FDA Denies Petition Seeking to Add Application Information to Drug Labels

By Kurt R. Karst –      

FDA recently denied a 2008 citizen petition (Docket No. FDA-2008-P-0291) requesting that the Agency amend its drug label regulations to require that product labels include the Orange Book-listed NDA number under which the product is approved.  According to the petition, “[i]ncreasingly, it has become more difficult for pharmacists to determine the status of the prescription drug products on his or her shelf.  Due, in part, to the accelerated pace of corporate mergers and acquisitions, the labels on many drug products no longer contain the information necessary for identification of that product in the Orange Book.”  Two examples used in the petition are authorized generics (defined at FDC Act § 505(t)(3)) and distributirs that relabel or repackage drug products.  In both cases, such products are not specifically identified in the Orange Book, but can be traced back to an approved drug product.  According to the petitioner, PRN Publishing, requiring the application number on drug product labels would allow pharmacists “to quickly and easily determine the equivalence status of any drug product by simply comparing the [application] number on the bottle to the [application] numbers listed in the Orange Book under the heading of the particular drug in question.”

FDA, in its petition denial, says that the Agency does not agree that a requirement to add the application number to product labels (both products approved under NDAs and ANDAs) would address the issues identified by PRN Publishing.  Tackling each of the petitioner’s examples, FDA says with respect to authorized generics that:

because an authorized generic drug shares the same NDA number as the branded innovator product, the authorized generic would not be identified separately from the branded drug in the Orange Book.  Pharmacists could be confused when they look up an NDA number in the Orange Book and find only a listing for the innovator product (which would not match in certain respects the label of the authorized generic drug in hand). 

And with respect to distributors, FDA comments that:

because distributors that relabel or repackage drug products do not separately identify their products for listing in the Orange Book, such marketed drugs would not be traceable by searching the Orange Book.  Pharmacists could be confused when they look up the application number in the Orange Book and find only a listing for the approved application holder (which would not match the label of the product in hand).

Finally, FDA notes that there are also several factors that need be taken into account when considering whether or not to amend the Agency’s drug label requirements, including “the Agency’s statutory mandate, space limitations, alternatives, potential for confusion, and potential safety risk.”  “Weighing these and other considerations in deciding how to use agency resources to efficiently and effectively promote and protect the public health,” FDA concluded that it is not necessary at this time to amend its drug label regulations to require companies to identify the application number under which the product is approved and marketed.

Curiously, neither the citizen petition nor FDA’s response discusses now-repealed FDC Act § 301(l).  Prior to the enactment of the 1997 FDA Modernization Act (“FDAMA”), FDC Act § 301(l) prohibited the use in labeling of any representation or suggestion that “approval of an application with respect to such drug . . . is in effect under section 505 . . . .”  FDAMA § 421 removed this vestigial remnant of the 1938 FDC Act.  Although the legislative history surrounding the repeal of FDC Act § 301(l) is a bit sketchy, it appears to be related to legislation introduced as far back as 1985 by Representative Henry Waxman (D-CA) – H.R. 2244, The FDA Approval Labeling Act – that proposed to amend the FDC Act to permit use of the statement “FDA Approved” in drug product labeling and advertising.  Subsequent to the repeal of FDC Act § 301(l), FDA has stated, in the context of the promotion and advertising of a drug, that companies can use the statement “FDA Approved” in labeling pieces and advertisements for prescription drugs, provided the company has approval for the drug product with respect to which the statement is made. 

We also note that in December 1998, FDA stated in a draft guidance document, titled “Placing the Therapeutic Equivalence Code on Prescription Drug Labels and Labeling” (FDA Docket No. 1998D-1266), that the Agency “believes it is legally permissible to allow the therapeutic equivalence code [identified in the Orange Book] linked to the proprietary name of the reference listed drug product to be placed on container labels and/or drug product labeling,” and that with the repeal of FDA Act § 301(l), “any legal arguments that therapeutic equivalence ratings should not be used in the labeling are moot.”  FDA never finalized the draft guidance, and, in fact, removed the draft guidance from its website after receiving adverse comments.  We understand that FDA currently has no public position on the issue of including in generic drug labeling a therapeutic equivalence code or similar information. 

While we’re on the topic of application numbers, we thought it would be helpful to provide folks with a Rosetta Stone of sorts with respect to FDA’s application numbering system, which changed not too long ago with FDA’s implementation of the Document Archiving, Reporting and Regulatory Tracking System (“DARRTS”).

• Application Nos. 00001 to 13000 (approximately): Pre-1962 NDA approvals (evaluated under DESI)
• Application Nos. 13000 (approximately) through 20,000 series applications: Post-1962 NDA approvals
• 40,000 Series Applications: ANDAs for generic versions of pre-1962 NDA approvals (A continuation of the 80,000 series applications.)
• 50,000 Series Applications: Old antibiotic NDAs approved under now-repealed FDC Act § 507
• 60,000 Series Applications: Old antibiotic ANDAs approved under now-repealed FDC Act § 507 (Some of the early 60,000 numbers could be considered innovator products.  For example, early in this numbering system when the NDA sponsor wanted a new manufacturing site, we understand that FDA assigned a 60,000 series application number. So the early 60,000's were probably NDAs in disguise. The 50,000 and 60,000 series numbers were the identification system used because of Form 5's and Form 6's.)
• 70,000 Series Applications: Contemporary, post-Hatch-Waxman ANDAs (The pre-/post-MMA ANDA No. cutoff – December 8, 2003 - is approximately ANDA No. 076925.)
• 80,000 Series Applications: ANDAs for generic versions of pre-1962 NDA approvals
• 90,000 Series Applications: Contemporary, post-Hatch-Waxman ANDAs (A continuation of the 70,000 series applications.  Beginning around October 2007, it is believed that the 90,000 series combined all ANDAs, such that the 40,000, 60,000, and 80,000 series numbers were no longer used.)
• 200,000 Series Applications: Post-DARRTS applications; numbers are assigned sequentially to NDAs and ANDAs