Text consolidated by Valsts valodas centrs (State Language Centre) with amending regulations of: 7 January 2014 [shall come into force from 10 January 2014]; 30 September 2014 [shall come into force from 4 October 2014]. 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. 47 Adopted 22 January 2013

Pharmacovigilance Procedures

Issued pursuant to
Section 5, Paragraph 24 of the Pharmacy Law

I. General Provisions

1. This Regulation prescribes the procedures for pharmacovigilance.

2. This Regulation applies to the medicinal products for human use.

3. The following terms are used in this Regulation:

3.1. serious adverse drug reaction - an adverse reaction that results in death, is life-threatening, requires inpatient hospitalisation or prolongation of the existing hospitalisation, results in persistent or severe disability or incapacity for work, is a congenital anomaly, or is otherwise medically significant;

3.2. non-serious adverse drug reaction - an adverse reaction that does not correspond to any criteria for a serious adverse drug reaction;

3.3. pharmacovigilance system - the system used by the marketing authorisation holder and the competent authorities of the European Economic Area states (hereinafter - the EEA states) to fulfil the laid-down pharmacovigilance tasks and responsibilities, and that has been designed to monitor the safety of authorised medicinal products and find any changes in their risk-benefit balance;

3.4. pharmacovigilance system master file - a detailed description of the pharmacovigilance system used by the marketing authorisation holder of the medicinal product with respect to one or more authorised medicinal products;

3.5. post-authorisation safety studies - any study conducted with the authorised medicinal product with the aim of identifying, characterising or quantifying a health hazard, confirming the safety profile of the medicinal product, or of measuring the effectiveness of the risk management measures;

3.6. risk management system - a set of such pharmacovigilance activities performed by the marketing authorisation holder the aim of which is to identify, characterise, prevent or minimize risks related to the use of medicinal products, including the assessment of the effectiveness of the aforementioned activities;

3.7. risk management plan - a detailed description of the risk management system of the marketing authorisation holder.

4. The pharmacovigilance system shall be set up to collect the information on the risks posed by medicinal products to the patients and public health and to participate in pharmacovigilance process in the European Union. This information shall mainly apply to adverse drug reactions in humans, if medicinal products are used according to the marketing authorisation documentation of the medicinal product (including the summary of product characteristics) or that specified therein is not conformed to, including to:

4.1. the excessive use of medicinal products which has occurred upon using medicinal products assigned by a medical practitioner, exceeding the permitted maximum recommended dose specified in information of the medicinal products or upon cumulative accumulation of medicinal products (overdose). A conclusion on the overdose of medicinal products shall always be justified with a clinical assessment;

4.2. purposeful therapeutic use of medicinal products, without conforming to the information approved in the marketing authorisation documentation of the medicinal product and that indicated in the summary of product characteristics and patient information leaflet of the medicinal product (off-label use);

4.3. purposeful misuse of medicinal products, without conforming to the information approved in the marketing authorisation documentation of the medicinal product, also that indicated in the summary of product characteristics and patient information leaflet of the medicinal product (misuse of a medicinal product);

4.4. misuse of a medicinal product for illegal purposes, also illegal marketing of medicinal products and their administration against the will of a person in order to achieve a specific condition of the person and to exert violence upon a person (misuse of a medicinal product for illegal purposes);

4.5. systematic and intentional abuse of medicinal products for achieving a specific physical or psychological condition (abuse of a medicinal product);

4.6. unexpected effect of medicinal products which is related to professional or unprofessional action of a person (occupational exposure to a medicinal product);

4.7. unintentional mistake in prescribing, issuing, assigning or supervising medicinal products while the medicinal products are under control of a medical practitioner, pharmacist, or patient (medication error).

[30 September 2014]

5. Pharmacovigilance system shall be used to collect and scientifically evaluate the information on the manifestations of adverse drug reactions developed in individuals using medicinal products according to or not according to the marketing authorisation documentation of the medicinal product, and to consider options for risk minimisation and prevention, and, where necessary, regulatory activities with respect to the marketing authorisation of the medicinal product.

6. When performing all laid-down pharmacovigilance activities, the marketing authorisation holder shall follow the regulations and decisions adopted by the European Commission.

II. Rights and Responsibilities of the Medical Practitioner, Pharmacist and Patient

7. In order to ensure effective functioning of the pharmacovigilance system, a medical practitioner or a pharmacist shall report on the observed suspected adverse drug reactions to the State Agency of Medicines (the sample report form is included in Annex 1 to this Regulation) or the respective marketing authorisation holder.

8. A medical practitioner or pharmacist shall report to the State Agency of Medicines in accordance with this Regulation also on such adverse drug reactions to medicinal products that have been observed with the administration of unauthorised medicinal products including those available for compassionate use, as well as when taking part in the post-authorisation safety studies with medicinal products.

9. In the report, a medical practitioner or pharmacist shall provide comprehensive and exact information on the suspected adverse drug reaction in order to ensure the possibility for a scientific evaluation of the report within the pharmacovigilance system.

9.¹ A medical practitioner and a pharmacist shall report to the State Agency of Medicines on adverse reaction, particularly on a serious adverse reaction, as soon as the potential relation with the use of the particular medicinal product is noticed. If at the moment of reporting not all information is available in accordance with Annex 1 to this Regulation, the medical practitioner and pharmacist shall repeatedly prepare a report by supplementing it with the necessary information, and send it to the State Agency of Medicines.

[30 September 2014]

10. A medical practitioner or pharmacist shall follow the additional monitoring and reporting terms and conditions (e.g., the note in the summary of product characteristics and patient information leaflet on additional monitoring of the medicinal product) if such are laid down for the specific medicinal product or active substance.

11. A patient has the right to report to the State Agency of Medicines or the marketing authorisation holder on the suspected adverse drug reactions (also by using the sample report form indicated in Annex 2 to this Regulation or the website of the State Agency of Medicines www.zva.gov.lv).

[30 September 2014]

11.¹ A medical practitioner, pharmacist or patient is entitled to submit a report on adverse drug reactions to the State Agency of Medicines or the marketing authorisation holder in the form of an electronic document, sending it to the electronic mail address, or in the form of a printed document, submitting it in person or sending it by post or fax. The report may also be submitted online by filling in an electronic report form on the website of the State Agency of Medicines.

[30 September 2014]

12. Upon a request of the State Agency of Medicines or the marketing authorisation holder, a medical practitioner, pharmacist or patient shall provide additional information regarding the observed suspected adverse drug reactions.

13. Medical treatment institutions, professional organisations of medical practitioners and pharmacists and patient organisations shall comply with the medicinal product administration risk minimisation measures and exchange information regarding pharmacovigilance issues (also on the adverse drug reactions) with the State Agency of Medicines in order to ensure effective functioning of the pharmacovigilance system.

14. The responsible authorities of the national healthcare system shall get involved in the implementation of the medicinal product administration risk minimisation measures within the scope of their competence, and shall exchange information regarding pharmacovigilance issues (also on the adverse drug reactions) with the State Agency of Medicines and marketing authorisation holders in order to ensure effective functioning of the pharmacovigilance system.

III. Responsibilities of the Marketing Authorisation Holder of a Medicinal Product

15. The marketing authorisation holder of a medicinal product shall:

15.1. ensure the establishment of a pharmacovigilance system and quality system in accordance with the system referred to in Paragraph 4 of this Regulation. The quality system shall be developed in accordance with Article 8 of Commission Implementing Regulation (EU) No 520/2012 of 19 June 2012 on the performance of pharmacovigilance activities provided for in Regulation (EC) No 726/EC of the European Parliament and of the Council and Directive 2001/83/EC of the European Parliament and of the Council (hereinafter - Regulation No 520/2012);

15.2. using the pharmacovigilance system referred to in the Sub-paragraph 15.1 of this Regulation, perform a scientific evaluation of the information, and, if necessary, implement appropriate risk minimisation measures;

15.3. have permanently and continuously at its disposal an appropriately qualified person responsible for pharmacovigilance (hereinafter - the responsible person) who is living and working in the European Union and is responsible for the establishment and maintenance of the pharmacovigilance system. The given name, surname, address of the site of operation, electronic mail address, telephone number, and fax number (if any) of the responsible person, including for communication outside working hours, shall be submitted to the State Agency of Medicines, as well as to the European Medicines Agency in the format which is used for electronic submission of information to the European Medicines Agency regarding all medicinal products for human use authorised in the European Union;

15.4. appoint a national level contact person for pharmacovigilance issues (hereinafter - the national level contact person) who lives and works in Latvia, if the responsible person does not live and work in Latvia. The contact details of the national level contact person - the given name, surname, address of the site of operation, electronic mail address, telephone number, and fax number (if any), including for communication outside working hours, as well as changes in the contact details (if any) shall be submitted to the State Agency of Medicines without delay;

15.5. maintain and, upon a request of the European Medicines Agency or the State Agency of Medicines, ensure availability of the copy of the pharmacovigilance system master file within seven days;

15.6. ensure that the risk management system has been established and is functioning with respect to all medicinal products, except for those with a marketing authorisation granted before 21 July 2012, unless otherwise provided for in the laws and regulations regarding the marketing authorisation procedures;

15.7. monitor the results of the risk minimisation measures included in the risk management plan or determined in accordance with the laws and regulations regarding the marketing authorisation procedures;

15.8. regularly update the risk management system and monitor pharmacovigilance data to determine, whether new risks have arisen, risks have changed or there are changes in the risk-benefit balance of the medicinal product. The risk minimisation measures drawn up for the medicinal product shall be submitted to the State Agency of Medicines for co-ordination;

15.9. perform a regular audit of the pharmacovigilance system, place a note concerning the main discrepancies found during the audits in the pharmacovigilance system master file, and ensure that an appropriate corrective action plan is prepared and implemented on the basis of the audit.

[30 September 2014 / The requirement referred to in Sub-paragraph 15.4 for the national level contact person to live and work in Latvia shall come into force on 1 July 2015. See Paragraph 71]

16. The national level contact person shall report to the responsible person on pharmacovigilance activities and act according to the instructions of the responsible person.

[30 September 2014]

17. With respect to the collection, recording, reporting and assessment of pharmacovigilance data, the marketing authorisation holder of the medicinal product shall:

17.1. record all serious suspected adverse drug reactions observed in any EEA state or in any third country which are brought to its attention from the report of a medical practitioner, pharmacist or patient, or occurring in the context of a post-authorisation study, and immediately, but no later than within 15 days after receipt of the information, shall send the report electronically for submission to the European Union adverse reactions database (hereinafter - the Eudravigilance database);

17.2. record all non-serious suspected adverse drug reactions observed in any EEA state, and shall send the report electronically for submission to the Eudravigilance database no later than within 90 days after receipt of the information;

17.3. ensure availability of the reports referred to in Sub-paragraphs 17.1 and 17.2 of this Regulation at the Eudravigilance database;

17.4. accept and examine the reports provided by the State Agency of Medicines, medical practitioners, pharmacists, including if they are forwarded by a parallel importer and parallel distributor, and patients on the suspected adverse drug reactions;

17.5. draw up written procedures for the collection of precise and verifiable data for the scientific evaluation of the report on suspected adverse drug reactions, and also additional information regarding the report on suspected adverse drug reactions;

17.6. co-operate with the European Medicines Agency and competent authorities of the EEA states to identify duplication of reports on suspected adverse drug reactions;

17.7. electronically submit to the European Medicines Agency periodic safety update reports (hereinafter - the periodic reports) in accordance with Chapter V of this Regulation;

17.8. submit an application to the State Agency of Medicines for variation to the marketing authorisation of the medicinal product, appending an updated summary of product characteristics and patient information leaflet in accordance with the laws and regulations regarding the procedures for the marketing authorisation of medicinal products;

17.9. inform the European Medicines Agency and the State Agency of Medicines if any new risks have arisen, the existing risks have changed, or changes in the risk-benefit balance have been identified;

17.10. after receipt of information regarding serious suspected adverse drug reactions which are brought to attention, as soon as possible, but not later than within 15 days, inform the State Agency of Medicines.

[30 September 2014]

18. When reporting on adverse drug reactions, the international terms shall be used in accordance with Article 25 of Regulation No 520/2012.

19. Prior to making a public announcement, the marketing authorisation holder shall inform the State Agency of Medicines, the European Medicines Agency and the European Commission on the safety of the authorised medicinal product. The marketing authorisation holder shall ensure that the provided information is objective, it may not be misleading.

20. Suspected adverse drug reactions established during the clinical trials shall be recorded in accordance with the laws and regulations regarding the procedures for conducting clinical trials and observations on the use of medicinal products.

III.¹ Responsibilities of a Parallel Importer of Medicinal Products and Parallel Distributor of Medicinal Products

[30 September 2014]

20.¹ If a parallel importer of medicinal products becomes aware of information regarding adverse drug reactions, it shall, as soon as possible, but not later than within two days after receipt of the report on adverse drug reactions, forward it to the State Agency of Medicines and the marketing authorisation holder, as well as inform the sender of information that adverse drug reactions must be reported directly to the State Agency of Medicines or the marketing authorisation holder.

20.² If a parallel distributor of medicinal products becomes aware of information regarding adverse drug reactions, it shall, as soon as possible, but not later than within two days after receipt of the report on adverse drug reactions, forward it to the marketing authorisation holder, as well as inform the sender of information that adverse drug reactions must be reported directly to the marketing authorisation holder.

20.³ A parallel importer and parallel distributor of medicinal products shall appoint a co-ordinator who is responsible for the fulfilment of the requirements referred to in Paragraphs 20.¹ and 20.² of this Regulation in relation to the medicinal products distributed, and submit contact details of the co-ordinator (given name, surname, address of the site of operation, electronic mail address, telephone number, and fax number (if any)) to the State Agency of Medicines.

IV. Responsibilities of the State Agency of Medicines

21. The State Agency of Medicines shall:

21.1. register all suspected adverse drug reactions which have been observed in the territory of the Republic of Latvia and on which medical practitioners, pharmacists, or patients, also parallel importers who have forwarded the relevant information have reported, as well as of which marketing authorisation holders have notified;

21.2. immediately make publicly available information on the observed pharmacovigilance problems when these result in a serious threat to the public health;

21.3. at least 24 hours prior to the publication of the information, inform the European Medicines Agency and the European Commission of the observed serious pharmacovigilance problems;

21.4. agree on risk minimisation measures included in the risk management plan of the marketing authorisation holder, and monitor their results;

21.5. assess updates of the risk management systems for the authorised medicinal products;

21.6. monitor the Eudravigilance database data in order to determine whether new risks have occurred, risks have changed or these risks have an impact on the risk-benefit balance;

21.7. ensure regular audit of their pharmacovigilance system and inform the European Commission of the results once in two years;

21.8. ensure a link of the website with the website of the European Medicines Agency set up in accordance with Article 26 of Regulation (EC) No 726/2004 of the European Parliament and of the Council of 31 March 2004 laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency (hereinafter - Regulation No 726/2004), and where at least the following information is available:

21.8.1. public assessment reports and their summaries;

21.8.2. summaries of product characteristics and patient information leaflets;

21.8.3. summaries of risk management plans for authorised medicinal products;

21.8.4. list of the medicinal products referred to in Article 23 of Regulation No 726/2004;

21.8.5. information regarding reporting options (also a form for reporting on suspected adverse drug reactions), as well as other essential information regarding pharmacovigilance issues;

21.9. draw up, maintain, and update the list with contact details of the responsible persons and national level contact persons (given name, surname, address of the site of operation, electronic mail address, telephone number, and fax number (if any), including for communication outside working hours);

21.10. after receipt of information regarding serious suspected adverse drug reactions which have become known in relation to the authorised medicinal products, as soon as possible, but not later than within 15 days, inform the marketing authorisation holder. Adverse drug reactions may be reported to the national level contact person referred to in Sub-paragraph 15.4 of this Regulation.

[30 September 2014]

22. After assessment of the reports referred to in the Sub-paragraph 21.1 of this Regulation, the State Agency of Medicines shall send the following reports to be entered in the Eudravigilance database in electronic form:

22.1. on serious suspected adverse drug reactions - within 15 days;

22.2. on non-serious suspected adverse drug reactions - within 90 days.

23. The State Agency of Medicines shall co-operate with the competent authorities of other EEA states, the European Medicines Agency and marketing authorisation holders to identify duplication of reports on suspected adverse drug reactions.

24. When the information referred to in the Sub-paragraph 21.2 of this Regulation is made publicly available, the requirements laid down in the Personal Data Protection Law with respect to the provision of information shall be conformed to, unless such information must be disclosed in order to ensure the protection of public health.

25. The State Agency of Medicines shall inform the competent authorities of other EEA states, the European Medicines Agency, as well as marketing authorisation holders if any new risks have arisen, the existing risks have changed or changes in the risk-benefit balance have been identified.

V. Periodic Safety Update Reports

26. When submitting the periodic report referred to in the Sub-paragraph 17.7 of this Regulation to the European Medicines Agency:

26.1. the marketing authorisation holder shall include the following therein:

26.1.1. summaries of data relevant to the benefits and risks of the medicinal product, also results of all studies with a consideration of their potential impact on the marketing authorisation terms;

26.1.2. a scientific evaluation of the risk-benefit balance of the medicinal product based on the available data, also data from clinical trials on unauthorised indications and populations;

26.1.3. all data on the sales volume of the medicinal product and any data in the possession of the marketing authorisation holder relating to the volume of prescriptions, also an estimate of the population exposed to the medicinal product;

26.2. the marketing authorisation holder with a marketing authorisation granted before 21 July 2012, and with no submission of periodic reports as a condition in the marketing authorisation, shall promptly submit a periodic report upon a request of the State Agency of Medicines or according to the following procedure:

26.2.1. if the medicinal product has not been marketed yet - at least once in six months after granting of the authorisation and until the placing on the market;

26.2.2. if the medicinal product has been marketed:

26.2.2.1. during the first two years - at least once in every six months after the initial placing on the market;

26.2.2.2. during the next two years - annually;

26.2.2.3. afterwards - once every three years.

27. The State Agency of Medicines shall assess the periodic reports in order to determine whether new risks have arisen, risks have changed or there are changes in the risk-benefit balance.

28. A single report shall be prepared by the member state nominated by the Co-ordination Group of the European Medicines Agency (hereinafter - the Co-ordination Group), or by a rapporteur appointed by the Pharmacovigilance Risk Assessment Committee of the European Medicines Agency.

29. If the reference state or the rapporteur is Latvia, the State Agency of Medicines shall prepare a periodic report assessment report within 60 days and send it to the European Medicines Agency, as well as the competent authorities of the EEA states.

30. If the reference state or the rapporteur is another EEA state, the State Agency of Medicines may submit its own considerations of the assessment report to the European Medicines Agency, the competent authority of the respective EEA state or the rapporteur within 30 days after receipt of the assessment report.

31. If the reference state or the rapporteur is Latvia, the State Agency of Medicines shall update the assessment report within 15 days after receipt of the considerations, taking into account all submitted comments, and shall forward them to the Pharmacovigilance Risk Assessment Committee.

32. After assessment of periodic reports the State Agency of Medicines shall, if necessary, decide on the maintenance, variation, suspension or revocation of the marketing authorisation, respectively, in accordance with the laws and regulations regarding the marketing authorisation of medicinal products.

VI. Urgent Union Procedure Related to the Safety of Medicinal Products

33. The State Agency of Medicines, on the basis of evaluation of the data obtained as a result of pharmacovigilance measures and considerations of the potential risk of use of medicinal products, shall initiate the Union procedure, informing the European Medicines Agency, the European Commission, as well as the competent authorities of the EEA countries if:

33.1. the marketing authorisation holder has informed the State Agency of Medicines that due to safety considerations it has discontinued the distribution of medicinal products, has acted in order to achieve revocation of the marketing authorisation for the medicinal product, or has an intention of acting in such a way, or has not submitted an application for the renewal of a marketing authorisation of medicinal products;

33.2. it decides to:

33.2.1. suspend or revoke the marketing authorisation for the medicinal product or to refuse the renewal of a marketing authorisation of the medicinal product in accordance with the laws and regulations regarding the procedures for the marketing authorisation of medicinal products;

33.2.2. prohibit the medicinal product supply in co-operation with the Health Inspectorate in accordance with the laws and regulations regarding the procedures for the distribution and quality control of medicinal products.

[7 January 2014]

34. The State Agency of Medicines shall inform the competent authorities of the EEA countries, the European Medicines Agency, and the European Commission if, of the basis of considerations of the potential risk of use of medicinal products which arises from evaluation of the data obtained as a result of pharmacovigilance measures, it is of the opinion that an indication of new contraindications of medicinal products, reduction of the recommended dose, or restriction to the indications is necessary. Upon providing the abovementioned information, the State Agency of Medicines shall offer the potential solution and its justification.

[7 January 2014]

34.¹ If urgent action is necessary, the State Agency of Medicines shall initiate the Union procedure in any of the cases referred to in Paragraph 34 of this Regulation.

[7 January 2014]

34.² If the Union procedure is not initiated for the medicinal products authorised under the decentralised procedure or mutual recognition procedure in accordance with the laws and regulations regarding the marketing authorisation of medicinal products, the State Agency of Medicines shall submit the issue to the Co-ordination Group for examination.

[7 January 2014]

34.³ If it is related to the interests of the European Union, the State Agency of Medicines and the marketing authorisation holder, in accordance with the laws and regulations regarding the marketing authorisation of medicinal products, is entitled to submit an issue for examination to the Committee for Medicinal Products for Human Use or the Pharmacovigilance Risk Assessment Committee of the European Medicines Agency.

[7 January 2014]

34.⁴ In relation to medicinal products which are authorised under the national authorisation procedure which is not the decentralised procedure or the mutual recognition procedure, the State Agency of Medicines shall solve the safety concern in accordance with this Regulation and the laws and regulations regarding the marketing authorisation for the medicinal products, as well as inform the relevant marketing authorisation holder that the Union procedure has been initiated.

[7 January 2014]

35. If urgent measures are required to ensure protection of the public health, the State Agency of Medicines has the right to suspend the marketing authorisation until the final decision is made, and to prohibit the use of the respective medicinal product in the territory of Latvia, informing the European Medicines Agency, the European Commission and the competent authorities of other EEA states thereof not later than on the next working day.

36. The Urgent Union procedure related to the safety of medicinal products may apply to individual medicinal products, to a range of medicinal products, or to a therapeutic class of medicinal products.

[7 January 2014]

37. The State Agency of Medicines shall provide all the important scientific data available thereto and all the assessments performed by the State Agency of Medicines to the European Medicines Agency in accordance with Paragraphs 33 and 34 of this Regulation.

[7 January 2014]

38. If the Co-ordination Group has decided to maintain, vary, suspend, revoke the marketing authorisation of the respective medicinal product or to refuse to renew a marketing authorisation for a marketing authorisation holder, and also has decided on the implementation schedule for the joint position, the marketing authorisation holder shall submit a variation application to the State Agency of Medicines in accordance with the defined implementation schedule, and shall append an updated summary of product characteristics and patient information leaflet in accordance with the laws and regulations regarding the marketing authorisation of medicinal products.

39. Upon receipt of the joint position referred to in the Paragraph 38 of this Regulation, the State Agency of Medicines shall perform activities to maintain, vary, suspend or revoke the marketing authorisation of a medicinal product, or to refuse to renew a marketing authorisation according to the implementation schedule.

VII. Post-Authorisation Safety Studies

40. A marketing authorisation holder shall collect safety data in non-interventional post-authorisation safety studies (hereinafter - the post-authorisation studies) from medical practitioners, pharmacists and patients; post-authorisation studies shall be initiated, managed or financed voluntarily or to implement the marketing authorisation conditions of the medicinal product in accordance with the laws and regulations regarding the marketing authorisation of medicinal products.

41. A marketing authorisation holder of the medicinal product shall be responsible for the conduct of post-authorisation studies in accordance with the professional standards, and shall ensure the rights and data protection of individuals involved in the study.

42. The purpose of a post-authorisation study is not to promote the use of the medicinal product.

43. During the study, a marketing authorisation holder shall monitor the collected data and consider their effect on the risk-benefit balance of the respective medicinal product.

44. Any new data (except for the data indicated by a marketing authorisation holder in the periodic safety update report) that may affect the assessment of the risk-benefit balance of the medicinal product shall be reported by the marketing authorisation holder of the medicinal product to the State Agency of Medicines.

45. If a study has been conducted in the Republic of Latvia, a marketing authorisation holder of the medicinal product shall submit the final report to the State Agency of Medicines within 12 months after finalisation of the post-authorisation study.

46. In order to fulfil the conditions of the marketing authorisation of medicinal products referred to in the laws and regulations regarding the procedures for marketing authorisation of medicinal products, a marketing authorisation holder shall submit a draft post-authorisation study protocol in accordance with the conditions for the performance of pharmacovigilance activities provided in Regulation No 520/2012:

46.1. to the Pharmacovigilance Risk Assessment Committee - if the study is to be conducted in more than one state;

46.2. to the State Agency of Medicines - if the study is to be conducted only in the Republic of Latvia.

47. The State Agency of Medicines shall prepare for a marketing authorisation holder of the medicinal product an opinion on the approval of the draft protocol or an opinion with justified objections within 60 days after receipt of the draft protocol referred to in the Paragraph 46 of this Regulation in any of the cases referred to in this Paragraph, if it is of the opinion that:

47.1. the conduct of the study will promote the use of the medicinal product;

47.2. the way the study will be conducted does not correspond to the study tasks;

47.3. the study is a clinical trial.

48. During the post-authorisation study referred to in the Sub-paragraph 46.2 of this Regulation, the marketing authorisation holder shall submit to the State Agency of Medicines any major amendments to the protocol for assessment prior to their implementation.

49. The State Agency of Medicines shall assess the submitted amendments within 30 days and notify the marketing authorisation holder of the medicinal product of the approval of the protocol or objections.

50. The marketing authorisation holder of the medicinal product shall submit to the State Agency of Medicines the final report of the study within 12 months after finalisation of the post-authorisation study.

51. The marketing authorisation holder of the medicinal product shall assess whether the results of the post-authorisation study have an impact on the marketing authorisation of the medicinal product and, if necessary, shall submit an application for variation to the marketing authorisation of the medicinal product to the State Agency of Medicines.

52. The marketing authorisation holder of the medicinal product shall submit the summary of the study results and the final report to the State Agency of Medicines in electronic form.

53. If post-authorisation study has been conducted in several EEA states, the study may be initiated only after the Pharmacovigilance Risk Assessment Committee has issued a written permission to the marketing authorisation holder of the medicinal product.

VIII. Pharmacovigilance Monitoring

54. In order to assess the conformity of the marketing authorisation holder of the medicinal product with good pharmacovigilance practice, the State Agency of Medicines shall check the conformity of the pharmacovigilance system of the marketing authorisation holder with the requirements laid down in this Regulation by performing routine inspections, re-inspections and for cause inspections.

55. In performing the inspections referred to in Paragraph 54 of this Regulation, the competent official of the State Agency of Medicines has the right to:

55.1. inspect the undertaking of the marketing authorisation holder and the affiliated undertakings and representations of the marketing authorisation holder of the medicinal product, including premises, equipment, staff, quality assurance measures related to the pharmacovigilance system of the marketing authorisation holder;

55.2. review the documentation of the object to be inspected and inspect the documentation records;

55.3. inspect the pharmacovigilance system master file.

[30 September 2014]

56. Authorised persons of the State Agency of Medicines shall prepare an inspection report after the inspection. It shall be indicated in the inspection report whether the marketing authorisation holder complies with the good pharmacovigilance practice. If it is concluded during the inspection that the pharmacovigilance system of the marketing authorisation holder does not conform to its description in the pharmacovigilance system master file or the requirements laid down in this Regulation, the State Agency of Medicines shall indicate the inspection findings in the inspection report and shall ensure a possibility for the marketing authorisation holder to provide explanations.

[30 September 2014]

57. The marketing authorisation holder of the medicinal product, if necessary, shall submit a corrective action plan to the State Agency of Medicines within 30 days.

58. The State Agency of Medicines shall prepare a final inspection report based on the plan referred to in Paragraph 57 of this Regulation, and send it to the marketing authorisation holder of the medicinal product, as well as to the competent authorities of other EEA states or the European Medicines Agency, if a justified request has been received.

59. If inspection results show that the pharmacovigilance system of the marketing authorisation holder does not correspond to the description in the pharmacovigilance system master file or the requirements laid down in this Regulation, the State Agency of Medicines shall evaluate and, if necessary, inform the competent authorities of other EEA states, the European Medicines Agency and the European Commission of the inspection findings.

60. The State Agency of Medicines shall suspend, revoke or vary the marketing authorisation documentation of a medicinal product, or extend the marketing authorisation based on the conditions referred to in the laws and regulations regarding the procedures for the marketing authorisation of medicinal products.

61. The State Agency of Medicines shall take a decision to revoke the decision to suspend the marketing authorisation referred to in Paragraph 60 of this Regulation, if the conditions which were the grounds for taking the decision have been eliminated.

62. The State Agency of Medicines, in accordance with Article 19 of Regulation No 726/2004, has the right to perform pre-authorisation pharmacovigilance inspections for a medicinal product, if necessary.

63. After the inspection referred to in Paragraph 62 of this Regulation, the State Agency of Medicines shall prepare a report to be electronically sent to the European Medicines Agency, the competent authorities of the EEA states and the European Commission.

64. The State Agency of Medicines and the Health Inspectorate shall co-operate according to their competence to ensure the fulfilment of the requirements laid down in this Regulation.

IX. Closing Provisions

65. Cabinet Regulation No. 919 of 6 December 2005, Regulations Regarding the Monitoring of Adverse Reactions Caused by the Use of Medicinal Products (Latvijas Vēstnesis, 2005, No. 196; 2008, No. 10), is repealed.

66. The State Agency of Medicines shall prepare and submit to the European Commission the first overview of the pharmacovigilance system audit until 21 September 2013.

67. The requirement referred to in Sub-paragraph 15.5 of this Regulation for a marketing authorisation holder to maintain and make available upon request the pharmacovigilance system master file on one or several medicinal products to which marketing authorisation has been granted before 21 July 2012, shall apply from the day when the decision on renewal of the marketing authorisation was made, or from 21 July 2015 (whichever date is earlier).

68. Chapter VII of this Regulation shall apply to the post-authorisation studies initiated after 21 July 2012.

69. Until the European Medicines Agency ensures full functionality of Eudravigilance database , any serious suspected adverse drug reactions observed in the territory of Latvia shall be reported by the marketing authorisation holder of the medicinal product not later than within 15 days after receipt of the information to the State Agency of Medicines, but any suspected adverse drug reactions observed in the territory of third countries - to the European Medicines Agency.

70. Until the European Medicines Agency can ensure the functionalities agreed for the repository of the periodic reports, the marketing authorisation holder of the medicinal product shall submit the periodic reports to the State Agency of Medicines, if the medicinal product has been authorised in Latvia.

71. The requirement referred to in Sub-paragraph 15.4 of this Regulation for the national level contact person to live and work in Latvia shall come into force on 1 July 2015.

[30 September 2014]

Informative Reference to the European Union Directives

[7 January 2014]

This Regulation contains legal norms arising from:

1) Directive 2010/84/EU of the European Parliament and of the Council of 15 December 2010 amending, as regards pharmacovigilance, Directive 2001/83/EC on the Community code relating to 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) Directive 2012/26/EU of the European Parliament and of the Council of 25 October 2012 amending Directive 2001/83/EC as regards pharmacovigilance.

Prime Minister V. Dombrovskis

Minister for Health I. Circene

 

Annex 1
Cabinet Regulation No. 47
22 January 2013

[30 September 2014]

TO THE STATE AGENCY OF MEDICINES

REPORT OF A MEDICAL PRACTITIONER, PHARMACIST ON AN ADVERSE DRUG REACTION

If, upon filling in the report form in printed form, you lack space for the provision of information, please use an extra sheet of paper, and submit it together with the filled-in report form.

1. INFORMATION REGARDING THE REPORTER		2. INFORMATION REGARDING THE PATIENT
Given name, surname		Initials of the given name, surname (or code)
Speciality		Sex		M F
Certificate number		Age (please provide the number of full years or months)
Address of the place of employment		Weight (please provide exact weight in kilograms)
Contact details (in order to specify (if necessary) the information in the report in more detailed way, please provide the contact phone and/or e-mail address)		Hospital (please provide, if the patient has been hospitalised)
3. DESCRIPTION OF THE ADVERSE DRUG REACTION
Date when the reaction started	(dd/mm/yyyy)	Start time of the reaction, hrs/min
Description (symptoms, laboratory and other examinations, treatment of the adverse drug reaction)
Caused patient's death		Did the adverse drug reaction resolve		Was the medicinal product used for the first time in one's life
Was life-threatening		Completely		Yes No
Required hospitalisation of the patient or prolongation of the hospitalisation		Not resolved yet
Resulted in persistent or severe disability or incapacity		With permanent consequences		If the medicinal product has been used repeatedly, were similar adverse drug reactions observed the previous time
Is a congenital anomaly		Not known		Yes No
Is otherwise medically important
4. MEDICINAL PRODUCT, WHICH IS THE POSSIBLE CAUSE OF THE ADVERSE REACTION
Name, form and manufacturer of the medicinal product, batch number (indicate the name assigned by the manufacturer, the name of the active substance - see information on the packaging of the medicinal product; it is particularly important to indicate the serial number for biological medicinal products)	Route of administration	Single dose/frequency	Start of the use	End of the use	Indication for the use
5. OTHER MEDICINAL PRODUCTS USED DURING THE LAST THREE MONTHS (INCLUDING SELF-TREATMENT)
Name and form of the medicinal product	Route of administration	Single dose/ frequency	Start of the use	End of the use	Indication for the use
6. ADDITIONAL INFORMATION For example: 1) regarding a severe concomitant disease, allergic reactions, hypersensitivity to medicinal products, pregnancy, important results of examinations; 2) parallel imported medicinal products, parallel distributed medicinal products, or unauthorised medicinal products have been used; 3) whether the medicinal product is biological medicinal product, for example, immunological preparations - vaccines, toxins, serums, allergens, medicinal product derived from human blood and human plasma, advanced therapy medicinal products, for example, gene therapy medicinal products, somatic cell therapy medicinal products.

Reporter's signature			Date
	(given name, surname)			(dd/mm/yyyy)

By signing this report I give a consent to employees of the State Agency of Medicines to contact me in order to verify the information referred-to in the report and to ask the necessary additional questions.

The detail of the document "Reporter's signature" shall not be completed if the electronic document has been prepared in accordance with the laws and regulations regarding drawing up of electronic documents.

Minister for Health I. Circene

 

Annex 2
Cabinet Regulation No. 47
22 January 2013

[30 September 2014]

TO THE STATE AGENCY OF MEDICINES

Report No.

(to be filled in by the employee of the State Agency of Medicines)

REPORT OF A PATIENT ON AN ADVERSE DRUG REACTION

Please provide as detailed information as possible on the observed adverse drug reaction. If you lack space on the report form for provision of information, please use an extra sheet of paper, and lodge it together with the filled-in report form.

1. INFORMATION REGARDING THE REPORTER
Given name					Surname
Contact phone					E-mail
In order to specify (if necessary) the information referred to in the report in more detailed way, please provide your contact phone and/or e-mail address.
2. INFORMATION REGARDING THE PERSON WHO HAD THE SUSPECTED REACTION
Regarding the reporter					Regarding another person (person whose legal or authorised representative is reporter, person's minor child, person who has been recognised as lacking capacity to act)
Regarding the effect on a foetus during pregnancy					Regarding the effect on a child during breast-feeding period
Given name					Surname
Sex	M F				Weight (please provide exact weight in kilograms)
Date of birth	(dd/mm/yyyy)				Age (please provide the number of full years or months)
Please provide the age as accurately as possible. When a specific birth date is not known, provide the age in full years or months.
3. DESCRIPTION OF THE ADVERSE DRUG REACTION
Date and time when the reaction started		(dd/mm/yyyy, hrs/min)			Date when the reaction ended (if the reaction has ended)		(dd/mm/yyyy)
Was the person's physician informed regarding the observed adverse drug reaction					Yes No (If the person has informed the physician regarding the adverse drug reaction, please fill in Paragraph 7 of this report)
Please provide a short description of the adverse drug reaction by providing the most essential information at your discretion (short description of symptoms, results of laboratory and other investigations, if available, treatment of the adverse drug reaction)
What were the consequences of the adverse drug reaction				Caused person's death (dd/mm/yyyy)
				In person's opinion, was a life-threatening condition
				Required hospitalisation or prolongation thereof
				Resulted in persistent or severe disability or incapacity
				Is a congenital anomaly
				None of the above mentioned
Was the use of the medicinal product discontinued when the adverse drug reaction was detected					Yes No
Did the adverse drug reaction resolve					Completely		With remaining consequences
					Not resolved yet		Not known
Was the medicinal product, which is the possible cause of the adverse effect, used for the first time in one's life					Yes No
If the medicinal product has been used repeatedly, were similar adverse drug reactions observed the previous time					Yes No
4. MEDICINAL PRODUCT, WHICH IS THE POSSIBLE CAUSE OF THE ADVERSE REACTION
Information regarding the medicinal product
Name of the medicinal product (see the information on the package of the medicinal product)
Marketing authorisation holder/parallel importer (see the information on the package of the medicinal product)
Batch number of the medicinal product (see the information on the package of the medicinal product)
Date when the use was started					(dd/mm/yyyy)
Information regarding the use of the medicinal product
What was the amount of the single dose (e.g., 2 tablets, 1 injection, other)
How often was the medicinal product used (e.g., twice a day, other)
What was the purpose of use of the medicinal product (what symptoms or disease was/were treated)
Where the medicinal product was obtained
At the pharmacy					At the hospital
On the Internet (if possible, indicate the website address)
Imported from another state (if possible, indicate the state)
Other (if possible, indicate other source)
5. OTHER MEDICINAL PRODUCTS USED DURING THE LAST THREE MONTHS
Has any other medicinal product been used during the last three months					Yes No
Name of the medicinal product (to be filled in if any other medicinal product was used during the last three months. See the information on the package of the medicinal product)
Name of the medicinal product (to be filled in if any other medicinal product was used during the last three months. See the information on the package of the medicinal product)
6. OTHER INFORMATION (severe concomitant disease, allergy, hypersensitivity to any medicinal product, pregnancy)
7. INFORMATION REGARDING THE PERSON'S PHYSICIAN
I allow the State Agency of Medicines to contact the primary care physician or other medical practitioner (including the physician who was informed of the observed adverse drug reaction) in order to specify in more detail (if necessary) the information referred to in the report, as well as also the information regarding the person's health condition and the medicinal products used.
Yes, with the primary care physician			Yes, with another medical practitioner			(given name, surname of the medical practitioner)
Yes, another			Do not allow			(name, contact information of the medical practitioner's practice)
I have no knowledge of the person's primary care physician/other medical practitioner

Reporter's signature			Date
	(given name, surname)			(dd/mm/yyyy)

By signing this report I give a consent to employees of the State Agency of Medicines to contact me in order to verify (if necessary) the information referred to in the report and to ask the necessary additional questions.

The detail of the document "Reporter's signature" shall not be completed if the electronic document has been prepared in accordance with the laws and regulations regarding drawing up of electronic documents.

Minister for Health I. Circene

 

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Translation © 2018 Valsts valodas centrs (State Language Centre)