SOP for Signal Management

Purpose

Purpose of this SOP is to lay down a process for Signal Management Activities in compliance with the Regulatory requirements for ANDA Holder. ANDA Holders have an obligation to perform signal detection for their authorized products. As per Legislative regulations of 21CFR314.80, it is responsibility of ANDA Holder.

Scope

The scope of this SOP is Client Pharmacovigilance signal detection and evaluation activities. This includes risk identification, assessment, and appropriate actions to manage the risk.

A signal management process is a set of activities performed to determine whether there are new risks associated with an active substance or a medicinal product or whether known risks have changed, and includes any related recommendations, decisions, communications, and tracking.

This procedure applies to all personnel of ANDA Holders, Service providers and affiliates of ANDA Holder.

Responsibility

Signal report Author: Responsible for signal detection, validation, signal analysis and preparation of signal management reports.

MR: Responsible for medical assessment of safety and potential signal.

Procedure

Signal Management Process

• According to the guidance provided in 21CFR314.80 Signal Management, signal detection and signal validation are the important steps to be carried out by the ANDA Holder. Designated authorities will work on signal confirmation, signal analysis and prioritization, signal assessment and will do recommendation for action.
• Signal detection may be performed by using a qualitative or quantitative method.

1. Qualitative process: This can be conducted by a review of individual cases, case series or line listings. This method is ideal for small data sets.
2. Semi Qualitative process: This can be conducted for less volumes of products.

• This process compares safety data from the defined review period, usually the last 12 calendar months, against the cumulative data.
• Signal management reports must be submitted within 60 calendar days from date of DLP.

Collection of Data

Data should be collected from all sources of ICSRs.

1. Literature reports (Form 1)
2. Agency Reports (Form 2)
3. Consumer reports, HCP reports etc (Form 3)
4. Data from FAERS system regarding potential signals need to be monitored.

The process as follows

• Check the FAERS data by the link as: https://www.fda.gov/drugs/questions-and-answers-fdas-adverse-event-reportingsystem-faers/potential-signals-serious-risksnew-safety-information-identified-fdaadverse-event-reporting-system
• Go to Quarterly reports
• Open the latest report section

The data need to be checked for any potential signals as per XXX Products. If so, that information needs to be tabulated in Signal report as below.

Any case identified after DLP must be included in next Review period report.

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Procedure

A. Collection of data:

1. Once collected data from all the relevant sources. Then process follows as
2. Gather data in one sheet (Form 4)
3. Delete all duplicates entries
4. MedDRA coding must be done for all identified events.
5. Get the data from Form 4 to Signal Analysis sheet (Form 5) for assessment
6. Calculate the number of occurrences of each adverse event
7. Do label assessment based on the current Client Labelling information for those events flagged as possible signals.

• Events with frequency ≥3 in the review period must be focused and included in the report.
• Events reported for the first time in the review period which are in the current Important Medic Events list /Designated Medical Events list.
• Events identified previously by Client as requiring close monitoring if any (Form 6).

Note: Identification of events reported for the first time may be limited to those in the Designated Medical Events list. These should be discussed and agreed before changes in place.

B. Review of Product Labelling:

1. Reviews the Client Product Labelling documents to determine if there are any differences between of the respective sections.
2. Based on this assessment indicates if the signal is a Confirmed signal, Uncertain signal, or No signal.
3. Prepare the Signal Management report (Form 7)
4. QC (Quality Check) of report for any corrections and findings (Form 8)
5. Prepares a Signal Detection Tracker (Form 9) for any identified signal (confirmed or uncertain) which requires a review.

C. If the signal is confirmed or unconfirmed:

Considers, the following actions if the signal is unconfirmed:

• Discusses/ notifies appropriate personnel within Client.
• Close monitoring of the event to enable better characterization and strengthening of the signal or additional data gathering (clinical or non-clinical).
• Client needs to communication to Regulatory Authorities

D. Client actions if Signal is confirmed:

• A modification to the product labelling as applicable to the local law.
• A safety alert and communication of new or reinforced information to the Regulatory Authorities, medical profession and/or the public as applicable
• Issuing a REMS or revision of existing, if applicable
• Restriction of product availability per local law if applicable
• Recall and/or withdrawal of the product from the market if applicable
• Further investigation if applicable. e.g. consultation with independent experts, post authorization safety study
• Additional risk minimization or pharmacovigilance activities if applicable
• If an event is considered to require close monitoring, updates the Close Monitoring List if applicable.

Abbreviation

QC: Quality Check.

DLP: Data Lock Point.

ICSR-Individual Case safety report.

Annexure

Form-1: Literature reports

Form-2: Agency Reports

Form-3: Consumer reports, HCP reports etc

Form-4: Gathering data sheet

Form-5: Signal Analysis sheet

Form-6: Close monitoring list

Form-7: Signal Management report

Form-8: QC Check list

Form-9: Signal Detection Tracker

FAERS Data sheet

References

USFDA Guidelines.

Revision History

Nil

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