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U.S. Department of Health and Human Services

Inspections, Compliance, Enforcement, and Criminal Investigations

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Enforcement Actions

Protherics, Inc. 19-Nov-04

Department of Health and Human Services' logoDepartment of Health and Human Services

Public Health Service
Food and Drug Administration

 

Center for Biologics Evaluation
and Research
1401 Rockville Pike
Rockville MD 20852-1448


November 19, 2004

CBER-05-003

VIA FACSIMILE AND CERTIFIED MAIL
RETURN RECEIPT REQUESTED

WARNING LETTER

Carol Clark-Evans
Vice President, Regulatory and Clinical Affairs
Protherics Inc.
5214 Maryland Way, Suite 405
Brentwood, TN 37027

Re: BLA STN #103910
DigiFab™ [Digoxin Immune Fab (Ovine)]

Dear Ms. Clark-Evans:

The Office of Compliance and Biologics Quality (OCBQ) in the Food and Drug Administration’s Center for Biologics Evaluation and Research (CBER) has reviewed a sell sheet (Enclosure A) and a file card (Enclosure B) for DigiFab™ [Digoxin Immune Fab (Ovine)] submitted by Protherics Inc. under cover of Form FDA 2253. These materials fail to reveal material facts regarding the risks associated with the use of DigiFab and, therefore, violate the Federal Food, Drug, and Cosmetic Act (the Act). See 21 U.S.C. 352(a), 321(n). By failing to include sufficient information on risks, you have encouraged the potentially unsafe use of DigiFab. The materials also violate section 502(e)(1)(B) of the Act (21 U.S.C. 352(e)(1)(B)) and 21 CFR 201.10(g)(2) by failing to represent the established name in letters that are at least half as large as the type used for the proprietary name.

Background

According to the FDA-approved professional labeling (PI), DigiFab is a sterile, purified, lyophilized preparation of the digoxin-immune ovine Fab (monovalent) immunoglobulin fragments. The PI states:

“DigiFab is indicated for the treatment of patients with life-threatening or potentially life-threatening digoxin toxicity or overdose.. . . DigiFab is not indicated for milder cases of digitalis toxicity.”

The PI also includes detailed risk information including contraindications, warnings, precautions, and adverse reactions.

Failure to Reveal Material Facts

The sell sheet and file card both promote DigiFab as, “the cost savings treatment for Digoxin Toxicity.” This statement identifies the indication for use of DigiFab. Because you included the indication in your sell sheet and file card, you do not meet the conditions of 21 CFR 201.100(f) that would exempt you from meeting the requirements of 21 CFR 201.100(d), such as including relevant risk information in the main part of those pieces and accompanying those pieces with the full PI.

The main parts of the sell sheet and file card fail to provide any risk information. This information is necessary to qualify the effectiveness claims appearing in the main parts of those pieces. It is true that the sell sheet directs the reader to the accompanying DigiFab brief summary on back, and that both the sell sheet and the file card refer the reader to www.founera.com for full prescribing information. Nevertheless, providing the brief summary on the back of the labeling and referring to the PI located elsewhere is not sufficient to provide the appropriate qualification or pertinent information about the risks associated with DigiFab. cf. 21 CFR 202.1 (e)(3)(i).

We recommend you revise these pieces to include appropriate fair balance risk information. Alternatively, you could remove all the representation or suggestion concerning the product’s safety, effectiveness, or indications for use.

In addition, the sell sheet and file card both misleadingly imply that DigiFab is indicated as the treatment for all digoxin toxicity when, according to the PI, “DigiFab is indicated for the treatment of patients with life-threatening or potentially life-threatening digoxin toxicity or overdose.. . . DigiFab is not indicated for milder cases of digitalis toxicity.”

Violative Labeling

Your sell sheet and file card also violate section 502(e)(1)(B) of the Act (21 U.S.C. 352(e)(1)(B)) and 21 CFR 201.10(g)(2) because they fail to represent the established name in letters that are at least half as large as the type used for the proprietary name. For that reason, the sell sheet and file card misbrand DigiFab within the meaning of the Act.

Conclusion and Requested Actions

The sell sheet and file card misbrand DigiFab within the meaning of sections 502(a) and 201(n) of the Act (21 U.S.C. 352(a), 321(n)) because they fail to reveal material facts and violate section 502(e)(1)(B) of the Act (21 U.S.C. 352(e)(1)(B)) and 21 CFR 201.10(g)(2) by failing to represent the established name in letters that are at least half as large as the type used for the proprietary name.

OCBQ requests that Protherics immediately cease the dissemination of violative promotional materials for DigiFab such as those described above. Please submit a written response to this letter within ten (10) business days of the date of this letter, stating whether you intend to comply with this request, listing all violative promotional materials for DigiFab such as those described above, and explaining your plan for discontinuing use of such materials. Because the violations described above are serious, we request, further, that your submission include a plan of action to disseminate truthful, non-misleading, and complete information to the audience(s) that received the violative promotional materials. Please direct your response to me at the Food and Drug Administration, Center for Biologics Evaluation and Research, Office of Compliance and Biologics Quality, HFM-600, 1401 Rockville Pike, Rockville, Maryland 20852-1448. In all future correspondence regarding this matter, please refer to the BLA/STN number and to CBER-O5-003. We remind you that only written communications are considered official responses.

The violations discussed in this letter do not necessarily constitute an exhaustive list. It is your responsibility to ensure that your promotional materials for DigiFab comply with each applicable requirement of the Act and FDA implementing regulations.

Failure to correct the violations discussed above may result in FDA regulatory action, including seizure or injunction, without further notice.

Sincerely,

/s/

James S. Cohen, J.D.
Acting Director
Office of Compliance and Biologics Quality
Center for Biologics Evaluation and Research

Enclosures:
A - Sell Sheet
B - File Card