CBER Data Standards Management Presented to: DC CDISC Group April 25, 2014

Agenda

• CBER Data Standards Management • CBER Data Standards Project Portfolio • Focus for Addressing Mandates and Processing Gaps for CDISC Data Standards

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Role of Data Standards

• FDA recognizes the need for standards to support standardization of industry regulatory submissions and to enable data reuse and cross reference throughout a product’s life cycle • Data standards support the need for

functional interoperability across FDA core functions

which is simplified as: “Data contained in disparate regulatory submissions is reused to support another regulatory function without having to understand how the source data was collected or the need to log into different systems to validate the same information” 3

Data Standards Groups

• Center Subject Matter Experts (SMEs)that are repurposed for multiple internal/external standards activities • Representatives are Center/Agency SMEs: CDISC, HL7, ICH, ISO Center Data Standards Groups: DSS, CDER DSPB Agency Data Standards Groups • Center SME liaisons to

Council

Standards Group

FDA Data Standards

and FDA Management International and /External Standards Development Organizations (SDOs) HHS OPDIV Collaborations and ONC workgroups • Representatives are Center/Agency SMEs: Electronic Health Record and Health Information Technology (HIT) Standards 4

CBER Data Standards Subcommittee (DSS)

• Provides a formal governance and project management process for data standards projects with interdependencies with FDASIA and user fee program goals for: – IT systems, especially support for structured electronic regulatory submissions – Business process changes as a result of new tools and systems – Regulatory policy changes: new or updated industry guidance to use the data standards – Data standards: development, testing, adoption and implementation • Projects are categorized by a Data Standards Lifecycle Phase 5

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CBER DSS Governance Relationships

CBER Information Management Coordinating Committee (IMCC) oversight ensures that DSS projects align with CBER’s IT Strategic Plan goals for projects that have IT interdependencies: 1. Information Management 2. Innovation 3. Partnerships • CBER Review Management Coordinating Committee (RMCC) coordination ensures that DSS projects align for interdependencies with CBER business processes and regulatory policies • Center-level informatics coordination ensures that DSS projects align with Agency/Center priorities and goals pertaining to Regulatory Science and Research 6

CBER Data Standards Portfolio

• Active projects are near term activities that require CBER review experts and IT resources that must be accounted for (e.g., project plans and budget submissions for IT systems or contractor support) • Some projects pertain to other Agency/non-CBER initiatives that require close monitoring, e.g., FDASIA or MDUFA • Projects are grouped by data standards lifecycle phase and include touch points for: – IT systems – Regulatory policy/guidance documents – Business process changes – Interactions with other internal/external groups 7

CBER Standards Portfolio by Working Group, Lifecycle Phase and IT Strategic Goal Area Data Standards Subcommittee

CBER CDISC Post Market Submissions FDA IDMP Regulated Product Submissions Development & Testing Implementation Adoption Adoption Development & Testing CDISC Data Submission XML Pilot eVAERS / ICSR (IT, Regulatory Policy, Business Process) ICH E2B(R3) IDMP Adoption (for ICSR) ISO IDMP Implementation Guides (ISO 11238) ISO IDMP Maintenance FDA SRS Redesign Product Dictionary/ Integrity IMDRF: RPS for Medical Devices ICH M8: eCTD v4.0 Project 8

Operations and Maintenance Phase

Operations and Maintenance Activity Electronic Submissions Formats Regulatory Policy & Guidance Documents Reviewer/Industry Training and Support SDTM 3.1.1 through 3.1.3

ICH E2B R2 SPL

ADaM 2.1

eCTD

eLDD eCTD

eSubs & FDASIA

eStudy Data Study Data Standards Technical Guide eSRR JReview Datasets loading requests Training CBER Website, SOPs Performance monitoring helps to identify problems and issues from the review community – Process improvements help to address regulatory requirements for data reuse and linking, e.g., pre and post market safety reports

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CDISC

Center Informatics Monitoring Projects

Data Standards Monitoring Activity External SDO Work

HL7 ISO TC 215 Workgroup 6 IMDRF CDASH TA Standards Initiative Project Plan SDTM 3.1.4

RCRIM RPS, SPL Pharmacy: Common Product Model Public Health Reporting Electronic Health Records ICSR Technical Report IDMP Standards IMDRF Device Table of Contents

Resources are repurposed for multiple projects everything we know about. Some review SMEs also monitor external groups: e.g., PhUSE, CPATH, CFAST, TransCelerate BioPharma but still cannot monitor

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CBER Data Standards Challenges

• CBER is relatively small Center and we have a very diverse product portfolio: – NDA – BLA – 510(K) – PMA • • – CBER must account for a wider variety of data standards applicability to different regulatory/legislative drivers which may not overlap FDA – CDC – Requires CBER to work more collaboratively internally and externally Regulatory Use Cases – Public Health Research and Reporting 11

Mandates and Submissions Processing Gaps

• PDUFA commitments state that FDA will require electronic submission of study data by 2017; however • CBER has identified several support gaps that must be addressed before this can be accomplished: – Understanding the business impact based upon review workload – Addressing known errors and inconsistencies in standards adoption – Understanding training requirements by review discipline – Closing the gap between development and implementation based upon tangible FDA business needs – Automation of submission receipt tracking and validation processes • Subject to other User Fee Programs: BsUFA, MDUFMA, GDUFA 12

PDUFA Business Impact by Review Workload

IND 2131 2004 NDA 37 BLA 766 PDUFA WORKLOAD 4 169 TOTAL 2934 2177

Number of CDISC Submissions by CY

2012

Unknown JAN-DEC

2013

JAN-APR

2014

30 20 *Based upon file validation tracking

TOTAL

50 13

Submissions by Product Type

Type Vaccines Blood Derivatives Cell/Tissue/Gene Therapy ADaM 1 17 0 SDTM 2 30 0 TOTAL 3 47 0 *Allergenic products are exempt 14

Standards Adoption and Use: Top 7 Errors

Error Type

Consistency

Description CDISC Validator Business Rules

SD0007 Presence Terminology Metadata Coss-reference Format Limit Inconsistent value for standard units of measurement NULL value in variable marked as required Value for AECONTRT not found in (NY) CT codelist Dataset variable not defined in define.xml

Invalid ARM/ARMCD Invalid ISO 8601 value Negative value for --DUR SD002 CT0070 SD0059 SD0071 SD1011 SD0015

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Near Term Activities

• Consistent project management process for CBER CDISC Workgroup: – Focus on managing activities by data standards lifecycle to meet agency mandates – Focus on meeting specific review needs by review discipline •

Slow down development and monitoring tasks

– Address long term training needs – Implement formal process for adoption and migration planning • Limit portfolio projects to what we can manage with operational excellence – Focus on addressing the operational issues with standards use by reducing errors and providing clear guidance (internal and external) about the data needed for review and data reuse

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Background Slides

DC-CDISC Group Meeting April 25, 2014

Data Standards Lifecycle Phases

Engage SDO: If standard no longer meets CBER requirements, propose major revision or new standards project Performance Monitoring: Ensure standard continues to meet business needs and adjust to changing environment Development: Create new or major revision of existing standard to address a specific regulatory need: data exchange, content, terminology. Includes SDO balloting and/or collaboration with internal/external stakeholders Testing: Simulate regulatory use case by applying the standard to the business problem. Includes creation of test tools used by industry and/or FDA reviewers. Assessment of performance and success criteria Adoption: Center “go/no go” decision based upon testing results and success criteria Operations and Maintenance: Leverage CBER CCB process to maintain systems for continued standards use Implementation: Execute processes to integrate standard into business practice: review, IT, regulatory policy

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CBER DSS Standards Portfolio

Data standards categories are used to help determine resource requirements for each project:

Standards Type

Data Exchange Data Format Terminology

Definition

Content and format in which particular types of data are to be presented and exchanged. Data exchange standards include file format specifications Structure, content, naming conventions, and variable formats for any given data domain Controlled vocabularies to improve communications and enhance analytical capabilities

Example

Structured Product Labeling (SPL) SAS transport files (SAS XPT) Standardized terms for anatomical body sites 19

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Data Standards Monitoring

DSS does not manage data standards monitoring activities Monitoring activity still requires CBER resource commitments

: – CBER Subject Matter Experts in review offices and ADRM – Participation in meetings and teleconferences/webinars – Review of documents against FDA business requirements • If an Agency, non-CBER or SDO project appears to be on an expedited timeframe that will have a future impact on CBER’s business, then projects are reprioritized and may be moved to the DSS active project portfolio: – CDRH: Unique Device Identifiers – CDER: CDISC Therapeutic Area Standards (TA) – ISO IDMP Implementation Guides • Coordination is managed and tracked under the Center Informatics Group with updates to DSS, IMCC and RMCC as appropriate 20