1. 1 APMA SPL: Electronic Drug Establishment Registration and Drug Listing/Content of Labeling October 10, 2008 CDR Vada Perkins, USPHS FDA/CBER/OD

2. 2 Content of Labeling Requirement Health Level Seven (HL7) Structured Product Labeling (SPL) in XML to be the only acceptable presentation in electronic format for the submission of content of labeling  CDER: In Effect (October 31, 2005)  CBER: beginning October 15, 2008 Applies to the content of labeling with original submissions, supplements, and annual reports. Content of labeling in SPL format is not required for annual reports unless there are changes from the currently approved SPL labeling. **Submit if this is the first time submitting to FDA in SPL format

3. 3 Memorandum to Docket 92S-0251 Notification of FDA readiness to accept electronic regulatory submissions for content of labeling.  Pursuant to 21 CFR part 11.2(b)(2)

4. 4 Labeling Continue to submit Word version with SPL labeling  SPL to PDF/Word Conversion Tool Currently in testing Would eliminate the requirement to submit content of labeling in Word

5. 5 FDA Data Standards Council- Supporting Documentation http://www.fda.gov/oc/datacouncil/spl.html  Directions for obtaining the SPL standard and schema from HL7  Links to the SPL FDA Implementation Guide, the companion document to the HL7 SPL standard providing additional details on creating SPL files  Link to the Guidance for Industry: Providing Regulatory Submissions in Electronic Format - Content of Labeling  Guidance for Industry: Providing Regulatory Submissions in Electronic Format-Drug Establishment Registration and Drug Listing (Draft Guidance)  Style sheet files for viewing SPL content of labeling files

6. 6 Controlled Terminology and Coding  Improved access to product information by health care providers and patients  Reduce medical errors and improve patient care Data integration/evaluation  Improved functionality across different data systems  Immediate access to information

7. 7 Source: Drug Listing Data Elements Health Level Seven (HL7): www.hl7.org/www.hl7.org/  Standards developing organization accredited by the American National Standards Institute (ANSI)  Support message standards for the exchange and interoperability of electronic health records.  SPL specification was initially developed by a group within the HL7 Regulated Clinical Research Information Management Technical Committee National Cancer Institute (NCI) Thesaurus: www.nciterms.nci.nih.govwww.nciterms.nci.nih.gov  Published monthly  Covers vocabulary for clinical care and research The Unified Code for Units of Measures (UCUM): www.regenstrief.orgwww.regenstrief.org  Code system intended to include all units of measures being contemporarily used in international science, engineering, and business

8. 8 Source: Drug Listing Data Elements (cont.) Logical Observation Identifier Names and Codes (LOINC®): www.loinc.orgwww.loinc.org  Code system for reporting laboratory and other clinical observations FDA/SRS: www.fda.gov/oc/datacouncil/SRS.htm www.fda.gov/oc/datacouncil/SRS.htm  Unique Identifier (UNII) Active ingredient Active moiety

9. 9 SPL: Drug Listing Data Elements Product – Proprietary and nonproprietary name and code (FDA DRLS) Description – Ingredients Active and inactive ingredient and active moiety name and code (Unique Identifier (UNII) from FDA SRS) Active and inactive ingredient strength (NCI Thesaurus, UCUM) – Dosage form (NCI Thesaurus) – Appearance (imprint, color, shape, size, score, coating, symbol) (NCI Thesaurus and HL7) – Route of administration (NCI Thesaurus) – DEA schedule (NCI Thesaurus) Packaging – Package type (NCI Thesaurus), quantity and code (FDA DRLS)

10. 10 SPL Terminology Verification Terminology for Drug Establishment Registration/Drug Listing and Content of Labeling Drug Registration and Drug Listing and Content of Labeling Terminology Lists in XML format – Drug Registration and Drug Listing and Content of Labeling Terminology Lists in XML format "Structured Product Labeling Validation Procedures for Drug Establishment Registration and Drug Listing" "Structured Product Labeling Validation Procedures for Drug Establishment Registration and Drug Listing"

11. 11 SPL Terminology Terminology for Drug Establishment Registration and Drug Listing and Content of Labeling Route of administration Dosage form Package type Units of measure and units of presentation Color Shape Coating Size Scoring Imprint codes Symbols SPL DEA Schedule Section headings Code system object identifiers (OIDs) Document Type including Content of Labeling Type Time Units: Unified Code for Units of Measure (UCUM) Substances/Unique Identifiers (UNIIs) Business Operation Marketing Category Marketing Status Equivalence Codes Flavor

12. 12 Term/Code Unavailable? If a term/code is unavailable, please contact www.spl.fda.hhs.govwww.spl.fda.hhs.gov **Applicant can provide reference source(s)

13. 13 http://spl-work-group.wikispaces.com

14. Courtesy of MICHAEL FAUNTLEROY, FDA/CBER/OD 14 FDA Electronic Submissions Gateway (ESG)

15. 15 What is the Gateway? An Agency-wide solution and central transmission point for accepting secure electronic regulatory submissions over the Internet. The FDA ESG is a conduit, or "highway", along which submissions travel to reach their final destination. It does not open or review submissions; it automatically routes them to the proper FDA Center or Office. FDA ESG Sponsor Gateway acknowledgement sent to sponsor Electronic Regulatory Submission Center

16. 16 Gateway Cost The FDA does not charge for the use of ESG The only costs incurred should relate to following; –Public Key Infrastructure (PKI) certificate Binds public keys with user IDs via a certificate authority duration of 1-3 years typically costs from $20-$30 –JAVA, which is available for free –Cost of desktop support

17. 17 FDA Electronic Submission Gateway - Benefits Improves costs, resource requirements, and time efficiencies for both Sponsors and the Agency Obviated need to burn CDs/DVDs or create tapes Eliminated QC of submission associated with creating media Eliminated courier fees associated with Regulatory submissions Provided a more efficient and secure transfer of electronic submissions *Facilitates earlier receipt of the submission by the Agency and access to the submission by the Reviewer

18. 18 Electronic Submissions Gateway Process - Before You Register Submit a Letter of Non-Repudiation Agreement –A letter of Non-Repudiation Agreement must be submitted to the FDA. The non-repudiation agreement allows the FDA to receive electronically signed submissions in compliance with 21 Code of Federal Regulations (CFR) Part 11.100. Send letter to Office of Regional Operations, (ORO) Send copy to ESG Project Manager –Sample letters are on the FDA ESG website Obtain a Digital Certificate –The FDA ESG uses digital certificates to secure the transaction and communications. –ESG website has information on how to obtain a digital certificate Determine Submission Method –Web-based (WebTrader) –Gateway-to-Gateway (B2B) submissions using industry standards for the transport protocol (AS2) –A separate registration will be required for each option selected

19. 19 ESG Account Registration and Setup Process 1.Send an email request to esgprep@fda.gov, include the submission method you intend to use, contact persons name and company name is the email.esgprep@fda.gov 2.FDA will email back the registration information 3.Register online using the information provided 4.FDA will review the registration and activate the account 5.FDA will send an approval notification and guidelines for test preparation 6.Complete the guidelines and send test submission

20. 20 ESG resources and contact information Website: http://www.fda.gov/esg/http://www.fda.gov/esg/ –Registration Information –System Requirements –User Guide and Tutorials –Digital Signatures and Certificates –System Status and Help Desk –Links to submission guidelines Email for preparation/Registration/Policy: esgprep@fda.govesgprep@fda.gov –This email is for question and help in setting up test and production accounts Email for technical issues: esgreg@gnsi.comesgreg@gnsi.com –This email is for system and submission related issues FDA project manager: Michael Fauntleroy –Email: michael.fauntleroy@fda.hhs.govmichael.fauntleroy@fda.hhs.gov –Phone: 301-827-5132 –Address: Office of the Director (HFM-25) Center for Biologics Evaluation and Research Food and Drug Administration 11400 Rockville Pike, Room 4119 Rockville, MD 20857