March 15, 2013
Jose A. Moreno Toscano
1700 Royston Lane
Round Rock, Texas 78664
Dear Mr. Toscano:
In 2004, the Food and Drug Administration (FDA) formed an internal committee to review available scientific and medical data on the safety and effectiveness of non-standardized allergenic extracts. FDA formed this committee to consider the previous evaluations performed by the allergenics advisory review panels convened under Title 21, Code of Federal Regulations 21 CFR 601.25 and 21 CFR 601.26, as well as to consider information about non-standardized allergenic extracts licensed since July 1, 1972, and therefore not subject to the 601.25 and 601.26 review. The internal committee collected and analyzed available literature associated with each product in order to assess the safety and effectiveness of non-standardized allergenic products, and designed a data file to document its review and supporting data.
The FDA announced the availability of its report of scientific and medical literature and information concerning the use of non-standardized allergenic extracts in the diagnosis and treatment of allergic disease in the Federal Register of September 26, 2011 (76 FR 59407). FDA requested comments from public and private stakeholders on the report it provided in a data file entitled "Center for Biologics Evaluation and Research Report of Scientific and Medical Literature and Information on Non-Standardized Allergenic Extracts in the Diagnosis and Treatment of Allergic Disease." FDA also sought input on the report from the Allergenic Products Advisory Committee and the public at a meeting held on October 25, 2011. We note that an Industry Representative was in attendance at the Advisory Committee meeting on October 25, 20111, and FDA has conducted outreach on this issue in its regular meetings with the Allergenic Product Manufacturers Association and with allergy professional groups.
FDA has completed a comprehensive review of the published literature, available manufacturer data, data from other external sources, and the comments it received on the 2011 report in order to assess the safety and effectiveness of non-standardized allergenic extracts. FDA's review has identified non-standardized allergenic extracts that do not meet the standards of safety and effectiveness. Therefore, at this time FDA has concluded that certain non-standardized allergenic extracts are not safe and effective for all of their intended uses or are misbranded with respect to any such use, and is initiating action to remove numerous allergenic extracts from the licenses for such products pursuant to 21 CFR 601.5(b)(1)(vi).
We note that this comprehensive review was the third review of non-standardized allergen extracts conducted under FDA auspices. Earlier reviews by external panels of data related to the safety, effectiveness, and labeling for non-standardized allergenic extracts, took place in 1974-1979 and 1982-1983. FDA reviewed those recommendations in accordance with a process FDA established in 21 CFR 601.25, which was later supplemented by 21 CFR 601.26. In each of these three reviews, we invited manufacturers and others to provide data related to the safety and effectiveness of non-standardized allergenic extracts, and each time, manufacturers failed to provide adequate information related to their products.
We are taking this action under 21 CFR 601.5, instead of sections 601.25 and 601.26, because sections 601.25 and 601.26 apply only to those products licensed before July 1, 1972. Few of these licenses for non-standardized allergenic extracts were issued before that date. Accordingly, FDA is electing to use the 601.5 revocation authority, which can be applied to all licensed products, even though a manufacturer may be able to establish that one of the identified allergenic extracts was in its approved license before July 1, 1972. In this way, FDA will provide manufacturers of all impacted non-standardized allergenic products with the same administrative process as FDA moves forward with proceedings for license revocation.
Pursuant to 21 CFR 601.5(b), this letter is to provide you with notice that it is the intent of FDA to institute proceedings to revoke your biologics license with regard to a subset of extracts as specified below:
Lic 1256 STN103753
Dust, House Mixture
Pollens – Weeds and Garden Plants, Castor Bean Ricinus communis
Pollens – Weeds and Garden Plants, Mexican Tea Chenopodium ambrosioides
The Agency intends to institute proceedings under 601.5(b)(1)(vi) to revoke the biologics license for these products, unless you do the following:
- Within ten (10) working days of receipt of this letter, advise the FDA in writing of your intention and commitment to provide additional data that has not already been considered and reviewed by FDA, regarding the safety and effectiveness for all of the intended uses of the extracts described above.
- Based on your commitment above to provide additional data, within thirty (30) working days of receipt of this letter, submit a detailed response including data that has not already been considered and reviewed by FDA, regarding the safety and effectiveness for all of the intended uses of the extracts described above which may include, but is not limited to:
- Published literature;
- Data from other external sources;
- Serological response evaluation in clinical studies or other laboratory assay evaluations;
- Investigations corroborated by partially controlled or uncontrolled studies;
- Documented clinical studies by qualified experts;
- Reports of significant human experience during marketing.
These submissions should be sent to Ms. Mary A. Malarkey, Director, Office of Compliance and Biologics Quality, HFM-600, Center for Biologics Evaluation and Research, Food and Drug Administration, 1401 Rockville Pike, Suite 200N, Rockville, Maryland 20852-1448. Ms. Malarkey may be reached at (301) 827-6190. Additionally, a copy of all submissions should be sent to Dr. Jay Slater, Director, Division of Bacterial, Parasitic, and Allergenic Products, Office of Vaccines Research and Review, HFM-422, Center for Biologics Evaluation and Research, Food and Drug Administration, 1401 Rockville Pike, Suite 200N, Rockville, Maryland 20852-1448.
If we do not receive an adequate response within the prescribed time the Agency intends to proceed pursuant to regulations governing formal evidentiary public hearings, as found in 21 CFR 12.21(b), and to publish in the Federal Register a notice of opportunity for a hearing on a proposal to revoke your biologics license with regard to the subset of extracts described above.
If you wish to waive the opportunity for a hearing, you should contact Ms. Malarkey within ten (10) calendar days of receipt of this letter. The waiver must be confirmed in writing and may be accomplished by your voluntary request that your biologics license be revoked with regard to the extracts described above.
Karen Midthun, M.D.
Center for Biologics Evaluation and Research
Mr. Andrew Ameye
35 Channel Drive
Port Washington, New York 11050
Mr. Pedro Aldahondo
35 Channel Drive
Port Washington, New York 11050