TASK ORDER 1 board copy.doc

10-223-SOL-00082 Attachment 1

TASK ORDER 1

1) Project Title:

AERS-DMP: D

ata Management Program for Post Market Adverse Event Report Information

2) Introduction:

Background

The FDA’s Center for Drug Evaluation and Research (CDER) and the FDA’s Center for Biologics Evaluation and Research (CBER) perform a crucial part of FDA's mission, pre-market and post-market safety and efficacy assessments of human drugs and biologics. The collection and analysis of adverse event and product problem reports by FDA staff must occur throughout the entire life cycle of the product in order to identify occurrences associated with the use of a drug or biologic in humans that could not have been predicted by clinical trials and bio-statistical analysis. These occurrences must be reported to FDA in order for the Agency to carry out its mission of performing safety surveillance. CDER and CBER receive reports submitted by stakeholders such as manufacturers, importers, health care professionals, attorneys, and consumers. In addition, FDA Safety Evaluators provide follow up information and FDA Field Investigators provide reports. CDER reviews reports for (NDA/ANDA/OTC/Pre-38) drugs as well as therapeutic biologics (BLA/PLA/STN) such as monoclonal antibodies and interferons. CBER reviews reports for biologics, blood products, human tissues, and cellular allograft products.

This task order shall encompass the FDA Adverse Event Reporting System Data Management Program, hereafter referred to as AERS-DMP. The AERS-DMP includes Adverse Event Reporting System (AERS) data entry, Drug Quality Reporting System (DQRS) data entry, and any future technology upgrades to these systems. The Contractor will not be responsible for upgrading the technology of the systems but shall adapt to any technology upgrades.

Adverse Event Reporting System (AERS)

Data entry begins with Individual Case Safety Reports (ICSRs) being entered into the AERS database. There are four main types of ICSRs:

1. Mandatory post-marketing 15-day alert reports (Expedited),

2. Mandatory periodic adverse drug experience reports (Periodic)

3. MedWatch voluntary reports (Direct).

4. Mandatory reporting of blood donor or transfusion recipient deaths

Periodic reports are further classified as Periodic Safety Reports (PSR) and Periodic Safety Update Reports (PSUR). The PSURs are the ICH recommended structure for periodic reporting, and companies must receive a waiver from FDA to use them in place of the PSR. ICSRs are either submitted electronically or on paper. The electronically submitted files can come in via the FDA gateway as xml files or on physical media as either xml or pdf files.

Electronic submissions are transferred directly into AERS. Electronic physical media are delivered from the FDA Central Document Room to the AERS contractor where the reports are entered into AERS. If the electronic record is an xml or a pdf record it is then uploaded to FDA’s Enterprise Search software tool and becomes available for viewing as images in AERS. The electronic ICSRs are coded and validated in AERS.

MedWatch voluntary reports are received by the contractor via mail, e-mail, fax, phone, or internet. Mandatory ICSRs include initial and follow-up submissions. Each ICSR must be legible, contain at least one identifiable suspect product, an identifiable reporter, identifiable patient, and a minimum of one identifiable event converted by the contractor to a MedDRA (preferred term) to be entered into AERS. Additional reports that the contractor might receive but are not entered into AERS are reports generated from non-approved products under an Investigational New Drug application (also known as 5-day (21 CFR 803.53 for Medical Devices) or 15-day (21 CFR 312.32 for Drug and Biologic safety reports (IND Safety Reports)), requests for information, and iPLEDGE Accutane Program Complaints. There are IND post-market reports for drug classes such as cancer and AIDS drug combinations that do go into AERS.

The contractor may also receive The Council for International Organizations of Medical Sciences (CIOMS) (World Health Organization Form) mandatory 15-day paper foreign reports, which are entered into AERS.

Known specific sources of direct reports received are: Drug-Induced Liver Injury (DILN), National Cancer Institute (NCI), and Institute for Safe Medication Practices (ISMP), Medco (a pharmacy benefit manager), Veterans Administration (VA), Field Alert Reports, and misdirected reports from other FDA Centers. FDA may accept other types of reports in the future. Some of the listed organizations have developed their own version of Form FDA 3500 to facilitate data entry. These forms are entered into AERS just like any other paper report.

Data contained in the paper ICSRs are entered into an electronic format using the Adverse Event Reporting System (AERS) relational database software, an Oracle client server application. Paper ICSRs are imaged using Electronic File System (EFS) image-base. The image-base is linked to the AERS database and provides end-user access to the original safety report. Stored images of ICSRs may be referenced in AERS and used to supplement typed narratives.

The FDA personnel typically locaed at the contractors site perform the initial assessment to triage MedWatch voluntary paper reports and sort reports and received documents to determine the appropriate FDA Center(s) or Office to send each report (CBER, CDER, CFSAN, CDRH, DQRS, CVM, IND Coordinator or Drug Information). The reports are then sent to the appropriate Center or Office through FAX or routing services.

FDA staff uses AERS to help perform passive post-market safety surveillance. Consistent with FDA’s mission of ensuring drug safety throughout the drug lifecycle, an essential requirement of this task order is that the selected contractor shall efficiently enter data accurately and timely to enhance the process of safety data screening and analysis of adverse events. Currently, the sampling of manufacturer coding is verified by the contractor for 10% of all ICSRs received.

Approximately 1,800 ICSRs may be received for processing each day. It is expected that the volume of reports received will increase by approximately 8% annually.

This contract shall provide AERS data entry services for processing reports commonly known as Individual Case Safety Reports (ICSRs) to include tasks such as triaging, registering (logging), tracking, imaging, data entry, MedDRA coding, data entry quality control (DEQC) (validation of manufacturer and product(s)), updating of data records, reviewing, editing, coding, filing, linking cases, quality control, and quality assurance.

Additionally, the MedWatch-to-Manufacturer Program (MMP) allows manufacturers to receive certain serious adverse event reports that are submitted directly to FDA associated with their new molecular entities. This contract shall provide services for processing a minimal volume of reports (10 to 20 per month) associated with this program.

The MedWatch forms are: FDA Form FDA 3500, used for voluntary direct reporting of adverse events, product problems, and product use errors; and FDA Form 3500A, used for mandatory reporting, 15-day expedited, and periodic reports by user-facilities, importers, distributors, and manufacturers. CIOMS form can be used for foreign 15-day reports at the discretion of manufacturers.

Business rules (BR) are developed by a Change Control Board (CCB) and then written and approved as standard operating procedures (SOPs) to describe each process or procedure that will be performed to support this contract. Business rules and SOPs may change as a result of changes in FDA mission, when new steps or processes are added, or as the need for new data formats, new types of submissions, or efficiencies change.

The following adverse event reporting metrics provide a glimpse of the scale, complexity, and timeframes in the FDA adverse event reporting data entry and quality control effort:

Total number of reports received in CY 2009 by type

Average number of MedDRA terms per ICSR in CY 2008*

Average narrative length (bytes used) per ICSR in CY 2008*

*The 2009 metrics are not available at this time. These reports are expected to remain approximately the same as 2008 metrics.

Note: For narratives greater than 20,000 characters additional steps are required. Paper ICSRs are abstracted by the FDA on-site representative. Historically, about 5 reports are received per month with greater than 20,000 characters.

The current AERS system is a client-server application consisting of Oracle Forms and Reports on the client-server, and Oracle RDBMS residing on a dedicated server. The relational database contains 264 tables, nearly 5 million adverse event reports, supports over 200 users, handles data entry operations, and handles real-time data capture and searches. The current AERS application was released in November 1997, and consists of AERS Core and electronic submissions (eSubs).

Drug Quality Reporting System (DQRS)

Another data entry component of this contract is the Drug Quality Reporting System (DQRS). DQRS is an important part of the post-marketing compliance phase of regulating pharmaceutical products. It rapidly identifies significant health hazards associated with the manufacturing, potency, packaging, and labeling of pharmaceuticals. DQRS is the central reporting system for detecting problem areas and trends requiring regulatory action. Like AERS, DQRS accepts MedWatch Forms that have been triaged with potential drug quality problems. Also, DQRS accepts NDA Field Alert Reports, FDA Form 3331, and a small amount of specialized reports. DQRS processing entails data entry, scanning of reports into the DQRS database, and generating District Memoranda, Office Referral Memoranda (labs), and Manufacturer Follow-up Letters.

The contractor shall provide team of dedicated DQRS data entry staff input these data. They are physically located in FDA offices within the Center for Drug Evaluation and Research (CDER) Office of Compliance on the White Oak campus.

Average Workload drug quality report for CY 2008*

*The 2009 metrics are not available at this time. These reports are expected to remain approximately the same as 2008 metrics.

AERS Technology Transition

The Food and Drug Administration is currently developing a new Safety Reporting Portal for the receipt all FDA-regulated products. When completed, this new system shall provide a single point of entry for reporters, and will enhance the current MedWatch program to include submission of reports for all regulated products. The Safety Reporting Portal will include an internet-based Rational Questionnaire for reporting and electronic data transfer into FDA individual Center databases.

During the period of this contract, FDA anticipates the transition from the Adverse Event Reporting System (AERS) to the FDA Adverse Event Reporting System (FAERS). FAERS will be the FDA’s new adverse event data repository and allow for enhanced analytic methods to enable staff to efficiently analyze thousands of safety reports and identify potential safety problems. As a result of these changes, the contractor shall be required to update business rules and standard operating procedures. In addition, as a result of the transition we anticipate a decrease in costs and processing times due to the following factors:

(1) An increase in electronic submission by manufacturers of industry mandated MedWatch reports

(2) An increase in electronic submissions by manufacturers of industry mandated periodic reports

(3) An increase in electronic submissions with use of adverse event data online Rational Questionnaire

The exact timing of this transition from AERS to FAERS is unknown. However, as the transition takes place, this will require substantial development of new business rules, standard operating procedures, testing, validation and verification of the software. As FDA transitions from paper based submissions to electronic submissions, the contractor should anticipate that the volume of paper data entry on this contract will decrease.

Start-up Implementation for AERS-DMP (One-Month)

The FDA has built into this contract a one month start-up period. During the start-up implementation period, the contractor shall become fully operational to meet the needs of this contract.

Statutory Authorization

For CDER and CBER, the statutory provisions for FDA’s requirement to record mandatory submission of adverse drug reports for an Investigational New Drug Application (IND) or New Drug Application (NDA), Abbreviated New Drug Application (ANDA) and OTC products in an adverse event reporting system is Section 505(k)(1) of the Federal Food, Drug and Cosmetic Act, 21 CFR 310.305, 312.32, 314.80, 371 and 600.80, and Public law 109-462 . The statutory provisions for DQRS are 21 CFR 314.81(b)(i) and (ii).

3) Objectives:

The primary objectives of this contract are data management services in support of the Adverse Event Reporting System Data Management Program (AERS-DMP) to include:

a) Data entry and quality assurance of mandatory and voluntary adverse event reports submitted to the FDA into the Adverse Event Reporting System (AERS)

b) Data entry of drug quality reports submitted to the FDA into the Drug Quality Reporting System (DQRS)

4) Scope of work:

Independently, and not as an agent of the Government, the Contractor shall perform the identified tasks within the performance standards outlined in each section of the Scope of Work. The Contractor shall provide the required materials, services, tracking systems, facilities, and otherwise do all things required for, or incident to, the performance of the work as described below.

This contract shall encompass the services required for the AERS-DMP. For each of the scope of work sections listed below, there are Performance Requirements, Performance Standards and a FDA Quality Assurance Plan with the exception of 4.1 Data Management Adverse Event Reporting Program One-Month Start-up, which also reference other appropriate SOW sections for additional applicable Performance Standards and FDA Quality Assurance Plans.

4.1 AERS-DMP One-Month Start-up Tasks

a) Performance Requirements

The Contractor shall develop and implement the following start-up tasks within one month of contract award:

(1) The Contractor shall coordinate and attend a kick-off meeting at FDA facilities and document the meeting minutes.

(2) The Contractor shall develop, issue, and post on the FDA provided server, standard operating procedures (SOPs) (See Appendix E)for the AERS-DMP, and implement within one month of contract award.

(a) Reference Section 4.9 Management Services for detailed requirements, performance standards, and the FDA Quality Assurance Plan

(b) Reference Appendix E for a list of Draft SOPs

(3) The Contractor shall maintain the intranet site as an accessible repository for the SOPs and supporting reference material on a FDA provided server.

(a) The Contractor shall back-up the server daily Monday through Thursday, and weekly backups are performed every Friday. A monthly backup is performed on the Friday of the last full week of every month.

(b) Reference Section 4.9 Management Services for detailed requirements, performance standards, and the FDA Quality Assurance Plan.

(4) The Contractor shall establish a Management Plan that describes how the Contractor shall manage this contract and ensure that data entered into either AERS or DQRS meet all standards, timelines, and quality metrics. The Management Plan shall be inclusive of all policies, processes and procedures necessary for the performance of this contract.

(a) Reference Section 4.9 Management Services, Section 4.10 Training Program, 4.11 Contingency Plan, 4.12 Personnel Staffing Plan, and 4.13 Communication Plan for detailed requirements, performance standards, and FDA Quality Assurance Plans.

(5) The Contractor shall develop staff plan for full performance at the end of the 60 day start-up period. All contract personnel will require network access and computer accounts. Before an account can be ordered contract personnel must go through security clearance. For personnel new to the government this can take a few months. The contractors plan must have strategies to minimize this potential problem. This may include hiring workers who already have FDA clearance.

(6) The contractor shall be at full performance at the end of the 60 day start-up period. There can be no interruption of service or backlog of un-entered reports. [Reference SOP 2.4 Tape Backup]

(7) Mandatory and Voluntary Report Tracking Database: The Contractor shall develop and implement a Tracking Assurance System (TAS) database to verify that performance standards are met with each type of report. This Tracking Assurance System database shall be developed on FDA provided hardware and software. The Contractor shall track the life-cycle of all physical media into the Tracking Assurance System including:

(a) Reference Section 4.4 Mandatory and Voluntary Paper Report Processing for detailed requirements, performance standards, and the FDA Quality Assurance Plan.

(8) Periodic Report Tracking System: The Contractor shall develop a Periodic Report Database to include receipt tracking, summary tracking, serious/non-serious counts, and safety evaluator distribution.

(a) Reference Section 4.4 Mandatory and Voluntary Paper Report Processing for detailed Performance Requirements, Performance Standards, and the FDA Quality Assurance Plan.

(9) Data Entry Quality Control: The Contractor shall develop a data entry quality control procedure using a double data entry process.

(a) Reference Section 4.4 Mandatory and Voluntary Paper Report Processing for detailed requirements, performance standards, and the FDA Quality Assurance Plan.

(10) The Contractor shall develop separate initial and ongoing comprehensive training programs for data-entry, scanning, quality control, and MedDRA coder personnel.

(a) Reference Section 4.10 Training Program for detailed requirements, performance standards, and the FDA Quality Assurance Plan.

(11) The Contractor shall ensure that their site is Federal Information Security Management Act (FISMA) compliant. FISMA on-site audits of the physical facility may be conducted.

(12) The Contractor shall be responsible for developing a Tracking Assurance System (TAS) (Reference Attachment 1 and 1a) which will track all paper reports.

b) Data Management Adverse Event Reporting Program One Month Start-up Standard Requirements

All the following tasks necessary for the performance of this contract shall be completed within 60 days after award.

(1) AERS-DMP Kick-Off Meeting

(2) AERS-DMP SOPs

(3) AERS-DMP Intranet Site

(4) AERS-DMP Management Plan

(5) AERS-DMP Mandatory and Voluntary Report Tracking Assurance System

(6) AERS-DMP Periodic Report Tracking System

(7) AERS-DMP Data Entry Quality Control

(8) AERS-DMP Training Program

(9) AERS-DMP FISMA Plan

c) Data Management Adverse Event Reporting Program One Month Start-up FDA Quality Assurance Plan

i) COTR shall review, edit, provide input, and approve 100% of all tasks within 35 days after award.

ii) COTR shall review and approve minutes including questions and answers identified during the kick-off meeting. If inaccuracies are found, the Contractor shall modify the minutes within 2 calendar days of original submission.

4.2 Adverse Event Reporting Systems (AERS)

The major Adverse Event Reporting Systems (AERS) tasks include receiving, logging, imaging, tracking, processing, validation, case-linking, medical coding, medical coding quality control, and medical coding quality assurance of both paper and electronically submitted adverse event reports. Currently, 80% of all reports are submitted electronically.

4.2.1 Adverse Event Reporting System (AERS) Electronic Submissions (esubs)

a) Performance Requirements:

The Contractor shall:

i) Reconcile esub reports without the minimum four data elements (identifiable reporter, identifiable patient, an adverse event, and a suspect product,). [Reference SOP 4.3 Data Entry Quality Control]

ii) Validate drug and manufacturer with AERS dictionaries (drug and manufacturer) [Reference SOP 4.3 Data Entry Quality Control]

iii) For Mandatory 15-Day Expedited Reports, and Mandatory Periodic Reports, the Contractor shall validate MedDRA coding and manufacturer information. [Reference SOP 5.1]

iv) Validate MedDRA preferred term (PTs) coding and MedDRA version discrepancies [Reference SOP 5.1 Medical Dictionary for Regulatory Activities (MedDRA) Coding]

v) Link related reports in AERS. For example, follow-up reports are linked to initial reports existing in AERS.

vi) Perform continuous quality control of manufacturer’s MedDRA coding at a 10% random sampling rate of all reports for compliance with FDA “Coding Principles for Post-marketing Adverse Event Reactions” document. Any missing MedDRA terms are to be added to the ICSRs in the AERS database.

vii) Perform quarterly quality evaluations on a 10% random sampling of Individual manufacturer’s MedDRA coding to a maximum of 50 reports to ensure compliance with the FDA “Coding Principles for Post-marketing Adverse Event Reactions”. [Reference SOP 5.3 Performing Quality Assurance of MedDRA Codes on Electronically Submitted (eSub)]

viii) Process Physical Media: After receipt of physical media from the Center for Drug Evaluation and Research (CDER) Central Document Room (CDR) the physical media is logged and tracked. [Reference SOP 3.5 Processing Physical Media]

ix) Copy files from media into an electronic staging area for processing. [Reference SOP 3.5 Processing Physical Media]

x) Upload media files into Enterprise Search for viewing in AERS.

xi) In the event that the electronic submission portal is unavailable due to technical failure for more than one calendar day, the Contractor shall receive and log physical media containing ICSRs and attachments from the Central Document Room (CDR). Historical records indicate that the Contractor shall anticipate this failure two times per year.

xii) Report, on a weekly basis to the FDA COTR, the number of esub reports entered and the number of calendar days the electronic submission portal is unavailable.

b) AERS Electronic Submissions (esubs) Performance Standards

The Contractor shall:

i) Enter eSub reports into the AERS database at or within the following performance levels:

· Expedited eSubs = 4 days

· Periodic eSubs = 30 days

ii) In the event that the electronic submission portal is unavailable due to technical failure for more than one calendar day, the Contractor shall develop a plan to receive and log physical media containing ICSRs and attachments from the Central Document Room (CDR). Physical media files are to be copied into a staging folder and uploaded into Enterprise Search within 24 business-day hours for viewing in AERS.

c) FDA AERS Electronic Submissions (esubs) Quality Assurance Plan

i) COTR or FDA on-site personnel shall review weekly, monthly, and annual statistic reports, and weekly summary reports of contract activities to ensure that all FDA reporting standards are met.

ii) FDA on-site personnel shall perform a periodic quality assurance check on completed reports and report to the COTR.

4.3 Central Triage Unit (CTU) Paper Report Processing

The CTU performs the initial sorting of reports received from the MedWatch Office and Parklawn Mail Room. The CTU receives the reports via the routing process. The CTU tasks include sorting by report type (i.e. Direct, Periodic, Expedited, High Profile, or New Molecular Entities (NMEs), by product quality issue, and according to the responsible Center(s). Additional tasks include data entry and tracking of reports into the FDA MEDEX system, distribution of reports, and generation of acknowledgement or rejection letters. The MEDEX system tracks all voluntary paper reports whether or not they are entered into the AERS system or sent to other Centers or Offices. It is not unusual to receive reports that are not regulated by CDER.

a) Performance Requirements (SOP 7.1 CTU)

The Contractor shall:

i) MedWatch Expedited Reporting Information System (MEDEX) Tracking:

(1) For Direct Reports, the Contractor shall track all Direct Reports from doctors, consumers, medical personnel and attorneys; however, there are no manufacturer reports tracked in MEDEX.

(2) The Contractor shall enter key elements of paper reports into MEDEX.

ii) Routing Reports: The Contractor shall route reports to the appropriate responsible Center(s) and also route misdirected reports to the appropriate recipient.

iii) Document how the reports are sent to the Center(s) such as fax, mail, and courier.

iv) As part of the MedWatch-to-Manufacturer Program (MMP), collect qualifying images (averaging 10 to 20 per month) of voluntary Direct Paper Reports, send these imaged reports to FOI for redaction, and send redacted ICSRs to qualifying manufacturers.

MedWatch-to-Manufacturer Program link: http://www.fda.gov/Safety/MedWatch/HowToReport/ucm166910.htm (Reference – MMP SOP 7.1)

v) As part of the MedWatch-to-Manufacturer Program (MMP), implement SOPs to provide ICSRs or non-confidential portions of ICSRs to qualifying manufacturers.

vi) Paper Acknowledgement Letters: The Contractor shall prepare mail labels and mail acknowledgement letters on a weekly basis.

vii) Rejection Letters: The contractor shall determine if the reports submitted are without one of the following pieces of information: identifiable reporter, an identifiable patient, an adverse reaction, and a suspect product.

viii) Track the preparation of rejection letters, the reason for the rejection, and date of when letters are mailed for all non-internet received ICSRs.

ix) Routing Services: The Contractor shall provide and maintain routing services for pick-up and delivery of paper reports on a daily basis. [Reference SOP 3.3 Handling and Delivering Mail and Appendix D: Route Diagram].

x) ICSR Imaging or Scanning: For all report types, the Contractor shall image or scan ICSRs received and shall identify duplication, monitor quality of scanned image, purge poor quality images, verify errors, and add missing images.

xi) ICSR Barcoding: For all report types, the Contractor shall assign an ICSR barcode number. [Reference SOP 3.1 Processing of Periodic Reports and 3.2 Processing of Expedited (15-Day) Reports].

xii) Provide CTU Reporting Statistics by running SQL statements on the MEDEX program. [Reference SOP 1.4 Reporting Statistics].

b) Central Triage Unit (CTU) Paper Report Processing Performance Standards (SOP 7.1 CTU)

The Contractor shall:

i) Completely process 100% of all MEDEX Reports within 24 hours.

ii) Assign a Central Triage Unit (CTU) number to 100% of all MEDEX Reports.

iii) As part of the MedWatch-to-Manufacturer Program (MMP), collect 10 to 20 qualifying images of voluntary Direct Paper Reports per month, and verify these imaged reports were sent to FOI for redaction, and redacted ICSRs were sent to qualifying manufacturers.

iv) Complete 100% of all acknowledgement letters within one week of receipt..

v) Complete 100% of rejection letters within one week of receipt and ensure that they contain the following information: identifiable reporter, an identifiable patient, an adverse reaction, and a suspect product.

vi) Track 100% of rejection letters processed.

vii) Provide courier services for picking up and delivering on a daily basis 100% of paper reports.

viii) Assign a barcode to 100% of all types of ICSRs.

ix) Direct and expedited paper reports shall be entered into the AERS database within 7 calendar days.

x) Periodic paper reports shall be processed into the AERS database within 60 calendar days.

c) FDA Central Triage Unit (CTU) Paper Report Processing Quality Assurance Plan (SOP 7.1 Central Triage Unit)

i) FDA on-site Representative shall verify that all reports received by fax, e-mail, mail, and courier services are processed by checking receipt log and route reports on a weekly basis. (Reference: Appendix F for CDER secure electronic mail system)

ii) FDA on-site Representative shall monitor the Contractor’s adherence to the MedWatch-to Manufacturer Program (MMP) processing operations on a monthly basis.

iii) FDA on-site Representative shall monitor courier activities to ensure they are performed in accordance with schedule requirements. Courier activities include ensuring that reports are delivered daily to the appropriate Center(s) and misdirected reports are delivered to the appropriate recipient.

iv) FDA on-site Representative shall monitor ICSR barcoding and imaging of paper reports into portable document format (PDF) to ensure all reports are captured.

v) FDA on-site Representative shall monitor the rejection letter processing operations in accordance with the SOPs. [Reference SOP 7.1 Central Triage Unit]

4.4 Mandatory and Voluntary Paper Report Processing

As a result of the increase of electronic submissions the percentage of paper reporting is currently 20% of all reporting.

a) Performance Requirements

The Contractor shall:

i) 15-Day Expedited Mandatory Reports Receipt: Sort reports according to foreign or domestic type.

ii) Periodic Mandatory Report Receipt: Forward the cover letters and tabbed periodic ICSRs to the FDA Representative for triaging of serious and non-serious reports.

iii) Date stamp receipt of all paper reports.

iv) Sort and stamp New Molecular Entities (NME) and designated high profile drugs.

v) Maintain the services of a courier for timely, daily, pick-up and delivery of paper reports. (Reference SOP 3.3 Handling and Delivering Mail and Appendix D: Courier Route Diagram).

vi) Mandatory and Voluntary Report Tracking System: The Contractor shall develop and implement a Tracking Assurance System (TAS) database to verify that performance standards are met with each type of report. This Tracking Assurance System database shall be developed on FDA provided hardware and software as detailed in Appendix H and shall become the property of the FDA. The Contractor shall track the life-cycle of physical media into the Tracking Assurance System to verify that performance standards are met with each type of report including:

· Verification of data entry

· Shredding and disposition of paper reports

· Paper records received via internet, e-mail, fax, or paper, even those records not entered into AERS but sent to other Centers (Reference: Appendix F secure electronic mail system)

· Mailing of acknowledgement and rejection letters

· Quality control of reports

· Quality assurance of personnel’s work.

vii) Periodic Report Tracking Module: A Module of the Tracking Assurance System will include periodic receipt tracking, summary tracking, serious/non-serious counts, and safety evaluator distribution.

viii) Data Entry Quality Control - Enter the following fields using double data entry procedure:

· Manufacturer Control Number

· ICSR type

· Report date

· Initial or follow-up designation

· Manufacturer

· Product name

· NDA/PLA number

· Outcomes

ix) Case-link mandatory reports, matching the manufacturer control number supplied by the reporter.

x) Verify and identify the presence of duplicate records. Duplicate records are linked in AERS. [Reference SOP 4.3 Data Entry Quality Control]

xi) Ensure there are no data entry errors through quality control data entry procedures.

b) Mandatory and Voluntary Paper Report Processing Performance Standards

The Contractor shall:

i) Paper Report Receipt: 100% of all Direct Reports and 15-day Expedited Paper Reports shall be completely processed into AERS within 7 calendar days. (SOP 2.1)

ii) Periodic Paper Report Receipt: 100% of all Periodic Paper Reports to include serious and NME reports for the first three years after approval shall be completely processed into AERS within 60 calendar days.

iii) High Profile Reports (including donor and transfusion death reports and tissue or cellular allograft infection reports): 100% of High Profile Reports shall be completely processed within 24 hours of receipt. [Reference SOP 3.1 Processing of Periodic Reports]

iv) Supplemental Data Entry (narratives): Enter paper ICSR information, patient information, adverse event or product problem narrative, relevant test/lab information, relative history, suspect product information, reporter information, manufacturer information, and comments added by FDA on-site representative into AERS.

v) Routing Services: Distribute reports daily to the appropriate responsible Center(s) and also distribute misdirected reports to the appropriate recipient.

vi) Verify receipt of all reports delivered on a daily basis. [Reference SOP 3.3 Handling and Delivering Mail]

vii) Courier Services: The Contractor shall oversee the routing service to ensure daily scheduled pick-up and delivery of paper reports. [Reference SOP 3.3 Handling and Delivering Mail]

viii) Mandatory and Voluntary Report Tracking Database: The Contractor shall develop a Tracking Assurance System (TAS) to verify that performance standards are met with each type of report within 60 days after award..

ix) Contractor shall enter appropriate data into the Tracking Assurance System such as data entry verification, shredding and disposition of documents within 60 days after award and in accordance with HIPAA regulations.

x) Periodic Report Tracking System: The Contractor shall develop a Periodic Report Tracking System to include receipt tracking, summary tracking, serious/non-serious counts, and safety evaluator distribution within 60 days after award. [Reference SOP 3.1 Processing of Periodic Reports]

xi) Develop a procedure to ensure 100% of the listed fields shall be entered into AERS using double data entry. [Reference SOP 4.3 DQCS]

xii) Develop a procedure to ensure data entry is 100% accurate, with no errors.

xiii) Develop a procedure to ensure 100% of initial and follow up mandatory reports shall be case linked.

xiv) Develop a procedure to ensure 100% of duplicate reports shall be deleted.

xv) Develop a procedure to ensure 100% quality control of data entry.

xvi) Develop a procedure to ensure 100% of all physical media shall be accounted for in the Tracking Assurance System

xvii) The Mandatory and Voluntary Report and the Periodic Report Module shall be in conformance with Section 508 requirements.

c) FDA Mandatory and Voluntary Paper Report Processing Quality Assurance Plan [SOP 4.4 Data Entry Quality Assurance (QA)]

i) COTR or FDA on-site representative shall review weekly, monthly, and annual statistic reports, and weekly summary reports of contract activities to ensure that all FDA reporting standards are met.

(1) Weekly report details the number of processing days for each type of report into AERS.

ii) FDA on-site representative shall perform a periodic quality assurance check on completed reports.

iii) FDA on-site representative shall monitor scientific and regulatory content of reports.

iv) FDA safety evaluators shall notify Contractor of all case linking discrepancies, duplicate records to be corrected, and data entry discrepancies.

4.5 AERS Processing

a) Performance Requirements

The Contractor shall:

i) Update legacy SOPs for MedDRA coding principles, procedures and quality control. [Reference SOP 5.1 Medical Dictionary for Regulatory Activities (MedDRA) Coding]

ii) Code Individual Case Safety Rreports (ICSRs) according to the MedDRA principles and procedures. [Refernece SOP 5.1 Medical Dictionary for Regulatory Activities (MedDRA) Coding]

iii) ICSR Barcoding: For all paper report types, the Contractor shall assign an ICSR barcode number. [Reference Attachment 1: Tracking Assurance System Technical Specification and Tracking Assurance Specification Periodic Module 1 (Reference Attachment 1a)

iv) Imaging Paper Reports: The Contractor shall image all paper reports into portable document format (PDF) files. [Reference SOP 6.1 Imaging]

v) Imaging Procedure: The Contractor shall implement SOPs for imaging or scanning of received paper ICSRs reports. This procedure shall work in conjunction with the paper records tracking system. The SOP shall address how the Contractor shall verify and identify duplication, quality of scanned image and purging of poor quality images, errors, and adding missing images. [Reference SOP 6.1 Imaging]

vi) The Contractor shall reconcile paper reports that are imaged and processed into AERS. [Reference SOP 6.1 Imaging]

b) AERS Processing Performance Standards:

The Contractor shall:

i) Perform MedDRA coding in accordance with the FDA instructions for MedDRA coding and ICH Coding Principles for documents, and include quality control and quality assurance procedures to ensure appropriate selection of MedDRA codes.

ii) Assign an ICSR barcode number to 100% of paper reports. [Reference Appendix X: Tracking Assurance System Technical Specification and Tracking Assurance Specification Periodic Module 1 (Reference Attachment 1 and 1a)

iii) Ensure that quality control and quality assurance procedures shall be performed by Subject Matter Experts.

iv) Imaging Procedure: The Contractor shall implement the SOPs within 60 days after award.

v) Comply 100% with the AERS imaging and scanning procedures.

vi) Reconcile 100% of paper reports that are imaged and processed into AERS with the Tracking Assurance System..

c) FDA AERS Processing Quality Assurance Plan:

i) 100% review and approval of the MedDRA coding SOPs by FDA COTR and FDA Representatives.

4.6 AERS Quality Assurance (QA)

a) Performance Requirements

The Contractor shall:

i) Update the quality assurance SOP that includes two types of 10 percent down-sampling of esubs. The first sample consists of a continuous review of all esubs received. The second sample shall be performed quarterly where 10 percent of esubs per manufacturer to a maximum of 50 reports are reviewed for compliance with established coding procedures. (SOP 5.2 Medical Dictionary for Regulatory Activities (MedDRA) Coding Quality Control.

ii) The Contractor shall provide a report of all manufacturers with inadequate coding quality issues to the MedDRA Coding Workgroup (CWG) to determine appropriate action. The Contractor shall consult the FDA COTR and FDA Representatives for guidance. [Reference SOP 5.3 MedQA-MFR Sampling Rates] Develop a metric plan for checking each individual data entry employee’s work performance to ensure that ICSRs are accurately entered into AERS. The plan shall include algorithms for reducing the number of checks performed, depending on the knowledge and skills of the data entry staff.

b) AERS Quality Assurance (QA) Performance Standards

The Contractor shall:

i) QA SOPs shall be evaluated to determine compliance with “Criteria to Use in Formal Evaluations of Manufacturer-Provided Coding for Electronically Submitted Reports.”

ii) QA SOPs shall be performed by Subject Matter Experts I, II and III.

iii) On-going, ten (10) percent down-sampling of all esubs received shall be reviewed by the Contractor.

iv) Quarterly, ten (10) percent down-sampling to a maximum of 50 reports of e-ICSRs per manufacturer will be reviewed by the Contractor.

v) The Contractor shall develop a metric plan within 60 days after award..

(1) ICSRs shall be entered into AERS at or above the following performance targets:

(a) Processing Step and ICSRs per hour:

(b) 5-6 ICSRs per hour per employee

(c) Initial Data Entry 25-30 per hour

(d) Supplemental Data Entry 5-7 narratives per hour

(e) Data entry quality control 10-15 reports per hour

(f) MedDRA Coding 10-15 reports per hour

(g) MedDRA Coding Quality Control 25-30 reports per hour

c) FDA AERS Quality Assurance (QA) Quality Assurance Plan

i) 100% Review and approval of the procedure by the FDA COTR and FDA Representatives.

ii) 100% review of manufacturer inadequate coding quality issue reports by MedDRA Coding Workgroup.

iii) 100% review of the metric plan by the FDA COTR and FDA Representatives.

4.7 MedDRA Coding and MedDRA Coding Quality Control

a) Performance Requirements

The Contractor shall:

i) Develop technical instructions for MedDRA coding and training of MedDRA coders. Consult the FDA COTR and/or FDA Representatives for guidance. [Reference SOPs 5.1; 5.2; 5.3]

ii) Develop quality control and quality assurance procedures for ICSR reports that have been through MedDRA coding procedures and contain MedDRA terminology.

iii) Develop a QA procedure that includes two types of 10 percent down-sampling of esubs. The first sample consists of a review of all esubs received. The second sample is performed quarterly where 10 percent of esubs per manufacturer to a maximum of 50 reports are reviewed for compliance with established coding procedures.

iv) Provide a report of all manufacturers with inadequate coding quality issue to the MedDRA Coding Workgroup (CWG) to determine appropriate action.

b) MedDRA Coding and MedDRA Coding Quality Control Performance Standards

The Contractor shall:

i) Develop instructions for MedDRA coding based on the FDA Coding Principles document and include QC and QA procedures to ensure appropriate selection of MedDRA codes within 60 calendar days of contract award.

ii) Include screen shots in the MedDRA coding instructions.

iii) Include iterative QC and QA procedures with evaluation criteria developed.

c) FDA Quality Assurance Plan for MedDRA Coding and MedDRA Coding Quality Control

i) The FDA COTR shall evaluate quality assurance procedures to determine compliance with “Criteria to Use in Formal Evaluations of Manufacturer-Provided Coding for Electronically Submitted Reports.”

ii) The FDA COTR shall review 100% of the manufacturer inadequate coding quality issue reports by MedDRA Coding Workgroup.

4.8 Drug Quality Reporting System (DQRS)

a) Drug Quality Reporting System Report Processing Performance Requirements

The Contractor shall:

i) Data Entry: Follow the DQRS Data Entry User Guide for identifying source type, numbering of the reports to facilitate sorting, tracking, and forwarding processes. (Reference Appendix C)

ii) Notification Letters: Prepare and mail standard notification letters to manufacturers.

iii) Weekly Reports: Develop weekly reports that track all work by:

(1) Number and type of reports added to the database.

(2) Number of reports and letters scanned.

(3) Number of letters generated and mailed.

(4) Current back-log of all work types.

(5) Number of hours worked by each employee.

iv) Schedule and attend meetings with FDA DQRS staff to assess status.

v) Ensure that the number of reports not entered do not exceed 300.

b) Drug Quality Reporting System Report Processing Performance Standards

The Contractor shall:

i) Develop all processes based on the DQRS Data Entry User Guide. The DQRS Data Entry User Guide will be provided by the COTR upon award of the contract.

ii) All priority 2 and 3 reports shall produce an assignment letter. Process 100% of assignment letters within 14 calendar days. Send processed assignment letters to the FDA Field Offices.

iii) All priority 1 reports shall be brought to the attention of the FDA’s consumer Safety Officer in charge within 24 hours.

iv) Total backlog of all types of unprocessed reports shall not exceed 300 reports.

v) Provide weekly reports on the second calendar day of each week.

vi) Schedule and attend meetings with FDA DQRS staff on a weekly basis.

vii) The number of reports not entered do not exceed 300.

c) FDA Drug Quality Reporting System Report Processing Quality Assurance Plan

i) FDA DQRS Compliance Staff shall report any process problems to the COTR.

ii) FDA COTR shall review and approve 100% of weekly reports for the volume of report types processed, any backlog of reports, meetings attendance, and hours worked by each individual contractor employee.

iii) 100% review and approval of all procedures by the FDA COTR and FDA Representatives.

iv) Weekly reviews by COTR, program manager, and FDA DQRS management of DQRS quality report.

4.9 Management Services

a) Standard Operating Procedure Performance Requirements

The Contractor shall:

i) Update, issue, and post legacy SOPs as needed.

ii) Maintain a change history of all SOPs related to this contract and assure that only current SOPs are posted on the FDA provided intranet. The SOPs are subject to change as a result of amendments to the FDA mission, new steps or processes added, or as a need for new data formats or new types of submissions, or efficiencies change.

iii) Ensure that appropriate FDA personnel review and approve all SOPs prior to issuance.

iv) Ensure that current SOPs are available electronically to all Contractor personnel and FDA/CDER intranet users.

v) Develop a process to ensure that all hyperlinks used within SOPs are maintained.

vi) Review SOPs on an annual basis and provide COTR with a summary of changes identified.

vii) Ensure that the Contractor’s program manager, supervisor, or designee shall be available (on-site or cell phone) 24-hours to address FDA operational shutdowns or emergency situations.

viii) Develop an intranet site as an accessible repository for the SOPs and supporting reference material on a FDA provided server that will have at a minimum the following functions:

(1) Posting of current SOP’s

(2) News about contract including organization charts

(3) Contract supporting reference material, such as the ‘Food and Drug Administration Coding Principles for Post-marketing Adverse Event Reports’

ix) Develop procedures for backing up Intranet server maintained at Contractor location.

x) Back up the intranet server maintained at the Contractor location.

xi) Use only the Contractor-developed FDA intranet site for employees to use for required contract work. The Contractor-developed site is owned by the FDA.

b) Standard Operating Procedure Performance Standards

The Contractor shall:

i) Update, issue, and post SOPs and have accessible to all users electronically on a CDER provided intranet site within 60 calendar days of contract award.

ii) Perform SOP revisions within 21 days from notification by COTR.

iii) Update SOPs consistent with Office of Information Management policies.

iv) Develop the intranet website in compliance with Section 508 of the Rehabilitation Act of 1973. (Reference Appendix D).

v) Comply with FDA Staff Manual Guides (SMG) 3250, Information Technology Security Program and the FDA Internet Web Site Security Plan (FDA SMG 3215.1, Intranet/Internet Management)

vi) Develop procedures for backing up intranet server maintained at contractor location within 60 calendar days of contract.

c) FDA Standard Operating Procedure Quality Assurance Plan

i) 100% review and approval by FDA COTR and FDA on-site Representatives of all SOPs.

ii) The FDA COTR and FDA on-site Representatives shall, on an annual basis, review updated SOPs submitted by the Contractor and approve.

iii) The FDA COTR shall review the intranet website for compliance with FDA Staff Manual Guides (SMG) 3250, and Information Technology Security Program and the FDA Internet Web Site Security Plan (FDA SMG 3215.1, Intranet/Internet Management).

iv) The FDA COTR shall review and approve written back-up procedures for the intranet server maintained at the Contractor’s facility.

v) COTR shall evaluate compliance through the with Section 508 standards. (Reference Appendices: D and E).

4.10 Training Program

a) Performance Requirements

i) The Contractor shall develop a comprehensive training program that shall include:

(1) Performance criteria to assure that data-entry, scanning, quality control, and MedDRA coder personnel are competent to perform their assigned duties.

(2) MedDRA coder training shall include simulations of actual coding events.

(3) Conducting double checks of all MedDRA coding performed during the first month of employment.

(4) All data entry shall have a quality assurance program. This shall consist of randomly selecting sample records for individual proficiency checks.

(5) Develop a numerical quantification to document the progress of a new or existing employee for MedDRA coding.

ii) The Contractor shall provide ongoing training throughout the life of the contract for all newly hired and existing MedDRA coders.

(1) The Contractor shall develop methods to monitor and evaluate competency of data-entry, quality control, and MedDRA coder personnel.

(2) The Contractor shall maintain written documentation of training, testing and quality control specific to the use of the FDA MedDRA auto-encoder.

b) Training Program Performance Standards

i) The Contractor shall provide training programs and trained personnel to assure that employees (data entry, scanning quality control, and MedDRA coders) are qualified to perform their assigned duties within 60 calendar days after contract award and for the duration of the contract.

ii) All data-entry and quality control personnel shall achieve a typing rate of a minimum of 40 words per minute with a maximum of 2 errors prior to entering narratives into AERS.

iii) The quality assurance program shall perform initial proficiency checks on personnel at 50% for all entered data, then as performance is verified, proficiency checks may be reduced to a minimum of 10%.

iv) Typing certifications shall be submitted to the FDA COTR.

v) All MedDRA coders shall pass a written test developed by the Contractor and approved by the FDA COTR with at least a score of 80% and at least 80% accuracy performing a simulation test of actual coding.

vi) The Contractor shall perform on-going assessments of competency for data entry, quality control, and MedDRA Coding personnel.

c) FDA Training Program Quality Assurance Plan

i) The FDA COTR or Representative shall review and approve training programs for data entry, quality control and MedDRA coder personnel within 5 days of receipt by the FDA.

ii) The FDA COTR or Representative shall review typing certifications and on-going competency assessments for data entry, quality control, and MedDRA coding personnel.

iii) The FDA COTR or Representative shall randomly audit quality assurance program…