Chinese regulations
Issued Date 2008/08/19 Issued by DOH Ref. No 0970329838 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: 0970329838
RE: To announce the “Guidance for Good Pharmacovigilance Practice”
Guidance for Good Pharmacovigilance Practice
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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
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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. 0940336107 22
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
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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. 0960323034 27
RE: Issues in final summary safety report at the end of monitoring period of
drug
Appendix 7: Suggested Template of Summary Bridging Report
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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 ICH1, the US2, the EU3, Japan4 and Australia5 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
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regulations and policies will enhance drug safety in Taiwan. Hence, except for stipulated by
laws or regulations, the contents of this Guidance are not mandatory.
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.
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(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. Internal trainings may cover these
materials.
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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
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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.
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(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.
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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 2nd December 2005 (Ref. No.
0940336107) 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 25th July 2007 (Ref. No. 0960323034) (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
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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) withdrawal or suspension of the product;
(II) 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,
email or official letter.
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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.
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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,
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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
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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.
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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.
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The annual training program shall ensure all related personnel are capable of
performing their duties in pharmacovigilance activities. The program should be
implemented based on an established schedule.
(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.
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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.
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(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.
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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.
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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 2005.
3. VOLUME 9A of The Rules Governing Medicinal Products in the European Union – Guidelines on Pharmacovigilance for Medicinal Products for Human Use –Final March 2007.
4. Pharmaceutical Administration and Regulations in Japan. March 2007.
http://www.jpma.or.jp/jpmalib/0607/index.html (Japanese)
http://www.jpma.or.jp/english/parj/0607.html (English)
5. Australian Guideline for Pharmacovigilance Responsibilities of Sponsors of Registered Medicines Regulated by Drug Safety and Evaluation Branch. July 2003 – Amended 31May 2005.
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Appendix 1: Regulation of Reporting Serious Adverse Reaction of Medical Products
Title: Regulation of Reporting Serious Adverse Reaction of Medical Products (31st August
2004)
Article 1: This regulation is established based on Pharmaceutical Affairs Law Article 45‐1.
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.
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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.
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Appendix 2: Regulation of Medical Products under Monitoring
Title: Regulation of Medical Products under Monitoring (9th September 2004)
Article 1: This regulation is established according to Pharmaceutical Affairs Law Article 45‐2.
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
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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.
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)
3. Date of center reception: (mo/day/yr)
The Adverse Drug Reaction
Reporting Form
Department of Health The Executive Yan, Republic of China
Tel : 886‐2‐2396‐0100
Fax : 886‐2‐2358‐4100
Mail : 2FI.,No.32,Roosevelt Rd., Sec. 1, Taipei 100 Taiwan
Web : http://adr.doh.gov.tw
4. Reporter:
Name: Organization:
Phone No. Email:
Address:
Occupation: □Health professional □Doctor □Pharmacist □Nurse □Other:
□Company
□common people
I. Patient information
0
5. Patient identifier:
(In confidence)
6. Sex: □male □female
7. Date of birth: (mo/day/yr) or Age:
8. Weight: kg
9. Height: cm
II. Adverse drug reaction
10. Outcomes attributed to adverse drug reaction
□A. Death date: (mo/day/yr) diagnosis:
□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) ________
12. Relevant tests/laboratory data, including dates
(e.g.,serum drug level, hepatic/renal functional indices, etc.)
1
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
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.)
16.Type of Device
2
17a.Manufacturer name & address
17b.Distributor:name & address
18.
model#
serial#
lot#
Mfg date:
Exp. date:
20. Date of usage: (mo/day/yr)
21. Date of discontinuation: (mo/day/yr)
19.Device operator:
Health professional□
Patient or his/her family□
Other□
22. Propose of usage:
23.Device available for evaluation?
yes no returned to manufacturer on □ □ □ (mo/day/yr)
3
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
(Please include therapy
dates)
#1
#2
Manufacturer /Lot# Exp. date
26. Suspect
medication(s)
#1
#2
27.Previous experience with similar drug
Drug:
Adverse action:
28. Event abated after use stopped or dose reduced
29. Event reappeared after reintroduction
□ yes □ no □ doesn't apply
□ yes □ no □ doesn't apply
□ yes □ no □ doesn't apply
4
2008.4
5
30. If concomitant with □Herbal medicine* □Western drug* □Health food □Other: * If yes, please fill in concomitant medical product
Appendix 4: Department of Health Announcement No. 0940336107
RE: Template of the Periodic Safety Update Reports
Official Letter from the Department of Health
Recipient: National Adverse Drug Reaction Reporting Centre
Date: 2nd December 2005
Ref. No: 0940336107
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.
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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
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)
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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
Type of Cases Taiwan Other countries
Serious
Non Serious
Total (Serious + Non Serious Cases)
4
Table II: Tabulation of all Adverse Drug Reactions by SOC in Taiwan
(Period covered: )
MedDRA System Organ Class
Serious
Case
Non‐
Serious
Cases
Total Cumulative
Total
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)
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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
Table III: Tabulation of all Adverse Drug Reactions by SOC in Others
Countries
(Period covered: )
MedDRA System Organ Class Serious
Case
Non‐
Serious
Cases
Total Cumulative
Total
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
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(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
Appendix 6: Department of Health Announcement No. 0960323034
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: 25th July 2007
Ref. No: 0960323034
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.
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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.
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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
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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
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