FDA UpdateRandy Levin, MD and William A. Hess, CAPT USPHS

HL7 16th Annual Working Group MeetingBaltimore, MDOctober 2002

FDA Update

New Ingredient DictionaryPharmaceutical Dosage Forms

E2BM Data ElementsLabeling Effort

NDC

FDA Update

New Ingredient Dictionary

•History•Need•Collaboration•Design•Non-structures

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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Need

•searchable structures•describe processes (vaccines)•randomly assigned unique identifier•drugs, biologics, foods, natural products, devices

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Collaboration

•FDA•NLM•HL7 •NCI•Others

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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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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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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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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

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Records 6 through 10 of 19 << Previous   Next >>

GK934KF1S 0002528AA Mixture Conjugated Estrogens

Search Register Structure

Register Mixture

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Non-structures

•Gelatin•Vaccines•Plants (e.g., oregano)

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Non-structures

•VSWG being formed•Mostly FDA•Advisors from Other Organizations •Ground-rule development

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Questions and Comments

FDA Update

Pharmaceutical Dosage Forms

•Initial HL7 terms•Australian and U.S. collaboration•Ordering •Definitions

FDA Update

E2BM Data Elements

• Data Elements for the Transmission of Individual Case Safety Reports

• International Conference on Harmonisation

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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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Labeling Effort

•Bar-coded Products•Hand-held Bar-code Scanner•Viewpad•Reformatted labels (8.5x11)

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Labeling Effort

FDA Update

Labeling Effort

FDA Update

National Drug Code (NDC)•Background

•Problems•Sufficiency

•Possible Solutions

Background

FDA UpdateNational Drug Code (NDC)

• 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

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•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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Problems

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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

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.

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The labeler code is assigned by the FDA when a person who owns or operates any

establishment registers their establishment.

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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.

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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.

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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.

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Problem 3: Package Code

•As with the product code, the package code is not controlled.

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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.

.

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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.

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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)

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

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...and then remove the hyphens, we get...

01234567890

12345067890

12345678900

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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

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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)

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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.

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Problem 7: Lack of a complete, up to date valid list

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•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.

•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.

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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.

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Sufficiency

The NDC, to be a robust identifier for packaged products, should include the following features...

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Unique identifier – each NDC should identify only one package product

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Comprehensive – there should be one NDC for each packaged product marketed legally marketed in the US

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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

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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)

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

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Non proprietary – the NDC should be free for all users

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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

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Automated management – the assignment and maintenance of the NDC should be automated to reduce costs and improve efficiency

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Works with bar codes – the NDC should work with current bar code technology

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Longevity – there should be sufficient codes to allow the NDC to be used in its current state for many years

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Possible solutions

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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.

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Additional codes

•Create codes for ingredients, clinical drug, and product to fulfill needs not adequately met by the 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.

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Questions and Comments

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The End

FDA UpdateNational Drug Code (NDC)