> ## Content Index
> Fetch the complete content index at: https://www.fdaweb.com/llms.txt
> Use this file to discover other available public pages before exploring further.

# Millennium Raises Generic Velcade Issues
- URL: https://www.fdaweb.com/millennium-raises-generic-velcade-issues/
- Published: 2017-06-14T12:00:00.000Z
- Updated: 2026-09-14T22:29:26.000Z
- Author: David McFarland
- Tags: Drugs, #legacy-id-D5138928

Takeda’s Millennium Pharmaceuticals unit is again raising issues related to ANDAs or 505(b)(2) applications for its Velcade (bortezomib) for injection, described as a first-in-class proteasome inhibitor approved to treat multiple myeloma and mantle cell lymphoma. In a 6/8 [citizen petition](https://www.regulations.gov/document?D=FDA-2017-P-3672-0001&ref=fdaweb.com), Millennium references its 8/13/13 [petition](http://fdaweb.com/login.php?sa=v&aid=D5126349&searchWords=velcade&cate=S&stid=%241%24Af4.J23.%24Y9DwiPU7LMVLMNFT6POci0&ref=fdaweb.com) about safety and legal issues it says were raised by a pending Fresenius application for a bortezomib product that it says contains a toxic ingredient, boric acid, not in Velcade.

On 1/14/14, the petition says, FDA said it was not ready to make a final determination on the Fresenius application and denied the Millennium petition without commenting on whether it would take the requested actions. Millennium says it is submitting the current petition “to ensure that FDA carefully considers those important issues during the agency’s review of the Fresenius application.”

The new petition also discusses developments that have occurred since the company’s 2013 petition, including an approval for an additional Velcade indication for use with mantle cell lymphoma, and approval to re-treat multiple myeloma patients who have relapsed following prior Velcade treatment.

The company expresses concern that due to extended exclusivity periods from the new indications, an ANDA applicant or 505(b)(2) applicant might seek to omit the protected safety and efficacy labeling information. “Product labeling that omits the protected information would raise significant safety and legal issues,” it says.

Millennium says that consistent with FDA’s regulatory framework, the agency should identify the Velcade active ingredient as the mannitol ester of bortezomib. Since the drug’s approval in 2003, it says, FDA has identified the active ingredient as the monomeric boronic acid. bortezomib. “However,” the petition says, “the active ingredient must be identified as the form that exists in the finished drug product. With respect to Velcade, the finished drug product contains the mannitol ester of bortezomib. The development of products, such as the Fresenius product, that omit mannitol or replace it with other components makes it critical for FDA to address this issue now.”

The company asks that FDA: 

- refrain from approving any ANDA or 505(b)(2) bortezomib product for any multiple myeloma indication with labeling that omits information regarding the safe and effective conditions of use for the retreatment of relapsed patients;
- refrain from approving any ANDA or 505(b)(2) bortezomib product for any mantle cell lymphoma indication with labeling that omits information regarding the safe and effective conditions of use for treatment in previously untreated patients or labeling that adds new language to modify Velcade’s current mantle cell lymphoma indication;
- seek public comment if FDA is considering allowing an ANDA applicant to revise Velcade’s currently mantle cell lymphoma indication by adding new language, consistent with FDA’s prior action in a similar situation;
- identify the active ingredient in Velcade as the mannitol ester of bortezomib;
- require Fresenius’ 505(b)(2) application for an injectable bortezomib formulation containing boric acid to be supported with defined types of data; and
- require the Fresenius 505(b)(2) application to identify each source of information relied on to support approval of its application, including any previously approved product relied on through FDA’s inactive ingredient database.