Amazon.com, Inc.

This letter concerns your firm’s distribution of products that violate the Federal Food, Drug, and Cosmetic Act (the “FD&C Act”). The United States Food and Drug Administration (FDA) purchased on your website, www.amazon.com, external analgesic drug products intended to be used prior to sensitive cosmetic procedures. As discussed further below, your firm is responsible for introducing or delivering for introduction into interstate commerce these products, which are unapproved new drugs under section 505(a) of the FD&C Act, 21 U.S.C. 355(a). These products are also misbranded under section 502(ee) of the FD&C Act, 21 U.S.C. 352(ee). As explained further below, introducing or delivering these products for introduction into interstate commerce is prohibited under sections 301(a) and (d) of the FD&C Act, 21 U.S.C. 331(a) and (d).

FDA purchased “Painless Tattoo: Tattoo Numbing Cream,” “Ink Scribd: Numbing Cream,” “Nupharmisto: Tattoo Numbing Cream,” “QWP: Painless Tattoo,” “Kaisasa: Tattoo Numbing Cream,” “Painless Tattoo: Tattoo Triple Numb,” and “TKTX 40%” through your website, www.amazon.com.

These products, which are drugs as defined by section 201(g)(1) of the FD&C Act, 21 U.S.C. 321(g)(1), were introduced or delivered for introduction into interstate commerce by Amazon via your Fulfillment by Amazon service.1

These products are marketed as, among other things,2 external analgesics to be used before, during, and/or after various sensitive cosmetic procedures such as tattooing, piercing, and laser hair removal. FDA has safety concerns about external analgesic drug products formulated with active ingredients at concentrations that exceed levels currently permitted for nonprescription external analgesic products, because they are intended to be used before or during certain cosmetic procedures in ways that could lead to increased absorption of the drug product through the skin. FDA is aware that use of these products before and/or during a cosmetic procedure may not be supervised by trained health professionals. Without this supervision, large amounts of topical analgesics may be applied to a person’s skin. FDA has specifically warned in multiple public health advisories3 about the use of similar lidocaine and other “-caine” type ingredient products when applied over large areas of skin, particularly on irritated or broken skin, for prolonged periods of time, and when the skin is covered after application. These uses increase the amount of active ingredient that passes into the bloodstream and, if used improperly, may cause serious injury.

“Painless Tattoo: Tattoo Numbing Cream,” “Ink Scribd: Numbing Cream,” “Nupharmisto: Tattoo Numbing Cream,” “QWP: Painless Tattoo,” “Kaisasa: Tattoo Numbing Cream,” “Painless Tattoo: Tattoo Triple Numb,” and “TKTX 40%” are drugs as defined by section 201(g)(1)(B) of the FD&C Act, 21 U.S.C. 321(g)(1)(B), because they are intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease and/or under section 201(g)(1)(C) of the FD&C Act, 21 U.S.C. 321(g)(1)(C), because they are intended to affect the structure or any function of the body. Specifically, these products are primarily intended for use as external analgesic drug products for pain-sensitive cosmetic procedures.

Examples of claims from the product labeling that provide evidence of the intended uses (as defined in 21 CFR 201.128) of the products include, but may not be limited to, the following:

Painless Tattoo: Tattoo Numbing Cream:

“PAINLESS TATTOO: TATTOO NUMBING CREAM ALL GAIN NO PAIN TOPICAL ANESTHETIC . . . Drug Facts . . . Active Ingredients . . . Lidocaine 5% . . . Prilocaine 5% . . . Epinephrine 1% . . . Suggested Use . . . For the temporary relief of pain associated with itching, swelling, inflammation or discomfort . . . WE NUMB 􀆒 YOU RELAX 􀆒 ART HAPPENS” [from the product label]

Ink Scribd: Numbing Cream:

“INK SCRIBD . . . NUMBING CREAM . . . 5% LIDOCAINE . . . TATTOOING . . . HAIR REMOVAL . . . BODY PIERCING . . .” [from the product label]

Nupharmisto: Tattoo Numbing Cream:

“Nupharmisto . . . TATTOO NUMBING CREAM . . . DRUG FACTS . . . Active Ingredient . . . Lidocaine 5% . . . Uses: For the temporary alleviation of localized discomfort, pruritus, pain, or burning sensation in the perianal area associated with anorectal disorders. . .. Apply a thick layer of numbing cream to the treatment area, making sure to cover both the tattooed area and its surroundings.” [from the product label]

QWP: Painless Tattoo:

“PAINLESS TATTOO . . . NO PAIN FOREVER, JUST RELAX NOW! . . . Drug Facts . . . Active ingredient . . . Lidocaine 5% . . . Uses: For temporary relief of local discomfort, itching, pain, soreness or burning in the perianal area associated with anorectal disorders. . . For the best numbing effect, follow the application steps, apply the cream thickly and wrap the area with a tattoo film. . .” [from the product label]

Kaisasa: Tattoo Numbing Cream:

“KAISASA . . . TATTOO NUMBING CREAM . . . Drug Facts . . . Active Ingredient . . . Lidocaine 5% . . . Purpose . . . For temporary relief of local discomfort, itching, pain, soreness or burning related to the tattoo process.” [from the product label]

Painless Tattoo: Tattoo Triple Numb:

“PAINLESS TATTOO . . . Tattoo Triple Numb . . . TATTOOS . . . BURNS . . . FIRST AID . . . COSMETICS . . . BENZOCAINE 20% . . . LIDOCAINE 4% . . . TETRACAINE 2%” [from the product label]

TKTX 40%:

“Deep Numb . . . TKTX . . . 40% More Numbing . . . Ingredients . . . Lidocaine 5%, Prilccaine 5% [sic], Epinephrine 1%, Cream Base and so on. . .. Usable Range . . . Mcro [sic] Needle Pain Tattooing Body Piercing, Laser Tattoo Removal, Laser Hair Removal, Waxing, Permanent Cosmetics.” [from the product label]

Based on the above labeling, “Painless Tattoo: Tattoo Numbing Cream,” “Ink Scribd: Numbing Cream,” “Nupharmisto: Tattoo Numbing Cream,” “QWP: Painless Tattoo,” “Kaisasa: Tattoo Numbing Cream,” “Painless Tattoo: Tattoo Triple Numb,” and “TKTX 40%” are intended for use as external analgesic drugs, among other intended uses. As described below, these drugs are unapproved new drugs marketed in violation of sections 505(a) and 301(d) of the FD&C Act, 21 U.S.C. 355(a) and 331(d).

A drug product is a “new drug” within the meaning of section 201(p) of the FD&C Act, 21 U.S.C. 321(p), if it is not generally recognized as safe and effective (GRASE) for use under the conditions prescribed, recommended, or suggested in its labeling. With certain exceptions not applicable here, a new drug may not be introduced or delivered for introduction into interstate commerce without an approved application from FDA in effect, as described in section 505(a) of the FD&C Act, 21 U.S.C. 355(a). No FDA-approved applications pursuant to section 505 of the FD&C Act, 21 U.S.C. 355, are in effect for these drug products identified above.

Under section 505G of the FD&C Act, certain nonprescription drugs marketed without an approved application —commonly referred to as “over-the-counter (OTC) monograph drugs”—may be legally marketed if they meet applicable requirements. With respect to nonprescription external analgesic drug products, in order to be GRASE and not new drugs, the products must, among other things, conform to the conditions in the applicable OTC monograph(s), here Over-the-Counter Monograph M017: External Analgesic Drug Products for Over-the-Counter Human Use (hereinafter “M017” or the “external analgesics monograph”).4 However, the products your firm distributed do not conform to the conditions specified in M017 for the reasons described below.

The labeled concentrations and/or combinations for the active ingredients identified in product labeling for “Painless Tattoo: Numbing Cream,” “Ink Scribd: Numbing Cream,” “Nupharmisto: Tattoo Numbing Cream,” “QWP: Painless Tattoo,” “Kaisasa: Tattoo Numbing Cream,” “Painless Tattoo: Tattoo Triple Numb,” and “TKTX 40%” do not conform to the conditions of use set forth in M017. Specifically, lidocaine, an active ingredient labeled to be in all these products, is listed as lidocaine 5% or lidocaine hydrochloride 5% in all of these products except for “Painless Tattoo: Tattoo Triple Numb.” This concentration is above the 0.5% to 4% concentration range of lidocaine or lidocaine hydrochloride permitted by M017.10(a). Furthermore, “Painless Tattoo: Numbing Cream” includes a combination of lidocaine, prilocaine, and epinephrine as active ingredients in the same drug product; “Painless Tattoo: Tattoo Triple Numb” includes a combination of lidocaine, tetracaine, and benzocaine as active ingredients in the same drug product; and “TKTX 40%” includes a combination of lidocaine, prilocaine, and epinephrine as active ingredients in the same drug product. These combinations of active ingredients in a single external analgesic drug product are not permitted under M017.20.

Additionally, labeling for “Painless Tattoo: Tattoo Numbing Cream,” “Ink Scribd: Numbing Cream,” “Nupharmisto: Tattoo Numbing Cream,” “QWP: Painless Tattoo,” “Kaisasa: Tattoo Numbing Cream,” “Painless Tattoo: Tattoo Triple Numb,” and “TKTX 40%” includes indications that are not permitted indications for external analgesic drug products under M017.50(b). Indications related to tattooing and piercing are not included in M017 or any other final administrative order in accordance with section 505G. As stated in the introduction to this letter, we have safety concerns related to the use of these products for these indications due to the potential for greater absorption of the active ingredients through irritated or broken skin.

Thus, “Painless Tattoo: Tattoo Numbing Cream,” “Ink Scribd: Numbing Cream,” “Nupharmisto: Tattoo Numbing Cream,” “QWP: Painless Tattoo,” “Kaisasa: Tattoo Numbing Cream,” “Painless Tattoo: Tattoo Triple Numb,” and “TKTX 40%” do not comply with the applicable conditions specified in M017 and have not otherwise been found GRASE.5 Accordingly, these products are new drugs within the meaning of section 201(p) of the FD&C Act, 21 U.S.C. 321(p), and there is no basis under section 505G of the FD&C Act under which these products would be legally marketed without an approved application. Because there are no approved applications in effect for these products, these products are unapproved new drugs. The introduction or delivery for introduction into interstate commerce of these unapproved new drug products violates sections 505(a) and 301(d) of the FD&C Act, 21 U.S.C. 355(a) and 331(d).

“Painless Tattoo: Numbing Cream,” “Ink Scribd: Numbing Cream,” “Nupharmisto: Tattoo Numbing Cream,” “QWP: Painless Tattoo,” “Kaisasa: Tattoo Numbing Cream,” “Painless Tattoo: Tattoo Triple Numb,” and “TKTX 40%” are misbranded under section 502(ee) of the FD&C Act, 21 U.S.C. 352(ee), because they are nonprescription drugs subject to section 505G of the FD&C Act, 21 U.S.C. 355h, but do not comply with the requirements for marketing under that section and are not the subject of applications approved under section 505 of the FD&C Act, 21 U.S.C. 355. The introduction or delivery for introduction of a misbranded drug into interstate commerce is prohibited under section 301(a) of the FD&C Act, 21 U.S.C. 331(a).

The violations cited in this letter are not intended to be an all-inclusive statement of past or present violations that may exist in connection with the products you distribute. You are responsible for investigating and determining the causes of any violations and for preventing their recurrence or the occurrence of other violations. It is your responsibility to ensure that your firm complies with all requirements of federal law, including FDA regulations.

This letter notifies you of our concerns and provides you an opportunity to address them. Failure to adequately address this matter may result in legal action including, without limitation, seizure and/or injunction. Please notify FDA in writing, within 15 working days of receipt of this letter, of the specific steps you have taken to correct any violations. Include an explanation of each step being taken to prevent the recurrence of violations, including steps you will take to ensure that Amazon will no longer introduce, deliver, or cause the introduction or delivery for introduction into interstate commerce of unapproved external analgesic drug products intended to be used prior to sensitive cosmetic procedures, as well as copies of related documentation. If you believe that the products you distribute are not in violation of the FD&C Act, include your reasoning and any supporting information for our consideration.

Your response should be sent to U.S. Food and Drug Administration, CDER/OC/Office of Unapproved Drugs and Labeling Compliance by email to FDAAdvisory@fda.hhs.gov. Please include your firm name and the unique identifier “689355” in the subject line of the email.