Standards for Drug Labels

1. Standards for Drug Labels Medical information standards in support of SPL

2. Standards within standards within standards within…

3. What sort of standards exist? • “Quality” standards • criteria against which accomplishments are judged. • standards for forensics competition • “Reference” standards • to assure that what I hear you say is what you meant to tell me. • to align communications

4. Judgment standards • Tolerance standards • “This tablet contains 40 ± 2 mg of esomeprazole” • AAHA Certification standards • “All AAHA certified hospitals will have an EKG machine” • The 10 Commandments • “Though shall not steal”

5. Reference standards • USP Drug Standards • Known concentration and purity • Information Standards • General: XML, HTML, etc. • Medical: HL7, SNOMED, NCI Thesaurus… • Rosetta Stone • demotic ↔ hieroglyphic ↔ Greek

6. Standards enhance communication • Common “language” between users and systems • Community consensus • Collaboration • Are we interoperable?

7. SPL is built on standards Message • XML • HL7 • CDA Architecture Terminology • LOINC • SNOMED-CT • NCI Thesaurus • UCUM • NDC • Etc.

8. XML standardizes the mechanics of the SPL • Hierarchical structure • Validate structure against schema <doseForm> <id>55325</id> <name>solution</name> </doseForm> • Values embedded in or nested within tags • Tags declare attributes <doseForm id=“55325” name=“solution”/> • Can include any digital artifact

9. XML facilitates information transformation Web XML Database Spreadsheet Print Any or all information in the XML document can be transformed (as needed)

10. XML Schema describes structure of XML document • Specify what is required within the XML document they support • Process specific documents against a schema • Document is “valid” (schema-valid) or “invalid” for its type

11. Attributes (qualities) and values Columns = attributes Rows = values Document / message standards tend to deal with attributes Vocabulary / terminology standards tend to deal with values

12. Attributes (qualities) and values (in XML) 1 <doseForm id=“55325” name=“solution” /> 2 <doseForm> <id>55325</id> <name>solution</name> </doseForm>

13. HL7 • Health Level 7 international • Open standard • Member only access • Dominated by corporate and government membership • Funded through membership fees • www.hl7.org

14. HL7 (why 7?) International Organization for standards (ISO) Organisation internationale de normalisation

15. HL7 • Establishes semantics • Specifies the structure of messages • Consensus-based (balloted) development of CDA architecture • Determines the SPL schema

16. HL7 • Version 2.x establishes attribute lists, a consistent syntax, and a “pipe-delimited” format • Version 3.x establishes an underlying information model, maintains a consistent syntax and uses XML • document/message schema, attribute definitions and components, uses

17. Clinical Document Architecture (CDA) • An XML-based markup standard • specify the encoding, structure and semantics of clinical documents for exchange. • HL7 version 3 standard • based on the HL7 Reference Information Model (RIM) • HL7 Version 3 Data Types. CDA documents are persistent in nature.

18. Clinical Document Architecture (CDA) • Mandatory textual part (for human interpretation of the document contents) • Optional structured parts (for software processing). • Structured parts rely on coding systems to represent concepts.

19. Multiple Terminologies • Content varies • Mechanics vary • Management varies • “Politics” and path to new modification or addition vary

20. Vocabulary / terminology standards • Dun and Bradstreet D-U-N-S number • National Cancer Institute (NCI) Thesaurus • FDA Substance Registration System (SRS) – Unique Ingredient Identifier (UNII) • Logical Observation Identifiers Names and Codes (LOINC) • ISO 3166-1 Alpha-3 Country Code (ISO 3166-1) • Unified Code for Units of Measure (UCUM) • Health Level Seven • Veterans Administration / Kaiser Permanente Problem List Subset of SNOMED-CT (VA/KP Subset)

21. Vocabulary / terminology standards • Dept. of Veterans Affairs National Drug File Reference Terminology (NDF-RT) • National Drug Code (NDC) System • FDA Firm Establishment Identifier (FEI) • FDA Application Number • Globally Unique Identifier (GUID) • US Postal Service • Code Object Identifier (OID) • Local company terminology • ISBT-128 site and product codes for licensed minimally manipulated cell products

22. Questions:

23. D-U-N-S number • Dun and Bradstreet (http://www.dnb.com) • A unique nine-digit number that tells the entire world you mean business • Global commercial database with 140 million business records • Obtain one by asking for a listing

24. NCI Thesaurus • A collection of terminologies that were developed to support research studies • National Cancer Institute • Stable, unique alphanumeric code • Synonyms, definitions, external link • Available for browsing and download from their website

25. SRS – UNII • FDA Substance Registration System – Unique Ingredient Identifier • Ingredient, moiety, reference drug • Managed by SRS Board • Unique ten character alphanumeric identifier • Request additions through email

26. LOINC • Logical Observation Identifiers Names and Codes • Lab tests, other clinical observations • Managed by the Regenstrief Institute • 3 to 7 character codes • Download Access database or text file • New search feature on website • Released twice a year

27. ISO 3166-1 • International Organization for Standardization (acronym is French) • Standard country names and code elements • Download Access database or text file list of codes • Updates when the UN updates its list • Changes in newsletter

28. UCUM • Unified Code for Units of Measure • Units of measure used in science, engineering and business • >250 unit symbols • Maintained by Regenstrief Institute • HTML and XML versions • Few requests needed

29. HL7 • Health Level 7 • Structure and some vocabulary

30. VA/KP Problem list subset of SNOMED-CT • Veterans Administration / Kaiser Permanente subset of the Systematized Nomenclature of Medicine – Clinical Terms • ~17,000 SNOMED concepts • Download from NCI Vocabulary Services

31. NDF-RT • Department of Veterans Affairs National Drug File Reference Terminology (NDF-RT) • Ingredients, chemical structure, dose form, physiologic effect, mechanism of action, pharmacokinetics, and related diseases. • Updated monthly

32. NDC • National Drug Code System • Managed by FDA • Universal product identifier for drugs • Unique 10-digit, three-segment number • Can request an NDC code through SPL

33. FEI • FDA Firm Establishment Identifier • Assigned to a facility • Managed by FDA • Up to 10 digits

34. (FDA) Application Number • NDA/ANDA or NADA/ANADA • Product approved for marketing by FDA

35. GUID • Globally Unique Identifier • Unique number generated by software • 32 character hexadecimal string • Example: 21EC2020-3AEA-1069-A2DD-08002B30309D

36. United States Postal Service • Official USPS state abbreviations • States plus 9 possessions/associated states and 6 military states • Full name and two character code • Codes available on USPS website

37. Code System Object Identifiers • OID - globally unique string representing an ISO Object Identifier • Identifies the coding (terminology) system from which a code is derived • Consists of numbers and dots (e.g., 2.16.840.1.113883.3.1) • Lacks single universal management structure

38. Example of Structure of OID – HL7 http://www.hl7.org/Oid/L-datyp2fig5.jpg

40. Local terminology • Device • Model • Lot • Serial number

41. ISBT - 128 • International Society of Blood Transfusion • Now managed through the International Council for Commonality in Blood Banking Automation (ICCBBA) • American Association of Blood Banks • System for identification, labeling and processing of human blood, tissue, cellular therapy products.

42. Reference standards support SPL • Share some commonalities • Some overlap • Vary in management, content, and application • Multiple users • Reuse within and outside FDA

43. FDA information management “sins” • Overloaded value fields • Misnamed value “fields” • There are obvious pragmatic reasons overloading has occurred with time • Alignment with terminology and message standard becomes difficult

44. Overloaded “approved species” field • “Dairy replacement heifers growing on pasture” • A common animal group (cattle) + • Animal use classification (dairy) + • Age range / repro status (heifer) + • Sex / repro status (heifer) + • Management practice (pasture) + • Future use (replacement)

45. Overloaded routes of administration • Intramuscular • Intramuscular is a route • “Intramuscular in neck” • Is route + site • “Topical with occlusive dressing” • Route + administration procedure

46. Mislabeled value field • Dose form • Solution in the bottle, administered intravenous as a solution then: • Dose form = “form of product” • Sterile powder for reconstitution as solution then: • Dose form ≠ “form of product”

47. Vocabulary drift • “bacterial pneumonia (shipping fever complex) caused by P. multocida susceptible to oxytetracycline” • Terramycin Soluble Powder (008-622) • For the treatment of bacterial pneumonia (shipping fever) caused by Pasteurella multocida • Procaine Pen G (065-010)

48. Vocabulary drift • “shipping fever, calf pneumonia and bovine pneumonia” • 055-030 (Polyflex) • Bovine respiratory disease (BRD) • 140-529 (Micotil) • 141-244 (Draxxin)

49. Adaption to standards at CVM • Some of the historical and current practices may need to change to align with standards

50. SPL recipe • 1 part HL7 CDA • 1 part LOINC • 2 parts SNOMED • 4 parts NCI Thesaurus • A dash of UCUM…