Waking From a Drug Coma: How to Bring a Drug Out of Discontinued Status – It’s As Easy As 1, 2, 3 . . . 4, and 5

By Kurt R. Karst –      

Finger through the “Discontinued Drug Product List” section of the Orange Book and youl’ll quickly realize that there are a lot of drug products no longer marketed.  The “Discontinued Drug Product List” spans 337 pages in the current annual edition of the Orange Book, and more drug products are added each month with the Cumulative Supplement.  You see the additions when the term “DISC” (defined as “Discontinued. The Rx or OTC listed product is not being marketed and will be moved to the discontinuedsection in the next edition.)” is added to a particular drug product listing.  The “Discontinued Drug Product List” encompasses several categories of drugs.  As explained in the Orange Book Preface, it is “a cumulative list of approved products that have never been marketed, are for exportation, are for military use, have been discontinued from marketing, or have had their approvals withdrawn for other than safety or efficacy reasons subsequent to being discontinued from marketing.” 

There are various reasons why a company may discontinue marketing a drug product.  Perhaps a brand-name manufacturer has lost interest in a product because of generic competition and loss of market share.  Or perhaps a company obtains approval of an ANDA and is not ready to market the drug because of ongoing patent infringement litigation or because of a settlement agreement that sets a marketing date that is years away.  In either case, the application is put into a coma-like state; it is effectlvely mothballed. 

But just as humans can awake from a coma after many years (here and here), so too can a drug.  Every once in a while you see the notation “CMFD” added to a monthly Orange Book Cumulative Supplement.  That notation is defined as “Change.  The product is moved from the Discontinued Section due to a change in marketing status.”  And just as there are various reasons why a company may discontinue a drug product, there are also several reasons why a drug product may be re-marketed.  For example, perhaps ownership in an NDA or ANDA has been transferred and the purchasing company intends to re-introduce the drug to the market.  In some cases, the approval for a product in the discontinued list has been withdrawn, and it will therefore never awaken from its coma.  (Though the drug can serve as a Reference Listed Drug for an ANDA applicant, provided FDA determines that the brand-name drug was not withdrawn for safety or effectiveness reasons – see our previous post here). 

For many years, the process of moving a drug from the “Discontinued Drug Product List” to the “Prescription Drug Product List” or to the “OTC Drug Product List” – i.e., from “DISC” to CMFD” – was relatively simple.  A company would notify FDA of the change and it would occur.  That changed, however, a couple of years ago after there was “an incident” (about which we don’t know the details) with a drug that was re-marketed after spending some time on the “Discontinued Drug Product List.”  Afterwards, FDA developed a more formal process for when a sponsor wants to have a drug product removed from the “Discontinued Drug Product List.”

When a sponsor notifies FDA that the company intends to remarket a dormant drug, the sponsor will probably receive correspondence from FDA asking a few questions.  That correspondence might look something like this:

Please submit a general correspondence to the application and a courtesy email copy to the Orange Book general inbox (DrugProducts@cder.fda.gov) with the following information:

1) What is the launch date of the product?
2) How long has it been off the market?  When was it last manufactured?
3) Has there been a transfer of ownership since the last manufacturing date?
4) Is the product using the same API supplier/facility, drug product manufacturer/facility and drug manufacturing process/equipment?
5) Will a supplement be needed before the product can be marketed?

We encourage you to submit your request two months before the launch date to allow the Orange Book to process your request in a timely manner.

A company’s responses to these questions ahead of a change to marketing status in the Orange Book gives FDA some cushion to evaluate the re-marketing situation for a particular drug (and presumably, to determine whether or not such a change is appropriate given the particulars of a case).