Date:
Food and Drug Administration
Center for Drug Evaluation and Research
Drug Registration and Listing, HFD-330
5901 B Ammendale Road
Beltsville, MD 20705-1266
Attention:
RE:
Mr. David Mazyck
Consumer Safety Officer
Clarification regarding Drug Listing of Export Only Products
Dear Mr Mazyck:
As a collective group of pharmaceutical companies, who comprise the SPL Drug Listing and
Establishment Registration Working Group, we are writing to you for the purpose of explaining
our position and obtaining the Agency’s position concerning the drug listing requirement for
drugs that are exported from the United States (US). The various regulations, guidances and
instructions pertaining to drug listing can be interpreted in different ways. Indeed, there appears
to be some inconsistencies across these various documents.
Many firms have interpreted these references to exclude export products from drug listing.
During the recent discussions pertaining to SLPr4, the topic of drug listing export products has
been discussed. In this correspondence, we will present our interpretations and concerns. In
addition, we will provide examples of the different configurations of Export Only products. We
will also discuss our concerns with the assumed method of drug listing in the electronic
environment and how we feel this proposed process is feasible.
For ease of review, the correspondence is formatted accordingly:
I.
II.
III.
IV.
Interpretation of various regulatory references.
Examples of Export Only product configurations.
Concerns regarding drug listing requirement for Export Only products.
Issues with electronic drug listing Export Only products.
In advance, we wish to thank you for your consideration of our concerns and your assistance
with clarifying the requirements for drug listing Export Only products, both in the paper and
electronic environments.
I. Interpretation of regulations, guidances and instructions.
a) The regulations define ‘commercial distribution’, as follows: “any distribution of a
human drug except for investigational use under part 312 of this chapter, and any
distribution of an animal drug or animal feed bearing or containing an animal drug
for noninvestigational uses, but the term does not include internal or interplant
transfer of a bulk drug substance between registered establishments within the same
parent, subsidiary, and/or affiliate company. For foreign establishments, the term
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“commercial distribution” shall have the same meaning except that the term shall not
include distribution of any drug that is neither imported nor offered for import into
the United States.” 21 CFR § 207.3 (a)(5)
This definition could be interpreted to mean distribution inside and outside the US or
just inside the US.
b) On the FDA Drug Registration and Listing webpage, the second paragraph, last
sentence reads as follows: “This information helps FDA maintain a catalog of all
human and veterinary drugs and biologics in commercial distribution in the United
States.” (Exhibit I)
c) In the Introduction Section of the FDA online Instructions for Drug Listing, the first
paragraph, last sentence reads as follows: “This act requires submission of
information on commercially marketed drugs and is a substantial help in the
enforcement of the Federal Food, Drug, and Cosmetic Act.” (Exhibit II)
This statement implies that only products distributed in the US would be included,
since the Federal Food, Drug, and Cosmetic Act applies only to the US.
d) Additionally, the Introduction Section makes reference to Annex B in the first
sentence, which includes the following statement: “All drugs exported by domestic
firms, whether in bulk or finished dosage forms, must similarly be listed.”
(Exhibit II)
e) Lastly, an FDA news release dated August 23, 2006, which addresses the FDA
Proposed New Rule to Automate Drug Registration and Listing, includes the
following three statements:
"The Electronic Drug Registration and Listing System would make the complete
list of drug products marketed in the United States readily accessible
electronically."
"The National Drug Code Directory relies primarily on drug listing information
to provide details on marketed drug products. Drug establishment registration
provides FDA with drug manufacturing, repacking, and relabeling locations and
contact information. FDA uses this information to identify sites for inspection
and for other regulatory and drug-safety purposes. These data are used, among
other things, to identify alternate product sources during drug shortages and to
facilitate drug recalls."
“By providing FDA better-organized and more reliable information about drugs
in the marketplace, this initiative also supports the agency’s continuing efforts to
ensure the safety and quality of drugs in the United States.”
These statements all imply that products required to be drug listed are those products
distributed in the US. (Exhibit III)
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II.
Examples of Export Only Product Configurations
a) API for export
 Drug substance is labeled "For further processing".
 No NDC assignment since product is for ex-US market.
 Text is in foreign language and based on regulatory requirements of the
foreign country.
b) Bulk Unlabeled Finished Dosage Form for export
 Shipper label on outer container; no other labeling provided.
 No NDC assignment since product is for ex-US market.
c) Finished Dosage Form for export
 Text is in foreign language of the receiving foreign country and based on
regulatory requirements of that foreign country.
 Name of product may be different than that of US name.
 No NDC assignment since product is for ex-US market.
III.
Concerns regarding drug listing requirement for Export Only products
Industry considers products that are exported to a foreign country for distribution to
be under the jurisdiction and control of that foreign country receiving the product. A
US firm works with and obtains approval from the foreign country to market that
product in the foreign country. The "FDA does oversee records which contain
sufficient information to match the foreign purchaser's specifications to a particular
export" (Exhibit IV). But, the US FDA is not involved in the approval process of
marketing the drug in the foreign country.
Therefore, industry would like to better understand the Agency’s rationale for
requiring export products to be drug listed. Perhaps, if the US version of a product is
drug listed, then any foreign language versions are considered listed. Industry needs
better clarification concerning the FDA expectation pertaining to the drug listing of
export products. The references quoted in Section I. of this correspondence
demonstrate that inconsistent instructions have been communicated.
Most products exported for ex-US distribution are based on products approved and
marketed in the US. These US marketed products would be drug listed, pursuant to
the US regulations. The export products would not be assigned NDC numbers, as
NDC numbers are US regulation based. The export products would be labeled with
foreign language labeling or shipped unlabeled for further processing in the foreign
country. The same scenarios apply to exported API.
If industry were required to drug list export products, the number of new package
codes would be tremendous. For a firm that utilizes an NDC format of 5-4-1, there
would not be enough package code numbers for the number of export products
requiring drug listing.
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These industry concerns are outside the scope of exported controlled substances
which do require compliance with provisions enforced by the U.S. Drug Enforcement
Administration (DEA).
IV.
Issues with electronic drug listing of Export Only products
a) For most export products (since most are not currently drug listed), no XML files
currently exist. As a result of discussions with the FDA SPL Team, we have
learned that a complete SPLr4 file is expected to be submitted for export products.
Therefore, an SPLr4-compliant files would have to be created, and it would
include the foreign language Content of Labeling. Some software vendors have
confirmed that the software cannot manage the special characters used in some
languages, for example, Arabic, Japanese, German, and French.
Additionally, we assume that a foreign language label would not be posted on
DailyMed, as these enclosures are not FDA-approved, but rather approved by the
foreign country regulatory authority. Often, the labeling has differences from that
of the FDA-approved version, so, for that reason, we assume the Agency would
not post such labeling for the US public to view.
A different method of submitting drug listing data for exports should be devised.
It would be of no benefit to require a full SPLr4 file to be created, when only the
drug listing data is required.
b) If posted to Daily Med, many additional Package Codes would be included in the
Data Elements section of the SPLr4 file and this would be extremely confusing to
the public.
We trust this correspondence has provided the Agency with a concise and complete explanation
of industry’s concerns with drug listing of export products, in both the paper-based and
electronic listing environments. We would be very willing to sponsor a teleconference for
additional discussion on this topic, if the Agency would so agree.
Should you have any questions or require additional information, please contact the undersigned.
Sincerely,
cc:
Mr. Lonnie Smith, FDA SPL Project Manager,
Structured Product Labeling & eList Team
H:/drug listing/export/industry export ltr
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