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  5. Honest Globe, Inc. - 597177 - 03/15/2021
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WARNING LETTER

Honest Globe, Inc. MARCS-CMS 597177 —

Product:
Drugs
Recipient:
Honest Globe, Inc.

3605 West Macarthur Boulevard, Suite 701
Santa Ana, CA 92704-6845
United States

Issuing Office:
Division of Pharmaceutical Quality Operations IV

United States

WARNING LETTER

March 15, 2021

Dear Mr. Kotler:

The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, Honest Globe, Inc., FEI 3015667771, at 3605 West Macarthur Boulevard, Suite 701, Santa Ana, from October 4 to 8, 2019.

This warning letter summarizes significant violations of current good manufacturing practice (CGMP) regulations for finished pharmaceuticals. See Title 21 Code of Federal Regulations (CFR), parts 210 and 211 (21 CFR parts 210 and 211).

Because your methods, facilities, or controls for manufacturing, processing, packing, or holding do not conform to CGMP, your drug products are adulterated within the meaning of section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 351(a)(2)(B).

This letter is to advise you that the FDA reviewed your website at www.elixicure.com and has determined that you take orders there for the products “ELIXICURE ORIGINAL PAIN RELIEF with CBD” (roll-on and pump versions) and “ELIXICURE LAVENDER PAIN RELIEF with CBD” (roll-on and pump versions) (hereinafter referred to as “ELIXICURE PAIN RELIEF with CBD” products). Your “ELIXICURE PAIN RELIEF with CBD” products are labeled to contain cannabidiol (CBD)1 and are made available for purchase by consumers without a prescription.

Your “ELIXICURE PAIN RELIEF with CBD” products are unapproved new drugs introduced or delivered for introduction into interstate commerce in violation of sections 505(a) and 301(d) of the FD&C Act, 21 U.S.C. 355(a) and 331(d). Furthermore, your “ELIXICURE PAIN RELIEF” products are misbranded drugs introduced or delivered for introduction into interstate commerce in violation of sections 502(a), 502(ee), and 301(a) of the FD&C Act, 21 U.S.C. 352(a), 352(ee), and 331(a).

Currently, a nonprescription drug product containing CBD cannot be legally marketed without an approved new drug application, regardless of whether the CBD is represented on the labeling as an active ingredient or an inactive ingredient. To date, no CBD-containing drug has met applicable FDA requirements to be legally marketed for nonprescription use. As explained below, nonprescription drug products that include CBD as an active ingredient are not generally recognized as safe and effective (GRASE) and are new drugs which require an approved application to be legally marketed.

Furthermore, even if CBD could be considered an inactive ingredient in a nonprescription drug product, that product would still need an approved new drug application to be legally marketed, because the product would not meet the general requirements for nonprescription drug products under section 505G of the FD&C Act. In particular, such product would not meet the general requirement with respect to the safety and suitability of inactive ingredients under 21 CFR 330.1(e).

Current Good Manufacturing Practice (CGMP) Charges

We reviewed your October 30, 2019, response to our Form FDA 483 in detail.

During our inspection, our investigator observed specific violations including, but not limited to, the following.

1. Your firm failed to establish an adequate quality control unit, and the responsibilities and procedures applicable to the quality control unit are not in writing and fully followed (21 CFR 211.22(a) and 211.22(d)).

Your Quality Unit (QU) lacked control over your topical over-the-counter drug manufacturing operations and failed to ensure that you had adequate procedures. For example, your QU failed to:

  • Evaluate product quality before batch release. Your firm obtained out-of-specification (OOS) camphor assay release testing results and then sent additional samples from these batches to your contract testing laboratory until passing results were obtained. You reported the passing results and released these batches to the market without investigating release testing assay failures.
  • Exercise adequate independent authority over manufacturing operations. Production staff interchangeably perform manufacturing activities and quality approval of manufacturing steps and batch release.
  • Establish procedures describing critical oversight responsibilities including, but not limited to, the following: batch review and release, developing and assessing corrective and preventive actions, implementing change controls, and establishing the reliability of component supplier analyses.

In your response, you committed to working with your contract laboratory to investigate the cited OOS results and future OOS results. Your response is inadequate because you did not address your responsibilities to investigate potential manufacturing deficiencies that may have led to the OOS results. Your response also failed to evaluate batches with OOS test results that had been distributed and were still within expiry.

Additionally, in your response, you designated (b)(4) to execute the independent Quality Assurance (QA) functions of the organization and committed to revise applicable procedures to reflect QA’s oversight responsibilities. However, the revised QA procedures you proposed only pertain to who is allowed to render final quality decisions. You have not proposed new or revised procedures that govern other deficient aspects of your QU, such as investigating deviations, developing corrective actions and preventive actions, implementing change controls, and auditing component suppliers’ test results.

Without adequate quality procedures and oversight, you cannot ensure the consistency of your manufacturing processes and the purported identity, strength, quality, and purity of drug products released to the market.

In response to this letter, provide the following:

  • An audit of all released batches for deviations and OOS results that have not been investigated. Also provide the status of any resulting investigations and retain testing, and your action plan to address any product quality or patient safety risks for your drug products in U.S. distribution within expiry, including potential customer notifications and recalls.
  • An audit of all incoming component specifications and necessary revisions to ensure that all components have appropriate written specifications for purity, strength, and quality.
  • A comprehensive assessment and remediation plan to ensure your QU is given the authority and resources to effectively function. The assessment should also include, but not be limited to:

  o A determination of whether procedures used by your firm are robust and appropriate.
  o The creation or revision of necessary standard operating procedures (SOPs).
  o Training and effectiveness plans to ensure QU procedures are followed for existing, new, and revised SOPs.
  o Provisions for QU oversight throughout your operations to evaluate adherence to appropriate practices, including but not limited to during manufacturing operations.
  o A complete and final review of each batch and its related information before the QU disposition decision.
  o Oversight and approval of investigations and discharging of all other QU duties to ensure identity, strength, quality, and purity of all products.

2. Your firm failed to prepare batch production and control records that include documentation of the accomplishment of each significant step in the manufacture, processing, packing, or holding of the batch, for each batch of drug product (21 CFR 211.188(b)).

Your batch production and control records lack adequate manufacturing details including, but not limited to, the following: weights of charged components, mixing times, mixing speeds, measured temperatures, hold times, amounts removed for in-process testing, in-process observations and testing results, and filling machine settings. Your current practice is to use manufacturing checklists without complete instructions. These checklists do not allow for the documentation of manufacturing information.

In your response, you committed to assessing the master production record for only the “ELIXICURE ORIGINAL FORMULA” to ensure steps are adequately defined and documented. Your response is inadequate. Your response does not provide sufficient information about how you plan to identify missing manufacturing information from distributed batches for all products, review your current documentation practices for deficiencies, make updates to master production records for all products, or how you will revise SOPs to comply with CGMP documentation requirements.

Completed batch production and control records are necessary to ensure that manufacturing processes are consistently followed and reproducible. Additionally, incomplete manufacturing records deprive you of the ability to adequately investigate deviations and batch failures.

In response to this letter, provide the following:

  • A retrospective analysis and gap assessment of your executed production records for both “ELIXICURE ORIGINAL” and “ELIXICURE LAVENDER” to identify all missing production information.
  • Revised master production records for all your drug products to demonstrate that, when executed, they fully document each manufacturing step.
  • A complete assessment of documentation systems used throughout your manufacturing and laboratory operations to determine where documentation practices are insufficient. Include a detailed corrective action and preventive action plan that comprehensively remediates your firm’s documentation practices to ensure you retain attributable, legible, complete, original, accurate, and contemporaneous records throughout your operation.

3. Your firm failed to establish written procedures for production and process control designed to assure that the drug products you manufacture have the identity, strength, quality, and purity they purport or are represented to possess, and your firm’s quality control unit did not review and approve those procedures, including any changes (21 CFR 211.100(a)).

Your firm failed to adequately qualify the equipment and validate the processes used to manufacture your drug products. You have not performed process performance qualification (PPQ) studies, nor do you have an ongoing program for monitoring process control to ensure stable manufacturing operations and consistent drug quality for products in U.S. distribution.

In your response, you committed to performing Installation Qualification (IQ) and Operational Qualification (OQ) for (b)(4) pieces of equipment and to qualify secondary packaging equipment with the assistance of a CGMP consultant. However, you did not provide details about how you plan to assess and establish equipment requirements for your manufacturing processes and how you will accordingly design appropriate equipment qualification protocols. Finally, you committed to drafting and completing a PPQ protocol but did not provide details about the study design and how it will demonstrate process robustness.

Process validation evaluates the soundness of design and state of control of a process throughout its lifecycle. Each significant stage of a manufacturing process must be designed appropriately and ensure the quality of raw material inputs, in-process materials, and finished drugs. Failure to conduct these studies can result in product quality attribute failures. Process qualification studies determine whether an initial state of control has been established. Successful process qualification studies are necessary before commercial distribution. Thereafter, ongoing vigilant oversight of process performance and product quality is necessary to ensure you maintain a stable manufacturing operation throughout the product lifecycle.

See FDA’s guidance document Process Validation: General Principles and Practices for general principles and approaches that FDA considers appropriate elements of process validation at https://www.fda.gov/media/71021/download.

In response to this letter, provide the following:

  • An assessment of each drug product process to ensure that there is a data-driven and scientifically sound program to identify and control all sources of variability, such that your production processes will consistently meet appropriate specifications and manufacturing standards. This includes, but is not limited to, evaluating suitability of equipment for its intended use, sufficiency of detectability in your monitoring and testing systems (including analytical methods used by you and contract testing labs), quality of input materials, and reliability of each manufacturing process step and controls.
  • A detailed summary of your validation program for ensuring a state of control throughout the product lifecycle, along with associated procedures. Describe your program for process performance qualification, and ongoing monitoring of both intra-batch and inter-batch variation to ensure a continuing state of control.
  • Your PPQ protocols, and written procedures for qualification of equipment and facilities.
  • A timeline for performing PPQ for each of your marketed drug products.

CGMP Consultant Recommended

In your response, you noted that you engaged a third-party consultant but you did not define the scope of the relationship. Based upon the nature of the violations we identified at your firm, we strongly recommend engaging a consultant qualified as set forth in 21 CFR 211.34 to assist your firm in meeting CGMP requirements.

Your use of a consultant does not relieve your firm’s obligation to comply with CGMP. Your firm’s executive management remains responsible for resolving all deficiencies and systemic flaws to ensure ongoing CGMP compliance.

Unapproved New Drugs Charges

Based on our review of your product labeling, including your website, www.elixicure.com, your “ELIXICURE PAIN RELIEF with CBD” products are drugs under section 201(g)(1) of the FD&C Act, 21 U.S.C. 321(g)(1), 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 any function of the body.

Examples of claims on your product labeling, including your website (where your products can be purchased) that provide evidence of the intended uses (as defined by 21 CFR 201.128) of your “ELIXICURE PAIN RELIEF with CBD” products as drugs include, but may not be limited to, the following:

On your website under “WHY ELIXICURE?” found at https://elixicure.com/cbd-pain-relief-hemp-organic-natural-medicine-why-elixicure/:

“DEEP-PENETRATING NATURAL PAIN RELIEF . . . NON-ADDICTIVE PAIN RELIEF > Muscle Strains > Back Aches > Neck Pain > Cramps > Arthritis > Tendonitis . . . Elixicure is the world’s first CBD-infused over the counter (OTC) topical pain relief cream product . . . Elixicure leverages nanotechnology in order to create cutting-edge pain relief products . . . powerful pain relief and all natural qualities of Elixicure. . . Elixicure uses only the purest hemp CBD extract for it’s (sic) variety of CBD-infused pain relief products and all of our products contain absolutely zero percent THC. . .”

On your website under “OUR STORY” found at https://elixicure.com/our-story/:

“Elixicure – the world’s first all natural CBD-infused pain relief cream.”

On your website under “ELIXICURE CBD PRODUCTS” found at https://elixicure.com/elixicure-cbd-products/:

“OUR CBD PAIN RELIEF PRODUCTS USE THE THE [sic] SAME HIGH QUALITY NATURAL INGREDIENTS AS OUR STANDARD PAIN RELIEF SOLUTION BUT WITH CBD ADDED. PLANT-BASED PAIN RELIEF WITH PREMIUM HEMP CBD.”

In your product brochure found on your website at https://elixicure.com/brochure/:

“In 2018, CBD was approved by the FDA as a medicinal compound for treating rare forms of epilepsy in the drug Epiodiolex and has since been studied for its effects on inflammation, arthritic pain, neuropathy, anxiety, nausea and more.”

“What are the Health Benefits of CBD? . . . Benefits of activating the CB1 receptors may include: relieving depression, lowering anxiety, lowering blood pressure, lowering intestinal inflammation and more.”

On your website under "CBD FAQs…How does CBD Work?" at https://elixicure.com/cbd-faq/ :

CBD functions by binding to cannabinoid receptors in the body’s endocannabinoid system. These receptors have been found in virtually every cell and tissue type in the human body (hence the seemingly endless array of CBD uses).

On your website under "What is CBD?" at https://elixicure.com/what-is-cbd-page/ :

CBD AND YOUR ENDOCANNABINOID SYSTEM

Your Endocannabinoid System (ECS) plays an important role in keeping your internal processes stable. According to the National Institute of Health, introducing external cannabinoids like CBD into the ECS could be useful in treating a variety of medical ailments, including pain and inflammation.

Claims observed on your Instagram social media site at https://www.instagram.com/elixicure/?hl=en:

“Did you know that Elixicure was the first over-the-counter CBD-infused topical pain cream product to receive FDA certified registration. Our all natural plant-based ingredients, like organic menthol, are strong enough for even your toughest pain. That lavender though! Believed to have antiseptic and anti-inflammatory properties, which can help to heal minor burns and bug bites. Research suggests that it may be useful for treating anxiety, insomnia, depression, and restlessness. Camphor has a wide variety of topical uses due to its antibacterial, anti-fungal, and anti-inflammatory properties. It can be used to treat skin conditions, improve respiratory function, and relieve pain.”

Based on the above labeling claims, your “ELIXICURE PAIN RELIEF with CBD” products are drugs intended for use as external analgesics. We are not aware of any adequate and well-controlled clinical studies in the published literature that support a determination that your "ELIXICURE PAIN RELIEF with CBD” products are GRASE for use under the conditions suggested, recommended, or prescribed in their labeling. Thus, your “ELIXICURE PAIN RELIEF with CBD” products are “new drugs” within the meaning of section 201(p) of the FD&C Act, 21 U.S.C. 321(p).

New drugs 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), unless they are nonprescription drugs governed by and lawfully marketed under section 505G2 of the FD&C Act, among other exceptions not applicable here. No FDA-approved application pursuant to section 505 of the FD&C Act, 21 U.S.C. 355, is in effect for any of these external analgesic products, nor do they meet the requirements for marketing without an approved application under section 505G of the FD&C Act, as described below. Accordingly, these products 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).

Section 505G of the FD&C Act governs nonprescription drugs marketed over-the-counter (or "OTC") without an approved drug application, such as your “ELIXICURE PAIN RELIEF with CBD” products.3 Under section 505G, certain nonprescription drug products may be lawfully marketed without an approved application if applicable requirements are met. However, your “ELIXICURE PAIN RELIEF with CBD” products do not meet the requirements for marketing under section 505G.

Specifically, they do not meet the applicable conditions under section 505G(a)(1) or (2) of the FD&C Act, 21 U.S.C. 355h(a)(1), (2), under which nonprescription drugs marketed without an approved application are deemed GRASE and not considered “new drugs” by operation of law.

Among these conditions is that a drug conforms with the general requirements for nonprescription drugs and that it conforms with the requirements for nonprescription use of a final monograph issued under 21 CFR part 330 or, for drugs classified in Category I for safety and effectiveness under a tentative final monograph (TFM), that a drug conforms with the proposed requirements of such TFM. Your “ELIXICURE PAIN RELIEF with CBD” products do not meet these conditions, notably because their active ingredient CBD was not an active ingredient in any applicable final monograph or TFM.4

Although CBD is listed as an inactive ingredient in the labels of your “ELIXICURE PAIN RELIEF with CBD” products, the product labeling clearly represents CBD as an active ingredient, which is a component of a drug intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease, or to affect the structure or function of the body (see 21 CFR 201.66(b)(2)).

For instance, your product labels and website repeatedly highlight the “benefits of CBD” for various conditions (see above claims), include numerous references to CBD with images of cannabis plants; repeatedly feature the product names "Elixicure Pain Relief with CBD [Wintergreen/Lavender/Original] ”; and prominently feature CBD on the principal display panels of all of your “ELIXICURE PAIN RELIEF with CBD” products. Further, on your webpage entitled “What’s the Best CBD Dosage?” you discuss how to determine the best quantity of CBD to use. On your webpage entitled "Why Elixicure?", your labeling even refers to CBD as “active” and “medicinal” when it describes CBD as “one of the main active chemical compounds naturally found in the hemp plant and contributes to the many beneficial medicinal qualities of medical hemp.”

Even if CBD could be considered an inactive ingredient in your "ELIXICURE PAIN RELIEF with CBD" products, these products would still need an approved drug application to be legally marketed because they would not meet the requirements for marketing under section 505G of the FD&C Act. In particular, these products would not meet the conditions under section 505G(a)(1) or (2), insofar as they would not conform with the general requirement in 21 CFR 330.1(e) that inactive ingredients must be safe and suitable.5 A suitable inactive ingredient generally provides a beneficial formulation function, such as a tablet binder or preservative, or improves product delivery (e.g., enhances absorption or controls release of the drug substance).6 CBD has no known functional role as an inactive ingredient in a finished drug product.

Additionally, an inactive ingredient should not exert pharmacological effects7 and must be safe when used at the intended dosage.8 CBD, however, has known pharmacological activity with demonstrated risks.9 It is unknown whether the levels of CBD used in your “ELIXICURE PAIN RELIEF with CBD” products have pharmacological activity or pose any concern for safety events.

Accordingly, CBD cannot be considered a safe and suitable inactive ingredient as required under 21 CFR 330.1(e). Consequently, if CBD is intended to be an inactive ingredient in your "ELIXICURE PAIN RELIEF with CBD" product, that product would not meet the general requirements for nonprescription drugs needed for legal marketing under sections 505G(a)(1) or (2).

Your “ELIXICURE PAIN RELIEF with CBD” products also do not meet the conditions under section 505G(a)(1) and (2) to be deemed GRASE and not "new drugs" by operation of law because the labeling for these products includes indications such as “relieving depression,” “lowering anxiety,” “lowering blood pressure,” and “lowering intestinal inflammation.” These indications were not covered under any applicable final monograph or TFM.10

In addition, your “ELIXICURE PAIN RELIEF with CBD” products do not meet the other conditions under section 505G under which nonprescription drug products can be lawfully marketed without an approved application. Specifically, they do not satisfy the requirements under section 505G(a)(3)11 nor is their marketing permitted by an order issued under section 505G(b).12

For the reasons described above, your “ELIXICURE PAIN RELIEF with CBD” products 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), 331(d).

Misbranded Drugs Charges

Your “ELIXICURE PAIN RELIEF with CBD” products are misbranded drugs introduced or delivered for introduction into interstate commerce in violation of sections 502 and 301(a) of the FD&C Act, 21 U.S.C. 352(a), 21 U.S.C. 331(a). Because your “ELIXICURE PAIN RELIEF with CBD” products 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 an application approved under section 505 of the FD&C Act, 21 U.S.C. 355, these products are misbranded under section 502(ee) of the FD&C Act, 21 U.S.C. 352(ee).

Your “ELIXICURE PAIN RELIEF” products are also misbranded under section 502(a) of the FD&C Act because the labeling of these products is false and misleading for several reasons.

First, the labeling for these products identifies CBD as an inactive ingredient but represents CBD as having purported active pharmacological properties such as pain relief, among others.

Even if CBD could be considered an inactive ingredient in these products, the prominent featuring of CBD on the labeling of your “ELIXICURE PAIN RELIEF” products causes the products to be misbranded under section 502(a) of the FD&C Act, which deems a drug to be misbranded if its labeling is “false or misleading in any particular,” and under 21 CFR 201.10(c)(4). Under 21 CFR 201.10(c)(4), “[t]he labeling of a drug may be misleading by reason … [of] the featuring in the labeling of inert or inactive ingredients in a manner that creates an impression of value greater than their true functional role in the formulation.”

Further, your firm’s website misleadingly implies that FDA has endorsed or approved the products in some manner. For example, you use such claims as “Elixicure is the world's first over the counter (OTC) CBD-infused topical pain cream product to have a certified registration with the Food and Drug Administration (FDA)” and “Elixicure is FDA registered and certified by GMP and BSCG.”13 Your product labels also state “FDA registered.” Additionally, your firm issued a press release that is available from your Instagram site that states, “Elixicure's Over-The-Counter Drug Registration has been Certified by the U.S. Food and Drug Administration (FDA) for its Elixicure CBD-Infused Pain Relief products following a successful year-long process . . . This marks the very first, and currently only, Over-The-Counter (OTC) Topical drug with Cannabidiol (CBD) to be registered and certified to date.”14

To state that any drug product is “FDA registered” is inaccurate; drugs are subject to listing with FDA, not registration. Moreover, registration of an establishment or listing of a drug does not denote approval of the establishment, the drug, or any other drugs of the establishment, nor does it mean that a product may be legally marketed. (21 CFR 207.77(a)). The general public is not likely to be familiar with the details of FDA regulation.

The assertion of “certified registration with the Food and Drug Administration” and “FDA registered” status in conjunction with your products misleadingly suggests that your “ELIXICURE PAIN RELIEF with CBD” products are approved or endorsed by FDA in some way when this is not true. Any representation that creates an impression of official approval or that a drug is approved or is legally marketable because of registration or listing is misleading and constitutes misbranding. (Id.)

Accordingly, your “ELIXICURE PAIN RELIEF with CBD” products are misbranded drugs introduced or delivered for introduction into interstate commerce in violation of sections 502(a), 502(ee), and 301(a) of the FD&C Act, 21 U.S.C. 352(a), 352(ee), and 331(a).

Conclusion

The violations cited in this letter are not intended to be an all-inclusive list of violations that exist at your facility or an all-inclusive statement of violations that exist in connection with your marketed products. 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 and FDA regulations.

Correct the violations cited in this letter promptly. Failure to promptly correct these violations may result in legal action without further notice, including, without limitation, seizure and injunction.

FDA may also withhold approval of requests for export certificates and approval of pending new drug applications or supplements listing your facility as a supplier or manufacturer until the above violations are corrected. We may re-inspect to verify that you have completed your corrective actions.

This letter notifies you of our findings and provides you an opportunity to address the above deficiencies. After you receive this letter, respond to this office in writing within 15 working days. Specify what you have done since our inspection to address any violations and to prevent their recurrence. In response to this letter, you may provide additional information for our consideration as we continue to assess your activities and practices. If you cannot completely address these violations within 15 working days, state your reasons for delay and your schedule for completion.

If you believe that your products are not in violation of the FD&C Act, include your reasoning and any supporting information for our consideration.

Your response should refer to unique identifier CMS 597177 and be sent electronically to ORAPHARM4_Responses@fda.hhs.gov or mailed to:

CDR Steven E. Porter, Jr.
Director, Division of Pharmaceutical Quality Operations IV
U.S. Food and Drug Administration
19701 Fairchild Road
Irvine, CA 92612

If you have any questions regarding this letter, please contact LCDR Rumany Penn, Compliance Officer, at 301-633-6789, or by email at Rumany.Penn@fda.hhs.gov.

Sincerely,
/S/

CDR Steven E. Porter, Jr
Director, Division of Pharmaceutical Quality Operations IV

________________________

1 Your firm uses “hemp CBD extract” interchangeably with “CBD” and “cannabidiol.” In this letter we refer to all these ingredients as CBD.

2 Section 505G of the FD&C Act was added under title III, subtitle F ("Over-the-Counter Drugs") of the CARES Act, Pub. L 116-136 (March 27, 2020).

3 As noted above, your "ELIXICURE PAIN RELIEF with CBD" products are made available for purchase by consumers without a prescription and their labels include ostensible "Drug Facts", which is part of the content and format required for OTC drug labeling under 21 CFR 201.66.

4 We note that OTC drug products intended for external analgesic indications, such as the temporary relief of pain, were addressed in the Tentative Final Monograph (TFM) for External Analgesic Drug Products for Over-the-Counter Human Use (external analgesic TFM; 48 FR 5852, February 8, 1983). CBD was not included as an active ingredient under this TFM.

5 21 CFR 330.1(e) requires that "the product contains only suitable inactive ingredients which are safe in the amounts administered and do not interfere with the effectiveness of the preparation or with suitable tests or assays to determine if the product meets its professed standards of identity, strength, quality, and purity."

6 See, e.g., "Using the Inactive Ingredient Database" Guidance for Industry (July 2019), p. 1 at https://www.fda.gov/media/128687/download, and "Nonclinical Studies for the Safety Evaluation of Pharmaceutical Excipients" Guidance for Industry (May 2005), pp. 1-2 at https://www.fda.gov/media/72260/download.

7 See, e.g., 21 CFR 314.3(b) and 21 CFR 210.3(b)(7), which define an active ingredient as “any component that is intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease, or to affect the structure or any function of the body of man.” All other components of a finished drug product are considered inactive ingredients (see CFR 314.3(b), 21 CFR 210.3(b)(8)).

8 See 21 CFR 330.1(e).

9 For example, the labeling for Epidiolex (cannabidiol) prescription oral solution includes risks for the drug such as liver injury, interactions with other drugs or supplements, potential for male reproductive toxicity, somnolence, insomnia, diarrhea, decreased appetite, abdominal pain, upset stomach, changes in mood, irritability, and agitation. See https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/210365s005s006s007lbl.pdf.

10 See Tentative Final Monograph (TFM) for External Analgesic Drug Products for Over-the-Counter Human Use (external analgesic TFM; 48 FR 5852, February 8, 1983). As noted above, the indications “relieving depression,” “lowering anxiety,” “lowering blood pressure,” and “lowering intestinal inflammation” were not covered under this TFM.

11 Under 505G(a)(3) of the FD&C Act, drugs that were classified as Category III for safety or effectiveness in a TFM that is the most recently applicable proposal or determination issued under 21 CFR Part 330 -- and that were not classified as Category II for safety or effectiveness -- are not required to have an approved application under section 505 in order to be marketed, as long as they are in conformity with the relevant conditions of use outlined in the applicable TFM, including labeling conditions, and comply with all other applicable requirements for nonprescription drugs. Drugs containing CBD as an active ingredient were not classified under any applicable TFM as Category III for safety and effectiveness. Thus, your “ELIXICURE PAIN RELIEF with CBD” products do not meet the conditions under section 505G(a)(3) for lawful marketing absent an approved application.

12 Your “ELIXICURE PAIN RELIEF with CBD” products are not the subject of an order issued under section 505G(b)(1) of the FD&C Act, 21 U.S.C 355h(b)(1), under which they are considered GRASE and can be lawfully marketed without an approved application.

13 See https://elixicure.com/certified-quality/

14 See https://www.prnewswire.com/news-releases/elixicure-cbd-infused-pain-relief-product-receives-fda-certification-300995041.html

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