- DrNaturalHealing Inc.
- Issuing Office:
- Philadelphia District Office
| || |
Department of Health and Human Services
|Public Health Service|
Food and Drug Administration
| ||PHILADELPHIA DISTRICT|
900 U.S. Customhouse
2nd and Chestnut Streets
Philadelphia, PA 19106
Delivered Via United Parcel Service
March 10, 2016
James Z. Lui, M.D., Ph.D.
111 McCoy Street
Milford, DE 19963
Dear Dr. Lui:
This letter concerns your firm’s marketing of the over-the-counter (OTC) drug product (b)(4), a bronchodilator containing the active ingredient epinephrine. (b)(4) is marketed both in the (b)(4), which is labeled as containing 20 epinephrine-containing capsules and is co-packaged with a dry powder inhaler, and in the (b)(4), which is labeled as containing 40 epinephrine-containing capsules. The directions for use for (b)(4), as provided on the labeling of both the (b)(4) and (b)(4), state that the epinephrine-containing capsules are to be administered via the dry powder inhaler.
As labeled, (b)(4) is a drug within the meaning of sections 201(g)(1)(B) and (C) of the Federal Food, Drug, and Cosmetic Act (the Act) [21 U.S.C. §§ 321(g)(1)(B) and (C)] because it is intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease and because it is intended to affect the structure or function of the body. Specifically, the product labeling, including the outer carton label for the (b)(4) and the (b)(4), states that these products are intended for the temporary relief of mild symptoms of intermittent bronchial asthma, including wheezing, tightness of chest, and shortness of breath.
In addition, based on the active ingredient and the claims made for this product, (b)(4) is a "new drug" within the meaning of section 201(p) of the Act [21 U.S.C. § 321(p)] because it is not generally recognized as safe and effective for its labeled uses. Certain drug products intended for indications such as those for which (b)(4) is labeled have been evaluated and determined by FDA to be generally recognized as safe and effective when marketed in compliance with the conditions set forth under the final monograph for Cold, Cough, Allergy, Bronchodilator, and Antiasthmatic Drug Products for OTC use, 21 CFR Part 341, (OTC bronchodilator final monograph).
The OTC bronchodilator final monograph, however, does not include epinephrine for use as an inhaled bronchodilator in a dry powder dosage form and when using a dry powder inhaler. See
21 CFR 341.76. Moreover, we are not aware of any other evidence establishing that a product such as (b)(4)
is generally recognized as safe and effective when directed for use with a dry powder inhaler.
Under sections 301(d) and 505(a) of the Act [21 U.S.C. §§ 331(d) and 355(a)], a new drug may not be introduced or delivered for introduction into interstate commerce unless an application approved by FDA under either section 505(b) or (j) of the Act [21 U.S.C. § 355(b) or (j)] is in effect for the product. Based upon our information, there is no FDA-approved application on file for (b)(4). The marketing of this product without an approved application constitutes a violation of these provisions of the Act.
In addition to the above violations, (b)(4) and (b)(4) are misbranded under Section 502(x) of the Act [21 U.S.C. § 352(x)] because the products’ labels fail to disclose a domestic address or domestic telephone number through which the responsible person may receive a report of a serious adverse event with such drug. Please note that Section 201(k) of the Act defines the term "label" as "...a display of written, printed, or graphic matter upon the immediate container of any article; and a requirement made by or under the authority of this Act that any word, statement, or other information appear on the label shall not be considered to be complied with unless such…also appears on the outside container….”
We are very concerned about the safety of (b)(4). Given the available information, it is unclear how much active ingredient would be delivered to a patient when using (b)(4), even if the conditions of use as set forth in the product labeling are strictly followed. Moreover, FDA believes that there is a significant risk that patients will either over- or under-dose themselves when using (b)(4), which could lead to serious and possibly fatal adverse outcomes. Because (b)(4) is intended to be used to relieve acute symptoms of asthma, if the dose of epinephrine delivered via the (b)(4) is not effective, patients may be at risk for serious or potentially fatal asthma exacerbations. At the other extreme, if the dose of epinephrine is too high, patients may be at increased risk for potentially serious adverse reactions. Cardiovascular adverse reactions may be of particular concern given that epinephrine is a non-selective adrenergic agonist.
Furthermore, given the capsule formulation, there is potential risk of consumers swallowing the capsules (http://www.fda.gov/downloads/drugs/drugsafety/medicationerrors/ucm080689.pdf
), instead of using them in the inhaler, which raises safety concerns about lack of efficacy and potential systemic side effects if swallowed. In addition, given the capsule formulation, there is potential for inhalation of capsule particles, which also raises safety concerns regarding aspiration.
The violations cited in this letter are not intended to be an all-inclusive list of deficiencies regarding your products. Please be aware that you are responsible for investigating and determining the causes of these violations and for preventing their recurrence and the occurrence of other violations. It is your responsibility to assure that your firm complies with all requirements of federal law and FDA regulations.
You should take prompt action to correct the violations cited in this letter. Failure to promptly correct these violations may result in legal action without further notice, including, without limitation, seizure and injunction.
Within fifteen working days of receipt of this letter, please notify this office in writing of the specific steps that you have taken to correct violations. Include an explanation of each step being taken to prevent the recurrence of violations, as well as copies of related documentation. If you cannot complete corrective action within fifteen working days, state the reason for the delay and the time within which you will complete the correction. Your written response should be sent to Joseph A. Morkunas, Compliance Officer, U.S. Food and Drug Administration, 900 U.S. Customhouse, 200 Chestnut Street, Philadelphia, Pennsylvania 19106. If you have any questions about this letter, please contact Mr. Morkunas at (215) 717-3079 or e-mail at Joseph.Morkunas@fda.hhs.gov.
Anne E. Johnson
Acting District Director
cc: Division of Professional Regulation
861 Silver Lake Blvd. Dover, De 19904
Attention: Director, Office of Controlled Substances, Executive Secretary, Board of Pharmacy
 The dry powder inhaler is intended to produce a vapor from the epinephrine capsules that patients are to inhale. Consumers are instructed to add an epinephrine-containing capsule to the dry powder inhaler, push two blue buttons on the inhaler inwards to pierce the capsule, and then orally inhale the contents of the capsule through the mouth piece making sure that all dry powder is inhaled into the lungs. The OTC bronchodilator final monograph only provides for inhaled OTC bronchodilator products to be distributed in an aqueous solution for use in a hand held rubber bulb nebulizer.