STANDARD OPERATING PROCEDURE

 
  Title: Collection, Processing and submission of
Individual Case Safety Reports (ICSRs)
Effective Date: 29-Dec-2021
Review Date: 29-Dec-2023 Number: LUOXIN/PHC-ICSR- Version: 02
SOP-001
 
                                                                      
Applicability: Pharmconsul

Process Owner: Quality Assurance

APPROVALS

Prepared by:
Jagadeesh Babu Joga 21-Dec-2021
Pharmacovigilance Manager Sign &Date

Checked by: 22-Dec-2021

N.V.Bhavya Sri
QA Co-Ordinator Sign &Date

Approved by: Swamy.Jinugu 22-Dec-2021

Quality Head Sign &Date

This SOP is the confidential property of Pharmconsul. Any unauthorised

distribution or copying of the SOP is strictly prohibited.

PHC-QA-SOP-001-01 Page 1 of 10
 
 
STANDARD OPERATING PROCEDURE
 
  Title: Collection, Processing and submission of
Individual Case Safety Reports (ICSRs)
Effective Date: 29-Dec-2021
Review Date: 29-Dec-2023 Number: LUOXIN/PHC-ICSR- Version: 02
SOP-001
 
                                                                      

1. Purpose:
Purpose of this SOP is to lay down a process for collection, Processing and Submission
of Suspected Adverse Drug Reactions for ANDA Holder products to the Regulatory
Agency.
As per Legislative regulations of 21CFR314.80, it is responsibility of ANDA Holder.

2. Scope and Aims:

ANDA Holder have legal obligation to maintain the records of all suspected Adverse
reactions to their products and maintain a proper pharmacovigilance system to ensure
about an appropriate action towards the drug to reduce the Adverse reports occurrence.
This procedure applies to all personnel of ANDA holder, Service providers and affiliates
of ANDA holder.
3. Responsibility:
3.1 Data entry Person: Responsible for entering the data from source document into the
database structural field.
3.2 Quality Check person: Responsible for performing quality check at data entry level and
to evaluate the entire case with no errors.
3.3 Medical Reviewer (MR): Responsible for mentioning the company causality and
labelling of the event and event subsuming.
Mentioning the Final medical assessment comment in the narrative

4. Procedure:

4.1. Sources of Adverse Event reports:

4.1.1. Unsolicited reports from health care providers/consumers
4.1.2. Reports from Regulatory Authorities
4.1.3. Reports from licensing partners, distributors, and others

PHC-QA-SOP-001-01 Page 2 of 10
 
 
STANDARD OPERATING PROCEDURE
 
  Title: Collection, Processing and submission of
Individual Case Safety Reports (ICSRs)
Effective Date: 29-Dec-2021
Review Date: 29-Dec-2023 Number: LUOXIN/PHC-ICSR- Version: 02
SOP-001
 
                                                                      
4.1.4. Medical information center reports, fax
4.1.5. Scientific literature
4.1.6. Reports from Media (Television, Internet, websites, Newspapers)
4.1.7. Reports from Non-interventional studies

Note: Apart from Literature, ANDA holder must forward whatever the reports from
other sources to Pharmconsul within 2 Business days.

4.2. Scenarios to be considered as ADRs:

4.2.1. Unexpected/expected ADRs/Unexpected benefits

4.2.2. Lack of efficacy cases
4.2.3. Drug exposure during pregnancy/breast feeding/contraception
4.2.4. Overdose/misuse/abuse/off-label use
4.2.5. Medication error/near miss/occupational exposure
4.2.6. Transmission of suspected infectious agent
4.2.7. Interactions (drug-drug, drug-food, drug-disease)

4.3. Collection and assessment of ADRs:

The minimum criteria to consider a case as valid is

a. Identifiable reporter (HCP or Consumer with contact details)
b. Identifiable Patient (Initials, Date of birth, age, gender, age-group)
c. Suspect drug
d. Suspected Adverse drug reaction
4.3.1. ANDA holder should not include the names and addresses of individual patients in
reports. instead, should assign a unique code for identification of the patient. The
applicant should include the name of the reporter from whom the information was
received as part of the initial reporter information, even when the reporter is the
patient. The names of patients, health care professionals, hospitals, and geographical
identifiers in adverse drug experience reports are not releasable to the public under
FDA's public information regulations.
4.3.2. Upon receipt of Adverse Reaction report, duplicate check will be done for the
respective case in Clinovo database. If it was found as duplicate, then this case will be
handled as follow-up as per scenario. If no duplicates were found, then a Unique
number as (ANDA holder (LUOX)-Service Provider (PHC)-Company Receive date

PHC-QA-SOP-001-01 Page 3 of 10
 
 
STANDARD OPERATING PROCEDURE
 
  Title: Collection, Processing and submission of
Individual Case Safety Reports (ICSRs)
Effective Date: 29-Dec-2021
Review Date: 29-Dec-2023 Number: LUOXIN/PHC-ICSR- Version: 02
SOP-001
 
                                                                      
(yyyy-mmm-dd)-Source (Lit or spon)-sequence number (0001)) to be given for
identification and further references. Eg as: LUOX-PHC-2021-Nov-20-LIT-0001
4.3.3. Cases can also have sequence number as per previous SOP during the Clinovo set up and
transition period.
4.3.4. All cases must be assessed for Severity and seriousness criteria.
4.3.5. Seriousness Criteria as follows:

Serious adverse drug experience. Any adverse drug experience occurring at any dose
that results in any of the following outcomes such as
a. Death,
b. A life-threatening adverse drug experience,
c. Inpatient hospitalization or prolongation of existing hospitalization,
d. A persistent or significant disability/incapacity, or a congenital anomaly/birth
defect.
e. Important medical events that may not result in death, be life-threatening, or
require hospitalization may be considered a serious adverse drug experience
when, based upon appropriate medical judgment. Examples of such medical
events include allergic bronchospasm requiring intensive treatment in an
emergency room or at home, blood dyscrasias or convulsions that do not result in
inpatient hospitalization, or the development of drug dependency or drug abuse.

4.3.6. Unexpected adverse drug experience:

Any adverse drug experience that is not listed in the current labeling for the drug product.
This includes events that may be symptomatically and patho-physiologically related to an
event listed in the labeling. but differ from the event because of greater severity or
specificity. For example, hepatic necrosis, elevated hepatic enzymes or hepatitis, cerebral
thromboembolism, cerebral vasculitis.

4.4. Processing of ADRs:

4.4.1. Day Zero 0 (the clock starts for reporting) is the date of receipt of spontaneous report by
any affiliates of ANDA holder. It is CRD (Company Receipt Date).
4.4.2. Post marketing 15-day Alert reports:

PHC-QA-SOP-001-01 Page 4 of 10
 
 
STANDARD OPERATING PROCEDURE
 
  Title: Collection, Processing and submission of
Individual Case Safety Reports (ICSRs)
Effective Date: 29-Dec-2021
Review Date: 29-Dec-2023 Number: LUOXIN/PHC-ICSR- Version: 02
SOP-001
 
                                                                      
The ANDA holder must report each adverse drug experience that is both serious and
unexpected, whether foreign or domestic, as soon as possible but no later than 15
calendar days from initial receipt of the information by the applicant. The follow ups for
the 15-day alert reports also to be submitted within 15 calendar days of receipt of new
information or as requested by FDA. If additional information is not obtainable, records
should be maintained.
4.4.3. Pharmconsul must evaluate a case report and send notification about reportable cases
to ANDA holder within 7 business days.
4.4.4. ICSRs for serious, expected, and nonserious adverse drug experiences must be
submitted in PADERs.
4.4.5. The EMEA website will be referred for IME/DME List
4.4.6. Information to be presented on ICSR as follows:

a. Patient information:
1. Patient identification code
2. Patient age at the time of adverse drug experience, or date of birth
3. Patient gender; and
4. Patient weight.
b. Adverse drug experience:
1. Outcome attributed to adverse drug experience
2. Date of adverse drug experience
3. Date of ICSR submission
4. Description of adverse drug experience (including a concise medical
narrative)
5. Adverse drug experience term(s)
6. Description of relevant tests, including dates and laboratory data; and
7. Other relevant patient history, including preexisting medical conditions.
c. Suspect medical product(s):
1. Name
2. Dose, frequency, and route of administration used
3. Therapy dates
4. Diagnosis for use (indication)
5. Whether the product is a prescription or nonprescription product
6. Whether adverse drug experience abated after drug use stopped or dose
reduced
7. Whether adverse drug experience reappeared after reintroduction of drug

PHC-QA-SOP-001-01 Page 5 of 10
 
 
STANDARD OPERATING PROCEDURE
 
  Title: Collection, Processing and submission of
Individual Case Safety Reports (ICSRs)
Effective Date: 29-Dec-2021
Review Date: 29-Dec-2023 Number: LUOXIN/PHC-ICSR- Version: 02
SOP-001
 
                                                                      
8. Lot number, Expiration date
9. Concomitant medical products and therapy dates.
d. Initial reporter information:
1. Name, address, and telephone number
2. Whether the initial reporter is a health care professional; and
3. Occupation, if a health care professional.
4. ANDA holder information, name and contact office address, Telephone
number
5. Report source, such as spontaneous, literature, or study
6. Date the report was received by ANDA holder
7. Application number and type
8. Whether the ICSR is a 15-day "Alert report"
9. Whether the ICSR is an initial report or follow up report; and
10. Unique case identification number, which must be the same in the initial
report and any subsequent follow up report(s)

4.4.7. All received ADRs must be tracked with identification numbers and must be archived.

4.5. Follow-up of ADRs:

4.5.1. Follow-up of ADRs must be done by timely manner by PV Department.

4.5.2. First follow-up to be done within 3 business days from CRD.
4.5.3. Follow-up of cases (serious/non serious) to be made for three attempts in 2 weeks of
LRD. If no response received, case can be closed
4.5.4. It is important to follow up all pregnancy cases where fetus could have been exposed
to product. Long half-life must be into consideration while assessing the pregnancy
cases.

4.6. Case Processing, QC (Quality Check), MR (Medical Review), Submission:

4.6.1. Case validity checking.

4.6.2. Duplicate checking: check the Clinovo Database to identify if any duplicate case or
new case.
4.6.3. The cases must be submitted to the FDA in electronic format through SRP (Safety
Reporting Portal) Portal or E2B Gate way via Clinovo data base.

PHC-QA-SOP-001-01 Page 6 of 10
 
  
STANDARD OPERATING PROCEDURE
 
  Title: Collection, Processing and submission of
Individual Case Safety Reports (ICSRs)
Effective Date: 29-Dec-2021
Review Date: 29-Dec-2023 Number: LUOXIN/PHC-ICSR- Version: 02
SOP-001
 
                                                                      

4.6.4. The ANDA holder must report each adverse drug experience that is both serious and
unexpected, whether foreign or domestic, as soon as possible but no later than 15
calendar days from initial receipt of the information by the applicant. The follow ups
for the 15-day alert reports also to be submitted within 15 calendar days of receipt of
new information or as requested by FDA. If additional information is not obtainable,
records should be maintained.
4.6.5. ICSRs for serious, unexpected must be processed. Must be submitted in 15 calendar days.
4.6.6. FDA has accepted electronic submissions of both expedited and non-expedited Individual
Case Safety Reports (ICSRs) for human drug and nonvaccine biologic products. To date,
FDA has only accepted electronic submissions of ICSRs in the XML format.
4.6.7. The case data need to be manually entered by the respective users in the Clinovo
Database and submitted to FDA via E2B Gateway. Related source attachments must be in
the PDF format.

4.6.8. Case Processing: Cases received from different sources of information.

A. Check the validity of case
B. Case needs to be created in Clinovo Database if no duplicates
C. A Unique number to be given to identify and track the case
D. All Valid and Reportable cases must be filled and archived
E. Supporting documents to be attached

4.6.9. Quality Check (QC):

A. QC findings and corrections must be recorded in the comments section of

Database.
B. Quality must be maintained not less than 95%. This step will be done at QC
level.

Any Significant errors (errors with respect to 4 Minimum criteria) noted in DE

(Data Entry) then, the Quality deduction for each error is 3%

Any Non-significant errors (errors with respect to other fields) noted in DE, then
the Quality deduction for each error is 2%

This evaluation will be tracker in Form 1 (Quality Metrics).

PHC-QA-SOP-001-01 Page 7 of 10
 
 
STANDARD OPERATING PROCEDURE
 
  Title: Collection, Processing and submission of
Individual Case Safety Reports (ICSRs)
Effective Date: 29-Dec-2021
Review Date: 29-Dec-2023 Number: LUOXIN/PHC-ICSR- Version: 02
SOP-001
 
                                                                      

4.6.10. Medical Review:

A. Medical Judgement and Causality assessment must be done in Medical Review

step and must be recorded in comments section of Database.
B. Listedness will be checked as per the product labelling information
C. MR refer the WHO Causality assessment guideline as a standard for the causality
assessment

4.6.11. Submission:

A. Submission of Valid cases through SRP Portal or Clinovo Database E2B

Gateway
B. Required supporting documents to be filed in PDF format.

4.6.12. Roles and responsibilities:

A. Case duplicate check, Data entry (DE), Quality Check, Medical Review and
Submission activities are handled by the users who has undergone the project
trainings and related activities as per their roles mentioned in the Job
Description.

5. Acronyms:
5.1 ANDA-Abbreviated new drug application.
5.2 SRP- Safety Reporting Portal.
5.3 MR-Medical Review.
5.4 WHO- World health organization.

6. Appendix:
Form-1: Quality Metrics

7. References:
USFDA Guidelines.

PHC-QA-SOP-001-01 Page 8 of 10
 
 
STANDARD OPERATING PROCEDURE
 
  Title: Collection, Processing and submission of
Individual Case Safety Reports (ICSRs)
Effective Date: 29-Dec-2021
Review Date: 29-Dec-2023 Number: LUOXIN/PHC-ICSR- Version: 02
SOP-001
 
                                                                      

8. Version Control:
Supersede Change Reason for revision
Version No. Control No.
LUOXIN/PHC- CC/21/004 1. MAH term has been replaced with ANDA Holder
SOP-ICSR-01 2. 4.6.5 serious expected (typo error) has been corrected
to serious unexpected
3. 4.6.6 “ICSR nonserious adverse drug experiences
must be submitted in 30 Days or else submitted in
PADER also” deleted.
4. 4.6.10 - Listedness will be checked as per the product
labelling information .
MR refer the WHO Causality assessment guideline as a
standard for the causality assessment has been included.
5. 4.4.5. The EMEA website will be referred for
IME/DME List has been included.
6. 4.6.2. modified as -------- Duplicate checking:
check the Clinovo Database to identify if any
duplicate case or new case
7. 4.6.3. modified as --------The cases must be
submitted to the FDA in electronic format through
SRP Portal or E2B Gate way via Clinovo data base.
8. 4.6.7 been modified.
9. 4.3.2. has been modified as Upon receipt of
Adverse Rection report, duplicate check will be done
for the respective case in Clinovo database. If it was
found as duplicate, then this case will be handled as
follow-up as per scenario. If no duplicates were found,
then a Unique number as (ANDA holder-Service
Provider-Initial Receive date-Source/sequence number)
to be given for identification and further references. Eg
as: LUOX-PHC-2021-Nov-20-LIT-0001
10. 4.6.9 has been added.

PHC-QA-SOP-001-01 Page 9 of 10
 
 
STANDARD OPERATING PROCEDURE
 
  Title: Collection, Processing and submission of
Individual Case Safety Reports (ICSRs)
Effective Date: 29-Dec-2021
Review Date: 29-Dec-2023 Number: LUOXIN/PHC-ICSR- Version: 02
SOP-001
 
                                                                      

END OF THE DOCUMENT

PHC-QA-SOP-001-01 Page 10 of 10