The change that forces a product to get a new number

The number is tied to a specific version of a product

A national drug code identifies a labeler, a product and a package. What is less well known is that it is also a version stamp, and the regulation lists what forces a new one.

Once a code has been assigned, the registrant must propose a new and unique code when any of the listed information changes after the drug is initially marketed.

Six changes require a new product code. The first is naming: "The drug's established name or proprietary name, if any".

The second is composition or dose: "Any active pharmaceutical ingredient or the strength of any active pharmaceutical ingredient".

Then the dosage form. A change in status between prescription and nonprescription. A change in intended use between human and animal.

And appearance: "The drug's distinguishing characteristics such as size, shape, color, code imprint, flavor, and scoring (if any)".

The new code is proposed through an updated listing rather than by a separate application.

The change that only moves part of the number

One kind of change is treated differently, and the distinction is useful when comparing two codes that look almost the same.

Where the only change is to the package size or type, including the immediate unit-of-use container, "the proposed new NDC must include only a new package code and retain the existing product code".

So two codes sharing a labeler and product code but differing in the package segment describe the same product in different packaging.

There is one exception. If every available package code has already been combined with that product code, a new product code becomes necessary.

The practical reading is that the product segment is the part that answers what is in it, and the package segment answers how much and in what container.

Three ways using the number is prohibited

The restrictions section is short and every clause in it describes something that happens in marketing.

It opens with a consequence rather than a prohibition. "A product may be deemed to be misbranded if an NDC is used" in any of three ways.

The first is using a code to represent a different drug than the one it was assigned for.

The second is the one worth knowing. Using a code "To denote or imply FDA approval of a drug".

The third is using a code on products that are outside the registration and listing rules, and the regulation gives examples: "such as dietary supplements and medical devices".

There is also a rule about coming back. If marketing resumes for a discontinued drug and nothing has changed that would require a new code, it must carry the same code it had before.

That last provision means a code is not recycled or reissued on a return. The history stays attached to it.

The listing data has a known refresh cycle

Anyone reading a listing record is reading something with a defined update schedule, and knowing the schedule tells you how stale the data can be.

At initial registration the first listing is quick. For each drug being made at an establishment at that time, listing information must be submitted "no later than 3 calendar days after the initial registration of the establishment".

After that the rhythm is fixed. "Registrants must review and update their drug listing information each June and December."

At each review the registrant lists anything not previously listed, and reports discontinuations and resumptions.

A discontinuation report is more informative than it sounds. It carries the date the activity stopped and must "provide the expiration date of the last lot manufactured, repacked, relabeled, or salvaged".

That expiry date is effectively a statement of how long the last of the product can still be in circulation.

Where nothing has changed, the registrant does not simply stay silent. It must "certify that no changes subject to reporting under paragraph (b)(1)(iv) of this section have occurred".

A silence in this system is therefore a positive certification, not an absence of activity.

The question the agency can ask about any listed drug

One short section gives the agency a targeted question it can put to a registrant.

For a particular listed drug, on request, the registrant must "briefly state the basis for its belief that the drug is not subject to" the new drug, new animal drug and biologics licensing provisions.

That is the whole section. It exists because listing is open to products that are not approved, and being listed says nothing about which legal pathway a product claims.

It is the formal version of the question a careful buyer asks about an unapproved product: on what basis does the seller think this does not need approval?

The answer is not published by this provision. But the fact that a registrant can be required to give one, in writing, tells you the question is a real one rather than a rhetorical one.

How the information gets in, and in what language

Submissions are electronic by default. All information under the part must be transmitted through the electronic registration and listing system in a form the agency can process, review and archive.

Language is specified. Registration and listing information must be provided in English, and the content of labeling at a minimum in English.

Where the labeling rules permit product labeling solely in a foreign language, the content of labeling is submitted in that language along with an accurate English translation.

A waiver from electronic submission exists but is narrow. It must be requested in writing before the information is due. The request must give the specific reasons why electronic submission is not reasonable for that registrant, plus a United States telephone number and mailing address.

Asking does not buy time. The rule states that submitting a waiver request does not excuse timely compliance with the registration and listing requirements.

A granted waiver may be limited in duration and comes with specified terms.

The contact requirements, and the sentence about mailboxes

Every registrant designates an official contact for each establishment, responsible for ensuring the accuracy of registration and listing information and for handling all communications from the agency, including emergency ones.

A foreign establishment must also designate a single United States agent, and the definition of what that agent may be is unusually pointed.

The agent must reside or maintain a place of business in the United States. It "may not be a mailbox, answering machine or service, or other place where a person acting as the United States agent is not physically present".

The agent handles agency communications, responds to questions about drugs imported or offered for import, and has one duty that reveals the purpose of the whole arrangement: "Assisting FDA in scheduling inspections".

And there is a service rule. If the agency cannot contact a foreign registrant directly or expeditiously, it may provide information or documents to the United States agent, and doing so is equivalent to providing them to the registrant.

So a foreign establishment cannot become unreachable by not answering. The agent is the address of record.

What this changes about reading a code

Three practical points follow for anyone using a drug code to check something.

A code identifies a version. If the strength, the active ingredient, the dosage form, the name or the appearance changed, the product code should have changed too. A code that has stayed constant across a visible product change is worth a second look.

A code is not an approval, and using it to suggest one is expressly named as a way a product may be deemed misbranded. It also does not belong on a supplement or a device.

And a listing record has a refresh cycle, with reviews each June and December. A record can therefore be up to about half a year behind a change that did not require a new code.

Two limits on this article. Only the sections of part 207 not already covered elsewhere on this site were read. The article covering what a code is, where it comes from and what its absence proves is cross-linked rather than repeated.

No listing record was looked up and no product's code history was traced, so nothing here describes any actual product.

Sources

Each document below is named as it names itself, with the date printed on that document rather than the day it was read.

1. Title 21 Code of Federal Regulations section 207.35, What changes require a new NDC, read in full — Electronic Code of Federal Regulations, Office of the Federal Register, August 2016
2. Title 21 Code of Federal Regulations section 207.37, What restrictions pertain to the use of the NDC, read in full — Electronic Code of Federal Regulations, Office of the Federal Register, August 2016
3. Title 21 Code of Federal Regulations section 207.45, When, after initial registration of an establishment, must drug listing information be provided, read in full — Electronic Code of Federal Regulations, Office of the Federal Register, August 2016
4. Title 21 Code of Federal Regulations section 207.55, What additional drug listing information may FDA require, read in full — Electronic Code of Federal Regulations, Office of the Federal Register, August 2016
5. Title 21 Code of Federal Regulations section 207.57, What information must registrants submit when updating listing information and when must it be submitted, read in full — Electronic Code of Federal Regulations, Office of the Federal Register, August 2016
6. Title 21 Code of Federal Regulations section 207.61, How is registration and listing information provided to FDA, read in full — Electronic Code of Federal Regulations, Office of the Federal Register, August 2016
7. Title 21 Code of Federal Regulations section 207.65, How can a waiver of the electronic submission requirement be obtained, read in full — Electronic Code of Federal Regulations, Office of the Federal Register, August 2016
8. Title 21 Code of Federal Regulations section 207.69, What are the requirements for an official contact and a United States agent, read in full — Electronic Code of Federal Regulations, Office of the Federal Register, August 2016