Official Letter from DOH

Transcription

1 Issued Date 2008/08/19 Issued by DOH Ref. No RE To announce the Guidance for Good Pharmacovigilance Practice Attachment Guidance for Good Pharmacovigilance Practice Official Letter from DOH Date: August 19, 2008 Ref. No: RE: To announce the Guidance for Good Pharmacovigilance Practice

2 Guidance for Good Pharmacovigilance Practice 2

3 Table of Contents Page No. Chapter 1 Introduction 1 Chapter 2 Adverse Drug Reaction Reporting and Requirements 3 I. Spontaneous Reporting 3 II. Periodic Safety Update Reports 5 III. Expedited Reporting 6 Chapter 3 Risk Management 8 I. Health Authority 8 II. Healthcare Providers and Pharmacies 8 III. Pharmaceutical Companies 9 IV. Risk Management Tools 10 Chapter 4 Training and Education 12 I. Health Authority 12 II. Healthcare Providers and Pharmacies 12 III. Pharmaceutical Companies 12 Chapter 5 Pharmacovigilance Inspection 14 I. Routine Inspection 14 II. Target Inspection 14 III. Inspection Report 15 IV. Continuous Follow ups 15 References 16 i

4 Appendixes Appendix 1: Regulation of Reporting Serious Adverse Reaction of Medical Products 17 Appendix 2: Regulation of Medical Products under Safety Monitoring 19 Appendix 3: Adverse Drug Reaction Reporting Form 20 Appendix 4: Department of Health Announcement No RE: Template of the Periodic Safety Update Reports Appendix 5: The information required from pharmaceutical companies for Periodic Safety Update Reports 23 Table 1: Summary of Adverse Drug Reaction Cases 24 Table 2: All Adverse Drug Reactions by SOC in Taiwan (Suggested template) 25 Table 3: All Adverse Drug Reactions by SOC in Other Countries (Suggested template) 26 Appendix 6: Department of Health Announcement No RE: Issues in final summary safety report at the end of monitoring period of drug Appendix 7: Suggested Template of Summary Bridging Report 28 ii

5 Chapter 1 Introduction In general, results from pre marketing clinical trials are sufficient to justify the efficacy of a drug so as to sustain the application of its license approval. However, study design and inclusion / exclusion criteria may restrict the detection of some potential, low incidence but serious adverse drug reaction. In order to identify the safety issue after a product is launched with a huge number of patients exposed to it, it is necessary to establish a good pharmacovigilance system so as to reduce the risks and take prompt measures to protect public health. Therefore, the Department of Health sets out the Guidance for Good Pharmacovigilance Practice to request healthcare providers, pharmacies and pharmaceutical companies to collect, evaluate and study drug safety information in a proactive manner and to take their responsibilities for adverse drug reaction reporting. The health authority should establish a good pharmacovigilance and inspection system suitable for the environment in Taiwan. This system should be able to help the authorities to handle drug safety information and take prompt and necessary measures, based on risk management principles, to assure drug safety, and to protect consumers right. To draft this Guidance, references from the latest versions of related regulations in other regulatory bodies, e.g. from ICH 1, the US 2, the EU 3, Japan 4 and Australia 5 were collected. After discussions, the Australian TGA s version was used as a base to draft the Guidance, then incorporated the strong points in other countries regulations as well as current regulatory requirements (e.g. Pharmaceutical Affairs Law Article 45, Article 45 1 and related subsidiary laws) and enforcement situations in Taiwan. This document aims to provide guidance for the health authorities and their delegate agencies, healthcare providers, pharmacies and pharmaceutical companies on pharmacovigilance activities. The Guidance targets on professional institutes, groups and personnel involved in pharmacovigilance activities to help them understand and develop an accurate manner in handling pharmacovigilance activities. Their compliance with professional ethics and government s 1

6 regulations and policies will enhance drug safety in Taiwan. laws or regulations, the contents of this Guidance are not mandatory. Hence, except for stipulated by The scopes and functions of the Guidance are described as follows, (1) In this Guidance, drugs refer to all drugs already approved and granted with licenses by the Department of Health and launched in Taiwan (2) Illegal drugs (e.g. counterfeit drugs, forbidden drugs) are unlawful and should be handled by law enforcement agencies; hence, they are not covered in the scope of this Guidance. (3) This Guidance is a reference of executing pharmacovigilance activities for the health authority and its delegate agencies, healthcare providers, pharmacies and pharmaceutical companies. (4) The health authority shall appoint other agencies or organizations to operate the collection, collation and assessment of suspected adverse drug reaction cases, and other drug safety issues. (5) The delegate agencies shall promptly forward important drug safety information to the health authority, relevant agencies and pharmaceutical companies involved. (6) When becoming aware of an adverse reaction that may be associated with drugs, healthcare providers, pharmacies and pharmaceutical companies are advised to report to the health authority or its delegate agencies. Other related regulations or laws shall also be observed. (7) When becoming aware of an adverse reaction that may be associated with drugs, healthcare providers and pharmacies shall also notify the drug license holders involved. (8) Pharmaceutical companies are advised to establish a feasible and integrated internal pharmacovigilance system and a risk management mechanism so as to ensure drug safety and to assure responsibilities and liabilities for their products. 2

7 (9) Each pharmaceutical company is advised to appoint a member of staff in charge of pharmacovigilance activities. It would be better that this person stationed in Taiwan and have suitable medical background or experiences in pharmacovigilance activities. (10) Healthcare providers are advised to establish an internal adverse drug reaction reporting system and related regulations. materials. Internal trainings may cover these 3

8 Chapter 2 Adverse Drug Reaction Reporting and Requirements An integrated pharmacovigilance system shall include the collection, collation, assessment and analyses of information on adverse drug reaction cases, research of risk factors, and risk assessment, prevention and management, etc. The collection of adverse drug reaction cases is the most important and basic task. Hence, in almost every medical advanced country, there is a national adverse drug reaction reporting center, which is responsible for processing suspected adverse drug reaction cases reported by health professionals, pharmaceutical companies or the general public and carrying out case assessment, safety signal detection and problem analyses. In order to assure their responsibility and liability for their products, pharmaceutical companies shall collect and collate suspected adverse drug reaction cases through various channels and methods, and provide latest drug information for the health authority, healthcare providers, health professionals and patients. Pharmaceutical companies shall also make good use of risk management tools to reduce the risk of adverse drug reaction events. The front line health professionals have the obligation to inform health authorities and drug license holders if any suspected adverse drug reactions occur. I. Spontaneous Reporting Healthcare providers, pharmacies and pharmaceutical companies are advised to inform the health authority or its delegate agencies of any suspected adverse drug reactions involved with drugs marketed in Taiwan, no matter whether the event is serious or not. Serious adverse drug reaction events shall be reported according to the Regulation of Reporting Serious Adverse Reaction of Medical Products (Appendix 1). Pharmaceutical companies shall collect suspected adverse drug reaction cases from post marketing studies and medical literatures and report serious events in accordance with the Regulation of Reporting Serious Adverse Reaction of Medical Products, while for drugs under post marketing surveillance, all the serious and non serious cases should be included in Periodic Safety Update Reports (PSUR) and submitted to the 4

9 health authority or its delegate agencies according to Regulation of Medical Products under Monitoring (Appendix 2). (I) When becoming aware of a serious adverse drug reaction, healthcare providers, pharmacies and pharmaceutical companies shall report to the health authority or its delegate agencies by submitting a completed reporting form and relevant information. Pharmaceutical companies or license holders have the obligation to provide any relevant product information upon request. (II) A serious adverse drug reaction refers to any of the following medical conditions that: 1. results in death; 2. is life threatening; 3. results in permanent disability; 4. is a congenital anomaly/birth defect; 5. requires inpatient hospitalization or prolongation of existing hospitalisation; 6. required intervention to prevent permanent impairment/damage (III) Time frame of reporting serious adverse drug reactions: Healthcare providers and pharmacies shall report within 7 days upon knowing of any serious adverse drug reaction has resulted in death or is life threatening. The license holder of the involved drug shall also be informed. If information of the report is not complete, follow up documents should be supplied within 15 days. The drug license holder involved shall report within 15 days upon knowing of a serious adverse drug reaction. (IV) All serious domestic adverse drug reactions have to be reported within the time frame as specified by the authority. License holders of medical products under monitoring shall include non serious adverse drug reactions as line listing in a Periodic Safety Update Reports and submit it according to a specified time frame. 5

10 (V) Reporting methods and template: Healthcare providers, pharmacies and pharmaceutical companies shall submit their reports by post, fax or via the internet. A verbal report is acceptable in urgent situations; but written submission should be completed before the deadline (Reporting Form is as in Appendix 3). (VI) When reporting adverse drug reactions, healthcare providers, pharmacies and pharmaceutical companies shall use the Adverse Drug Reaction Reporting Form (Appendix 3) declared by the health authority or its delegate agencies. The minimum information required for the submission of an initial report includes an identifiable patient s information, an identifiable reporter s information, a suspected reaction, and suspect drug(s). (VII) Additional information on a serious adverse drug reaction report, not available at the time of the initial report, should be provided in follow up reports. When necessary, the health authority or its delegate agencies have the right to request healthcare providers, pharmacies or pharmaceutical companies to provide patients medical records, medication records or product information. Healthcare providers, pharmacies or pharmaceutical companies have to comply with the request. (VIII) When becoming aware that patients are injured because of drug product defects, healthcare providers, pharmacies and pharmaceutical companies shall report to the health authority or its delegate agencies following the Regulation of Reporting Serious Adverse Reaction of Medical Products. Other events concerning drug product defects may also be reported to the health authority or its delegate agencies in an expedited manner. 6

11 II. Periodic Safety Update Reports (PSUR) Drug safety data collected from pre marketing clinical trials may not be sufficient to reflect the product safety profile. Therefore, the health authorities in many medical advanced countries impose the post marketing drug safety monitoring period on newly launched new drugs. During the safety monitoring period, license holders shall proactively collect post marketing safety data, prepare Periodic Safety Update Reports and submit them to the health authority or its delegate agencies. All non serious adverse drug reactions involved drugs under surveillance should be reported as line listings in PSURs. If necessary, the health authority may set a schedule for the submission of PSURs. According to the Regulation of Medical Products under Monitoring (Appendix 2), if pharmaceutical companies fail to submit Periodic Safety Update Report as required, then the health authority may reassess the safety of the concerned product. (I) Periodic Safety Update Reports should at least include the contents mentioned in the Department of Health announcement issued on 2 nd December 2005 (Ref. No ) as in Appendix 4. A template is in Appendix 5. (II) The last Periodic Safety Update Report (PSUR) should be submitted before the expiration of the drug safety monitoring period. According to the Department of Health announcement on 25 th July 2007 (Ref. No ) (Appendix 6), the last Periodic Safety Update Report shall include a summary bridging report in addition to routine PSUR contents. The summary bridging report is a drug safety review at the point of the expiration of the drug safety monitoring period. This will help the health authority to carry out post marketing drug safety assessment. (III) The summary bridging report provides summarized information. There is no need to repeat the contents in previous PSURs; but, quotations would be 7

12 appropriate. A line listing of cases would not be necessary for the summary bridging report; however, the information shall cover the whole period of the drug under monitoring. The summary bridging report may also include the marketing situations in other countries, pharmaceutical companies contingency measures, and changes in safety regulations, drug safety data, indications and package inserts occurred during the period of the drug under monitoring. The suggested template of the summary bridging report is as in Appendix 7. III. Expedited Report Based on the results of drug safety assessment or risk benefit assessment or the notice from foreign manufacturers / head quarters, drug license holders shall report to the health authorities in an expedited manner (within 72 hours) when expecting or becoming aware of any of the following critical events: (I) (II) withdrawal or suspension of the product; serious drug safety related addition or modification in contraindication, warning or precaution statement of the approved package inserts. When reporting, drug license holders shall provide all related information that they have already obtained, such as associated evidence and corresponding measures adopted by foreign health authorities, etc. Reporting can be made via telephone, fax, or official letter. 8

13 Chapter 3 Risk Management The health authority, healthcare providers, pharmacies and pharmaceutical companies shall follow risk management principles and conduct the assessment on known risks, investigation on potential risks and continuous follow up on materially omitted information on post marketing drug safety issues so as to ensure patients safety. I. Health Authority (I) The health authority and its delegate agencies shall proactively collect drug safety information and promptly inform the pubic and health professionals so as to safeguard the nation s medication safety. (II) The health authority shall carefully assess the risk benefit balance of drugs with safety concerns and make proper decisions. (III) The health authority and its delegate agencies shall regularly review the database of the adverse drug reaction reporting system in Taiwan and prepare a report in the view to identify known risks, to detect potential risks and to supplement importantly omitted information. When necessary, a drug reassessment can be conducted for analyzing its risk benefit balance so as to improve drug safety. (IV) The health authority shall make relevant policies to enhance drug safety, make appropriate planning and arrangement, and seek resources to support the research and activities related to the drug safety, in order to build up the nations knowledge about the drug safety and to set up the domestic drug safety information. 9

14 II. Healthcare Providers and Pharmacies (I) Healthcare providers and pharmacies shall follow the health authority s regulations to handle adverse drug reaction reporting. (II) Healthcare providers and pharmacies shall proactively collect safety information on drugs used in their institutes, create a drug safety database and set guidelines on using high alert drugs. Drug safety information should be promptly forwarded to health care professionals. (III) In order to improve drug safety, healthcare providers and pharmacies shall regularly review the internal reporting system and mechanism to identify known risks and detect potential risks and importantly omitted information. III. Pharmaceutical Companies (I) Considering that drugs approved by the health authority may still have some unknown risks of adverse reactions, pharmaceutical companies should establish a mechanism for continual monitoring and collecting drug safety information. The mechanism should also clearly state actions to be taken upon safety concerns. Routine pharmacovigilance tasks, such as the submission of adverse drug event reports, periodic safety update reports (PSUR), etc. should be performed according to the descriptions in Chapter 2. A pharmacovigilance plan should be devised based on the safety specification of each individual product, especially for those with safety concerns. (II) Pharmaceutical companies shall collate and analyze all collected information. Pharmaceutical companies shall carry out safety assessment if any new safety signals are detected. Also, if there are evidences suggesting potential risks that may lead to serious adverse reactions, the concerned pharmaceutical company shall submit a report and inform the health authority and its delegate agencies, 10

15 healthcare providers and pharmacies in an expedited manner. Reports should be submitted according to the descriptions of spontaneous reporting in Chapter 2 Paragraph 3. (III) In addition to general drug information, drug safety data should also be stated in package inserts, including population not studied in clinical trials, adverse drug reactions, known / potential risks, drug food interactions, drug drug interactions, epidemiology, common side effects, and other related information. Pharmaceutical companies should devise a mechanism for updating package inserts in a timely manner. (IV) In the case of concerns over drug safety, for instance, there are serious known risks, potential risks or the deficiency of important drug safety data on some patient groups, etc., pharmaceutical companies should come up with a risk management plan subject to the safety profiles of the concerned product. The following items are suggested in the risk management plan: 1. Safety specification 2. Pharmacovigilance plan 3. Evaluation of the need for risk minimisation activities 4. Risk minimization plan 5. Conclusions of the risk management plan 6. Contact persons in charge of the risk management plan (V) Pharmaceutical companies shall refer to their risk management policies of overseas manufacturers or their head quarters and work out risk management measures suitable for domestic environment. Pharmaceutical companies also have the obligation to inform their headquarters promptly of changes in health authority policies. (VI) If commitments for safety concerns are attached to the new drug approval notification issued by the health authority, then, in addition to the general 11

16 requirements, pharmaceutical companies should also establish a pharmacovigilance plan to actively collect and continually monitor drug safety information and make improvements to prevent adverse reactions from happening. Reports should be submitted to the health authority for future inspection within a specified time frame. IV. Risk Management Tools (I) Risk management tools may include: update WARNINGS section on the package inserts to highlight drug safety data; generate patient labeling to provide information, e.g. treatment guidance, prevention measurements, precautions, etc, and registering patients for continuous monitoring. (II) The health authority and its delegate agencies shall establish a signal detection method to identify high risk and high frequency adverse reactions and suspected drugs from collected drug safety database. Related information on reported cases should be further analyzed and assessed to evaluate the degree of risk of adverse reactions, such as causes, severity, frequency, etc. Once a risk is identified, risk factors and the potential mechanism should be discussed. The monitoring of drugs involved also need to be reinforced. When necessary, the target adverse drug reaction can be incorporated into pharmacovigilance plan and epidemiology project or external research proposals to verify the actual risk factors affecting domestic population. 12

17 Chapter 4 Training and Education The pharmacovigilance management covers a full spectrum of topics. The health authority, healthcare providers, pharmacies and pharmaceutical companies are advised to provide pharmacovigilance trainings for relevant personnel and to encourage staff to participate in external trainings. I. Health Authority (I) The health authority shall encourage and help healthcare providers, pharmacies, pharmaceutical companies to organize pharmacovigilance trainings. (II) The health authority shall preferably assist personnel in charge of pharmacovigilance affairs in obtaining knowledge and building accurate concept about drug safety. II. Healthcare Provider and Pharmacies (I) Healthcare providers shall provide pharmacovigilance training and education courses for health staff or set out plans to encourage staff to participate in external courses so as to build up accurate perception and attitude towards drug safety. (II) Pharmacies shall have plans to encourage pharmacists to participate in on going training or education courses about pharmacovigilance. III. Pharmaceutical Companies (I) Pharmaceutical companies shall establish a training program and keep all training records in order to meet the requirements of pharmacovigilance management. 13

18 The annual training program shall ensure all related personnel are capable of performing their duties in pharmacovigilance activities. implemented based on an established schedule. The program should be (II) Pharmaceutical companies shall appoint a person in charge of drug safety affairs. This person is responsible for establishing the post marketing pharmacovigilance SOP based on related regulations and for executing pharmacovigilance training courses. (III) The person in charge of drug safety affairs shall be also responsible in preparing materials for post marketing pharmacovigilance training, including related regulations on post marketing drug safety, pharmacovigilance SOP and the importance of collecting drug safety information. (IV) A pre service training should be given to all new staff; while current staff shall participate in periodic on the job training. All training records have to be kept properly. (V) If the training program is executed by someone other than the person in charge of drug safety affairs, then he/she has to ensure that training records are completed and that written documents are submitted to the person in charge of drug safety affairs. (VI) The person in charge of drug safety affairs shall follow related regulations and keep records of all training documents. 14

19 Chapter 5 Pharmacovigilance Inspection The health authority may carry out pharmacovigilance inspection, when necessary. The purpose of this inspection is to ensure pharmaceutical companies compliance with pharmacovigilance regulations. There are two types of inspection, general inspection and key inspection. The health authority shall provide inspection reports for pharmaceutical companies inspected. Pharmaceutical companies are eligible to comment on the report. The inspection results should be kept as a reference for future pharmacovigilance activities. The initiation and procedures of the inspection are to be established by the health authority. I. Routine Inspections The purpose of a routine inspection is to make sure that pharmaceutical companies have the ability in performing pharmacovigilance activities that comply with related regulations. An inspection shall include more than one product. The management of drug safety information of the inspected products should meet the inspection standards and justify the functions of the pharmacovigilance system set by pharmaceutical companies. II. Targeted Inspections The health authority shall request a targeted inspection in any of the following circumstances: (I) Inspections irrelevant to specific concerns on drug safety or non compliance pharmaceutical companies that have not yet been inspected; 1. pharmaceutical companies that launch their first product; 2. newly merged pharmaceutical companies. 15

20 (II) Inspections relevant to specific concerns on drug safety or non compliance 1. pharmaceutical companies that delay or fail to take their obligations on safety monitoring, or are required to improve follow up pharmacovigilance activities; 2. pharmaceutical companies that delay to submit or submit incomplete Periodic Safety Update Reports. 3. pharmaceutical companies that fail to report drug safety related issues; (1) making public announcement about drug safety information without firstly or simultaneously reporting to the competent authorities; (2) without reporting to the health authorities about product s withdrawal or drug safety related recalls. 4. there are inconsistency between reports and information from other sources; 5. risk benefit profile of a drug has been changed, or the changes have not been reported; 6. taking references from previous inspection results; 7. taking references from drug safety information in other countries. III. Inspection Reports Inspectors shall complete the report within a limited time frame and forward to the health authority and inspected pharmaceutical companies. The time frame shall be established by the health authority. 16

21 IV. Follow up Management Pharmaceutical companies failed to comply with pharmacovigilance regulations have to make an action plan for improvement. Pharmaceutical companies shall prepare an execution report to show the improvement results. The health authority shall inspect again to justify the improvement, if necessary. 17

22 References: 1. ICH Topic E 2 E Pharmacovigilance Planning (Pvp). European Medicines Agency. June 2005 CPMP/ICH/5716/03 2. Good Pharmacovigilance Practices and Pharmacoepidemiologic Assessment. Clinical Medical. March VOLUME 9A of The Rules Governing Medicinal Products in the European Union Guidelines on Pharmacovigilance for Medicinal Products for Human Use Final March Pharmaceutical Administration and Regulations in Japan. March (Japanese) (English) 5. Australian Guideline for Pharmacovigilance Responsibilities of Sponsors of Registered Medicines Regulated by Drug Safety and Evaluation Branch. July 2003 Amended 31May

23 Appendix 1: Regulation of Reporting Serious Adverse Reaction of Medical Products Title: Regulation of Reporting Serious Adverse Reaction of Medical Products (31 st August 2004) Article 1: This regulation is established based on Pharmaceutical Affairs Law Article Article 2: In this regulation, the term drugs is as defined in Pharmaceutical Affairs Law Article 4. Article 3: When an adverse reaction in association with drugs occurs, healthcare providers, pharmacies and pharmaceutical companies shall follow this regulation to report the adverse drug reaction to the health authority or its delegate agencies by submitting a complete reporting form and relevant information. Article 4: The serious adverse drug reaction refers to any of the following medical occurrences that: 1. results in mortality; 2. is life threatening; 3. results in persistent disability; 4. is a congenital anomaly / birth defect; 5. requires inpatient hospitalization or prolongation of existing hospitalisation; 6. needs treatment to prevent from persistent disability. 19

24 Article 5: In situations of items 1 and 2 or the previous article, healthcare providers and pharmacies shall make a report according to Article 3 within 7 days and notify drug license holders involved. Any deficient documents should be made up within 15 days. Pharmaceutical companies should not reject to provide any product related information required for the reporting. Article 6: Drug license holders should follow Article 3 and report the serious adverse drug reaction event within 15 days from the time it is first known. Article 7: Healthcare providers, pharmacies and pharmaceutical companies may submit their reports by post, fax or the internet. A verbal report is acceptable in urgent situations; but written submission may be completed before the deadline. Article 8: When necessary, the health authority or its delegate agencies have the right to request healthcare providers, pharmacies or pharmaceutical companies to provide patients records, medication records or product information. Healthcare providers, pharmacies or pharmaceutical companies have to comply with the request. Article 9: This regulation takes effect from the date of announcement. 20

25 Appendix 2: Regulation of Medical Products under Monitoring Title: Regulation of Medical Products under Monitoring (9 th September 2004) Article 1: This regulation is established according to Pharmaceutical Affairs Law Article Article 2: This regulation applies to the following scopes: 1. new drug as defined by Pharmaceutical Affairs Law Article 7; 2. medical devices as specified by the Department of Health; 3. other scopes as announced by the Department of Health. Article 3: New drugs passing the examination and registration assessment are subject to a 5 year medical products under monitoring staring from the date of license issuance. For item 2 of previous article, the period of medical products under monitoring is 3 year staring from the date of license issuance. For item 3 of previous article, the period of medical products under monitoring is decided by the Department of Health. Article 4: During the period of medical products under monitoring, drug license holders shall proactively collect international and domestic drug safety information. Serious adverse drug reactions should be reported according to regulations; and all other adverse drug reactions should be reported as line listings in the Periodic Safety Update Report, which has to be submitted according to a schedule set by the Department of Health. The Department of Health may reassess drug safety if drug companies fail to comply with the reporting regulations. 21

26 Article 5: For a new drug already completing local clinical trials or bridging studies and is granted with Department of Health approval, healthcare providers may not request further experiments or clinical trials for formulation listing during the period of medical products under monitoring, except for tests to check on product delivery. Article 6: This regulation takes effect from the date of announcement. 22

27 Appendix 3: Adverse Drug Reaction Reporting Form Case sequence# ( filled by adverse drug reaction reporting center) ADR Reporting form (01) 1. Date of event: (mo/day/yr) 2. Date reporter was informed: (mo/day/yr) The Adverse Drug Reaction Reporting Form Department of Health The Executive Yan, Republic of China Tel : Fax : Mail : 2FI.,No.32,Roosevelt Rd., Sec. 1, Taipei 100 Taiwan Web : 3. Date of center reception: (mo/day/yr) 4. Reporter: Name: Organization: Phone No. Address: Occupation: Health professional Doctor Pharmacist Nurse Other: Company common people I. Patient information 0

28 5. Patient identifier: 6. Sex: male female 8. Weight: kg In confidence 7. Date of birth: (mo/day/yr) or Age: 9. Height: cm II. Adverse drug reaction 10. Outcomes attributed to adverse drug reaction 12. Relevant tests/laboratory data, including dates A. Death date: (mo/day/yr) diagnosis: (e.g.,serum drug level, hepatic/renal functional indices, etc.) B. Life threatening C. Hospitalization initial D. Disability E. Hospitalization prolonged F. Required intervention to prevent permanent impairment/damage G. Congenital anomaly H. Nonserious (please describe) 1

29 11. Describe event Please fill this form according to date of event. The reaction site, seriousness of the adverse reaction, and treatment should be included. 13. Other relevant history (e.g., diagnosis, allergies, pregnancy, smoking and alcohol use, hepatic/renal dysfunction, etc.) III. Suspect medical device 14. Brand Name 15. License Number 16.Type of Device 2

30 17a.Manufacturer name & address 18. model# 17b.Distributor:name & address serial# lot# Mfg date: Exp. date: 19.Device operator: 20. Date of usage: (mo/day/yr) Health professional 21. Date of discontinuation: (mo/day/yr) Patient or his/her family 22. Propose of usage: Other 23.Device available for evaluation? yes no returned to manufacturer on (mo/day/yr) 3

31 IV. Suspect medication(s) Generic Name/Brand Name Unit Content/Dosage Route used Dose/Frequency Therapy dates(from/to) Indication 24. Suspect medication(s) #1 #2 25.Concomitant medical products #1 (Please include therapy #2 dates) Manufacturer /Lot# Exp. date 27.Previous experience with similar drug yes no doesn't apply Drug: 26. Suspect #1 Adverse action: medication(s) #2 28. Event abated after use stopped or dose reduced yes no doesn't apply 29. Event reappeared after reintroduction yes no doesn't apply 4

32 30. If concomitant with Herbal medicine* Western drug* Health food Other: * If yes, please fill in concomitant medical product

33 Appendix 4: Department of Health Announcement No RE: Template of the Periodic Safety Update Reports Official Letter from the Department of Health Recipient: National Adverse Drug Reaction Reporting Centre Date: 2 nd December 2005 Ref. No: RE: To announce the template of the Periodic Safety Update Report According to: Administrative Procedure Law Article 154 Contents: I. The template is designed by the Department of Health. II. The establishment is based on Article 4 of the Regulation of Medical Products under Monitoring. 0

34 III. In order to fully implement the pharmacovigilance system, to integrate the drug safety databank and to protect the public s medication rights, the Department of Health designs the template of the PSUR as in the appendix. License holders of drugs under surveillance should use this template to submit information to appointed agency (the National Adverse Drug Reaction Reporting Centre) according to a schedule set by the Department of Health. 1

35 Appendix 5: The information required from pharmaceutical companies for Periodic Safety Update Reports I. Drug information 1. scientific term of the product 2. brand name of the product (English) 3. brand name of the product (Chinese) 4. dosage form, dosage 5. manufacturer 6. country where the manufacturer is 7. license holder (Chinese) 8. sales volume (Recommended. Please provide this information as detail as possible) II. The scope of drug safety data and the surveillance period III. Collection of adverse drug reaction (ADR) information 1. local serious ADR 2. local non serious ADR (line listings) 3. foreign serious ADR 4. foreign non serious ADR (line listings) 2

36 5. case reports published on international or local literatures or academic conferences Summary of Periodic Safety Update Report for <Drug name> (Period covered: ) Table I: Summary by number of cases Number Of Cases 3

37 Type of Cases Taiwan Other countries Serious Non Serious Total (Serious + Non Serious Cases) 4

38 Table II: Tabulation of all Adverse Drug Reactions by SOC in Taiwan (Period covered: ) MedDRA System Organ Class Serious Non Total Cumulative Case Serious Total Cases Blood and lymphatic system disorders Cardiac disorders Ear and labyrinth disorders Eye disorders Gastrointestinal disorders General disorders and administration site conditions Hepatobiliary disorders Immune system disorders Infections and infestations Injury, poisoning and procedural complications Investigations Metabolism and nutrition disorders Musculoskeletal and connective tissue disorders Neoplasms benign, malignant and unspecified (including cysts and polyps) 5

39 Nervous system disorders Pregnancy, puerperium and perinatal conditions Psychiatric disorders Renal and urinary disorders Reproductive system and breast disorders Respiratory, thoracic and mediastinal disorders Skin and subcutaneous tissue disorders Vascular disorders Total Cumulative Total 6

40 Table III: Tabulation of all Adverse Drug Reactions by SOC in Others Countries (Period covered: ) MedDRA System Organ Class Serious Non Total Cumulative Case Serious Total Cases Blood and lymphatic system disorders Cardiac disorders Ear and labyrinth disorders Eye disorders Gastrointestinal disorders General disorders and administration site conditions Hepatobiliary disorders Immune system disorders Infections and infestations Injury, poisoning and procedural complications Investigations Metabolism and nutrition disorders Musculoskeletal and connective tissue disorders Neoplasms benign, malignant and unspecified 7

41 (including cysts and polyps) Nervous system disorders Pregnancy, puerperium and perinatal conditions Psychiatric disorders Renal and urinary disorders Reproductive system and breast disorders Respiratory, thoracic and mediastinal disorders Skin and subcutaneous tissue disorders Vascular disorders Total Cumulative Total 8

42 Appendix 6: Department of Health Announcement No RE: Issues in final summary safety report at the end of monitoring period of drug Official Letter from the Department of Health Recipient: National Adverse Drug Reaction Reporting Centre Date: 25 th July 2007 Ref. No: RE: To announce issues concerning the summary bridging report submitted at the expiration of the medical products under monitoring period According to: Regulation of Medical Products under Monitoring Article 4 Contents: I. In order to fully implement the pharmacovigilance system, to effectively detect risk signals and to perfect the risk management, license holders of medical products under monitoring should submit a summary bridging report along with the last submission of Periodic Safety Update Report. 9

43 The contents of the summary bridging report should include post marketing safety review. The summary bridging report should be submitted to the appointed agency (the National ADR Reporting Centre). II. Information attached to the Periodic Safety Update Report can be in electronic files. 10

44 Appendix 7: Suggested Template of Summary Bridging Report The following contents are suggested being included in the summary bridging report: I. Drug Information 1. generic name of the product 2. brand name of the product (English) 3. brand name of the product (Chinese) 4. dosage form, dosage 5. manufacturer 6. country where the manufacturer is 7. license holder company (Chinese) 8. sales volume II. The scope and pharmacovigilance period of the drug safety data III. The situations in international markets IV. Changes in safety regulations or pharmaceutical companies contingency plans (Including product withdrawal or termination, unsuccessful license renew, restrictions on drug sales, the termination of clinical trials due to safety concerns, modification of dosages, changes in indications or application groups, changes in formula, etc.) V. Changes in drug safety information in other countries 11

45 VI. Clinical trials (Including clinical studies or analysis results in relation to drug safety after product launches, as well as publications of drug safety clinical studies) VII. Benefit risk analyses and risk management plan VIII. Overall safety assessment IX. Conclusion 12