicinal products prepared from these starting materials shall be withdrawn.

[4 August 2008]

92. If violations, which may affect the quality of the medicinal products prepared, are determined repeatedly within a year, the Health Inspectorate shall notify the Pharmaceutical Activity Licensing Commission.

[4 August 2008]

93. The State Agency of Medicines and the Health Inspectorate shall ensure, according to their competence, the prompt information exchange for the promotion of the enforcement of these Regulations, and shall provide law enforcement institutions and the Ministry of Health with information regarding the circumstances that are the evidence of the deviation of medicinal products to illegal circulation.

[4 August 2008]

94. The Ministry of Health, the State Agency of Medicines, the Health Inspectorate and other authorities shall not disclose information related to the commercial secret of a medicinal product manufacturer and which information has become known to the authorities in the course of enforcing these Regulations.

[4 August 2008]

VIII. Closing Provisions

95. The following regulations are repealed:

95.1. Cabinet Regulation No. 432 of 12 December 2000, Regulations Regarding the Manufacture and Control of Medicinal Products (Latvijas Vēstnesis, 2000, No. 454/457; 2003, No. 114); and

95.2. Cabinet Regulation No. 396 of 11 September 2001, Procedures for Issue of Medicinal Product Good Manufacturing Practice Conformity Assessments and Medicinal Product Good Manufacturing Practice Certificates to Medicinal Product Manufacturing Undertakings (Latvijas Vēstnesis, 2001, No. 131; 2003, No. 167).

96. A person who fulfilled the duties of a qualified person up to 16 December 2000, but whose qualification and professional experience do not conform to the requirements referred to in these Regulations has the right to continue the fulfilment of the referred to duties in the European Union and in the European Economic Area States. In the field connected with investigational medicinal products such person has the right to continue the performance of the duties of a qualified person in the Republic of Latvia.

97. If a person has a diploma, a certificate or another attestation regarding the qualification granted prior to 16 December 2000 upon the completion of a programme or study course at an institution of higher education, recognised in Latvia as being equivalent to what is referred to in Paragraph 13 of these Regulations, such person may perform the duties of a qualified person if he or she has at least 2 years experience in one or more medicinal product manufacturing undertakings that have the special permit (licence) for the manufacture of medicinal products, in a field related to the supervision of the manufacture of medicinal products, the qualitative and quantitative analysis of active substances, as well as to the performance of inspections required for the quality assurance of finished medicinal products under direct control of a qualified person. If the practical work experience of the relevant person exceeds 10 years but during the last 2 years he or she has not been employed in the supervision of manufacturing - in the medicinal product quality control under direct supervision of a qualified person, such person shall work for at least 1 year in the supervision of manufacturing - in the medicinal product quality control under the direct supervision of a qualified person in order to obtain the right to work as a qualified person.

[4 August 2008]

98. In respect of herbal medicinal products, which comply with the traditional herbal medicinal product criteria, which have been specified in the regulations regarding the registration of medicinal products and which are on the market on the day of coming into force of these Regulations, the requirements of these Regulations shall be implemented up to 20 May 2011.

99. Up to the receipt of the special permit (licence) referred to in Paragraph 5 of these Regulations for the manufacture/importation of medicinal products, but no longer than up to 31 December 2006, merchants, to whom the special permit (licence) has been issued for the following types of pharmaceutical operations on the day of coming into force of these Regulations, are entitled to perform the manufacturing operations of medicinal products referred to in Paragraph 6 of these Regulations:

99.1. the opening (operation) of a medicinal product manufacturing undertaking;

99.2. the manufacture of medicinal products in a pharmacy; and

99.3. the manufacture (re-packaging and re-dividing up) of medicinal products at a medicinal product wholesaler.

100. These Regulations shall come into force on 1 July 2006.

Informative Reference to European Union Directives

These Regulations contain legal norms arising from:

1) Directive 2001/20/EC of the European Parliament and of the Council of 4 April 2001 on the approximation of the laws, regulations and administrative provisions of the Member States relating to the implementation of good clinical practice in the conduct of clinical trials on medicinal products for human use;

2) Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal products for human use;

3) Commission Directive 2003/94/EC of 8 October 2003 laying down the principles and guidelines of good manufacturing practice in respect of medicinal products for human use and investigational medicinal products for human use (Text with EEA relevance)

4) Directive 2004/24/EC of the European Parliament and of the Council of 31 March 2004 amending, as regards traditional herbal medicinal products, Directive 2001/83/EC on the Community code relating to medicinal products for human use;

5) Directive 2004/27/EC of the European Parliament and of the Council of 31 March 2004 amending Directive 2001/83/EC on the Community code relating to medicinal products for human use;

6) Commission Directive 2005/28/EC of 8 April 2005 laying down principles and detailed guidelines for good clinical practice as regards 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); and

7) Directive 2002/98/EC of the European Parliament and of the Council of 27 January 2003 setting standards of quality and safety for the collection, testing, processing, storage and distribution of human blood and blood components and amending Directive 2001/83/EC

[4 August 2008]

Prime Minister A. Kalvītis

Minister for Health G. Bērziņš

 

Annex 1
Cabinet Regulation No. 304
18 April 2006

Inspection Report of Good Manufacturing Practice

European Union Standard Form

Report Reference no.:
Inspected site(-s) Name and full address of the inspected site
Manufacturing activities carried out: Manufacture of active substances  
Manufacture of finished products  
Manufacture of intermediate products or bulk products  
Packaging (only)  
Importation  
Testing in a laboratory  
Batch control and batch release  
Storage and distribution  
Investigational medicinal products  
Other _____________________________________  
Inspection date(-s) Date(-s), month, year
Inspector (-s) Given name, surname of the inspector(-s)
Given name, surname of the expert (assessor) (if applicable)
Name of the competent inspection authority
References Medicinal product registration number (authorisation) and/or the number of the special permit (licence) for the manufacture of medicinal products

Reference number(-s) of the European Medicines Agency (if the inspection is an inspection of the European Medicines Agency)

Introductory section Short description of the undertaking and the operation of the undertaking
If the inspection is performed in a state other than the European Economic Area state, it shall be indicated, whether the competent authority of that state in which the inspection is carried out, is notified regarding the inspection and whether this competent authority has participated in the inspection
Date of the previous inspection
Given name(-s), surname(-s) of the inspector(-s) who participated in the previous inspection
Most important (greatest) changes since the previous inspection
Brief report of the inspection activities undertaken  

Scope of the inspection Short description of the inspection (the inspection of the product, the inspection of the process and/or the general inspection of good manufacturing practice. Indicate the reason for the inspection, for example, a new application for the registration of medicinal products, routine inspection, the investigation of the defect of the product
Inspected area(-s) Indicate each area inspected
Activities not inspected If necessary, indicate the areas or operations, which were not inspected
Personnel met during the inspection Indicate the key personnel encountered (the given name, surname, position). (The list shall be attached to the annex to the report)
Observations of the inspectors and detected deficiencies Relevant headings from The Rules Governing Medicinal Products in the European Community, Good Manufacturing Practice for Medicinal Products Vol. IV. (Guide to GMP, Basic Requirements, relevant for scope of inspection).

This section may be linked with the section on deficiencies discovered in order to explain the classification thereof.

The detail in the narrative of this section of the report may be reduced where a Site Master File acceptable to the reporting authority has been submitted to the Competent Authority.

Chapter headings

(Relevant new headings of chapters may be introduced)

Overview of inspection findings from last inspection and the corrective action taken
Quality management
Personnel
Premises and equipment
Documentation
Production
Quality control
Contract manufacturing and Analysis
Complaints record and recall of production
Self-inspection
Distribution and shipment For example, compliance with good distribution practice
Questions which apply to the assessment of the application for the registration of medicinal products For example, a inspection before the registration (authorisation) of medicinal products
Other specific matters identified For example, important changes in future announced by the undertaking
Site Master File Evaluation of the Site Master File, if any. Data of the Site Master File
Miscellaneous information

(Samples taken)

 
Annexes attached List of the annexes attached
Deficiencies (critical, major and other) Indicate all the deficiencies and provide the relevant reference to the guidelines of the European Commission regarding good manufacturing practice of medicinal products and investigational medicinal products and other relevant recommendations of the European Union.

Indicate all the deficiencies, which have been discovered also in such case, if corrective operations have been carried out immediately.

If the deficiencies apply to the assessment of the application for the registration of medicinal products, it shall be clearly specified.

Ask the undertaking to notify a competent authority regarding the corrective operations, as well as offer the period of time for the performance of these operations

Recommendations For the authority upon the request of which the inspection is carried out or the competent control authority of the state, in which the undertaking inspected is located
Summary and conclusions Inspector(-s) shall indicate, whether the undertaking is operating in the inspected field in accordance with the rules for good manufacturing practice of the European Union, if necessary, indicate that the relevant corrective operations have been carried out, as well as other conditions in order to notify the authority, which requested the inspection. Reference may be made to the conclusions, which have been made in other documents, for example, in the accompanying letter to the inspection report, depending on the national procedures.
Given name, surname

Signature(-s)

Authority(-ies)

Date

Distribution of the report

The inspection report shall be signed and dated by the inspector(-s)/observer(-s) who participated in the inspection

Notes.

1. Critical deficiencies - the deficiencies due to which a product harmful to human and animal health has been produced or there is a significant risk to produce such product, or a product, which leaves harmful residual substances in animal bodies from which food products of animal origin are obtained.

2. Major deficiencies (non-critical deficiencies) are the deficiencies:

2.1. due to which a product non-complying with the registration (authorisation) documentation has been produced or such product may be produced;

2.2. which indicate great deviations from the requirements of good manufacturing practice of the European Union;

2.3. which indicate great deviations from the terms in the special permit (licence) for the manufacture of medicinal products (within the European Union);

2.4. which indicate that satisfactory procedures are not carried out for the batch release and (within the European Union) a qualified person fails to fulfil the duties thereof; and

2.5. the combination of several other deficiencies, where each individual deficiency is not important, but it becomes a major deficiency in the combination thereof.

3. Other deficiencies - the deficiencies which have not been classified as critical or major, but which indicate a departure from the principles of good manufacturing practice. There may be also other deficiencies, if they are evaluated as unimportant or the information is insufficient in order to classify them as major or critical.

Minister for Health G. Bērziņš

 

Annex 2
Cabinet Regulation No. 304
18 April 2006

LATVIJAS REPUBLIKA
ZĀĻU VALSTS AĢENTŪRA

REPUBLIC OF LATVIA
STATE AGENCY OF MEDICINES

  (adrese, reģistrācijas numurs, tālruņa numurs, faksa numurs, e-pasta adrese)    

(address, registration number, phone, fax number, e-mail)

 

Sertifikāts Nr. _ _ _/_ _ _/_ _ _

Certificate No. _ _ _/_ _ _/_ _ _

ZĀĻU RAŽOTĀJA LABAS RAŽOŠANAS PRAKSES ATBILSTĪBAS SERTIFIKĀTS
CERTIFICATE OF GMP COMPLIANCE OF A MANUFACTURER

1.daļa

Part 1

Izsniegts pēc oficiālas pārbaudes (inspicēšanas) saskaņā ar Direktīvas 2001/83/EK 111.panta 5.punktu vai Direktīvas 2001/20/EK 15.pantu*

Issued following an inspection in accordance with Art. 111(5) of Directive 2001/83/EC as amended or Art. 15 of Directive 2001/20/EC*

vai/or

izsniegts saskaņā ar Savstarpējās atzīšanas līgumu starp Eiropas Savienības un Eiropas Ekonomikas zonas valstīm un [Savstarpējās atzīšanas līguma partnervalsts]*

Issued under the provisions of the Mutual Recognition Agreement between the European Community and [MRA Partner]*

Zāļu valsts aģentūra apliecina:

State Agency of Medicines confirms the following:

Zāļu ražotājs/The manufacturer …………………………………………………………….......

Ražošanas vietas adrese/Site address ……………………………………………………….......

……………………………………………………….….…………………………………….....

ir oficiāli pārbaudīts nacionālās uzraudzības un kontroles programmas ietvaros par atbilstību speciālajai atļaujai (licencei) zāļu ražošanai Nr. …………………………….. saskaņā ar Direktīvas 2001/83/EK 40.pantu/Direktīvas 2001/20/EK 13.pantu*, kas pārņemta šādos Latvijas Republikas tiesību aktos:

Ministru kabineta 2006.gada 18.aprīļa noteikumi Nr.304 "Noteikumi par zāļu ražošanas un kontroles kārtību, par zāļu ražošanu atbildīgās amatpersonas kvalifikācijas prasībām un profesionālo pieredzi un kārtību, kādā zāļu ražošanas uzņēmumam izsniedz labas ražošanas prakses sertifikātu"

Has been inspected under the national inspection programme in connection with manufacturing authorisation No. …………………… in accordance with Art. 40 of Directive 2001/83/EC / Art. 13 of Directive 2001/20/EC* transposed in the following national legislation: Regulations of the Cabinet of Ministers of 18 April 2006 No. 304 "Regulations Regarding the Procedures for the Manufacture and Control of Medicinal Products, the Requirements for the Qualification and Professional Experience of a Qualified Person and the Procedures for the Issuance of the Certificate of Good Manufacturing Practice to a Medicinal Products Manufacturing Undertaking"

vai/or

ir oficiāli pārbaudīts par zāļu ražotāja, kas atrodas ārpus Eiropas Ekonomikas zonas, atbilstību zāļu reģistrācijas apliecībā norādītajam saskaņā ar Eiropas Parlamenta un Padomes 2004.gada 31.marta Regulas (EK) Nr. 726/2004, ar ko nosaka cilvēkiem paredzēto un veterināro zāļu reģistrēšanas un uzraudzības Kopienas procedūras un izveido Eiropas zāļu aģentūru, 8.panta 2.punktu/19.panta 3.punktu* vai Direktīvas 2001/83/EK 111.panta 4.punktu, kas pārņemta šādos Latvijas Republikas tiesību aktos:

Ministru kabineta 2006.gada 18.aprīļa noteikumi Nr.304 "Noteikumi par zāļu ražošanas un kontroles kārtību, par zāļu ražošanu atbildīgās amatpersonas kvalifikācijas prasībām un profesionālo pieredzi un kārtību, kādā zāļu ražošanas uzņēmumam izsniedz labas ražošanas prakses sertifikātu"

Has been inspected in connection with marketing authorisation(s) listing manufacturers located outside of the European Economic Area in accordance with Art. 8(2)/19(3)* of Regulation (EC) 726/2004 or Art. 111(4) of Directive 2001/83/EC transposed in the following national legislation: Regulations of the Cabinet of Ministers of 18 April 2006 No 304 "Regulations Regarding the Procedures for the Manufacture and Control of Medicinal Products, the Requirements for the Qualification and Professional Experience of a Qualified Person and the Procedures for the Issuance of the Certificate of Good Manufacturing Practice to a Medicinal Products Manufacturing Undertaking"

un/vai* / and/or*

ir aktīvo vielu ražotājs, kas ir oficiāli pārbaudīts saskaņā ar Direktīvas 2001/83/EK 111.panta 1.punktu, kas pārņemta šādos Latvijas Republikas tiesību aktos:

Ministru kabineta 2006.gada 18.aprīļa noteikumi Nr.304 "Noteikumi par zāļu ražošanas un kontroles kārtību, par zāļu ražošanu atbildīgās amatpersonas kvalifikācijas prasībām un profesionālo pieredzi un kārtību, kādā zāļu ražošanas uzņēmumam izsniedz labas ražošanas prakses sertifikātu"

Is an active substance manufacturer that has been inspected in accordance with Art. 111(1) of Directive 2001/83/EC transposed in the following national legislation:

Regulations of the Cabinet of Ministers of 18 April 2006 No 304 "Regulations Regarding the Procedures for the Manufacture and Control of Medicinal Products, the Requirements for the Qualification and Professional Experience of a Qualified Person and the Procedures for the Issuance of the Certificate of Good Manufacturing Practice to a Medicinal Products Manufacturing Undertaking"

vai/or

Cits (norādīt)/Other (please specify) ………………………………………………………….

……………………………………………………………………………………..………….*

Ražotāja oficiālajās pārbaudēs, no kurām pēdējā tika veikta ……/……/…… [datums], iegūtā informācija ļauj uzskatīt, ka tas atbilst labas ražošanas prakses prasībām1), kas noteiktas Savstarpējās atzīšanas līgumā starp Eiropas Savienības un Eiropas Ekonomikas zonas valstīm un [Savstarpējās atzīšanas līguma partnervalsts]/labas ražošanas prakses principiem un pamatnostādnēm, kas noteiktas Direktīvā 2003/94/EK1)/aktīvo vielu labas ražošanas prakses principiem1)*.

From the knowledge gained during inspection of this manufacturer, the latest of which was conducted on …../...…/...… [date], it is considered that it complies with the Good Manufacturing Practice requirements1) referred to in the Agreement of Mutual Recognition between the European Community and [MRA partner]/The principles and guidelines of Good Manufacturing Practice laid down in Directive 2003/94/EC1)/The principles of GMP for active substances1)*.

Šis sertifikāts atspoguļo ražošanas vietas statusu minētās oficiālās pārbaudes laikā, un tas nevar atspoguļot atbilstības statusu, ja ir pagājuši vairāk nekā trīs gadi kopš oficiālās pārbaudes, kad tika izsniegts šis sertifikāts.

This certificate reflects the status of the manufacturing site at the time of the inspection noted above and should not be relied upon to reflect the compliance status if more than three years have elapsed since the date of that inspection, after which time the issuing authority should be consulted.

Sertifikāta autentiskumu var apliecināt Zāļu valsts aģentūra.

The authenticity of this certificate may be verified with the issuing authority.

1) Šīs prasības atbilst Pasaules veselības organizācijas (PVO) labas ražošanas prakses ieteikumiem.

These requirements fulfil the GMP recommendations of the World Health Organisation (WHO).

2.daļa

Part 2

Cilvēkiem paredzētās zāles*

Human Medicinal Products*

Cilvēkiem paredzētās pētāmās zāles* klīnisko pētījumu I, II, III fāze*

Human Investigational Medicinal Products* for phase I, II, III clinical trials*

1. RAŽOŠANAS DARBĪBAS*

MANUFACTURING OPERATIONS*

- licencētās ražošanas darbības ietver pilnīgu un daļēju ražošanu (tai skaitā dažādus sadalīšanas, iepakošanas un noformēšanas procesus), sērijas izlaidi un sertifikāciju, noteiktu dozējuma formu uzglabāšanu un izplatīšanu

- authorised manufacturing operations include total and partial manufacturing (including various processes of dividing up, packaging or presentation), batch release and certification, storage and distribution of specified dosage forms unless informed to the contrary

- kvalitātes kontroles (testēšanas) un/vai sērijas izlaides un sertifikācijas darbības bez ražošanas darbībām norāda attiecīgajiem produktiem

- quality control testing and/or release and batch certification activities without manufacturing operations should be specified under the relevant items

- ja uzņēmums ir iesaistīts zāļu ražošanā, kurām ir īpaši nosacījumi, piemēram, radiofarmaceitiskie preparāti, zāles, kas satur penicilīnu, sulfonamīdus, citotoksīnus, cefalosporīnu, vielas ar hormonālu iedarbību vai citas potenciāli bīstamas aktīvās vielas, to norāda pie atbilstošā zāļu veida un dozējuma formas

- if the company is engaged in manufacture of products with special requirements e.g. radiopharmaceuticals or products containing penicillin, sulphonamides, cytotoxics, cephalosporins, substances with hormonal activity or other or potentially hazardous active ingredients this should be stated under the relevant product type and dosage form

1.1. Sterilie produkti*

Sterile Products*

1.1.1. Aseptiski iegūti (dozējuma formu saraksts)*

Aseptically prepared (list of dosage forms)*

1.1.2. Galaprodukta sterilās formas (dozējuma formu saraksts)*

Terminally sterilised (list of dosage forms)*

1.1.3. Tikai sērijas sertifikācija (dozējuma formu saraksts)*

Batch certification only (list of dosage forms)*

1.2. Nesterilie produkti (dozējuma formu saraksts)*

Non-sterile products (list of dosage forms)*

1.2.1. Tikai sērijas sertifikācija (dozējuma formu saraksts)*

Batch certification only (list of dosage forms)*

1.3. Bioloģiskas izcelsmes zāles* (norāda zāļu veidus pa grupām, piemēram, alergēni, antigēni, vakcīnas, pretvīrusu vakcīnas, no ribosomālās DNS atvasinātie produkti)

Biological medicinal products* (product types should be specified under the relevant sections e.g. allergens, antibodies, vaccines, viral vaccines, rDNA etc.)

1.3.1. No cilvēka asinīm un plazmas iegūtas zāles*

Blood products*

1.3.2. Imunoloģiskie preparāti*

Immunological products*

1.3.3. Šūnu terapijas preparāti*

Cell therapy products*

1.3.4. Gēnu terapijas preparāti*

Gene therapy products*

1.3.5. Biotehnoloģijas preparāti*

Biotechnology products*

1.3.6. No cilvēka vai dzīvnieku materiāliem izdalīti preparāti*

Human or animal extracted products*

1.3.7. Tikai sērijas sertifikācija* (saraksts, kurā norādīts zāļu veids (1.3.1.-1.3.6.)/dozējuma

forma)

Batch certification only* (list of product types from 1.3.1.-1.3.6./dosage forms)

1.4. Citi produkti vai ražošanas darbības* (citas līdzīgas ražošanas darbības vai zāļu veidi, kas nav iepriekš minēti, piemēram, aktīvo vielu sterilizācija, bioloģiski aktīvu izejvielu ražošana, medicīniskās gāzes, augu izcelsmes zāles vai homeopātiskās zāles, pilna vai daļēja ražošana)

Other products or manufacturing activity* (any other relevant manufacturing activity/ product type that is not covered above e.g. sterilisation of active substances, manufacture of biological active starting materials, medicinal gases, herbal or homoeopathic products, bulk or partial manufacturing etc.)

1.5. Tikai iepakošana*

Packaging only*

1.5.1. Primārā iepakošana (saraksts, kurā norādīts zāļu veids/dozējuma forma)*

Primary packing (list of product types/dosage forms)*

1.5.2. Sekundārā iepakošana*

Secondary packing*

1.6. Kvalitātes kontroles testēšana*

Quality Control testing*

2. ZĀĻU IMPORTĒŠANA*

IMPORTATION OF MEDICINAL PRODUCTS*

- importēšana bez ražošanas darbībām

- importation activities without manufacturing activity

- importēšana, kas ietver uzglabāšanu un izplatīšanu

- importation activities include storage and distribution unless informed to the contrary

2.1. Importēto zāļu kvalitātes kontroles testēšana*

Quality control testing of imported medicinal products*

2.2. Importēto zāļu sērijas sertifikācija*

Batch certification of imported medicinal products*

2.2.1. Sterilie produkti*

Sterile Products*

2.2.1.1. Aseptiski iegūti (dozējuma formu saraksts)*

aseptically prepared (list of dosage forms)*

2.2.1.2. Galaprodukta sterilās formas (dozējuma formu saraksts)*

terminally sterilised (list of dosage forms)*

2.2.2. Nesterilie produkti (dozējuma formu saraksts)*

Non-sterile products (list of dosage forms)*

2.2.3. Bioloģiskas izcelsmes zāles (norāda zāļu veidus pa grupām, piemēram, alergēni, antigēni, vakcīnas, pretvīrusu vakcīnas, no ribosomālās DNS atvasinātie produkti)*

Biological products (product types should be specified under the relevant sections e.g. allergens, antibodies, vaccines, viral vaccines, rDNA etc.)*

2.2.3.1. No cilvēka asinīm un plazmas iegūtas zāles*

Blood products*

2.2.3.2. Imunoloģiskie preparāti*

Immunological products*

2.2.3.3. Šūnu terapijas preparāti*

Cell therapy products*

2.2.3.4. Gēnu terapijas preparāti*

Gene therapy products*

2.2.3.5. Biotehnoloģijas preparāti*

Biotechnology products*

2.2.3.6. No cilvēka vai dzīvnieku materiāliem izdalīti preparāti*

Human or animal extracted products*

2.2.4. Citi produkti* (citas līdzīgas importēšanas darbības, kas nav iepriekš minētas, piemēram, radiofarmaceitisko preparātu, medicīnisko gāzu, augu izcelsmes zāļu vai homeopātisko zāļu importēšana)

Other products* (any other relevant importation activity that is not covered above e.g. importation of radiopharmaceuticals, medicinal gases; herbal or homoeopathic products etc.)

Aktīvo vielu ražošana. Pārbaudīto vielu nosaukumi*

Manufacture of active substance. Names of substances subject to inspection* …………………………………………………………………………………………………..

…………………………………………………………………………………………………...............................................................................................................................

Jebkādi ierobežojumi vai paskaidrojumi saistībā ar šī sertifikāta jomu*

Any restrictions or clarifying remarks related to the scope of this certificate* …………………………………………………………………………………………………..

…………………………………………………………………………………………………..............................................................................................................................

…………………………………………………………………………………………………..............................................................................................................................

……/……/……

(datums/date)

Zāļu valsts aģentūras pilnvarotās amatpersonas vārds, uzvārds un paraksts**

Name and signature of the authorised person of the Competent Authority of Latvia**

……………………………………………………………..

………………………………………………………………

(vārds, uzvārds, amats, kompetentā iestāde, tālruņa un faksa numurs/name, title, national authority, phone & fax numbers)

Place for a seal

Stamp

Notes.

1. *Izdzēst neatbilstošo.

Delete that which does not apply.

2. **Paraksts, datums un kontaktinformācija ir uz katras sertifikāta lapas.

The signature, date and contact details should appear on each page of the certificate.

Minister for Health G. Bērziņš

 

Annex 3
Cabinet Regulation No. 304
18 April 2006

Devices, Apparatus, Equipment, and Reagents to be Used for Analytical Work in a Pharmacy

1. Devices and apparatus:

1.1. a photoelectrical colorimeter:

1.2. a device for the mechanical impurity control in solutions;

1.3. a laboratory thermometer from 0 °C to 100 °C (with the graduation value up to 1 °C);

1.4. a laboratory water bath;

1.5. a test tube stand;

1.6. a pH meter

1.7. a refractometer;

1.8. hand scales (for weighing of reagents) with the weighing limitation:

1.8.1. from 0.02 g to 1 g

1.8.2. from 0.1 g to 5 g

1.8.3. from 1 g to 20 g

1.8.4. from 5 g to 100 g;

1.9. an alcohol burner

1.10. a stand for the fixation of laboratory vessels and devices;

1.11. a set of glass alcoholmeters

1.12. technical scales and a set of technical weights from 10 mg to 0.5 kg;

1.13. an ultraviolet irradiator for the determination of vitamins in a solution;

1.14. a cabinet dryer with a thermometer from 0°C to 200 °C.

2. Laboratory vessels:

2.1. a pharmacy pipette with an outlet tube with a capacity of 3 ml and 6 ml;

2.2. indicator and reagent droppers;

2.3. calcium chloride pipes with a ball-shaped part (for protection of purified water against the carbon dioxide);

2.4. flasks, cone-shaped with a capacity of 50 ml, 100 ml, 200 ml;

2.5. a flask with a ground stopper with a capacity of 100 ml;

2.6. chemical test tubes;

2.7. measuring cylinders with ground stoppers with a capacity of 10 ml, 25 ml, 50 ml, 100 ml;

2.8. graduated cylinders with a capacity of 10 ml, 25 ml, 50 ml, 100 ml, and 250 ml;

2.9. volumetric flasks with ground stoppers with a capacity of 25 ml, 50 ml, 100 ml;

2.10. microburettes with a capacity of 3 ml and 5 ml;

2.11. Moor's pipettes with a capacity of 5 ml and 10 ml;

2.12. a mortar and pestle;

2.13. funnels;

2.14. graduated pipettes with a capacity of 1 ml, 2 ml, 5 ml, and 10 ml;

2.15. porcelain evaporating dishes with a capacity of 25 ml, 50 ml, 100 ml;

2.16. porcelain crucibles;

2.17. bottles for the storage of reagents;

2.18. glass or porcelain spot plates with or without wells for the analysis of drops;

2.19. syringe-flask;

2.20. separatory funnels with a capacity of 50 ml and 100 ml;

2.21. a burette with a tap; and

2.22. flat-bottomed vessels.

3. Ancillary materials:

3.1. eye pipettes;

3.2. eye spatula;

3.3. goggles;

3.4. brushes for washing of test tubes and flasks;

3.5. filter paper;

3.6. a flame needle or a graphite pin;

3.7. a rubber balloon for micorburettes and pipettes;

3.8. test tube rack;

3.9. a permanent marker;

3.10. forceps;

3.11. glass rods;

3.12. spreading rods;

3.13. crucible tongs;

3.14. cotton wool, hygroscopic.

4. Titrated solutions:

No.

Solution name

Molar concentration

Normal concentration

4.1. Ammonium thiocyanate solution

0.1 M

0.1 N

4.2. Sodium ethylene diamine tetra acetate (trilon B) solution

0.05 M

-

4.3. Mercury (II) nitrate solution

0.05 M

0.1 N

4.4. Hydrochloric acid solution

0.1 M

0.1 N

4.5. Iodine solution

0.05 M

0.1 N

4.6. Potassium bromate solution

0.0167 M

0.1 N

4.7. Potassium permanganate solution

0.02 M

0.1 N

4.8. Sodium hydroxide solution

0.1 M

0.1 N

4.9. Sodium nitrite solution

0.1 M

-

4.10. Sodium thiosulphate solution

0.1 M

0.1 N

4.11. Silver nitrate solution

0.1 M

0.1 N

Note. Titrated solutions shall be kept at a temperature of 18 °C - 20 °C in tightly closed bottles in a dark place. Iodine, potassium bromate, potassium permanganate, sodium nitrite and silver nitrate solutions shall be kept in dark glass bottles. Sodium hydroxide and sodium thiosulphate solution shall be protected from exposure to air carbon dioxide. Titrated solutions shall be received from the State Agency of Medicines.

5. Indicators:

5.1. Ammonium ferrous sulphate solution 30 %
5.2. Bromphenol blue solution 0.1 %
5.3. Bromothymol blue solution 0.1 %
5.4. Starch solution 1 %
5.5. Eriochrome black  
5.6. Phenolphthalein solution 1 %
5.7. Acid chrome dark blue  
5.8. Potassium chromate solution 5 %
5.9. Methylene blue solution 0.15 %
5.10. Methyl red solution 0.1 %
5.11. Methyl orange solution 0.1 %
5.12. Sodium eosinate solution 0.1 % and 0.5 %; or
5.13. Tropaeoline 00 solution 0.1 %

6. Indicator paper:

No.

Name

Colour transition pH

6.1. Red litmus paper > 8.0
6.2. Blue litmus paper < 5.0
6.3. Universal indicator paper pH 1.0-10.0
6.4. Universal indicator paper for specification of basicity pH 7.0-14.0

Note.

1. Indicator paper is used in order to specify pH of water solutions and suspensions with the precision of 1.0 -2.0 pH units. pH shall be determined at a room temperature for solutions and suspensions which do not contain heavy oxidising substances, organic solvents and salts in large concentration.

2. Indicator paper shall be kept in a dry room, not contaminated with gases, protecting from the effects of light, humidity, acids vapours, ammonium and other chemically active compounds.

7. Reagents:

7.1. Activated carbon  
7.2. Ammonium ferrous (III) sulphate  
7.3. Ammonium molybdate solution in concentrated sulphuric acid (Froede's reagent)  
7.4. Ammonium oxalate solution 4 %
7.5. Ammonium thiocyanate  
7.6. Ammonium vanadate solution in hydrochloric acid  
7.7. Ammonia buffer solution  
7.8. Ammonia solution 10 %
7.9. Barium hydroxide solution 5 %
7.10. Barium chloride or barium nitrate solution 5 %
7.11. b - naphthol alakaline solution 2 %
7.12. Iron trichloride solution 3 %
7.13. Acetic acid, diluted 30 %
7.14. Fehling's reagent I  
7.15. Fehling's reagent II  
7.16. Formaldehyde solution (formalin)  
7.17. Formaldehyde solution in concentrated sulphuric acid (Marquis reagent)  
7.18. Formol mixture  
7.19. Tosylchloramide sodium solution  
7.20. Potassium dihydrogen phosphate  
7.21. Potassium dichromate solution 5 %
7.22. Potassium iodide  
7.23. Potassium hexacyanoferrate (II) solution (yellow prussiate) 1 %; 5 %; 20 %
7.24. Potassium hexacyanoferrate (III) solution (red prussiate) 2 %; 5 %; 10 %
7.25. Potassium monohydrigenphosphate  
7.26. Potassium permanganate  
7.27. Cobalt chloride solution 5 %
7.28. Cobalt nitrate alcoholic solution 1 %
7.29. Cobalt nitrate solution 5 %
7.30. Lugol reagent  
7.31. Sodium hydrogencarbonate  
7.32. Sodium hydroxide solution 10 %; 2 M
7.33. Sodium carbonate solution 1 %; 5 %; 10 %
7.34. Sodium nitrite  
7.35. Sodium nitropruside solution 1 %; 5 %; 10 %
7.36. Disodium sulphide solution 2 %
7.37. Nesler's reagent  
7.38. Perhydrol  
7.39. Hydrochloric acid 25 %
7.40. Hydrochloric acid, diluted 8.3 %
7.41. Sulphuric acid, diluted 16 %
7.42. Sulphuric acid, concentrated  
7.43. Nitric acid diluted 16 %
7.44. Ammoniacal silver nitrate  
7.45. Silver nitrate solution 2 %
7.46. Sulphanilic acid solution  
7.47. Lead diacetate solution 10 %
7.48. Tannin solution 0.1 %; 5 %
7.49. Hydrogen peroxide solution 3 %
7.50. Vanillin  
7.51. Cupric acetate solution 5 %
7.52. Copper dinitrate solution 5 %
7.53. Copper wire  
7.54. Cupric sulphate  
7.55. Tartaric acid solution 20 %

Note. Reagents shall be received from the State Agency of Medicines. If reagents are prepared in a pharmacy, the methodology, provisions for storage and term of validity thereof shall be co-ordinated with the State Agency of Medicines.

8. Solvents:

8.1. acetone;

8.2. ethyl alcohol, 90 %; 95-96 %;

8.3. diethyl ether;

8.4. glycerol;

8.5. chloroform.

Minister for Health G. Bērziņš

 

Annex 4
Cabinet Regulation No. 304
18 April 2006

[4 August 2008]

Contents of the Register of the Medicinal Product Quality Control Results Performed in the Pharmacy

1. Register of the testing results of the medicinal products prepared on individual prescriptions (requests of medical treatment institutions)

Date

No.
(also the analysis number)

Prescription or request number

Composition of the medicinal product

Testing results

Given name, surname of the manufacturer

Given name, surname and signature of the tester

organoleptic

physical

qualitative

quantitative

1

2

3

4

5

6

7

8

9

10

                   

2. Register of the testing results of the purified water obtained in the pharmacy

Date

No. (also the analysis number)

Testing results

Conclusion

Given name, surname and signature of the tester

chloride ions

sulphate ions

calcium and magnesium ions

ammonium ions

reducing agents

1

2

3

4

5

6

7

8

9

                 

3. Register of the testing results of the concentrates, partially processed products, ethyl alcohol

Date

No.
(also the analysis number)

Name, concentration

Testing results

Given name, surname of the manufacturer

Given name, surname and signature of the tester

organoleptic

qualitative

quantitative

1

2

3

4

5

6

7

8

               

4. Register of the inspection results of the starting materials identity

Date

No. (also the analysis number)

Name

Manufactured batch number

Substance under analysis

Conclusion

Given name, surname and signature of the filler

Given name, surname and signature of the tester

1

2

3

4

5

6

7

8

               

Minister for Health G. Bērziņš

 

Annex 5
Cabinet Regulation No. 304
18 April 2006

Report
regarding the quality control of medicinal products in the pharmacy
20___(year)

 

(holder company of the special permit (licence) for pharmaceutical activities)

 

(legal address and the registration number in the Commercial Register)

 

(pharmacy name and address)

 

No.

Name of the site analysed

Number of analyses performed

Of them with dissatisfactory results

physical

qualitative

quantitative

1. Concentrates        
2. Partially processed products        
3. Purified water        
4. Medicinal products prepared on individual prescriptions and requests of medical treatment institutions        
5. Starting materials for the preparation of medicinal products        
 

Total

       
The Head of the Pharmacy  
 

(given name, surname, signature)

 

Date _________________

Minister for Health G. Bērziņš

 

Annex 6
Cabinet Regulation No. 304
18 April 2006

Maximum One-time or Daily Doses of Powerfully Acting Substances which are Used for the Preparation of Medicinal Products in a Pharmacy

1. Maximum one-time or daily doses of powerfully acting substances for children up to the age of 14, administering orally (the amounts of the substances are indicated in grams if other units of measurement are not specified)

No.

Drug substance name

Up to 6 months

From 6 months to 1 year

2 years

3-4 years

5-6 years

7-9 years

10-14 years

single dose administration

daily dose

single dose administration

daily dose

single dose administration

daily dose

single dose administration

daily dose

single dose administration

daily dose

single dose administration

daily dose

single dose administration

daily dose

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

1. Acidum arsenicosum anhydricum

*

*

*

*

0.0002

0.0006

0.0003

0.001

0.0005

0.0015

0.00075

0.002

0.001

0.003

2. Acidum hydrochloricum dilutum

1 drop

3 drops

2 drops

6 drops

2 drops

6 drops

3 drops

9 drops

5 drops

15 drops

7-8 drops**

20 drops

8-10 drops

30 drops

3. Acidum nicotinicum

0.005

0.015

0.008

0.024

0.01

0.03

0.015

0.045

0.025

0.075

0.03

0.09

0.05

0.15

4. Adonisidum

1 drop

2 drops

2 drops

4 drops

3 drops

6 drops

5 drops

10 drops

6 drops

12 drops

8 drops

15 drops

10-15 drops

20-30 drops

5. Aethylis aminobenzoas (Anaesthesinum)

0.025

0.075

0.04

0.12

0.06

0.18

0.08

0.24

0.12

0.36

0.16

0.5

0.2

0.6

6. Aethylmorphini hydrochloridum

*

*

*

*

0.003

0.01

0.005

0.015

0.006

0.018

0.0075

0.025

0.01

0.03

7. Ambenonii chloridum (Oxazylum)

*

*

0.0015

0.0015

0.0025

0.0025

0.003

0.003

0.004

0.004

0.006

0.006

0.0075-0.01

0.0075-0.01

8. Aminarsonum

0.04

0.12

0.08

0.24

0.1

0.3

0.15

0.45

0.15

0.45

0.2

0.5

0.25

0.75

9. Aminasinum

0.005-0.0075

0.01-0.015

0.01

0.02

0.015

0.03

0.025

0.05

0.05

0.1

0.075

0.15

0.1

0.2

10. Aminophenazonum (Amidopyrinum)***

0.025

0.075

0.05

0.15

0.05

0.15

0.075

0.2

0.1

0.3

0.15

0.45

0.2-0.3

0.6-0.9

11. Aminophyllinum (Euphyllinum)

*

*

0.01

0.03

0.02

0.06

0.03

0.09

0.05

0.15

0.075

0.25

0.1

0.3

12. Apomorphini hydrochloridum

*

*

*

*

0.001

0.003

0.0015

0.0045

0.002

0.006

0.0025

0.0075

0.003

0.009

13. Atropini sulfas

0.0001

0.0002

0.0002

0.0004

0.0002

0.0004

0.00025

0.0005

0.0003

0.0006

0.0004

0.0008

0.0005

0.001

14. Barbamylum

0.01

0.02

0.01

0.02

0.02

0.04

0.025-

0.03

0.05-0.06

0.04

0.08

0.05-0.075

0.1-0.15

0.1-0.15

0.2-0.3

15. Barbitalum natricum

0.03

0.06

0.075

0.15

0.1

0.2

0.15

0.3

0.2

0.4

0.25

0.5

0.3

0.6

16. Bendazolum (Dibazolum)

0.001

0.001

0.001

0.001

0.002

0.002

0.004

0.004

0.005

0.005

0.006

0.006

0.008

0.008

17. Bromisovalum

0.05

0.1

0.1

0.2

0.15

0.3

0.2

0.4

0.25

0.5

0.3

0.6

0.3-0.4

0.6-0.8

18. Carbromalum

*

*

0.1

0.2

0.15

0.3

0.2

0.4

0.2

0.4

0.25

0.5

0.3-0.4

0.6-0.8

19. Chloramphenicolum (Laevomycetinum)

one-time 0.02; daily 0.12 for 1 kg of child's weight

0.25

1.5

0.25

1.5

0.3

1.8

0.4

2.0
20. Chlorali hydras

0.1

0.3

0.15

0.45

0.2

0.6

0.25

0.75

0.3

0.9

0.4

1.2

0.5-0.75

1.5-2.0

21. Chlortetracyclini hydrochloridum

0.025 for 1 kg of child's weight daily

0.075

0.3

0.1

0.4

0.15

0.6

0.2-0.3

0.8-1.0
22. Codeinum

*

*

*

*

0.002

0.006

0.004

0.012

0.005

0.015

0.006

0.02

0.006-0.01

0.02-0.03

23. Codeini phosphas

*

*

0.0025

0.0075

0.004

0.012

0.005

0.015

0.006-0.008

0.02-0.025

0.01

0.03

0.015-0.02

0.045-0.06

24. Coffeinum

*

*

*

*

0.04

0.12

0.05

0.15

0.06

0.18

0.075

0.25

0.075-0.1

0.25-0.3

25. Coffeinum natrii -benzoas

0.05

0.15

0.06

0.18

0.07

0.2

0.08

0.25

0.1

0.3

0.15

0.5

0.15-0.2

0.5-0.6

26. Digalen - neo

1 drop

3 drops

2 drops

6 drops

4 drops

12 drops

6 drops

18 drops

7 drops

21 drops

8 drops

24 drops

10 drops

30 drops

27. Diphenhydraminum (Dimedrolum)

0.002

0.006

0.005

0.015

0.01

0.03

0.015

0.045

0.02

0.06

0.03

0.09

0.04

0.1

28. Ephedrini hydrochloridum

0.0025

0.0075

0.006

0.02

0.01

0.03

0.015

0.045

0.015

0.045

0.02

0.06

0.025

0.075

29. Erythromycinum

0.005-0.008 for 1 kg of child's weight one-time

0.125

0.5

0.15

0.6

0.2

0.8

0.25

1.0
30. Extractum Belladonnae siccum

*

*

0.0025

0.0075

0.003

0.009

0.004

0.012

0.005

0.015

0.0075

0.025

0.01-0.015

0.03-0.045

31. Extractum Filicis maris spissum

*

*

*

*

1.0

1.0

1.5-2.0

1.5-2.0

2.5-3.0

2.5-3.0

3.5-4.0

3.5-4.0

5.0

5.0

32. Extractum Opii siccum

*

*

*

*

*

*

0.0025

0.0075

0.005

0.015

0.0075

0.025

0.01

0.03

33. Folium Digitalis

0.005

0.02

0.01

0.04

0.02

0.08

0.03

0.12

0.04

0.16

0.05

0.2

0.05-0.075

0.2-0.3

34. Ftivazidum (Phthivasidum)

0.04 for 1 kg of child's weight daily

0.3

0.6

0.35

0.7

0.4

0.8

0.5-0.75

1.0-1.5
35. Herba Adonidis vernalis

0.03

0.12

0.05

0.2

0.1

0.4

0.15

0.6

0.2

0.8

0.3

1.2

0.3-0.5

1.2-2.0

36. Herba Thermopsidis

0.005

0.015

0.005

0.015

0.01

0.03

0.015

0.045

0.02

0.06

0.025

0.075

0.03-0.05

0.1-0.15

37. Lantosidum

1 drop

3 drops

2 drops

6 drops

3 drops

9 drops

5 drops

15 drops

6 drops

18 drops

10 drops

30 drops

15 drops

45 drops

38. Mepacrinum hydrochloridum (Acrichinum)

0.0125

0.025

0.0125

0.025

0.025

0.05

0.04

0.08

0.05

0.1

0.075

0.15

0.1-0.125

0.2-0.25

39. Metamizolum natricum (Analginum)

0.025

0.075

0.05

0.15

0.1

0.3

0.15

0.45

0.2

0.6

0.25

0.75

0.3-0.5

0.9-1.5

40. Morphini hydrochloridum

*

*

*

*

0.001

0.002

0.0015

0.003

0.0025

0.0075

0.003

0.01

0.003-0.005

0.01-0.015

41. Neostigmini methylsulfas (Proserinum)

*

*

0.001

0.001

0.002

0.002

0.003

0.003

0.005

0.005

0.007

0.007

0.01

0.01

42. Nicethamidum (Cordiaminum)

2 drops

6 drops

3 drops

9 drops

4 drops

12 drops

5 drops

15 drops

6 drops

18 drops

7-8 drops

20-25 drops

10-15 drops

30-40 drops

43. Omnoponum

*

*

*

*

0.002

0.004

0.003

0.006

0.005

0.015

0.006

0.02

0.0075-0.01

0.02-0.03

44. Opium pulveratum

*

*

*

*

*

*

0.005

0.015

0.01

0.03

0.015

0.045

0.015-0.02

0.045-0.06

45. Oxytetracyclini dihydras

0.025 for 1 kg of child's weight daily

0.15

0.3

0.2

0.4

0.25

0.5

0.3

0.6

46. Papaverini hydrochloridum

*

*

0.005

0.01

0.01

0.02

0.015

0.03

0.02

0.04

0.03

0.06

0.05-0.06

0.15-0.2

47. Pentetrazolum (Corazolum)

0.02

0.04

0.02

0.06

0.03

0.09

0.05

0.15

0.06

0.18

0.075

0.2

0.08

0.25

48. Pentobarbitalum natrium (Aethaminalum natrium)

0.01

0.02

0.01

0.02

0.02

0.04

0.025-0.03

0.05-0.06

0.04

0.08

0.05-0.075

0.1-0.15

0.1-0.15

0.2-0.3

49. Phenasonum (Antipyrinum)

*

*

0.05

015

0.075

0.2

0.1

0.3

0.15

0.45

0.2

0.6

0.25-0.3

0.75-0.9

50. Phenobarbitalum

0.005

0.01

0.01

0.02

0.02

0.04

0.03

0.06

0.04

0.08

0.05

0.1

0.075

0.15

51. Phenylbutazonum (Butadionum)

*

*

0.01

0.03

0.02

0.06

0.03

0.09

0.04

0.12

0.05-0.06

0.15-0.18

0.08-0.1

0.24-0.3

52. Plasmocidum

*

*

*

*

0.005

0.01

0.0075

0.015

0.01

0.02

0.015

0.03

0.02-0.025

0.04-0.05

53. Platyphyllini hydrotartras

0.0004

0.0012

0.0006

0.0025

0.001

0.003

0.0015

0.0045

0.0025

0.0075

0.003

0.009

0.005

0.015

54. Prednisolonum

0.001 for 1 kg of child's weight daily

-

0.02

-

0.025-0.03

-

0.025-0.04
55. Prednisonum

0.001 for 1 kg of child's weight daily

-

0.02

-

0.025-0.03

-

0.025-0.04
56. Proguanili hydrochloridum (Bigumalum)

0.0125

0.025

0.0125

0.025

0.025

0.05

0.03-0.04

0.06-0.08

0.04-0.05

0.08-0.1

0.075

0.15

0.1-0.125

0.2-0.25

57. Solutio Iodi spirituosae 5%

*

*

*

*

*

*

*

*

4 drops

12 drops

5 drops

15 drops

8 drops

24 drops

58. Strychnini nitras

*

*

*

*

0.00025

0.0005

0.0003

0.0006

0.0005

0.001

0.0006-0.00075

0.0012-0.0015

0.00075-0.001

0.0015-0.002

59. Sulfacetamidum natricum (Sulfacylum - natrium)

0.2 for 1 kg of child's weight daily

0.35

2.0

0.4

2.5

0.5

3.0

0.5

3.0

60. Sulfadimidinum (Sulfadimezinum)

0.2 for 1 kg of child's weight daily

0.35

2.0

0.4

2.5

0.5

3.0

0.5

3.0

61. Sulfaguanidinum (Sulginum)

0.2 for 1 kg of child's weight daily

0.35

2.0

0.4

2.5

0.5

3.0

0.5

3.0

62. Sulfanilamidum (Streptocidum)

0.2 for 1 kg of child's weight daily

0.35

2.0

0.4

2.5

0.5

3.0

0.5

3.0

63. Sulfathiasolum (Norsulfazolum)

0.2 for 1 kg of child's weight daily

0.35

2.0

0.4

2.5

0.5

3.0

0.5

3.0

64. Sulfaethidolum (Aethazolum)

0.2 for 1 kg of child's weight daily

0.35

2.0

0.4

2.5

0.5

3.0

0.5

3.0

65. Tetracyclinum

0.025 for 1 kg of child's weight daily

0.15

0.3

0.2

0.4

0.25

0.5

0.3

0.6

66. Theophyllinum

*

*

*

*

0.04

0.12

0.05

0.15

0.06

0.2

0.08

0.25

0.1

0.3

67. Thymolum

*

*

*

*

0.05

0.2

0.1

0.4

0.15

0.6

0.25

1.0

0.3

1.2

68. Thyreoidinum

0.01

0.03

0.02

0.06

0.03

0.09

0.05

0.15

0.075

0.25

0.1

0.3

0.15

0.45

69. Tinctura Belladonnae

1 drop

3 drops

1 drop

3 drops

2 drops

6 drops

3 drops

9 drops

3 drops

9 drops

4 drops

12 drops

4-6 drops

12-18 drops

70. Tinctura Opii simplex

*

*

*

*

*

*

1-2 drops

2-4 drops

3 drops

6 drops

4 drops

8 drops

5-7 drops

10-15 drops

71. Tinctura Strychni

*

*

*

*

1 drops

2 drops

2 drops

4 drops

3 drops

6 drops

4 drops

8 drops

5-6 drops

10-12 drops

72. Trimeperidini hydrochloridum (Promedolum)

*

*

*

*

0.005

0.01

0.0075

0.015

0.01

0.02

0.01

0.02

0.015

0.03

73. Vicasol (Vikasolum)

0.002-0.005

0.006-0.015

0.002-0.005

0.006-0.015

0.006

0.018

0.008

0.025

0.01

0.03

0.01

0.03

0.015

0.045

Notes.

* Substance is not prescribed.

** If two doses are indicated, the lower is applicable for younger children, the highest - for older children.

***In treating rheumatism, the daily dose of 0.15-0.2 for one year of life is permissible.

2. Maximum one-time or daily doses of powerfully acting substances for children from the age of 14 and adults (the amount of substances is indicated in grams if other units of measurement are not specified)

No.

Name of the powerfully acting substance

Method of administration

Maximum one-time dose

Maximum daily dose

1

2

3

4

5

1. Acetarsolum (Osarsolum)

Orally

0.25 1.0
2. Acidum arsenicosum anhydricum

Orally

0.005 0.015
3. Acidum hydrochloricum dilutum

Orally

  2 ml (40 drops)   6 ml (120 drops)
4. Acidum nicotinicum

Orally

0.1 0.5
5. Adonisidum

Orally

  40 drops 120 drops
6. Aethacridini lactas

Orally

0.05 0.15
7. Aether anaestheticus (Aether medicinalis)

Orally

0.33 ml (20 drops)   1 ml (60 drops)
8. Aethoxydum

Orally

1.5 4.5
9. Aethylis aminobenzoas (Anaesthesinum)

Orally

0.5 1.5
10. Aethylis biscoumacetas (Neodicumarinum)

Orally

0.3 0.9
11. Aethylmorphini hydrochloridum

Orally

0.03 0.1
12. Ambenonii chloridum (Oxazylum)

Orally

0.025 0.05
13. Aminarsonum

Orally

0.25 1.0
14. Aminophenazonum (Amidopyrinum)

Orally

0.5 2.0
15. Aminophyllinum (Euphyllinum)

Orally

0.5 1.5
16. Amphetamini sulfas (Phenaminum)

Orally

0.01 0.02
17. Apomorphini hydrochloridum

Orally

0.01 0.03
18. Aprofenum

Orally

0.03 0.1
19. Argenti nitras

Orally

0.03 0.1
20. Atropini sulfas

Orally

0.001 0.003
21. Barbamylum

Orally

0.3 0.6
22. Barbitalum

Orally

0.5 1.0
23. Barbitalum natricum

Orally

0.5 1.0
24. Bephenii hydroxynaphthoas (Naphthammonum)

Orally

5.0 5.0
25. Bendazolum (Dibazolum)

Orally

0.05 0.15
26. Benzobarbitalum (Benzonalum)

Orally

0.3 1.0
27. Betasinum

Orally

0.075 0.2
28. Bromisovalum

Orally

1.0 2.0
29. Carbacholum

Orally

0.001 0.003
30. Carbromalum

Orally

1.0 2.0
31. Chingaminum (Chloroquini phosphas)

Orally

0.5 1.5
32. Chiniofonum

Orally

1.0 3.0
33. Chloracizinum

Orally

0.05 0.15
34. Chlorali hydras

Orally;rectally

2.0 6.0
35. Chlorambucilum (Chlorbutinum)

Orally

0.015 0.015
36. Chloramphenicolum (Laevomycetinum)

Orally

1.0 4.0
37. Chloroformium

Orally

0.5 ml 1 ml
38. Chlorpromazini hydrochloridum (Aminasinum)

Orally

0.3 1.5
39. Chlorpropamidum

Orally

0.3 1.0
40. Chlortetracyclini hydrochloridum

Orally

0.5 2.0
41. Chlorotrianisenum

Orally

0.012 0.048
42. Cocaini hydrochloridum

Orally

0.03 0.03
43. Codeini phosphas

Orally

0.1 0.3
44. Codeinum

Orally

0.05 0.2
45. Coffeinum

Orally

0.3 1.0
46. Coffeinum - natrii benzoas

Orally

0.5 1.5
47. Cortisoni acetas

Orally

0.15 0.3
48. Cotarnini chloridum

Orally

0.1 0.3
49. Cupri sulfas

Orally

0.5 (to be used one-time as emetic) -
50. Diaethylstilboestrolum

Orally

0.001 0.003
51. Dicolinum

Orally

0.3 1.0
52. Dicumarinum

Orally

0.1 0.3
53. Diethylcarbamazini citras (Ditrazini citras)

Orally

0.25 0.75
54. Digalen - neo

Orally

0.65 ml (20 drops) 1.95 ml (60 drops)
55. Digitoxinum

Orally

0.0005 0.001
56. Diiodthyrosinum

Orally

0.075 0.2
57. Diphenhydraminum (Dimedrolum)

Orally

0.1 0.25
58. Diphenyltropini hydrochloridum (Tropacinum)

Orally

0.03 0.1
59. Diprophyllinum

Orally

1.0 3.0
60. Ephedrini hydrochloridum

Orally

0.05 0.15
61. Erythromycinum

Orally

0.5 2.0
62. Ethisteronum (Praegninum)

Orally

0.02 0.06
63. Extractum Belladonnae siccum

Orally

0.1 0.3
64. Extractum Belladonnae spissum

Orally

0.05 0.15
65. Extractum Filicis maris spissum

Orally

8.0 (administer at one time)  
66. Extractum Opii siccum

Orally

0.05 0.15
67. Folium Belladonnae

Orally

0.2 0.6
68. Folium Digitalis

Orally

0.1 0.5
69. Folium Hyoscyami

Orally

0.4 1.2
70. Folium Stramonii

Orally

0.2 0.6
71. Ftivazidum (Phthivasidum)

Orally

1.0 2.0
72. Furazolidonum

Orally

0.2 0.8
73. Ganglefeni hydrochloridum (Gangleronum)

Orally

0.075 0.3
74. Herba Adonidis vernalis

Orally

1.0 5.0
75. Herba Convallariae

Orally

0.5 1.5
76. Herba Thermopsidis

Orally

0.1 0.3
77. Hexamethonii benzosulfonas (Benzohexonium)

Orally

0.3 0.9
78. Hexestrolum (Synoestrolum)

Orally

0.002 0.004
79. Hexobarbitalum

Orally

0.5 1.0
80. Homatropini hydrobromidum

Orally

0.001 0.003
81. Hydralazini hydrochloridum (Apressinum)

Orally

0.1 0.3
82. Hydrocodoni phosphas

Orally

0.02 0.06
83. Hyoscini hydrobromidum (Scopolamini hydrobromidum)

Orally

0.0005 0.0015
84. Imipramini hydrochloridum (Imizinum)

Orally

0.1 0.3
85. Isoniazidum

Orally

0.6 0.9
86. Kanamycini sulfas

Orally

1.0 4.0
87. Khellinum

Orally

0.04 0.12
88. Lanatosidum C (Celanidum)

Orally

0.0005 0.001
89. Lantosidum

Orally

0.5 ml (25 drops) 1.5 ml (75 drops)
90. Mebhydrolinum (Diazolinum)

Orally

0.3 0.6
91. Mepacrinum hydrochloridum (Acrichinum)

Orally

0.3 0.6
92. Meprobamatum (Meprotanum)

Orally

0.8 2.4
93. Mercaptopurinum

Orally

0.2 0.3
94. Mercazolylum

Orally

0.01 0.04
95. Metamizolum natricum (Analginum)

Orally

1.0 3.0
96. Methacinium iodide (Methacinum)

Orally

0.005 0.015
97. Methadonum (Phenadonum)

Orally

0.01 0.03
98. Methandriol (Methylandrostendiolum)

Orally; under the tongue

0.025 0.1
99. Methandrostenolonum

Orally

0.01 0.05
100. Methazidum

Orally

1.0 2.0
101. Methyltestosteronum

Orally

0.05 0.1
102. Methylthiouracilum

Orally

0.25 0.75
103. Morphini hydrochloridum

Orally

0.02 0.05
104. Myelosanum

Orally

0.006 0.01
105. Natrii nitras

Orally

0.3 1.0
106. Neostigmini methylsulfas (Proserinum)

Orally

0.015 0.05
107. Neriolinum

Orally

0.0002 0.0004
108. Nicethamidum (Cordiaminum)

Orally

  2 ml   6 ml
109. Nitranolum

Orally

0.01 0.02
110. Nitrofuralum (Furacilinum)

Orally

0.1 0.5
111. Nitrofurantoinum (Furadoninum)

Orally

0.3 0.6
112. Omnoponum

Orally

0.03 0.1
113. Opium pulveratum

Orally

0.1 0.3
114. Oxytetracyclini dihydras

Orally

0.5 2.0
115. Oxytetracyclini hydrochloridum

Orally

0.5 2.0
116. Pachycarpini hydroiodidum

Orally

0.2 0.6
117. Papaverini hydrochloridum

Orally

0.2 0.6
118. Paracetamolum

Orally

0.5 1.5
119. Pempidini tosylas (Pirilenum)

Orally

0.01 0.03
120. Pentetrazolum (Corazolum)

Orally

0.2 0.5
121. Pentobarbitalum natricum (Aethamininalum - natrium)

Orally

0.3 0.6
122. Phenacetinum

Orally

0.5 1.5
123. Phenasonum (Antipyrinum)

Orally

1.0 3.0
124. Phenatinum

Orally

0.2 0.6
125. Phenylephrini hydrochloridum (Mesatonum)

Orally

0.03 0.15
126. Phenindionum (Phenylinum)

Orally

0.05 0.2
127. Phenobarbitalum

Orally

0.2 0.5
128. Phenylbutazonum (Butadionum)

Orally

0.2 0.6
129. Phthalylsulfathiazolum (Phthalazolum)

Orally

2.0 7.0
130. Plasmocidum

Orally

0.03 0.06
131. Platyphyllini hydrotartras

Orally

0.01 0.03
132. Prednisolonum

Orally

0.015 0.1
133. Prednisonum

Orally

0.015 0.1
134. Primidonum (Hexamidinum)

Orally

0.75 2.0
135. Procainamidi hydrochloridum (Novocainamidum)

Orally

1.0 4.0
136. Procaini hydrochloridum (Novocainum)

Orally

0.25 0.75
137. Proguanili hydrochloride (Bigumalum)

Orally

0.3 0.6
138. Promazini hydrochloridum (Propazinum)

Orally

0.25 2.0
139. Promeranum

Orally

0.036 0.144
140. Promethazini hydrochloridum (Diprazinum)

Orally

0.075 0.5
141. Quateronum

Orally

0.05 0.2
142. Qinocidum (Chinocidum)

Orally

0.03 0.03
143. Racemelphalanum (Sarcolysinum)

Orally

0.05 (1 time in 7 days) -
144. Reserpinum

Orally

0.002 0.01
145. Salsolini hydrochloridum

Orally

0.1 0.3
146. Santoninum

Orally

0.1 0.3
147. Secale cornutum

Orally

1.0 5.0
148. Securinini nitras

Orally

0.005 0.15
149. Solutio Iodi spirituosae 5 %

Orally

  20 drops   60 drops
150. Solutio Iodi spirituosae 10 %

Orally

  10 drops   30 drops
151. Solutio Lanatosidum C (Solutio Celanidi) 0,05 %

Orally

  1 ml   2 ml
152. Solutio Neriolini 0,022 %

Orally

0.75 ml (37 drops) 1.5 ml (75 drops)
153. Sphaerophysini benzoas

Orally

0.05 0.1
154. Strychnini nitras

Orally

0.002 0.005
155. Sulfacarbamidum (Urosulfanum)

Orally

2.0 7.0
156. Sulfacetamidum natricum (Sulfacylum - natrium)

Orally

2.0 7.0
157. Sulfadimidinum (Sulfadimezinum)

Orally

2.0 7.0
158. Sulfaethidolum (Aethazolum)

Orally

2.0 7.0
159. Sulfaethidolum natricum (Aethazolum - natrium)

Orally

2.0 7.0
160. Sulfaguanidinum (Sulginum)

Orally

2.0 7.0
161. Sulfanilamidum (Streptocidum)

Orally

2.0 7.0
162. Sulfathiasolum (Norsulfazolum)

Orally

2.0 7.0
163. Sulfathiasolum - natricum (Norsulfazolum - natrium)

Orally

2.0 7.0
164. Tetracyclini hydrochloridum

Orally

0.5 2.0
165. Tetracyclinum

Orally

0.5 2.0
166. Thecodinum

Orally

0.01 0.03
167. Theobrominum

Orally

1.0 3.0
168. Theophyllinum

Orally; rectally

0.4 1.2
169. Trixexyphenidyli hydrochloridum (Thiphenum)

Orally

0.1 0.3
170. Thymolum

Orally

1.0 4.0
171. Thyreoidinum

Orally

0.3 1.0
172. Tinctura Belladonnae

Orally

0.5 ml (23 drops) 1.5 ml (70 drops)
173. Tinctura Opii benzoica

Orally

  2 ml   5 ml
174. Tinctura Opii simplex

Orally

0.5 ml (22 drops) 1.25 ml (55 drops)
175. Tinctura Strophanthi

Orally

0.2 ml (10 drops) 0.4 ml (20 drops)
176. Tinctura Strychni

Orally

0.3 ml (15 drops) 0.6 ml (30 drops)
177. Tolbutamidum (Butamidum)

Orally

1.5 4.0
178. Trihexyphenidyli hydrochloridum (Cyclodolum)

Orally

0.01 0.02
179. Trimeperidini hydrochloridum (Promedolum)

Orally

0.05 0.2
180. Trimethinum

Orally

0.4 1.2
181. Vicasol (Vikasolum)

Orally

0.03 0.06

Minister for Health G. Bērziņš

 

Annex 7
Cabinet Regulation No. 304
18 April 2006

Prescription Register

Minister for Health G. Bērziņš

 

Annex 8
Cabinet Regulation No. 304
18 April 2006

Information to Be Indicated on a Control Counterfoil

1. The date.

2. The prescription number or the request number of the medical treatment institution;

3. The name and amount of starting materials.

4. Semi-finished products and concentrates used (if any used), the quantitative proportions thereof and the concentration.

5. Total weight. For powders, suppositories and pellets - also the weight of one dose and the number of doses.

6. Stabilising and isotonising agents (if any added) and the amount thereof, if eye drops are being prepared.

7. Water absorption coefficients used in calculations, if crude herbal medicinal plants are used in the preparation of medicinal products.

8. Coefficients for magnification of capacity of aqueous solutions used for calculations, if the solution of substances is used in the preparation of medicinal products.

9. The given name, surname, signature of the pharmacist/pharmacist assistant.

Minister for Health G. Bērziņš

 

Annex 9
Cabinet Regulation No. 304
18 April 2006

Permissible Deviations of the Total Mass or Volume of a Pharmaceutical Form and the Amount of Certain Substances

1. Permissible deviations of the total mass, weighing out in doses

No.

Powder mass in grams

Permissible deviation in per cent

1.1. up to 0.1  

± 15

1.2. more than 0.1 to 0.2  

± 10

1.3. more than 0.2 to 0.3  

± 7

1.4. more than 0.3 to 0.5  

± 5

1.5. more than 0.5 to 0.8  

± 4

1.6. more than 0.8 to 1  

± 3

1.7. more than 1 to 2  

± 4

1.8. more than 2 to 5  

± 3

1.9. more than 5 to 10  

± 2

1.10. more than 10  

± 1

2. Permissible deviations of the mass of certain components in powders and suppositories

No.

Amount prescribed in grams

Permissible deviation in per cent

2.1. from 0.01 to 0.02  

± 20

2.2. more than 0.02 to 0.05  

± 15

2.3. more than 0.05 to 0.2  

± 10

2.4. more than 0.2 to 0.3  

± 8

2.5. more than 0.3 to 0.5  

± 6

2.6. more than 0.5 to 1  

± 5

2.7. more than 1 to 2  

± 4

2.8. more than 2 to 5  

± 3

2.9. more than 5 to 10  

± 2

2.10. more than 10  

± 1

3. Permissible deviations of the total volume in liquid pharmaceutical forms manufactured using the mass-volume method.

No.

Amount prescribed in millilitres

Permissible deviation in per cent

3.1. up to 10  

+ 10

3.2. more than 10 to 20  

+ 8

3.3. more than 20 to 50  

+ 4

3.4. more than 50 to 150  

+ 3

3.5. more than 150 to 200  

+ 2

3.6. more than 200  

+ 1

4. Permissible deviations of the mass of certain components in liquid pharmaceutical forms manufactured using the mass-volume method.

No.

Amount prescribed in grams

Permissible deviation in per cent

4.1. from 0.01 to 0.02  

± 20

4.2. more than 0.02 to 0.1  

± 15

4.3. more than 0.1 to 0.2  

± 10

4.4. more than 0.2 to 0.5  

± 8

4.5. more than 0.5 to 0.8  

± 7

4.6. more than 0.8 to 1  

± 6

4.7. more than 1 to 2  

± 5

4.8. more than 2 to 5  

± 4

4.9. more than 5  

± 3

5. Permissible deviations of the total volume in liquid pharmaceutical forms manufactured using the mass method.

No.

Amount prescribed in grams

Permissible deviation in per cent

5.1. up to 10  

+ 10

5.2. more than 10 to 20  

+ 8

5.3. more than 20 to 50  

+ 5

5.4. more than 50 to 150  

+ 3

5.5. more than 150 to 200  

+ 2

5.6. more than 200  

+ 1

6. Permissible deviations of the mass of certain components in liquid pharmaceutical forms manufactured using the mass method.

No.

Amount prescribed in grams

Permissible deviation in per cent

6.1. up to 0.1  

± 20

6.2. more than 0.1 to 0.2  

± 15

6.3. more than 0.2 to 0.3  

± 12

6.4. more than 0.3 to 0.5  

± 10

6.5. more than 0.5 to 0.8  

± 8

6.6. more than 0.8 to 1  

± 7

6.7. more than 1 to 2  

± 6

6.8. more than 2 to 10  

± 5

7. Permissible deviations of the total mass for ointments

No.

Amount prescribed in grams

Permissible deviation in per cent

7.1. up to 5  

+ 15

7.2. more than 5 to 10  

+ 10

7.3. more than 10 to 20  

+ 8

7.4. more than 20 to 30  

+ 7

7.5. more than 30 to 50  

+ 5

Minister for Health G. Bērziņš

 


Translation © 2012 Valsts valodas centrs (State Language Centre)

 
Document information
Title: Noteikumi par zāļu ražošanas un kontroles kārtību, par zāļu ražošanu atbildīgās amatpersonas .. Status:
In force
in force
Issuer: Cabinet of Ministers Type: regulation Document number: 304Adoption: 18.04.2006.Entry into force: 01.07.2006.Theme: COVID-19Publication: Latvijas Vēstnesis, 70, 08.05.2006.
Language:
LVEN
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