June 24, 2011
VIA FACSIMILE AND UPS RETURN RECEIPT REQUESTED
John P. Barry, Ph. D.
Senior Manager, Drug Regulatory Affairs
Novartis Vaccines and Diagnostics, Inc.
350 Massachusetts Ave.
Cambridge, MA 02139
Re: BLA STN # 125300
MENVEO® [Meningococcal (Groups A, C, Y and W-135) Oligosaccharide
Diphtheria CRM197 Conjugate Vaccine]
Dear Dr. Barry:
The Advertising and Promotional Labeling Branch (APLB) in the Food and Drug Administration's Center for Biologics Evaluation and Research (CBER) has reviewed your professional telephone script (NVDMEN716) submitted May 12, 2011, and professional slides (NVDMEN665) submitted March 11, 2011 under cover of Form FDA 2253 for your product MENVEO® [Meningococcal (Groups A, C, Y and W-135) Oligosaccharide Diphtheria CRM197 Conjugate Vaccine].
Your promotional materials are false and misleading because they imply that MENVEO’s FDA-approved use is consistent with a published recommendation by the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP). Therefore, your materials misbrand MENVEO under Sections 502(a) and 201(n) of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. §352(a) and §321(n), and FDA implementing regulations, Cf. 21 CFR §202.1(e)(6)(i).
The 2010 updated ACIP guidelines for the use of quadrivalent (serogroups A, C, Y, and W-135) meningococcal conjugate vaccines in adolescents and persons at high risk for meningococcal disease recommend
1) routine vaccination of adolescents, preferably at age 11 or 12 years, with a booster dose at age 16 years and 2) a 2-dose primary series administered 2 months apart for persons aged 2 through 54 years with persistent complement component deficiency (e.g., C5–C9, properidin, factor H, or factor D) and functional or anatomic asplenia, and for adolescents with human immunodeficiency virus (HIV) infection.1
The FDA-approved prescribing information (PI) for MENVEO states
MENVEO is approved for use in persons 2 through 55 years of age.
MENVEO should be administered as a single 0.5mL intramuscular injection, preferably into the deltoid muscle (upper arm). For children 2 through 5 years of age at continued high risk of meningococcal disease a second dose may be administered 2 months after the first dose…. The duration of protection is not known. The persistence of bactericidal antibody has been studied through 21 months following immunization in adolescents….
False and Misleading Presentation
Under 21 CFR §202.1(e)(6)(i), advertisements are false, lacking in fair balance, or otherwise misleading if they contain a representation or suggestion, not approved or permitted for use in the labeling, that a drug is better, more effective, useful in a broader range of conditions or patients, safer, has fewer, or less incidence of, or less serious side effects or contraindications than has been demonstrated by substantial evidence or substantial clinical experience whether or not such representations are made by comparison with other drugs or treatments, and whether or not such a representation or suggestion is made directly or through use of published or unpublished literature, quotations, or other references.
Under “Screen 3” of the MENVEO telephone script (NVDMEN716) there is a summary of the 2010 updated ACIP recommendations along with the statement
Vaccinating with MENVEO allows you to meet these ACIP recommendations.
This statement appearing along with the ACIP recommendation suggests that MENVEO is approved for use consistent with the recommendations. However, MENVEO is not FDA-approved for the dose and schedule outlined in the ACIP recommendations (i.e. routine vaccination of adolescents, preferably at age 11 or 12 years, with a booster dose at age 16 years). Therefore, your promotional materials are false and misleading under 21 CFR §202.1(e)(6)(i) for misrepresenting FDA-approved uses for MENVEO as they relate to the ACIP recommendations.
Along with the statement described above, your professional slides (NVDMEN665) also are false and misleading pursuant to 21 CFR §202.1(e)(6)(i) for presenting ACIP recommendations without providing a clear distinction between general disease information, including ACIP recommendations, and specific information about MENVEO. In the absence of such a distinction, your materials misleadingly imply that there are adequate and well controlled clinical data demonstrating that Menveo has been used safely and effectively in this manner. In order to provide both types of information in a non-misleading manner, it is necessary to make a clear distinction between the ACIP recommendations and FDA-approved uses for your product.
Conclusion and Requested Actions
For the reasons discussed above, your promotional materials misbrand MENVEO under sections 502(a) and 201(n) of the Act, 21 U.S.C. §352(a) and §321(n), and FDA implementing regulations, Cf. 21 CFR 202.1(e)(6)(i).
We request that Novartis immediately cease the dissemination of this violative promotional material for MENVEO, as well as promotional materials with the same or similar claims and representations. Please submit a written response 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 MENVEO, and explaining your plan for discontinuing use of such materials. Please direct your response to Lisa Stockbridge, Ph. D., Branch Chief at the Food and Drug Administration, Center for Biologics Evaluation and Research, Office of Compliance and Biologics Quality, Division of Case Management, Advertising and Promotional Labeling Branch, HFM-602, 1401 Rockville Pike, Rockville, MD 20852-1448. In all future correspondence regarding this matter, please refer to the BLA/STN number. 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 MENVEO comply with each applicable requirement of the Act and FDA implementing regulations.
If you choose to revise your promotional materials, APLB is willing to assist you in assuring that your revised materials comply with applicable provisions of the Act by reviewing your revisions before you use them in promotion.
Robert A. Sausville
Director Division of Case Management
Office of Compliance and Biologics Quality
Center for Biologics Evaluation and Research
1 Center for Disease Control and Prevention. Updated Recommendations for Use of Meningococcal Conjugate Vaccines — Advisory Committee on Immunization Practices (ACIP), 2010..http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6003a3.htm. Accessed June 1, 2011