FDA Issues Draft Guidance for Marketing Status Notifications

On Wednesday, January 30th, FDA issued a draft guidance which clarifies what information must be shared with the Agency regarding the marketing status of branded and generic drugs.  The draft guidance, entitled “Marketing Status Notifications Under Section 506I of the Federal Food, Drug, and Cosmetic Act; Content and Format,” will assist Sponsors of new drug applications (NDAs) and abbreviated new drug applications (ANDAs) with the submission of marketing status notifications as required under section 506I of the Federal Food, Drug, & Cosmetic (FD&C) Act.  Specifically, the document identifies the content and format requirements that Sponsors must follow when preparing and submitting these notifications should to the FDA.

Background

Under the Drug Price Competition and Patent Term Restoration Act of 1984, FDA was required to make a publicly-available list of all drug products approved under section 505(c) of the FD&C Act for safety and effectiveness or approved under section 505(j) of the FD&C Act.  In October 1980, the FDA fulfilled this requirement with its publication of the Approved Drug Products with Therapeutic Equivalence Evaluations, also known as the Orange Book.  The. The Orange Book is a crucial tool for generic drug companies in planning their development efforts; it provides many benefits to patients, providers, and generic drug developers, making it critical that the list remain modern and up-to-date.

The Orange Book contains two sections for different drug product lists: active and discontinued drug products. The active section includes the “Prescription Drug Product List” and the “Over-the-Counter (OTC) Drug Product List”. The discontinued section includes the “Discontinued Drug Product List”, which sets forth drug products “(1) which have been identified by the application holder as not being marketed or (2) whose marketing has been discontinued for reasons other than safety or effectiveness, as determined by FDA.”

In August 2017, the FDA Reauthorization Act of 2017 (FDARA) was enacted, adding section 506I to the FD&C Act.  Under this legislation, drugmakers are required to provide additional marketing status information for drug products approved under NDAs and ANDAs, including:

• Notification of withdrawal from sale – requires written notification be provided to FDA 180 days prior to removing an approved drug from sale
• Notification of drug not available for sale – requires written notification to FDA “within 180 days of the date of approval of a drug if that drug will not be available for sale within 180 days of the date of approval.”
• One-time report on marketing status – required written notification be provided to FDA within 180 days of enactment of FDARA, stating whether the NDA and ANDA holder’s drug(s) in the active section of the Orange Book were available, had been withdrawn from sale, or had never been available for sale.

FDA has previously indicated that withdrawal from sale not only include permanent withdrawal but can include any decision to discontinue marketing. A routine temporary interruption in the supply, unless triggered by safety or effectiveness, would not be considered a withdrawal.

If any of the above marketing status notifications are not submitted, section 506I of the FD&C Act authorizes FDA to move the drug product from the active to discontinued section of the Orange Book.

Content & Format Requirements for Marketing Status Notifications

In the draft guidance, the Agency notes that the notification may serve as its own cover letter, and therefore a separate cover letter is not necessary.

A notification of a withdrawal from sale must include:

1. The National Drug Code(s) under which the drug is listed (21 CFR part 207)
2. The established name of the drug
3. The proprietary name of the drug, if applicable
4. The NDA or ANDA number
5. The strength of the drug
6. The date on which the drug is expected to no longer be available for sale
7. The reason for the withdrawal

A letter containing the notification of withdraw from sale should be filed through the electronic submissions gateway under the applicable NDA or ANDA file. The submission should be identified as “ADMINISTRATIVE CHANGE / NOT AVAILABLE FOR SALE.” This letter does not replace the 21 CFR 314.150(c) submission by an application holder if voluntary withdrawal of its approved application is requested.

A notification of a drug not available for sale must include:

1. The established name of the drug
2. The proprietary name of the drug, if applicable
3. The NDA or ANDA number
4. The strength of the drug
5. The date on which the drug will be available for sale, if known
6. The reason for not marketing the drug after approval

The notification must also be submitted through the applicable NDA or ANDA file through the electronic gateway and should be identified as “ADMINISTRATIVE CHANGE / NOT AVAILABLE FOR SALE.” Once marketing has commenced, FDA recommends notifying the Agency in a letter filed in the same way to ensure that changes are reflected in the Orange Book. This notification should identify the submission as “ADMINISTRATIVE CHANGE /NOTIFICATION OF COMMERCIAL MARKETING.”

One-time report on marketing status

FDARA was enacted August 18, 2017, and the one-time report on marketing status was due by Wednesday, February 14, 2018.  “This one-time written report was required to indicate whether:

1. All of the NDA or ANDA holder’s drugs in the active section of the Orange Book were available for sale
2. One or more of the NDA or ANDA holder’s drugs in the active section of the Orange Book had been withdrawn from sale or had never been available for sale”

Further Action

In a recent statement, Scott Gottlieb, M.D., Commissioner of the FDA, mentioned that future actions will be taken by the Agency in 2019 to clarify Orange Book processes. Gottlieb specifically mentioned an upcoming draft guidance that will increase transparency around FDA’s policies by identifying how the Agency evaluates therapeutic equivalence (TE) and assigns therapeutic equivalence codes, which are published in the Orange Book. An additional draft guidance will also be issued to assist drug product applicants and application holders by providing answers to commonly asked questions regarding the Orange Book. Separately from the guidances, Gottlieb revealed that FDA will be soliciting public comment on Orange Book use and potential enhancements. The Agency hopes that this information will help keep the Orange Book updated accurately and efficiently.

The Marketing Status Notifications draft guidance is being distributed for comment purposes only and comments can be submitted in written or electronic format and must be received by April 1, 2019.

Are you in the process of developing a NDA or ANDA for submission to the FDA?  Do you hold an approved NDA or ANDA and manufacture an FDA approved drug? Regardless of where you are in the drug development life cycle, we can help you achieve successful interactions with the FDA.  To learn more about our services and how we can help you, contact us today.