Organization and objectives of ICH, expedited reporting, ICSR, PSURs, post approval expedited reporting, pharmacovigilance Planning, good clinical practices

1. ICH Guidelines for
Pharmacovigilance
Dr. Ramesh Bhandari
Asst. Professor,
Department of Pharmacy Practice,
KLE College of Pharmacy, Belagavi

2. Organization and
Objectives of ICH
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3. Organization and objectives of ICH
INTERNATIONAL CONFERENCE ON HARMONISATION (ICH) of Technical
Requirements for Pharmaceuticals for Human Use
◉ Established in April 1990
◉ Initiative for regulators and pharmaceutical industries
◉ Reformed as a non-profit legal entity under Swiss Law on 23 October
2015
◉ Formed to assure safety, quality and efficacy of medicines, the members
of ICH who include members from drug regulatory authorities and
research based industries of European Union, US and Japan will discuss
on the technical procedures and documents required.
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4. Need for harmonization
◉ The difference in the technical requirements and the
procedures followed by different countries made the global
marketing of drugs as time consuming and expensive
◉ To reduce the cost and time required for the global
marketing of drugs
◉ Harmonization of technical requirements has to be promoted
◉ Special guidelines to be framed to ensure the quality, safety
and the efficacy of the drugs

5. Purpose or Objectives of ICH
◉ Harmonized interpretation and application of technical
guidelines and requirements for marketing authorization to:
Reduce duplication of testing of the drugs under
investigation
Increase economical use of resources
Eliminate unnecessary delay in availability of new
medicines
◉ Safeguarding quality, safety and efficacy
◉ Accomplished through Technical Guidelines that are
implemented by the regulatory authorities.

6. Categories agreed for Harmonization
◉ New types of medicinal products
◉ Lack of harmonization of current technical
requirements
◉ Transitions to technically improved testing
procedures
◉ Review of existing ICH guidelines resulting in
major changes &
◉ Maintenance of existing ICH guidelines
requirement minor changes

7. ICH Members
ICH covers 3 regions:
◉ European Union
◉ United States of America
◉ Japan
“Six Parties”
1. The European commission, (representing 28 members states of EU)
2. The European federation of pharmaceutical industries and associations (IFPMA)
3. The Ministry of Health, Labour and Welfare of Japan
4. The Japanese Pharmaceutical Manufactures Association (JPMA)
5. The US Food and drug Administration (FDA)
6. The Pharmaceutical Research and Manufacture of America (PhRMA)

8. ICH Members
18 Members:
Founding Regulatory Members
◉ European Union
◉ FDA, United States of America
◉ MHLW/PMDA, Japan
Founding Industry Members
◉ EFPIA
◉ JPMA
◉ PhRMA
Standing Regulatory Members
◉ Health Canada, Canada
◉ Swissmedic, Switzerland
Regulatory Members
◉ ANVISA, Brazil
◉ HSA, Singapore
◉ MFDS, Republic of Korea
◉ NMPA, China
◉ SFDA, Saudi Arabia
◉ TFDA, Chinese Taipei
◉ TITCK, Turkey
Industry Members
◉ BIO
◉ Global Self-Care Federation
◉ IGBA

9. ICH Guidelines for
Pharmacovigilance - Introduction

10. ICH Guidelines for Pharmacovigilance
◉ The ICH has published a number of documents setting
standards for safety, both clinical and pre-clinical.
◉ Pre-clinical guidelines have an “S” designation e.g. S1, S2
etc. It should be noted that the clinical safety guidelines are
designated as “E”
◉ These documents provide a high degree of detail about the
expected manner, method, timing, frequency and
circumstances in which pharmaceutical companies and other
relevant parties need to report suspected adverse reactions
and other vital clinical data to the regulatory authorities.

11. ICH Guidelines for Pharmacovigilance
◉ Each of the following clinical safety guideline has an identifying code, and
during the lifetime of the ICH the codes have already been revised to reflect the
development and evolution of those standards documents:
E1 Clinical Safety for Drugs Intended for Long-Term Treatment of Non-Life
Threatening Conditions
E2A Clinical Safety Data Management: Definitions and Standards for
Expedited Reporting
E2B (R2) Maintenance of the Clinical Safety Data Management including
Data Elements for Transmission of Individual Case Safety Reports
E2B (R3) Clinical Safety Data Management: Data Elements for Transmission
of Individual Case Safety Reports

12. ICH Guidelines for Pharmacovigilance
E2C (R1) Clinical Safety Data Management: Periodic Safety Update Reports for
Marketed Drugs
E2C (R2) Periodic Benefit-Risk Evaluation Report
E2D Post-Approval Safety Data Management: Definitions and Standards for
Expedited Reporting
E2E Pharmacovigilance Planning
E2F Development Safety Update Report

13. EXPEDITED
REPORTING
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14. EXPEDITED REPORTING
CLINICAL SAFETY DATA MANAGEMENT: DEFINITIONS AND
STANDARDS FOR EXPEDITED REPORTING (E2A)
It is important to harmonise the way to gather and, if necessary, to take
action on important clinical safety information arising during clinical
development. Thus, agreed definitions and terminology, as well as
procedures, will ensure uniform Good Clinical Practice standards in this
area.
This guideline addresses the following:
1. the development of standard definitions and terminology for key
aspects of clinical safety reporting, and
2. the appropriate mechanism for handling expedited (rapid) reporting, in
the investigational (i.e., pre-approval) phase.

15. EXPEDITED REPORTING
◉ Expedited Report: SAEs which are unexpected (not labelled), be
reported in 15 Calendar days from the first notification of anyone
in the company including its agent, business partners, contractors,
distributors, and vendors. Also known as alert report, 15-day
report.
◉ 7-day report: Patient in question has died or had life threatening
SAE which is also unexpected and possibly related. This report
should be sent to the health authorities within 7 calendar days.
Note: All 7-day reports are also 15-day report. It must also be followed
up as a 15 day report

16. EXPEDITED REPORTING
STANARDS FOR EXPEDITED REPORTING
What Should be Reported?
1. Single Cases of Serious, Unexpected ADRs:
◉ All adverse drug reactions (ADRs) that are both serious and unexpected are
subject to expedited reporting.
◉ This applies to reports from spontaneous sources and from any type of
clinical or epidemiological investigation, independent of design or purpose.
◉ Information obtained by a sponsor or manufacturer on serious, unexpected
reports from any source should be submitted on an expedited basis to
appropriate regulatory authorities if the minimum criteria for expedited
reporting can be met.
◉ Causality assessment is required for clinical investigation cases.

17. EXPEDITED REPORTING
2. Other Observations:
◉ There are situations in addition to single case reports of "serious"
adverse events or reactions that may necessitate rapid
communication to regulatory authorities
Examples include:
◉ For an "expected," serious ADR, an increase in the rate of
occurrence which is judged to be clinically important.
◉ A significant hazard to the patient population, such as lack of
efficacy with a medicinal product used in treating life-threatening
disease.

18. EXPEDITED REPORTING
STANARDS FOR EXPEDITED REPORTING
Whom Should be Reported?
Determination Sponsor Investigator
Serious/Life-Threatening Yes Yes
Causality (Responsible Possibility) Yes Yes
Expectedness (Labeled/Unlabeled) Yes Yes

19. EXPEDITED REPORTING
1. Fatal or Life-Threatening Unexpected ADRs
◉ Fatal or life-threatening, unexpected ADRs occurring in
clinical investigations qualify for very rapid reporting.
Regulatory agencies should be notified (e.g., by telephone,
facsimile transmission, or in writing) as soon as possible but
no later than 7 calendar days after first knowledge by the
sponsor that a case qualifies, followed by as complete a
report as possible within 8 additional calendar days.
Reporting Time Frames:

20. EXPEDITED REPORTING
2. All Other Serious, Unexpected ADRs
◉ Serious, unexpected reactions (ADRs) that are not fatal or life-
threatening must be filed as soon as possible but no later than 15
calendar days after first knowledge by the sponsor
3. Minimum criteria for reporting
◉ An identifiable patient; a suspect medicinal product; an identifiable
reporting source; and an event or outcome that can be identified as
serious and unexpected, and for which, in clinical investigation
cases, there is a reasonable suspected causal relationship.
Reporting Time Frames:

21. EXPEDITED REPORTING
How to Report:
◉ The CIOMS-I form has been a widely accepted standard for
expedited adverse event reporting. However, no matter what the
form or format used, it is important that certain basic
information/data elements, when available, be included with any
expedited report, whether in a tabular or narrative presentation.
◉ All reports must be sent to those regulators or other official parties
requiring them in countries where the drug is under development.

22. EXPEDITED REPORTING
KEY DATA ELEMENTS FOR INCLUSION IN EXPEDITED REPORTS OF
SERIOUS ADVERSE DRUG REACTIONS

23. EXPEDITED REPORTING

24. EXPEDITED REPORTING

25. EXPEDITED REPORTING

26. EXPEDITED REPORTING

27. Individual Case Safety
Reports (ICSR)

28. Individual Case Safety Reports (ICSR)
◉ It is a document providing the most complete
information related to an individual case at a certain
point of time.
◉ An Individual Case Study Report (ICSR) is a safety service
document which includes information required for reporting
the adverse events and problems related to products and
complaints filed by consumers with respect to any product.
◉ It is an important facet of adverse event reporting which is a
source of data in PV (pharmacovigilance).

29. Individual Case Safety Reports (ICSR)
Sources of individual case safety reports
1. Unsolicited Sources
■ Spontaneous reports
■ Literature
■ Internet
■ Other sources- such as lay press and other media
2. Solicited sources
3. Contractual Agreements
4. Regulatory Authority Sources

30. Individual Case Safety Reports (ICSR)
◉ Because of national and international agreements, rules, and
regulations, individual case safety reports of adverse drug reactions
and adverse events need to be transmitted
 from identified reporting sources to regulatory authorities and
pharmaceutical companies;
 between regulatory authorities;
 between pharmaceutical companies and regulatory
authorities;
 within authorities or pharmaceutical companies;
 from clinical investigators, via the sponsor, to ethics
committees;
 from authorities to the World Health Organization (WHO)
Collaborating Center for International Drug Monitoring.

31. Individual Case Safety Reports (ICSR)
◉ The transmission of such individual case safety reports
currently relies on paper-based formats (e.g., Yellow cards,
CIOMS forms, MedWatch) or electronic media.
◉ Considering the large number of potential participants in a
world-wide exchange of information, there is a need for an
electronic format capable of accommodating direct database
to database transmission

32. Individual Case Safety Reports (ICSR)
◉ Successful electronic transmission of information relies on
the definition of common data elements and standard
transmission procedures
◉ The format for individual case safety reports includes
provisions for transmitting all the relevant data elements
useful to assess an individual adverse drug reaction or
adverse event report. Structured data are strongly
recommended in electronic transmission.

33. Individual Case Safety Reports (ICSR)
Minimum information:
◉ The minimum information for the transmission of a report
should include at least one identifiable patient (section B.1),
one identifiable reporter (section A.2), one reaction/event
(section B.2), and one suspect drug (section B.4).
◉ Because it is often difficult to obtain all the information, any
one of several data elements is considered sufficient to
define an identifiable patient or an identifiable reporter.

34. Individual Case Safety Reports (ICSR)
◉ It is also recognized that the patient and the reporter can be
the same individual and still fulfill the minimum reporting
criteria.
◉ In addition, to properly process the report, the following
administrative information should be provided: the sender’s
(case) safety report unique identifier (A.1.0.1), the date of
receipt of the most recent information (A.1.7), the
worldwide unique case identification number (A.1.10) and
the sender identifier (A.3.1.2).

35. GUIDELINE: CONTENT OF THE DATA ELEMENTS

36. Elements of the specifications in the ICSR
◉ Pre-Clinical:
Toxicity
General Pharmacology
Drug Interactions
Other toxicity related information
◉ Clinical:
Limitations of the Human Safety Database
Populations not studied in the pre-approval phase
Adverse events/adverse drug reactions
Identified risks that require further evaluation
Potential risks that require further evaluation
Identified and potential interactions

37. PERIODIC SAFETY
UPDATE REPORTS (PSUR)

38. PERIODIC SAFETY UPDATE REPORTS
◉ The periodic safety update report (PSUR) is a document that
allows a periodic, comprehensive assessment of the worldwide
safety data of a marketed drug or biological product.
◉ The concept evolved from the Council for International
Organizations of Medical Sciences (CIOMS) Working Group II
report (CIOMS, 1992).
◉ The PSUR creates the opportunity for a periodic overall safety
evaluation to show whether a product’s safety profile has remained
the same or has undergone change since it was authorized and to
indicate whether changes should be made to product information
to optimize the use of a product.

39. PERIODIC SAFETY UPDATE REPORTS
Purpose of the PSUR:
◉ The reason such a review is needed periodically is because clinical
trials tend to be of short duration and to include a limited number of
patients.
◉ Moreover, clinical trials have inclusion and exclusion criteria. After a
product is launched, it may be used by patients not studied in clinical
trials, for example children, the elderly, pregnant or breastfeeding
women or patients with comorbidities such as hepatic or renal disease.
◉ After approval, a drug becomes so available for immediate use in large
populations, so rare adverse drug reactions (ADRs) can be more easily
identified. The drugs also become available for indefinite use (unless
prescribing information indicates otherwise), and delayed onset ADRs
become easier to identify.

40. PSUR – GENERAL PRINCIPLES
ONE REPORT FOR PRODUCTS CONTAINING ONE ACTIVE SUBSTANCE
AUTHORISED TO ONE MARKETING AUTHORISATION HOLDER
◉ Ordinarily, all dosage forms and formulations as well as
indications for a given pharmacologically active substance
authorized to one marketing authorization holder (MAH) may be
covered in one PSUR.
◉ Within the single PSUR, separate presentations of data for
different dosage forms, indications or populations (e.g. children
versus adults) may be appropriate.

41. PSUR – GENERAL PRINCIPLES
PRODUCTS AUTHORISED TO MORE THAN ONE MAH
◉ Each MAH is responsible for submitting PSURs, even if different
companies market the same product in the same country.
COMBINATION PRODUCTS
◉ Safety information for the fixed combination may be reported
either in a separate PSUR or included as separate presentations in
the report for one of the separate components, depending on the
circumstances.

42. PERIODIC SAFETY UPDATE REPORTS
GENERAL SCOPE OF INFORMATION
◉ All relevant clinical and non-clinical safety data should cover only
the period of the report (interval data).
Exception- Regulatory status information on authorization
application and data on serious unlisted ADRs- can be provided
with cumulative summary tabulations.
◉ The safety information contained within the PSUR comes from a
variety of different sources. These include spontaneous reports of
adverse events from different countries, the literature, clinical
trials, registries, regulatory ADR databases and important animal
findings.

43. PERIODIC SAFETY UPDATE REPORTS
◉ Reports of lack of efficacy specifically for drugs used in the
treatment of life-threatening conditions and for certain other
medicinal products, such as contraceptives and vaccines, may
represent a significant hazard, and in that sense may be a safety
issue. These types of cases should be discussed in the PSUR.
Frequency of reporting
◉ Each PSUR should cover the period since the last update report.
The need for a report and the frequency of report submission to
authorities are subject to local regulatory requirements. The age of
a medicinal product on the market may influence this process.

44. PERIODIC SAFETY UPDATE REPORTS
◉ In the EU, reports be submitted every 6 months for the first 2 years
after authorization, annually for the three following years and then
five yearly
◉ In the United States, the FDA requires quarterly reports during the
first 3 years, then annual reports; and
◉ In Japan, the authorities require annual survey report on a cohort of
a few thousand patients established by a certain number of
identified institutions during the 6 years following authorization.
◉ Regarding other marketing experience, adverse reactions which are
non-serious, but both mild in severity and unlabeled, must be
reported every 6 months for 3 years and annually thereafter.

45. PSUR Content

46. PSUR Content
TITLE
◉ PSURs contain proprietary information, so the title page should contain a statement
on the confidentiality of the data and conclusions included in the report.
EXECUTIVE SUMMARY
◉ The executive summary should consist of a brief overview providing the reader with a
description of the most important information.
INTRODUCTION
◉ The introduction puts the report in context, describing those products/formulations
that are included and excluded, outlining the pharmacology of the product, its
indications (both marketed and in clinical trials)
WORLDWIDE MARKETING AUTHORISATION STATUS
◉ The PSUR should include a short summary of the worldwide marketing authorisation
status

47. PSUR Content
UPDATE ON REGULATORY AUTHORITY OR MAH ACTIONS TAKEN FOR
SAFETY REASONS
◉ The update on regulatory authority or MAH actions taken for safety reasons
refers to marketing authorization, withdrawal or suspension; failure to obtain a
marketing authorization renewal; restrictions on distribution; clinical trial
suspension; dosage modification/formulation changes and changes in target
population or indications.
CHANGES IN REFERENCE SAFETY INFORMATION
◉ The changes in reference safety information section refers to changes in the
CCSI (company core safety information). The CCDS (company core data sheet),
which incorporates the CCSI, should be included as an appendix.

48. PSUR Content
PATIENT EXPOSURE
◉ Patient exposure refers to both market exposure and clinical trials (if relevant).
Estimates of patient exposure for marketed drugs often rely on gross
approximations of in-house or purchased sales data or volume.
PRESENTATION OF INDIVIDUAL CASE HISTORIES
◉ There is no specific guidance in E2C on the presentation of individual case
histories, but because it is impractical to present all case reports for the reporting
period, a brief description of the criteria used to select cases for presentation
should be given.
◉ This section of the PSUR should contain a description and analysis of selected
cases, including fatalities, presenting new and relevant safety information and
grouped by medically relevant headings

49. PSUR Content
STUDIES
◉ Studies refer to only those company-sponsored studies and published safety
studies, including epidemiology studies, that produce findings with potential
impact on product safety information.
OTHER INFORMATION
◉ Other information may include risk management programmes the MAH has put
in place and/or a benefit–risk analysis report.
◉ If such an analysis has been conducted separately, a summary of the analysis
should be included in this section.
◉ This section can also include important information received after the DLP (data
lock point).

50. PSUR Content
OVERALL SAFETY EVALUATION
◉ The overall safety evaluation should highlight new information on serious and
non-serious unlisted ADRs. If there are no new safety issues, this should be
stated with a note that the information is in keeping with the established safety
profile. This section should also review reports of
○ drug interactions;
○ overdose: deliberate or accidental and treatment;
○ abuse or misuse;
○ pregnancy or lactation: positive and negative experiences;
○ special patient groups (e.g. children, elderly, organ
○ impaired) and
○ effects of long-term treatment.

51. PSUR Content
CONCLUSION
◉ The conclusion should indicate safety data which are not in accordance with
previous experience and/or with the CCSI and specify and justify any action
recommended or initiated.

52. PSUR process
A. Intake of ADR information
B. Case processing
C. Data retrieval
D. Data analysis and
E. Medical review and risk assessment
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53. POST APPROVAL
EXPEDITED REPORTING

54. Post approval safety management guideline
 Post approval safety management (E2D) guideline was
finalized in 2003 and provides a standardized procedure for
post approval safety data management, including post
approval expedited reporting to the concerned authority.
 It parallels and adds to the E2A document, which covered
preapproval (clinical trial) safety data management, by
covering postmarketing safety data management.
 This document standardizes data management of cases from
consumers, literature, internet, and other types of
postmarketing cases.

55. DEFINITIONS
i. Adverse Event
ii. ADR
iii. Serious AE/ADR
iv. Unexpected ADR
v. Healthcare professional: Any medically-qualified person
such as a physician, dentist, pharmacist, nurse, coroner, or as
otherwise specified by local regulations.
vi. Consumer: A person who is not a healthcare professional,
such as patient, lawyer, friend or relative of the patient.

56. SOURCES
1. Unsolicited Sources
Spontaneous reports
Literature
Internet
Other sources- such as lay press and other media
2. Solicited sources
3. Contractual Agreements
4. Regulatory Authority Sources

57. STANDARDS FOR EXPEDITED REPORTING
◉ Serious ADRs:
Serious and unexpected cases of ADRs are subject to
expedited reporting.
For reports from studies and other solicited sources, all
cases judged by either the reporting health care
professionals or the MAH for causal relationship to the
medicinal product qualifying as ADRs.
Spontaneous reports associated with approved drugs
imply a possible causality

58. STANDARDS FOR EXPEDITED REPORTING
◉ Other observations:
Any significant unanticipated safety findings, including in
vitro, animal, epidemiologic, or clinical studies, that
suggest a significant human risk and could change the
benefit–risk evaluation should be communicated to the
regulatory authorities as soon as possible.
Lack of efficacy observations should not be expedited but
should be discussed in PSURs unless local requirements
oblige their being expedited.

59. STANDARDS FOR EXPEDITED REPORTING
Overdoses with no associated adverse outcome should not be
reported as adverse reactions.
Minimum criteria for reporting include an identifiable reporter, an
identifiable patient, an adverse reaction, and a suspect product.
Reporting time frames for expedited reports are normally 15
calendar days from initial receipt of the minimal information by
any personnel of the MAH. This is day 0. Additional medically
relevant information for a previously submitted report restarts the
clock.
Non-serious ADRs are not normally expeditable whether expected
or not

60. PHARMACOVIGILANCE
PLANNING (E2E)

61. PHARMACOVIGILANCE PLANNING
This guideline was finalized in 2004 and is
intended to aid in planning pharmacovigilance
activities, especially in preparation for the early
postmarketing period of a new drug.
The main focus of this guideline is on a Safety
Specification and Pharmacovigilance Plan that
might be submitted at the time of the application
for marketing.

62. PHARMACOVIGILANCE PLANNING
All three regions of the ICH (United States,
European Union, and Japan) have been turning
their attention to risk management and
pharmacovigilance planning throughout the life
cycle of a drug.
This document reflects ICH’s views.

63. Principles of Pharmacovigilance Planning
guidelines
i. Planning of pharmacovigilance activities
throughout the product life cycle
ii. Science-based approach to risk documentation
iii. Effective collaboration between regulators and
industry
iv. Applicability of the pharmacovigilance plan across
the three ICH region

64. Sections of Pharmacovigilance Plan
1. Safety Specification
2. Pharmacovigilance plan
3. Annex-Pharmacovigilance methods

65. Sections of Pharmacovigilance Plan
1. Safety Specification:
The safety specification is a summary of the
important identified risks of a drug, important
potential risks, and important missing information.
It should refer to the three safety sections in the
Common Technical Document:
 Non-clinical
 Clinical
 Epidemiology

66. Sections of Pharmacovigilance Plan
2. Pharmacovigilance Plan:
The pharmacovigilance plan should be based on the safety
specification and developed by the sponsor.
This includes:
• Summary of ongoing safety issues, including the important
identified risks, potential risks, and missing information.
• Routine pharmacovigilance practice
• Summary of actions to be completed, including milestones

67. Sections of Pharmacovigilance Plan
3. Pharmacovigilance Methods:
The best method to address a specific situation may vary
depending on the product, indication, population treated.
 Sponsors should choose the most appropriate design.
 Design and conduct of observational studies
 Annexure - A detailed discussion of pharmacovigilance
methods is appended to the document.

68. GOOD CLINICAL PRACTICES
IN PHARMACOVIGILANCE
STUDIES
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69. GOOD CLINICAL PRACTICES (GCP)
◉ GCPs are stand alone document and its guidelines are given
in ICH E6.
◉ Good Clinical Practice (GCP) is an international ethical and
scientific quality standard for designing, conducting,
recording and reporting trials that involve the participation
of human subjects.
◉ Compliance with this standard provides public assurance
that the rights, safety, and well-being of trial subjects are
protected, consistent with the principles that have their
origin in the Declaration of Helsinki, and that the clinical
trial data are credible.
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70. GOOD CLINICAL PRACTICES (GCP)
1) Clinical trials should be conducted in accordance with the ethical principles
that have their origin in the Declaration of Helsinki, and that are consistent
with GCP and the applicable regulatory requirement(s).
2) Before a trial is initiated, foreseeable risks and inconveniences should be
weighed against the anticipated benefit for the individual trial subject and
society. A trial should be initiated and continued only if the anticipated
benefits justify the risks.
3) The rights, safety, and well-being of the trial subjects are the most
important considerations and should prevail over interests of science and
society.
4) The available nonclinical and clinical information on an investigational
product should be adequate to support the proposed clinical trial.
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71. GOOD CLINICAL PRACTICES (GCP)
5) Clinical trials should be scientifically sound, and described in a clear,
detailed protocol.
6) A trial should be conducted in compliance with the protocol that has
received prior institutional review board (IRB)/independent ethics
committee (IEC) approval/favourable opinion.
7) The medical care given to, and medical decisions made on behalf of,
subjects should always be the responsibility of a qualified physician or,
when appropriate, of a qualified dentist.
8) Each individual involved in conducting a trial should be qualified by
education, training, and experience to perform his or her respective
task(s).
9) Freely given informed consent should be obtained from every subject
prior to clinical trial participation.
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72. GOOD CLINICAL PRACTICES (GCP)
10)All clinical trial information should be recorded, handled, and
stored in a way that allows its accurate reporting, interpretation and
verification.
11) The confidentiality of records that could identify subjects should
be protected, respecting the privacy and confidentiality rules in
accordance with the applicable regulatory requirement(s).
12) Investigational products should be manufactured, handled, and
stored in accordance with applicable good manufacturing practice
(GMP). They should be used in accordance with the approved
protocol.
13)Systems with procedures that assure the quality of every aspect of
the trial should be implemented.
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73. GOOD CLINICAL PRACTICES (GCP)
INVESTIGATOR’S RESPONSIBILITIES:
 All SAEs should be reported immediately by the investigator to the
sponsor except for those SAEs which the protocol or other document
identifies not needing immediate reporting.
 Identify the subject by trial code number rather than by subject name,
personal information and/or address
 Investigator should comply with the applicable regulatory requirement
while reporting unexpected SAEs to the regulatory authorities
 Adverse events or laboratory abnormalities should be reported to the
Sponsor within the time periods specified by sponsor.
 For reported death, the investigator should provide additional information
if requested by sponsor or IRB/IEC.
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74. GOOD CLINICAL PRACTICES (GCP)
INVESTIGATOR’S RESPONSIBILITIES:
 If the investigator terminates or suspended trial without prior agreement of
the sponsor, the investigator should promptly inform the institute and
where applicable (such as Institutions, IRB/IEC) by providing detailed
information.
 If the sponsor terminates or suspended trial, the investigator should
promptly inform the institutes and where applicable (such as Institutions,
IRB/IEC) by providing detailed information.
 If IRB/IEC terminates or suspends its approval/favourable opinion of a
trial, the investigator should inform the institution where applicable.
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75. GOOD CLINICAL PRACTICES (GCP)
SPONSOR’S RESPONSIBILITIES:
 Sponsor is responsible for the ongoing safety
evaluation of the investigational product(s).
 Should notify all concerned
investigator(s)/institution(s) and the regulatory
authorities of findings that could adverse affect
the safety of subjects, impact the conduct of trial.
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76. GOOD CLINICAL PRACTICES (GCP)
ADR Reporting guidelines:
 Sponsor should expedite the reporting to all concerned
investigator(s)/Institution(s) to the IRB/IEC, where required
to the regulatory authority of all ADRs that are both serious
and unexpected.
 Expedited reports should comply with the applicable
regulatory requirement and with the ICH guidelines for
clinical safety data management.
 Sponsor should submit to the regulatory authority(ies) all
safety updates and periodic reports as required by applicable
regulatory requirement(s).
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77. REFERENCES
1. Borton Cobert. Cobert’s Manual of Drug Safety and
Pharmacovigilance. 2nd Edition. Jones and Bartlett
Learning. 2012.
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78. Thanks!
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