Attachment C - PWS Appendices.pdf

Case Processing and Data Management in FDA Adverse Event Reporting System (FAERS) Page 1 of 9 Draft 1, 6/8/22

Standard Operating Procedures

Case Processing and Data Management in FDA Adverse Event Reporting

System (FAERS)

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Table of Contents PURPOSE ________________________________________________________________________ 3

SCOPE __________________________________________________________________________ 3

BACKGROUND ___________________________________________________________________ 4

Premarketing Reports ____________________________________________________________________ 4

Postmarketing Reports ___________________________________________________________________ 4

Data Formats ___________________________________________________________________________ 4

LSMV Case Processing Metrics _____________________________________________________________ 5

RESPONSIBILITIES _______________________________________________________________ 5

PROCEDURES ____________________________________________________________________ 6

CTU FLARe Activities _____________________________________________________________________ 6

LSMV Data Entry ________________________________________________________________________ 6

LSMV Product and Manufacturer Coding _____________________________________________________ 6

LSMV MedDRA Coding ___________________________________________________________________ 7

APPENDICES ____________________________________________________________________ 8

A. FAERS Case Processing Diagram ________________________________________________________ 8

B. FAERS Document History Change History ________________________________________________ 9

C. FAERS Change History ________________________________________________________________ 9

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PURPOSE

This document describes both guidance and requirements for processing Adverse Event, Medication Error, and Product Complaint (product quality or defect) reports. This process includes receipt of reports, data entry, and coding activities in FAERS. The personnel perform case processing and data management activities under the Comprehensive Data Management Services (CDMS) contract.

Appendix A is a graphic of the FAERS case processing steps.

SCOPE

This SOP describes the staff roles for processing reports of adverse side effects possibly associated with FDA-regulated products for human use. The FDA broadly categorizes reports as shown in the table below.

FDA-Regulated Report Categories

Reports Safety Product Quality Premarketing, products pending FDA approval;

industry submissions

Yes Yes

Postmarketing, FDA-approval products

1. Industry or Mandatory submissions

2. Voluntary or Direct submissions

Yes Yes

CDER/CBER Reports for Adverse Event, Medication Error, and Product Complaint/Product Quality are received through various media, such as the postal service, fax, or electronically; and are processed into the LSMV (LifeSphere MultiVigilance) application.

By federal law, industry submissions or Individual Case Safety Reports (ICSRs) must be filed in an electronic, standardized format.1 These ICSRs or E2Bs—from submission through completion—move automatically through the three LSMV case processing steps:

• Data Entry

• Product and Manufacturing Coding (PMC)

• Medical Dictionary for Regulatory Activities (MedDRA) Coding or MC

However, they are routed to CDMS for manual processing if the reported product or manufacturer data does not automatically code to existing terms in the respective FDA Product and Manufacturer Dictionaries.

1 Some report types, for example, tissue reports, are exempt.

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Direct (or Voluntary) reports are received by fax, mail, electronically, or email. The Central Triage Unit (CTU) 2 performs initial processing within the First Look at Reports (FLARe)3 application. Direct reports are then processed as required through the LSMV steps: Data Entry, PMC, and MC.

BACKGROUND

Upon completion of all processing steps, CDMS forwards case data to FDA Safety Evaluators (SEs), where data is retained in Rx Logic, an LSMV tool for data analytics. In addition, data is extracted quarterly and publicly disseminated through the FDA Public Dashboard.

Premarketing Reports

Referred to as Investigational or IND reports, these reports are LSMV uses a different, separate pathway to ensure data for an unapproved product is not co-mingled with postmarketing data.

This is especially important because the latter data is part of the postmarketing repository that is released to the public.

LSMV routes INDs, as necessary, to CDMS for product and/or manufacturer data validation, when reported data does not validate against entries in the FDA Dictionaries. CDMS staff complete the steps to validate the products before routing the case to SEs.

Postmarketing Reports

Voluntary or Direct reports—CTU forwards cases electronically into the LSMV Data Entry Workflow.

Safety and product quality reports for Center for Drug Evaluation and Research (CDER) and non-vaccine biologic reports for Center for Biologics Evaluation and Research (CBER) are processed in

LSMV.

Mandatory reports—Occasionally a paper-copy Mandatory report is received, which CTU will process for disposition into LSMV. Its initial processing steps are the same as those for Direct reports, that is, converting the reported data on the paper-copy report into an LSMV-compatible format.

Data Formats

Fax/Paper/Email Submissions (*.pdf) are received in CTU. Scanning and OCR technologies are used to load fax and email reports into FLARe for processing. Paper submissions are manually scanned and uploaded to FLARe during the Registration Step. OCR technologies are being investigated to convert report data into an *.xml format compatible with FLARe.

2 Central Triage Unit (CTU): Comprises the people and processes that encompass the first review/processing of direct ICSRs submitted to the FDA from ICSR intake to the end of triage.

3 First Look at Reports (FLARe): An Aris-Global developed, cloud-based application for tracking, initial data entry and triaging of Voluntary reports.

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Electronic Submissions (*.xml) or E2B submissions originate at the manufacturer or firm site and terminate with the addition of the reported data in the LSMV database. FDA imports the .xml-formatted data directly into mapped data fields in LSMV Data Entry. Case processing is designed for full automation but can be interrupted when exceptions occur. If any error during the validation of the product, manufacturer, or MedDRA coding occurs, the report is then sent to the PMC step for updating. If it is determined that MedDRA coding is incorrect, the report is then forwarded to the MC step for manual correction.

MedWatch Online submissions are Direct reports received in FLARe in an LSMV-compatible data file format (.xml). FLARe creates a case summary (instead of an image of the 3500 or 3500B report form) and assigns a Registration (RCT) number to each case. The CTU Registration unit verifies the accuracy of key data elements—patient, reporter, and suspect product—before moving the case to the CTU Triage Pharmacists. Triaged reports are forwarded into LSMV. All tasks are performed online/paperless.

LSMV Case Processing Metrics

Upon completion of case processing, LSMV data repository provides an array of data analytics for staffing, case management, and trend analysis.

RESPONSIBILITIES

Experienced CDMS staff enter data at each phase of FLARe and LSMV case processing. The Responsibility and Procedure Sections describe CDMS activities relevant for FLARe and LSMV case processing of premarketing safety reports, and postmarketing reports of safety and product quality issues. When LSMV begins processing product quality reports, this document will be updated accordingly.

CTU Data Entry Specialists perform data entry in FLARe. They enter or correct data submitted on all Direct (or Voluntary) submissions, and certain Mandatory submissions.4

Triage Pharmacists perform tasks in FLARe. They review Voluntary submissions to determine whether it concerns an FDA-regulated product and whether it meets the criteria for a complete Individual Case Safety Report (ICSR) and/or a product quality report. They route submissions to the appropriate FDA centers and offices, including CDER and CBER. (CDER and CBER reports are processed in LSMV).

LSMV Data Entry Specialists perform verbatim data entry for reports entered into the LSMV database and verify the accuracy of previously entered data.

LSMV Product and Manufacturer Coders assign product and manufacturer codes for the suspect product using the FDA product and manufacturer dictionaries. They communicate with the Dictionary teams as needed and verify the accuracy of previously entered data. They access FDA-approved

4 The FDA exempts some firms and/or types of reports (e.g., tissue reports) from mandated electronic submission. CTU staff perform initial entry on these Mandatory reports, and FDA compliance is verified.

Adverse Event Reporting System (FAERS) Page 6 of 9 Draft 1, 6/8/22 resources and consult with the FDA Dictionary teams as appropriate to identify and code valid Dictionary entries. Their research may lead to corrections or additions of new entries in the FDA Dictionaries.

MedDRA Coders assign MedDRA code(s) to each relevant component of the report (i.e., adverse event, medication/product use error, indication, tests, procedures, and previous diagnosis).

PROCEDURES

CTU FLARe Activities

The CTU Data Entry Specialist (Registration):

• Verifies the accuracy of specific key data elements—patient, reporter, and suspect product

• Processes reports received through various modes of transmission, such as fax and email

• Forward triaged or reviewed reports to appropriate center(s) as instructed on behalf of triaging pharmacist

NOTE: Mandatory reports may also need to be reviewed by the triaging pharmacist for compliance issues.

The CTU Triaging Pharmacist (Triage):

• Confirms that appropriate key data elements are present — patient, reporter and suspect product, and issues of complaint

• Forwards CDER and CBER cases into LSMV Data Entry; forwards other cases to the appropriate FDA Center or Office

A separate Direct MedWatch ICSR Handling SOP is available on the intranet.

LSMV Data Entry

The remaining procedures occur in LSMV. LSMV imports mapped data from FLARe .xml-formatted outputs. Staff perform all steps online; no paper-copy reports are handled.

If the document has been annotated by the Triaging Pharmacist, it becomes the source document for use in Data Entry.

The LSMV Data Entry Specialist performs the following tasks:

• Performs verbatim data entry of specified fields.

• Reviews previously entered data to ensure accuracy.

• Consults with team lead or CTU manager/FDA onsite representative if necessary.

• Moves the case to Product and Manufacturer Coding upon completing data entry.

LSMV Product and Manufacturer Coding

This unit receives and processes all reports that do not automatically code. These are often referred to as ‘fall outs’.

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The Product and Manufacturer Coder performs the following tasks:

• Reviews previously entered data to ensure accuracy.

• Codes the suspect product and the sender organization using FDA Dictionaries

• Consults with team lead or CTU manager/FDA onsite representative if necessary.

• Forwards additions and corrections to the Product and/or Manufacturer Dictionary teams.

• Moves the case to MedDRA Coding upon completion.

LSMV MedDRA Coding

This unit receives reports from PMC.

The MedDRA Coder performs the following tasks:

• Reviews ICSR and updates previous data entry, as needed.

• Assigns appropriate MedDRA code(s) to each relevant component of the ICSR such as adverse event, medication/product use error, indication, tests, procedures, and previous diagnosis(es).

• Consults the team lead or CTU Manager/FDA onsite representative, as necessary throughout the validating process.

• Reviews previously entered data to ensure accuracy.

• Moves the case into ‘Safety Evaluator Ready’ status. (The data/case remains on the LSMV platform, but with respect to case processing, it is an “out of workflow”.

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APPENDICES

A. FAERS Case Processing Diagram for Pre- and Postmarketing and Product Quality Reports

Link to return to "PURPOSE"

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B. FAERS Document History Change History

Document History Version

Status* Date Author Name and Title Approving Official Name and Title

0 I, D 06/06/2022 Draft sent

1 I, D 6/8/2022

* D: Draft, I: Initial, R: Revision, W: Withdrawn, NU: Reviewed, No Updates Required

C. FAERS Change History

Change History Version

Section Description of change

0 All Initial draft. Incorporates LSMV with FLARe and supporting roles and processes under FAERS.

1 All Updates to draft document with minor questions to proceed to final approval.

names withheld for this reviewing activity names withheld for this reviewing activity names withheld for this reviewing activity names withheld for this reviewing activity

Office of Surveillance and Epidemiology Center for Drug Evaluation and Research

Document #:

OSE-IO-RSS-

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Effective Date:

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Uncontrolled when printed on: 6/29/2022 For the most current and official copy, check the Master List

Table of Contents

1. PURPOSE

2. SCOPE

3. BACKGROUND

4. RESPONSIBILITY

5. PROCEDURE

6. DEFINITIONS/GLOSSARY

7. APPENDICES

8. REFERENCES

9. RECORDS

10. SUPPORTING DOCUMENTS

11. ATTACHMENTS

12. DOCUMENT AND CHANGE HISTORY

1. Purpose The purpose of this Standard Operating Procedure (SOP) is to describe the processing of direct (otherwise known as voluntary) Individual Case Safety Reports (ICSRs) submitted directly to the FDA through the MedWatch Program.

2. Scope

This SOP applies to the processing of direct ICSRs submitted for FDA-regulated products. This SOP does not describe the processing of ICSRs that are required for submission by FDA regulatory or statutory requirements.

3. Background FDA Adverse Event Reporting System Data Management Program (FAERS DMP) manages the processing of all ICSRs received through MedWatch Online, fax, or mail.

There are multiple ways the public can submit MedWatch ICSRs including the Voluntary Reporting Form 3500 or 3500B (see Attachments A & B). All electronic and faxed ICSRs are automatically uploaded to First Look at Reports (FLARe). All paper ICSRs are manually added to FLARe by the FAERS DMP staff.

FAERS DMP is comprised of four units: Central Triage, Data Entry, Product/Manufacturer Coding and MedDRA Coding. All direct ICSRs received through the MedWatch program are first processed by the Central Triage Unit (CTU) and routed to the relevant FDA centers. ICSRs routed to other centers or offices are further

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4. Responsibility

4.1. Registration Coordinator reviews the submission and enters or updates required information within the FLARe system. All submissions are assigned a registration code, which is then used to track the ICSR during the triage process.

4.2. Triage Pharmacist reviews the submission to determine whether it concerns an FDA-regulated product and whether it meets the criteria for an ICSR. Routes the submission to the appropriate FDA center or office.

4.3. Data Entry Specialist performs verbatim data entry for ICSRs to be entered into the

FAERS database.

4.4. Product/Manufacturer Coder assigns product and manufacturer codes for the suspect product within the ICSR using the FAERS product and manufacturing dictionaries. Reviews data entered by Data Entry Specialists and verifies data entry accuracy.

4.5. MedDRA Coder assigns Medical Dictionary for Regulatory Activities (MedDRA) code(s) to each relevant component of the ICSR (i.e., adverse event, medication/product use error, indication, tests, procedures, and previous diagnosis).

Corrects data entry errors if identified.

4.6. CTU Manager provides oversight for all aspects of procedures for the CTU. Resolves issues identified by any staff named above concerning key data elements within submissions. Supports all FAERS DMP staff and ensures staff meet ICSR processing expectations such as timelines and verbatim data capturing.

5. Procedure

5.1. CTU Intake

Once a submission is received or is entered by the CTU through FLARe it acquires a registration code.

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The procedures described in 5.1 occur in FLARe.

Registration Coordinator:

5.1.1. Performs basic data entry for paper and fax submissions on specific key elements—patient, reporter and suspect product.

5.1.2. Confirms that specific key data elements—patient, reporter and suspect product—are present for electronic submissions.

Note: If Registration Coordinator identifies an issue with the key data elements, the submission is forwarded to the CTU Manager. The CTU Manager reviews the submission and determines if it has sufficient information to proceed to triage.

5.2. Triage

The procedures described in 5.2 occur in FLARe.

Triaging Pharmacist:

5.2.1. Reviews the submission to determine if the submission is an ICSR (see Appendix A.)

5.2.2. Identifies the suspect product category (biologic, cosmetic, device, drug, food, tobacco, etc.) using naming conventions, key words and other information. (For details regarding identification of homeopathic and compounding products see Appendix B.)

5.2.3. Annotates the ICSR to clarify key data elements as necessary. For example, the suspect product may be listed in the narrative but not in the structured data field. The annotated ICSR is saved as a new version with annotations demarcated in red.

5.2.4. Routes the ICSR to the center that regulates that suspect product. (For details on the method of transmitting ICSRs to different FDA centers, see Appendix C.)

5.2.4.1. If the suspect product is regulated by more than one center, the ICSR is routed to all appropriate centers.

5.2.4.2. An ICSR for a certain suspect product may be routed to more than one center as agreed upon by the CTU and the centers. For example, an FDA center may request to receive ICSRs for products of interest that are typically submitted to a different center.

5.2.4.3. The Triaging Pharmacist routes all ICSRs describing drug or biologic quality issues to the CDER or CBER quality teams. If the ICSR describes only a product quality issue, it is not entered into the FAERS database (see Appendix D.)

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5.2.4.4. ICSR disposition or routing is generally based on the active ingredient and not the suspect product’s use or indications for use. However, there are situations where a product is routed to a specific FDA center based on the use of the product. For example, a baking soda /NaHCO3 ICSR is routed to Center for Food Safety and Applied Nutrition (CFSAN) when used in food products but routed to CDER when used for heartburn treatment. If an active ingredient is regulated by more than one FDA center, it can be routed to both centers or one center based on the indication for use, if provided.

5.2.4.5. If the Triaging Pharmacist reviews a submission and determines it is not an ICSR, the submission is removed from the work flow but remains in FLARe as an inactive submission.

5.2.5. Consults the CTU Manager as necessary throughout the triage process (see Appendices E & F for Triaging Pharmacist Helpful Hints and Frequently Asked Questions.)

5.2.6. Marks ICSR as urgent for all suspect products identified on the Code 24 list.

5.2.7. Once triage is completed, ICSRs that are routed to CDER (i.e. the suspect product is identified as a small molecule drug, therapeutic recombinant protein or monoclonal antibody) and ICSRs that are routed to CBER (i.e. the suspect product is a non-vaccine, biologic product that is not regulated by CDER) are entered into the FAERS database and the ICSR moves to Data Entry. If the Triaging Pharmacist reviews an ICSR from MedWatch Online and determines that no updates are needed, he or she forwards the ICSR straight to the Coding unit in FAERS.

5.3. Data Entry

The procedures described in 5.3 occur in FAERS.

Data entry is dependent on the submission source media.

If the document has been annotated by the Triaging Pharmacist, it becomes the source document for use in data entry.

Data Entry Specialist:

5.3.1. For paper submissions, enters data verbatim from the MedWatch 3500, 3500B forms or the source document.

5.3.2. For fax submissions, compares the data digitized by the optical character reader to the source document and corrects/updates as appropriate.

5.3.3. For submissions received through MedWatch Online, compares the data electronically captured to the source document and corrects/updates data as appropriate.

5.3.4. Consults the CTU Manager as necessary throughout the data entry process.

For additional details regarding data entry, see References 8.6.

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5.3.5. Once data entry is completed, the ICSR is moved to Product/Manufacturer Coding.

5.4. Product/Manufacturer Coding

The procedures described in 5.4 occur in FAERS.

Product/Manufacturer Coder:

5.4.1. Reviews ICSR to ensure accuracy of previous data entry.

5.4.2. Analyzes ICSR and codes the suspect product and the suspect product’s manufacturer using the appropriate dictionaries.

5.4.3. If a suspect product or manufacturer is not listed in the dictionary, the Coder notifies the FAERS Product Dictionary team or the FAERS Manufacturer Dictionary team. Communication can occur by email, phone or in person. Once the Coder receives notification from the dictionary team that the term has been added, the Coder completes the ICSR coding.

5.4.4. Consults the CTU Manager as necessary throughout the coding process. For additional details regarding coding, see References 8.5.

5.4.5. Once coding is completed, the ICSR is moved to MedDRA Coding.

5.5. MedDRA Coding

The procedures described in 5.5 occur in FAERS.

MedDRA Coder

5.5.1. Reviews ICSR and updates previous data entry as needed.

5.5.2. Assigns appropriate MedDRA code(s) to each relevant component of the ICSR such as adverse event, medication/product use error, indication, tests, procedures and previous diagnosis.

5.5.3. Consults the CTU Manager as necessary throughout the validating process. For additional details regarding validation, see References 8.7.

5.5.4. Marks the ICSR “Safety Evaluator Ready” which completes the data processing. The ICSR is then made available in FAERS to appropriate FDA staff.

6. Definitions/Glossary

6.1. Adverse Event: Any undesirable experience associated with the use of a medical product in a patient. Events that result in the following outcomes are considered Serious Adverse Events: death, life-threatening event, hospitalization (initialized or

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6.2. Central Triage Unit (CTU): Comprises the people and processes that encompass the first review/processing of direct ICSRs submitted to the FDA from ICSR intake to the end of triage.

6.3. Code 24 Cases: Are MedWatch reports for products that FDA leadership has identified for increased monitoring. These product lists are updated and compiled by staff within Office of Surveillance and Epidemiology (OSE). These reports are treated in an expedited manner and processed within a 24-hour window.

6.4. Case Routing/Disposition: Transfer of the ICSR to the FDA office or center that has the regulatory authority for the suspect product or is responsible for the review of the submission.

6.5. FDA Adverse Event Reporting System (FAERS): Is a database that contains adverse event reports, medication error reports, and product quality complaints resulting in adverse events that were submitted to FDA. The database is designed to support the FDA's post-marketing safety surveillance program for drug and therapeutic biologic products. FAERS is composed of case management workflow functions, management reports, query modules, batch printing, and interfaces with the Electronic Submission Gateway (ESG), the Safety Reporting Portal (SRP), and First Look at Reports (FLARe).

6.6. First Look at Reports (FLARe): FLARe is a web-based software application that unifies report imaging, processing and tracking. Two integrated modules—the Correspondence Module and the Batch Acknowledgment by Post module—automate the processes for 1) sending emails to FDA Centers and teams and 2) Acknowledgement letters to reporters, respectively. FLARe creates an image (source document) for every report registered in the application, and then logs, tracks, and archives that image. Upon receipt into FLARe, reports are initially sorted according to three modes of delivery (source media)—MedWatch Online submissions, fax and Direct Scan (paper copies received by USPS and emails sent directly to the CTU Manager.) MedWatch Online submissions are received in FLARe in a file format (.xml) compatible with FAERS. Fax and Direct Scan report data are converted into a file format (.pdf) that an integrated Optical Character Recognition software extracts to populate the FLARe data fields.

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6.7. Individual Case Safety Report (ICSR): Is a description of adverse events, medication/product use errors, product problems and consumer complaints associated with the use of FDA-regulated products related to an individual subject, patient or consumer.

6.8. Medical Dictionary for Regulatory Activities (MedDRA): Is an extensive medical terminology with a unique architecture and features that support public health monitoring, data analysis, communication (both electronic and traditional) and data management. This terminology is hierarchical, multiaxial, multilingual, regularly-updated, and strictly maintained.

6.9. Reporter: Is any member of the public who voluntarily reports an event either for themselves or others. For example, the reporter can be a consumer, their agents, or healthcare providers.

6.10. Safety Evaluator Ready: The status of the ICSR following the completion of case processing.

7. Appendices

Appendix A: Determining Whether a Submission Qualifies as an ICSR

Involves a patient or consumer.

Describes an adverse event, medication/product use error, product quality issue or other product complaint.

Includes a reporter.

Includes an identifiable FDA-regulated product.

Note: Direct ICSRs generally contain some but may not always contain all four of the basic data elements listed above.

Appendix B: Identifying the Suspect Product and Routing the ICSR

Suspect Product is a Pointers Routing Drug Triaging Pharmacist uses reported drug naming conventions such as common, chemical, brand or generic names to recognize drug

ICSRs concerning small molecule drugs, therapeutic recombinant proteins and monoclonal antibodies are

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routed to CDER and further processed into FAERS.

Biologic Triaging Pharmacist utilizes reported biologic naming conventions such as common, chemical, brand or generic names to recognize biologic ingredients.

May also use distinguishing terms such as “tissue product” or “blood product” in recognizing biologics.

ICSRs concerning other non-vaccine, biologic products that are not regulated by CDER are routed to CBER and further processed into FAERS.

Homeopathic Triaging Pharmacist uses specific indicating terms such as “homeopathic” or “homeopathy,” presence of drug dilution factors, e.g., 12X or 3C, and/or a list of ingredients with plant or mineral names present in the ICSR or product label.

If these indicators are present, the ICSR is routed to CDER. If these indicators are absent, the ICSR is routed to CFSAN.

Compounded drug Triaging Pharmacist reviews the ICSR for specific terms such as “compounding” or “compounded”.

On occasion, a reporter may leave the checkbox for compounding product blank but mention compounding key words in the narrative section or suspect product section in the ICSR.

If a compounded product is suspected, the Triaging Pharmacist updates the compounding box or annotates the ICSR prior to routing it to CDER.

Drug versus Food

When it’s unclear if a suspect product is considered a drug versus a food, Triaging Pharmacist uses resources such as DailyMed product list, Drugs@FDA product list and NIH Dietary Supplement Label databases for additional clarification (see References).

If the suspect product has a nutrition/supplement facts label, Triaging Pharmacist routes ICSR to CFSAN. If the product has a drug facts label, the ICSR is routed to

CDER.

Unsupported medical claim(s) and

Triaging Pharmacist searches the submission for specific key words

ICSRs are routed to the Office of Unapproved Drugs

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and Labeling Compliance (OUDLC) by email.

Appendix C: How ICSRs are routed from CTU to Different FDA Centers CDER MedWatch ICSR transferred by XML files using ICH E2B standards.

CBER MedWatch ICSR transferred by XML files using ICH E2B standards.

CDRH MedWatch ICSR sent by Email.

CFSAN MedWatch ICSR transferred by XML files using ICH E2B standards.

CTP MedWatch ICSR sent by Email.

CVM MedWatch ICSR sent by Email.

Appendix D: ICSRs related to Drug/Biologic Product Quality

ICSRs for small molecule drugs, therapeutic recombinant proteins and monoclonal antibodies reporting quality issues only are routed to the Drug Quality Reporting System (DQRS) by email.

ICSRs for small molecule drugs, therapeutic recombinant proteins and monoclonal antibodies reporting both adverse events and quality issues are routed to CDER and emailed to DQRS.

ICSRs for non-vaccine, biologic products not regulated by CDER reporting quality issues only are routed to Office of Biostatistics and Epidemiology/ Division of Epidemiology (CBER/OBE/DE) by email.

ICSRs for non-vaccine, biologic products not regulated by CDER reporting both adverse events and quality issues are routed to CBER and emailed to OBE/DE.

Appendix E: Triaging Pharmacist Helpful Hints

If… Then… Submission determined not to be an ICSR Example: Insurance policy complaint

Submission is removed from FLARe.

No FDA-regulated suspect product is identified Example: reports of consumer products, such as toys, or general unidentifiable descriptions, such as “statins”

Submission is removed from FLARe.

The product reported is a food, dietary supplement or cosmetic

ICSR is routed to the Center for Food Safety and Applied Nutrition (CFSAN).

The product reported is a device ICSR is routed to the Center for Devices and Radiological Health (CDRH).

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The product reported is tobacco ICSR is routed to the Center for Tobacco Products (CTP).

The product reported is a veterinary drug ICSR is routed to the Center for Veterinary Medicine (CVM).

The product reported is a vaccine ICSR is routed to the Vaccine Adverse Event Reporting System (VAERS).

Appendix F: Frequently Asked Questions

1. Question: Does the Triaging Pharmacist search by suspect product dosage form to ensure that the product has been utilized in an FDA approved dosage form?

Answer: No, this is beyond the scope of what happens at the level of the CTU.

2. Question: Does the Triaging Pharmacist use indication to identify a suspect product?

Answer: No, Triaging Pharmacist uses reported active product ingredient to determine ICSR routing or disposition.

3. Question: Is the National Drug Code (NDC) used to identify a suspect product?

Answer: NDC information may be used in specific situations, such as when the drug name provided is not readily recognized by the Triaging Pharmacist, but in general the recognized drug name is used to determine ICSR disposition.

4. Question: What is an example of an ICSR lacking a clear suspect product?

Answer: Examples like “30 mg tablet from Pfizer” or “Tablet taken for tennis elbow” are instances when the suspect product is not identifiable based on naming conventions used by the reporter.

8. References

8.1. Code of Federal Regulations Title 21

8.2. DailyMed Product List

8.3. Drug@FDA Product List

8.4. FAERS General Information

8.5. FAERS-DMP: Coding SOP

8.6. FAERS-DMP: Data Entry SOP

8.7. FAERS-DMP: MedDRA Coding Quality Assurance Program SOP

8.8. FDA Resources: What is a Serious Adverse Event?

8.9. MedWatch Voluntary Reporting Form

8.10. NIH Dietary Supplement Label Database

9. Records https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=314.80 https://dailymed.nlm.nih.gov/dailymed/ https://www.accessdata.fda.gov/scripts/cder/daf/ http://inside.fda.gov:9003/ProgramsInitiatives/FDAAdverseEventReportingSystemFAERS/FAERSGeneralInformation/default.htm http://inside.fda.gov:9003/downloads/CDER/OfficeofSurveillanceandEpidemiology/UCM574191.pdf http://inside.fda.gov:9003/downloads/CDER/OfficeofSurveillanceandEpidemiology/UCM440005.pdf http://inside.fda.gov:9003/downloads/CDER/OfficeofSurveillanceandEpidemiology/UCM560277.pdf https://www.fda.gov/safety/medwatch/howtoreport/ucm053087.htm https://www.accessdata.fda.gov/scripts/medwatch/ https://www.dsld.nlm.nih.gov/dsld/index.jsp

SOP-381

Version #: 1.0

Processing Individual Case Safety Reports Submitted Directly to MedWatch

Records created by this procedure are stored in the appropriate FDA adverse event databases according to each center’s procedures.

10. Supporting Documents

None.

11. Attachments

SOP-381

Version #: 1.0

Processing Individual Case Safety Reports Submitted Directly to MedWatch

Attachment A: MedWatch Voluntary Form 3500

MedWatch FDA Safety Information and Adverse Event Reporting Program Form 3500 is located online.

https://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM163919.pdf

SOP-381

Version #: 1.0

Processing Individual Case Safety Reports Submitted Directly to MedWatch

Attachment B: MedWatch Voluntary Form 3500B

MedWatch FDA Safety Information and Adverse Event Reporting Program Form 3500B is located online.

https://www.fda.gov/media/85598/download

Document #:

OSE-IO-RSS-

SOP-381

Version #: 1.0

Processing Individual Case Safety Reports Submitted Directly to MedWatch

Effective Date:

11/10/2021

Uncontrolled when printed on: 6/29/2022 For the most current and official copy, check the Master List

12. Document and Change History

Document History Version

Status* Date Author Name and Title

Approving Official Name and Title

2 R 11/17/2021 names withheld for this reviewing activity 1 I, D 10/1/19 names withheld for this reviewing activity names withheld for this reviewing activity

* - D: Draft, I: Initial, R: Revision, W: Withdrawn, NU: Reviewed, No Updates Required

Change History Version

Section Description of change

2 5.2.7 ICSR is moved to data entry in FAERS after triaging 2 5.3 Data Entry is done in FAERS 2 All sections Revisions reflect system modernization replacing OAERS and deployment of LSMV on 11/10/2021.

List date and approvers for all versions of a procedure, as well as the change history of the document.

DAILY COURIER ROUTE: Mon-Fri (excluding the federal holidays)

CDER Central Document Room (CDR) at Beltsville:

The courier picks up mail from the CDR at 5901 Ammendale Road, Beltsville

MedWatch Mailroom at Rockville:

The courier picks up mail (direct reports) from the Parklawn Building mailroom, Room 4-72

White Oak, FDA main campus:

The courier deliver mail to and from this mailbox:

<FAERS Data Management> and Thang La's mailboxes in Bldg 22, Room 4316 (Note that Medwatch reports often also come to FDA rep Thang La's mailbox - hence same slot for FAERS DMP’s and Thang La's mailboxes.

MedWatch Admin program mailbox at White Oak campus, Silver Springs:

Mail to be picked up from Building 32 Room 5353

White Oak, FDA main campus:

Reports will be collected daily M-F from WO-22 Rm 4316 (above) and scanned by DMP

FAERS Data Management Program 6-month Review

Date xx/xx/xxxx

Food and Drug Administration Comprehensive Data Management Services

Agenda

• Introductions and Opening Remarks 12:35 – 12:40 p.m.

• Planning/Preparation for LSMV 12:41 – 12:45 p.m.

• Activities and Accomplishments 12:46 – 12:50 p.m.

• Workload Review 1:01 – 1:05 p.m.

• FLARe Performance and Statistics 12:51 – 12:55 p.m.

• FAERS/LSMV Performance and Statistics 12:56 – 1:00 p.m.

• Financial Status 1:06 – 1:10 p.m.

• Questions, Discussion & Action Items 1:11 – 1:25 p.m.

Planning & Preparation for the Deployment of the LifeSphere MultiVigilance Platform (LSMV)

• Participated in daily status update meetings Contributed to daily conference calls between FDA personnel, contractors, and technical support to provide status updates and resolve technical issues

• Prepared Detailed plans Developed and implemented a detailed plan and work schedule to maximize resource utilization before, during, and after deployment

• Delivered comprehensive training Developed and conducted comprehensive training on LSMV Data Entry, Product/Manufacturing Coding, and MedDRA Coding elements

• Cleared FAERS queues completely Restructured staff assignments to prioritize and expedite processing, especially Product/Manufacturing and MedDRA Coding sections, to clear the FAERS queues completely prior to LSMV deployment

• Monitored progress and delivered daily reports Developed a model and monitored the backlog of reports prior to, during, and after LSMV deployment. Used the model to track the backlog reduction and provide daily reports to

FDA.

LSMV Activities and Accomplishments

Contract Accomplishments

• Continued operating in a telework environment in response to the pandemic

• Compliant with HHS, FDA, and CDER directives to minimize on site staffing

• xx% of staff teleworked, promoting staff health and safety as well as flexible schedules to accommodate work fluctuations

• x% reported to work on site to support Registration/Triage activities

• Ensured continuity of operation without affecting Safety Evaluators and the Program Office

• Improved production throughput by augmenting resources (additional hours) to accommodate the FDA’s business needs

• Received commendation for excellent performance prior, during, and after the rollout of LSMV

• Completed the xx project

• Met and exceeded every contractual SLA and AQL

Performance, Actual vs. Contract Target

Graph: performance Actual vs Target for Triaging in terms of reports/hr/fte over a time period

Graph: performance Actual vs Target for Registration in terms of reports/hr/fte over a time period

Graph: performance Actual vs Target for Data Entry in terms of reports/hr/fte over a time period

Graph: performance Actual vs Target for Product Coding in terms of reports/hr/fte over a time period

Graph: performance Actual vs Target for Meddra Coding in terms of reports/hr/fte over a time period

Performance, Actual vs. Contract Target (cont.)

• exceeded performance measures month after month in every processing section

• Quality levels in every processing phase were also met or exceeded

• Overall, by exceeding contract requirements, we delivered increased value to FDA

Provide commentary/summary over these performance graphs such as:

Total Workload: 2012 – 2021

FAERS Reports Processed over Last 10 Years

FAERS Total Workload Growth

Total Processing Workload Analysis (specific for the contract)

FLARe Performance and Statistics

FAERS/LSMV Performance and Statistics

• Commentary about the stats and trends as necessary

Financial Status

• Commentary on the trends as necessaryFinancial status graphs: Invoiced

Amt and Budgeted Amt vs Months for base year and subsequent years as appropriate

Questions, Discussions, and Action Items

Summary of Activities Last Week xx/xx/xxxx to xx/xx/xxxx

Total reports for Products of concerns / Urgent issues 176 (include an excel file/graph of products breakdown as necessary, for example:

Product of Concerns

Product A Product B Product C

Counts 23 18 57

Report Type Rec'vd in FLARe &

FAERS

Processed to FAERS

Sent to Other Centers

To SE Delet ed

Directs 2167 1551 554 1698 177 Exp Tissue Reports (paper) 4 4 Exp Reports - - Non-Exp Reports - - Exp E2B 628 628 334 Non-Exp E2B 342 342 13 Total 3141 2525 554 2045 177

Current Reports Received but not Processed:

Fall-Out Electronic Cases Received into FAERS: 970 as compared to the previous week 770 cases

628 Expedited E2bs

342 Non-Expedited E2bs

E2B Fall-Out Rate

Expedited E2B 628/27854 2.25%

Non-Expedited E2B 342/17477 1.96%

Landover FAERS-DMP Reported (to CDER Compliance Office): 0

0 Expedited paper cases

0 Non-Expedited paper cases

Paper Cases Received Into FLARe

2167 Direct Reports

4 Expedited Tissue Reports

0 Expedited Reports

0 Non-Expedited Reports

Oldest Reports

Direct 03 Days

Expedited 00 Days -

Periodic 00 Days -

EXP E2B 02 Days 6/10/2022

PER E2B 02 Days 6/10/2022

Date Range by Section – Direct Reports

Registration 6/12/2022 6/12/2022

Triage 6/12/2022 6/12/2022

Data Entry 6/9/2022 6/10/2022

P/M Coding 6/9/2022 6/9/2022

MedDRA Coding 6/9/2022 6/9/2022

PENDING HIGHLIGHTS:

354 Registration Total

19 Triage Total

373 FLARe Pipeline Total (Registration + Triage)

281 Data Entry Total

17 Product/Manufacturer Coding Total

102 MedDRA Coding Total

400 FAERS Pipeline Total

773 FLARe + FAERS Pipelines Totals

(maintain a separate excel sheet of daily report counts for each of these steps Reg/triage/DE/PM Coding/ meddra coding in case of request for details by FDA. For example:

Direct cases are being Completed at 3 Days to SE.

Expedited Initial/Follow-up paper cases are being Completed at 0 Days to SE.

Non-Expedited paper Cases are being completed at 0 Days to SE.

Expedited E2B Cases are being completed at 2 Days to SE.

Non-Expedited E2B Cases are being completed at 2 Days to SE.

TOTAL REPORTS

Date Day Registration Triage Data Entry P/M Coding MedDRA Coding P/M Coding MedDRA Coding P/M Coding MedDRA Coding Unfinished Direct Expedited E2B Non-Expedited E2B

12/1/2021 WED 72 22 1147 101 391 50 2 7 9 1801 22-Nov 1-Dec 1-Dec 12/2/2021 THU 92 73 1016 97 493 107 5 7 16 1906 24-Nov 2-Dec 2-Dec 12/3/2021 FRI 44 10 1036 130 348 53 0 0 0 1621 24-Nov 3-Dec 3-Dec 12/4/2021 SAT 152 24 900 44 277 53 1 0 0 1451 26-Nov 3-Dec 3-Dec 12/5/2021 SUN 108 116 771 21 52 51 0 0 0 1119 27-Nov 3-Dec 3-Dec 12/6/2021 MON 50 13 726 159 7 0 0 0 4 959 1-Dec N/A 6-Dec 12/7/2021 TUE 71 9 474 171 341 26 2 0 9 1103 1-Dec 7-Dec 6-Dec

DIRECT REPORTS EXPEDITED ELECTRONIC REPORTS NON - EXPEDITED ELECTRONIC REPORTS OLDEST REPORTS

Plus other topics as necessary