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FDA UpdateRandy Levin, MD and William A. Hess, CAPT USPHS
HL7 16th Annual Working Group MeetingBaltimore, MDOctober 2002
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FDA Update
New Ingredient DictionaryPharmaceutical Dosage Forms
E2BM Data ElementsLabeling Effort
NDC
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FDA Update
New Ingredient Dictionary
•History•Need•Collaboration•Design•Non-structures
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FDA UpdateNew Ingredient Dictionary
History
•Original Ingredient Dictionary
•two tables•no structures (WLN)•no processes•non-random identifier•mostly drugs, some biologics
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FDA UpdateNew Ingredient Dictionary
Need
•searchable structures•describe processes (vaccines)•randomly assigned unique identifier•drugs, biologics, foods, natural products, devices
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FDA UpdateNew Ingredient Dictionary
Collaboration
•FDA•NLM•HL7 •NCI•Others
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FDA UpdateNew Ingredient Dictionary
Design Architecture
Platform: Active Server Pages (ASP) running on Microsoft Internet Information Server (IIS)
Scripting language: JavaScript, for special processing and navigation
Database: A standard RCG chemical database, set up using MDL tools, with fields allocated for needed extra data (see Data Model, below). This database runs on an Oracle 8.1.7.1 platform.
Database access: ActiveX Data Objects (ADO)
MDL Software:
• ISIS/Direct 2.0, for access to stored structures using SQL commands
• ChimePro 2.6, for visual rendering of molecular structures
• ISIS/Draw 2.4, for creating and editing molecular structures
• Autonom 2000 TT, for generating IUPAC names
Other Software: Visual Basic 6.0 run time DLLs, for Autonom support
• Browser: Microsoft Internet Explorer 5.x
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FDA UpdateNew Ingredient Dictionary
Design Data Model
Structure: A binary field containing the chemical structure, in MDL standard molecule format. Structures will be represented in two dimensions.
MDLNum: An alphanumeric string that will identify each unique structure in the database. It should have at least 9 characters, and should be generated non-sequentially, such that two consecutively-generated numbers are not related.
BDNum: An alphanumeric identifier that will link each compound to the associated chemical in CDER's current Ingredient Dictionary. This field may be blank. A BDNum may be associated with more than one MDLNum.
Name: A text field, of 240 characters, that will contain the chemical name.
OR Group: An integer field that is associated with each structure in a mixture. If two or more structures in a mixture have the same OR Group number, at least one of them is present in the mixture.
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FDA UpdateNew Ingredient Dictionary
Design Data Model
User
Username: varchar(30)
Password: varchar(30)Role: varchar(10)
Mixture
MDLNum: varchar(9)StructureID: int
OR_Group: int
Substance
MDLNum: varchar(9)
StructureID: intBDNum: varchar(9)Name: varchar(240)Username: varchar(30)
Structure
StructureID: int
Structure: binary
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FDA UpdateNew Ingredient Dictionary
ScreenDesign
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Please enter search criteria
Search
Structure
MDL Number
Name
BD Number
Structure MDLNum BDNum Type Name
A8VIERA3F 0002346AA Structure Neomorphine
8C9KSKL22 0002391AA Structure Pseudomorphine
Zoom
Records 6 through 10 of 19 << Previous Next >>
GK934KF1S 0002528AA Mixture Conjugated Estrogens
Search Register Structure
Register Mixture
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FDA UpdateNew Ingredient Dictionary
Non-structures
•Gelatin•Vaccines•Plants (e.g., oregano)
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FDA UpdateNew Ingredient Dictionary
Non-structures
•VSWG being formed•Mostly FDA•Advisors from Other Organizations •Ground-rule development
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FDA UpdateNew Ingredient Dictionary
Questions and Comments
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FDA Update
Pharmaceutical Dosage Forms
•Initial HL7 terms•Australian and U.S. collaboration•Ordering •Definitions
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FDA Update
E2BM Data Elements
• Data Elements for the Transmission of Individual Case Safety Reports
• International Conference on Harmonisation
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FDA Update
E2BM Data Elements
•Seriousness criteria (death, life threatening, etc)•Qualification (physician, pharmacist, etc)•Study Type (clinical trials, etc)•Sender type (Pharmaceutical Company, Health Professional, etc)•Receiver Type (similar to above)•Patient Age Group (Neonate, Infant, etc)•Outcome (Recovered/Resolved, Fatal, etc)•Characterization of Drug Role (Suspect, Interacting, etc)•Actions Taken with Drug (Dose Reduced, Drug Withdrawn, etc)
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FDA Update
Labeling Effort
•Bar-coded Products•Hand-held Bar-code Scanner•Viewpad•Reformatted labels (8.5x11)
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FDA Update
Labeling Effort
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FDA Update
Labeling Effort
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FDA Update
National Drug Code (NDC)•Background
•Problems•Sufficiency
•Possible Solutions
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Background
FDA UpdateNational Drug Code (NDC)
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• The NDC was originally established as a voluntary essential part of out-of-hospital reimbursement program under Medicare in the late1960’s.
Original Audience:Medicare
FDA UpdateNational Drug Code (NDC)
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FDA UpdateNational Drug Code (NDC)
•The NDC has expanded to include a number of additional functions
•These functions are beyond the original purpose of the NDC
•Significant deficiencies for the effectiveness of the NDC as an identifier even for the packaged product
•Current processes for creating and maintaining the NDC is imperfect
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FDA UpdateNational Drug Code (NDC)
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Problems
FDA UpdateNational Drug Code (NDC)
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FDA UpdateNational Drug Code (NDC)
Basic Problems with the NDC as a robust identifier
•NDC consists of three different “codes” separated by hyphens
•NDC format design allows companies to independently assign NDC
•The lack of control leads to reliability problems
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Problem 1: Labeler Code
•Companies could have more than one labeler code.
•When companies change, such as through a merger or split, the labeler code does not necessarily change.
FDA UpdateNational Drug Code (NDC)
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The labeler code is assigned by the FDA when a person who owns or operates any
establishment registers their establishment.
4 - 4 - 25 - 3 - 25 - 4 - 1
FDA UpdateNational Drug Code (NDC)
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Problem 2: Product Code
•Product code is not controlled.
•More than one product code can be assigned to the same drug formulation.
FDA UpdateNational Drug Code (NDC)
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The product code assigned by the person who owns or operates any establishment. Product codes have
either 3 or 4 digits.
4 - 4 - 25 - 3 - 25 - 4 - 1
FDA UpdateNational Drug Code (NDC)
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•Even within the same company, a single product code can represent two different drug formulation because the company may have two different labeler codes.
•A product code should not be relied on as a unique identifier for a drug formulation even with a within a single company or a single labeler code.
FDA UpdateNational Drug Code (NDC)
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Problem 3: Package Code
•As with the product code, the package code is not controlled.
FDA UpdateNational Drug Code (NDC)
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The package code is also assigned by the person who owns or operates any establishment. Package codes
have either 1 or 2 digits.
.
4 - 4 - 25 - 3 - 25 - 4 - 1
FDA UpdateNational Drug Code (NDC)
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Problem 4: NDC lacks a standardized form
•The NDC is a standard but is not standardized.
•It consists of three codes separated by hyphens for a total of 10 digits.
•Because of differences in the length of the three codes, the NDC can be in one of three formats: 5-4-1, 5-3-2 or 4-4-2.
FDA UpdateNational Drug Code (NDC)
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Frequently the NDC is stored in a “normalized” 11 digit format of 5-4-2 by padding the “short” code with an extra zero.
This changes the actual number if the hyphens are removed such as for use in bar coding.
FDA UpdateNational Drug Code (NDC)
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For example, if we ‘pad’ the short code, so that we always have a 5-4-2 configuration, then:
1234-5678-90 (4-4-2 configuration)becomes 01234-5678-90
12345-678-90 (5-3-2 configuration)
becomes 12345-0678-90
12345-6789-0 (5-4-1 configuration)becomes 12345-6789-00
FDA UpdateNational Drug Code (NDC)
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...and then remove the hyphens, we get...
01234567890
12345067890
12345678900
FDA UpdateNational Drug Code (NDC)
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Problem 5: NDC is not a unique identifier for bar codes
NDC hyphens cannot be removed without potentially introducing redundant codes.
•NDC relies on the separation of the three codes to maintain its uniqueness
FDA UpdateNational Drug Code (NDC)
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Each 10 digit number can have up to three NDC codes.
For example, 1234567890 represents:
1234-5678-90 (4-4-2 configuration) 12345-678-90 (5-3-2 configuration)12345-6789-0 (5-4-1 configuration)
FDA UpdateNational Drug Code (NDC)
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Problem 6: An NDC can be reused
The labeler code can be reused after a firm has been out of business for at least 5 years.
•The product code for a discontinued product can be reused 5 years after the expiration date or after the last shipment, if no expiration date.
•This means the NDC lacks permanence and is not unique for a specific package product.
FDA UpdateNational Drug Code (NDC)
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Problem 7: Lack of a complete, up to date valid list
FDA UpdateNational Drug Code (NDC)
•The FDA does not have an up to date, or complete, list of all NDC used on packaged products.
•Since the companies assign their own NDC, the FDA must rely on the companies to tell them when they have assigned a new number.
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•A company might not inform the FDA of a new NDC for months, if at all, after it is being used.
•Most people who use the NDC receive the list of codes from third parties and not from the FDA. This results in products being included that are not legally marketed drugs.
FDA UpdateNational Drug Code (NDC)
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This demonstrates that while the individual codes in the NDC
appears to have meaning, the controls on these individual codes
are not sufficient to be reliable.
FDA UpdateNational Drug Code (NDC)
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Sufficiency
The NDC, to be a robust identifier for packaged products, should include the following features...
FDA UpdateNational Drug Code (NDC)
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Unique identifier – each NDC should identify only one package product
FDA UpdateNational Drug Code (NDC)
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Comprehensive – there should be one NDC for each packaged product marketed legally marketed in the US
FDA UpdateNational Drug Code (NDC)
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Unambiguous – the NDC should represent only a single concept
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Permanence - the NDC should be associated with the same packaged product indefinitely
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Non semantic identifier (Meaningless concept identifier, nonsense codes) - the NDC should not be hierarchical allowing for later relocation and multiple classification
FDA UpdateNational Drug Code (NDC)
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Centrally assigned- the NDC should be assigned by a central authority to enforce rules and eliminate invalid codes
FDA UpdateNational Drug Code (NDC)
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Publication and distribution by central authority – a complete and up to date list of all valid NDC should be published and freely distributed to all users
FDA UpdateNational Drug Code (NDC)
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Non proprietary – the NDC should be free for all users
FDA UpdateNational Drug Code (NDC)
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Timely assignment – a new NDC should be available in a timely manner as not to unreasonably slow the movement of products to the market
FDA UpdateNational Drug Code (NDC)
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Automated management – the assignment and maintenance of the NDC should be automated to reduce costs and improve efficiency
FDA UpdateNational Drug Code (NDC)
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Works with bar codes – the NDC should work with current bar code technology
FDA UpdateNational Drug Code (NDC)
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Longevity – there should be sufficient codes to allow the NDC to be used in its current state for many years
FDA UpdateNational Drug Code (NDC)
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Possible solutions
FDA UpdateNational Drug Code (NDC)
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Code format
Change to a non semantic, unambiguous, standardized code. Maintain current 10 digits allowing NDC to continue to fit into current bar codes and potential future international bar codes systems.
•Numeric codes alone allow up to 10 billion codes
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NDC assignment NDC assigned by FDA as the central authority to oversee that only valid products are assigned codes
Assign NDC to products when listed to ensure a complete list of NDC for all marketed packaged products
Use automated systems with quality controls to allow timely assignment of standardized codes
•NDC permanence assured by never deleting codes and not allowing a new code to be assigned to the same product.
FDA UpdateNational Drug Code (NDC)
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Additional codes
•Create codes for ingredients, clinical drug, and product to fulfill needs not adequately met by the NDC
FDA UpdateNational Drug Code (NDC)
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Distribution
•NDC freely distributed in FDA/NLM system associated with other useful medication codes and information including: ingredient, product, RxNorm, imprint codes and labeling.
FDA UpdateNational Drug Code (NDC)
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Questions and Comments
FDA UpdateNational Drug Code (NDC)
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The End
FDA UpdateNational Drug Code (NDC)