FDA Safety Communication - March 3, 2023

Purpose: To inform the public and healthcare providers that the U.S. Food and Drug Administration (FDA) has required and approved safety labeling changes to the Prescribing Information for all allergenic extracts for the diagnosis of food allergy. FDA required all manufacturers of allergenic extracts for the diagnosis of food allergy to revise the Prescribing Information to include the following language in the Warnings or Warnings and Precautions section:

Anaphylaxis Following False Negative Food Allergen Skin Test Results

False negative skin test results associated with anaphylaxis from subsequent exposure to the allergen have been reported during postmarketing diagnostic use of some food allergenic extracts. Based on the patient’s clinical history and the index of suspicion, healthcare providers should consider confirming negative skin testing with serologic testing by measuring specific serum IgE or with a medically-supervised oral food challenge.

Summary of the Safety Issue

In 2022, during safety monitoring of FDA Adverse Event Reporting System (FAERS) data, FDA became aware of increased postmarketing adverse event reporting of false negative skin test results with certain lots of ALK-Abello’s Allergenic Extract – Peanut (Arachis hypogaea) – For Diagnostic Use Only. Some of these reports of false negative test results were associated with life-threatening anaphylaxis from subsequent exposure to peanut. On December 20, 2022, FDA notified the public that the manufacturer initiated voluntary withdrawal of four lots due to the increased adverse event reporting. Prior to this, FDA listed the association of certain product lots with increased reports of false negative skin test results, with some cases of anaphylaxis from subsequent peanut exposure as a potential signal of serious risk/new safety information identified by FAERS. FDA determined that the risk of anaphylaxis following false negative food allergen skin test results is applicable to all allergenic extracts for the diagnosis of food allergies. Therefore, the FDA initiated safety labeling changes for all allergenic extracts for the diagnosis of food allergy to include a Warning regarding anaphylaxis following false negative food allergen skin test results.

Allergenic Extracts for the Diagnosis of Food Allergy

Allergenic extracts for the diagnosis of food allergy are sterile liquids that are manufactured from natural substances (e.g., peanut) known to elicit allergic reactions in susceptible individuals. Among allergenic extracts, some are standardized; for these products there is an established method to determine the potency (or strength) of the product on a lot-by-lot basis. For other allergenic extracts there is no U.S. standard of potency, and these are called "non-standardized." All allergenic extracts for the diagnosis of food allergy currently licensed by FDA for distribution in the United States are non-standardized.

In January 2023, FDA issued safety labeling change (SLC) notification letters to the manufacturers of allergenic extracts for the diagnosis of food allergy (SLC notification letters available at 2023 Safety and Availability Communications | FDA).

Manufacturers of allergenic extracts for the diagnosis of food allergy currently* licensed by FDA for distribution in the United States include:

• ALK-Abelló, Inc.
• Greer Laboratories, Inc.

ALK-Abelló, Inc. and Greer Laboratories, Inc. then submitted Biologics License Application (BLA) supplements to FDA with proposed changes to the Prescribing Information to reflect the new safety information. The Center for Biologics Evaluation and Research approved those supplements on February 24, 2023.

*Note that as of February 27, 2023, per the request of Allergy Laboratories, Inc., FDA has revoked the biologics license of this manufacturer for all of their approved products, including their allergenic extracts for the diagnosis of food allergy. Please see CBER-Regulated Products: Permanent Discontinuations | FDA.

Information for Patients

• Some people who have had false negative food allergen skin test results, have experienced anaphylaxis after subsequent exposure to the food allergen.
• Discuss negative food allergen skin test results with your healthcare provider to determine if any further testing is needed to evaluate for food allergy.
• Symptoms of a severe allergic reaction (including anaphylaxis) that may require emergency treatment can include:
  • Difficulty breathing
  • Swelling of the face and throat
  • A fast heartbeat
  • A bad rash all over the body
  • Dizziness and weakness

Information for Healthcare Professionals

• Some people who have had false negative food allergen skin test results, have experienced anaphylaxis after subsequent exposure to the food allergen.
• Based on the patient’s clinical history and the index of suspicion, healthcare providers may wish to confirm negative skin testing with serologic testing for peanut-specific IgE or a medically-supervised oral food challenge.¹
• Do not use product from the four lots voluntarily withdrawn by the manufacturer that are listed on the FDA website: Voluntary Lot Withdrawals of Allergenic Extract – Peanut (Arachis hypogaea)- For Diagnostic Use Only, Manufactured by ALK-Abelló, Inc. for Increased Reports of False Negative Test Results.

Contact FDA

To report adverse events or product problems for any allergenic extract, contact the manufacturer or FDA at 1-800-FDA-1088 or http://www.fda.gov/medwatch. Please include lot number in the report.

References

¹1Greenhawt M, Shaker M, Wang J, Oppenheimer JJ, Sicherer S, Keet C, Swaggart K, Rank M, Portnoy JM, Bernstein J, Chu DK, Dinakar C, Golden D, Horner C, Lang DM, Lang ES, Khan DA, Lieberman J, Stukus D, Wallace D. Peanut allergy diagnosis: A 2020 practice parameter update, systematic review, and GRADE analysis. J Allergy Clin Immunol. 2020 Dec;146(6):1302-1334. doi: 10.1016/j.jaci.2020.07.031. Epub 2020 Aug 15. PMID: 32810515.