Inspections, Compliance, Enforcement, and Criminal Investigations
ALK-Abello, Inc. 06-Sep-06
Department of Health and Human Services
Public Health Service
Center for Biologics Evaluation and Research
September 6, 2006
VIA FACSIMILE AND CERTIFIED MAIL
RETURN RECEIPT REQUESTED
Jose A. Moreno Toscano
1700 Royston Lane
Round Rock, TX 78664
Re: BLA STN #103754
Histatrol® (Positive Skin Test Control - Histamine)
Dear Mr. Moreno Toscano,
The Office of Compliance and Biologics Quality (OCBQ) in the Food and Drug Administration's Center for Biologics Evaluation and Research has reviewed promotional material (Fax #949) for your product Histatrol® (Positive Skin Test Control- Histamine) submitted by your firm under cover of Form FDA 2253 (copy enclosed). This promotional material is misleading because it fails to reveal material facts regarding the risks associated with Histatrol and, therefore, misbrands Histatrol in violation of section 502(a) and 201(n) of the Federal Food, Drug, and Cosmetic Act (the Act). See 21 U.S.C. 352(a) and 321(n). The material is also apparently disseminated without adequate directions for use, in violation of section 502(f) of the Act. See U.S.C. 352(f). By failing to include sufficient information on risks and adequate directions for use, you have encouraged the potentially unsafe use of Histatrol.
According to the FDA-approved professional labeling (PI), Histatrol is a sterile solution that contains histamine base. The Indications and Usage section of the PI states:
For use as a positive control in evaluation of allergenic (immediate hypersensitivity or "Type I") skin testing.
The PI also includes detailed risk information including contraindications, warnings, and adverse reactions, including the following:
Histamine should not be injected into individuals with hypotension, severe hypertension, severe cardiac, pulmonary, or renal disease. Not to be used for diagnosis of pheochromocytoma or to test the ability of the gastric mucosa to secrete hydrochloric acid.
Care must be taken in intracutaneous testing to avoid injection into a venule or capillary.
Small doses by any route of administration may precipitate asthma in patients with bronchial hyperactivity. This product is not intended for inhalation, or subcutaneous injection. The utmost caution is advised in using histamine in such patients and in those with a history of bronchial asthma.
Reactions such as wheal, erythema and localized pruritus are to be expected, but if very large (i .e., greater than 4+ as described dosage and administration) may be the first manifestation of a systemic reaction.
Following the injection of large doses of histamine, systemic reactions may include flushing, dizziness, headache, bronchial constriction, urticaria, asthma, marked hypertension or hypotension, abdominal cramps, vomiting, metallic taste, and local or generalized allergic manifestations.
Failure to Reveal Material Facts
Fax #949 (copy enclosed) presents the indication, dosage, and multiple efficacy claims for Histatrol but fails to provide any risk information. For example, the fax includes the following claims:
"Are you POSITIVE about the reliability of your SKIN TEXT?"
"ONLY readily available positive control for INTRADERMAL Skin Testing"
The fax also included information from the PI regarding administration and interpretation of skin test results. The omission of risk information results in your product being misbranded within the meaning of section 502(a) and 201(n) of the Act.
In addition, it appears that the fax was disseminated without a PI. The failure to disseminate the fax with the PI would render your product misbranded within the meaning of section 502(f) of the Act. 21 U.S.C. 352(f). See 21 CFR 201.100(d).
Conclusion and Requested Actions
Your fax misbrands Histatrol within the meaning of section 502(a) and 201(n) of the Act because it fails to reveal material facts regarding the risks associated with the use of this product and is, therefore, misleading. 21 U.S.C. 352(a) and 321(n). In addition, the failure to disseminate the fax with the PI would render your product misbranded within the meaning of section 502(f) of the Act. 21 U.S.C. 352(f). See 21 CFR 201.100(d).
We request that ALK-Abello immediately cease the dissemination of violative promotional material for Histatrol such as the fax 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 Histatrol such as that 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 comprehensive plan of action to disseminate truthful, non-misleading, and complete corrective messages about the issues discussed in this letter to the audience(s) that received the violative promotional material. 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-06-O10. 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 Histatrol 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.
Mary A. Malarkey
Office of Compliance and Biologics Quality
Center for Biologics Evaluation and Research