- Issuing Office:
- Center for Drug Evaluation and Research
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10903 New Hampshire Avenue
Silver Spring, MD 20993
FROM: The United States Food and Drug Administration
RE: Notice of Unlawful Sale of Unapproved and Misbranded Drug Products to United States Consumers over the Internet
DATE: September 19, 2017
The United States (U.S.) Food and Drug Administration (FDA) recently reviewed your websites (listed at the bottom of this letter) and determined that they offer products for sale in violation of the Federal Food, Drug, and Cosmetic Act (FD&C Act). More specifically, the websites listed below offer unapproved new drugs and misbranded drugs for sale in U.S. commerce in violation of sections 301(a), 301(d), 301(k), 503(b), and 505(a) of the FD&C Act [21 U.S.C. §§ 331(a), 331(d), 331(k), 353(b), and 355(a)]. FDA requests that you immediately cease marketing violative drug products to U.S. consumers.
Unapproved New Drugs
As labeled, certain products offered for sale through your websites are drugs within the meaning of section 201(g) of the FD&C Act [21 U.S.C. § 321(g)] because they are intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease and/or because they are intended to affect the structure or function of the body. These products, as marketed through your websites, are also new drugs as defined by section 201(p) of the FD&C Act [21 U.S.C. § 321(p)], because they are not generally recognized as safe and effective for their labeled uses. New drugs may not be introduced or delivered for introduction into interstate commerce without prior approval from FDA, as described in section 505(a) of the FD&C Act [21 U.S.C. § 355(a)]. No approved applications pursuant to section 505 of the FD&C Act [21 U.S.C. § 355] are in effect for these products. Accordingly, their introduction or delivery for introduction into interstate commerce violates sections 301(d) and 505(a) of the FD&C Act [21 U.S.C. §§ 331(d) and 355(a)].
For example, your websites offer unapproved new drugs, including hydrocodone and acetaminophen 10/500 mg, which is described as a “combination of narcotic drug (Hydrocodone) and non narcotic drug (Acetaminophen)…. used to treat Moderate to severe pain.” While there are FDA-approved versions of hydrocodone and acetaminophen on the market in the U.S., there are currently no approved drug applications pursuant to section 505 of the FD&C Act [21 U.S.C. § 355] in effect for the hydrocodone products that contain 500 mg of acetaminophen offered for sale on your websites. In January 2011, due to the risk of severe liver injury, FDA issued a Drug Safety Communication and asked drug manufacturers to voluntarily limit the strength of acetaminophen in prescription drugs to 325 mg per tablet or capsule to make these products safer for patients. FDA announced via a Federal Register notice its intention to intitiate withdrawal proceedings pursuant to section 505(e)(2) of the FD&C Act for any prescription acetaminophen combination products with acetaminophen strengths greater than 325 mg still on the market as of January 2014.which is the strongest warning FDA requires, indicating that the drug carries a significant risk of serious or even life-threatening adverse effects. The boxed warning addresses risks including, addiction, abuse, misuse, life-threatening respiratory depression (breathing problems), neonatal opioid withdrawal syndrome (withdrawal symptoms in newborn baby), and hepatotoxicity (liver failure).
In March 2014, FDA announced the withdrawal of 108 abbreviated new drug applications (ANDA) for prescription pain drug products containing more than 325 mg of acetaminophen.
In addition, FDA-approved hydrocodone and acetaminophen also bears a boxed warning, commonly referred to as a “black box warning,”
Your websites also offer for sale tramadol, marketed as “Tramal SR,” and described as an “opioid pain medication… to treat moderate to moderately severe pain.” While there are FDA-approved versions of tramadol on the market in the U.S., there are no approved drug applications pursuant to section 505 of the FD&C Act [21 U.S.C. § 355] in effect for the “Tramal SR” product marketed on your website. FDA-approved tramadol bears a boxed warning addressing risks including addiction, abuse, misuse, life-threatening respiratory depression, and neonatal opioid withdrawal syndrome. In addition, when taken in conjunction with other central nervous system depressants, including alcohol, use may result in coma or death.
Your websites also offer for sale prescription drugs without a prescription. Prescription products, as defined in FD&C Act § 503(b)(1) include those that, because of their toxicity or other potentiality for harmful effect, and/or the method of their use, and/or the collateral measures necessary for their use, are not safe for use except under supervision of a practitioner licensed by law to administer them. Prescription drugs offered for sale on your website include opioids such as tramadol and hydrocodone drug products. Offering these drugs for sale on your websites is particularly concerning given potential for abuse and dependency, especially amid the growing epidemic of opioid abuse in the U.S. The Centers for Disease Control and Prevention found that opioid overdose deaths involving prescription opioids have quadrupled since 1999, and in 2015, opioids were involved in the deaths of 33,091 people in the U.S.
In addition, deaths by drug overdose, including overdose from prescription opioids, are now the leading cause of injury death in the U.S.
Under U.S. law, prescription drug products can be dispensed only pursuant to a prescription from a healthcare practitioner licensed by law to administer prescription drugs. Your offering prescription drug products without requiring a prescription jeopardizes patient safety and misbrands the drug products under section 503(b)(1) of the FD&C Act [21 U.S.C. § 353(b)(1)]. Dispensing a prescription drug without a prescription is an act which results in the drug being misbranded while held for sale, in violation of section 301(k) of the FD&C Act [21 U.S.C. § 331(k)].
In addition, a drug is misbranded under section 502(f)(1) of the FD&C Act [21 U.S.C. § 352(f)(1)] if it fails to bear adequate directions for its intended use(s). “Adequate directions for use” means directions under which a layperson can use a drug safely and for the purposes for which it is intended (21 CFR 201.5). Prescription drugs, as defined in 503(b)(1)(A) of the FD&C Act [21 U.S.C. § 353(b)(1)(A)], can only be used safely at the direction, and under the supervision, of a licensed practitioner.
Because the aforementioned drugs are prescription products intended for condition(s) that are not amenable to self-diagnosis and treatment by a layperson, adequate directions cannot be written such that a layperson can use these products safely for their intended use(s). Consequently, the labeling for these products fails to bear adequate directions for their intended use(s), causing them to be misbranded under section 502(f)(1) of the FD&C Act [21 U.S.C. § 352(f)(1)]. Because these drugs are not approved in the U.S., they are also not exempt under 21 CFR 201.115 from the requirements of section 502(f)(1) of the FD&C Act. By offering these drugs for sale to U.S. consumers, your websites are causing the introduction of misbranded drugs into interstate commerce in violation of section 301(a) of the FD&C Act [21 U.S.C. § 331(a)].
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FDA is taking this action against Bulk2USA because of the inherent risk to consumers who purchase unapproved new drugs and misbranded drugs. Unapproved new drugs do not have the same assurance of safety and effectiveness as those drugs subject to FDA oversight, and drugs that have circumvented regulatory safeguards may be contaminated, counterfeit, contain varying amounts of active ingredients, or contain different ingredients altogether.
This letter is not intended to identify all the ways in which your activities might be in violation of law. It is your responsibility to ensure that all products that you market are in compliance with the FD&C Act and its implementing regulations. You should take prompt action to correct the violations noted above as well as any other violations of the FD&C Act (which would include the offer for sale of all unapproved and/or misbranded drug products by your websites, not just the products noted above). Failure to correct violations may result in FDA regulatory action, including seizure or injunction, without further notice.
Please notify this office in writing within 10 working days of receipt of this letter of any steps you have taken or will take to correct the violations set forth above and to prevent their recurrence.
If the corrective action(s) cannot be completed within 10 working days, state the reason for the delay and the time within which the correction(s) will be completed. Your response and any other inquiries concerning this letter should be sent to FDA’s Internet Pharmacy Task Force at FDAInternetPharmacyTaskForce-CDER@fda.hhs.gov
Table of Websites:
Office of Drug Security, Integrity, and Response
Office of Compliance
Center for Drug Evaluation and Research
Food and Drug Administration
 Prescription Drug Products Containing Acetaminophen: Actions to Reduce Liver Injury from Unintentional Overdose, FDA-2011—N-0021, January 14, 2011.