WARNING LETTER
Dr. Brite, LLC
MARCS-CMS 684466 —
November 21, 2024
Delivery Method:
VIA UPS
Reference #:
320-25-20
Product:
Drugs
Recipient:
Recipient Name
Dr. Pooneh Ramezani, DDS, Dr. Paris Sabo, MD
Recipient Title
Owners
Dr. Brite, LLC
2700 S. Bristol Street #B
Santa Ana
,
CA
92704
United States
Issuing Office:
Center for Drug Evaluation and Research (CDER)
United States
Secondary Issuing Offices
United States
November 21, 2024
WARNING LETTER
Dear Drs. Ramezani & Sabo:
The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, Dr. Brite, LLC, 3016665985, at 1536 Kimberly Avenue, Fullerton, California from April 2 to 5, 2024.
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).
In addition, your “Dr. Brite® Kids Anti-Plaque Toothpaste, Hydroxyapatite, Berrylicious,” “Dr. Brite® Extreme Whitening Toothpaste, Hydroxyapatite, Fresh Mint,” “Dr. Brite® Healthy Gums Toothpaste, Vitamin C, Hydrating Mint,” “Dr. Brite® Kids Anti-Plaque Mouth Spray, Hydroxyapatite, Berrylicious,” and “Dr. Brite® Kids Mineral Mouth Spray, Hydroxyapatite, Strawberry Sky” products are unapproved new drugs introduced or delivered for introduction into interstate commerce in violation of sections 505(a) and 301(d) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 355(a), 331(d). Introduction or delivery for introduction of such products into interstate commerce is prohibited under sections 301(d) of the FD&C Act, 21 U.S.C. 331(d).
These products are also misbranded under section 502(ee) of the FD&C Act, 21 U.S.C. 352(ee). Furthermore, your “Dr. Brite® Hand Sanitizer Spray, Citrus, 70% Isopropyl Alcohol,” “Dr. Brite® Hand Sanitizer Spray, Eucalyptus, 70% Isopropyl Alcohol,” “Dr. Brite® Hand Sanitizer Spray, Unscented, 70% Isopropyl Alcohol,” “Dr. Brite® Citrus Hand Wipes, 70% Isopropyl Alcohol,” “Dr. Brite® Eucalyptus Hand Wipes, 70% Isopropyl Alcohol,” and “Dr. Brite® Unscented Hand Wipes, 70% Isopropyl Alcohol” products are misbranded drugs under section 502(c) of the FD&C Act, 21 U.S.C. 352(c). Introduction or delivery for introduction of such products into interstate commerce is prohibited under sections 301(a) of the FD&C Act, 21 U.S.C. 331(a). These violations are described in more detail below.
Furthermore, Dr. Brite, LLC (FEI: 3016665985) is not duly registered with FDA as required by section 510 of the FD&C Act and 21 CFR Part 207. In addition, Dr. Brite Hand Sanitizer Spray, Dr. Brite Extreme Whitening Toothpaste, Dr. Brite Healthy Gums Toothpaste, Dr. Brite Kids Anti-plaque Toothpaste, Dr. Brite Hand Wipes, Dr. Brite Kids Anti-plaque Mouth Spray, and Dr. Brite Kids Mineral Mouth Spray are not listed with FDA as required by section 510(j) of the FD&C Act.
Failure to register in accordance with section 510 of the FD&C Act and failure to provide listing information in accordance with 510(j) of the FD&C Act are prohibited under section 301(p) of the FD&C Act, 21 U.S.C. 331(p), and will render a drug misbranded under section 502(o) of the FD&C Act, 21 U.S.C. 352(o). 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). These violations are described in more detail below.
We have not received a response from your firm, after numerous requests, stating the actions you are taking to address the deficiencies identified during the inspection and cited on our Form FDA 483. During our inspection, our investigators observed specific violations including, but not limited to, the following.
CGMP Violations
1. Your firm failed to test samples of each component for identity and conformity with
all appropriate written specifications for purity, strength, and quality (21 CFR 211.84(d)(1)) and 211.84(d)(2)).
Your firm manufactures over-the-counter (OTC) drug products including toothpaste and mouth spray, some intended for children. Your firm failed to adequately test each shipment of your incoming components for identity, purity, strength, and quality before using the components to manufacture your drug products. Your firm’s process for accepting incoming components only consisted of visual examinations for leakage or damage, and verification of quantities received. Suppliers’ certificates of analysis (COAs) are not reviewed.
Glycerin
You failed to adequately test each shipment of each lot of glycerin for identity, a component at higher risk for diethylene glycol (DEG) and ethylene glycol (EG) contamination. We note that glycerin is an ingredient used in some of your oral drug products, including those intended for infants and children. Records collected during the inspection show that your firm received at least one lot of glycerin from a region with confirmed or suspected contamination with high levels of DEG and EG.
Identity testing of glycerin, along with other high-risk drug components include a limit test in the United States Pharmacopeia (USP) to ensure that the component meets the relevant safety limits for levels of DEG or EG. Because you did not perform identity testing on each shipment of each glycerin lot using the USP identification test that detects these hazardous impurities, you failed to assure the acceptability of these components for use in the manufacture of your drug products.
The use of ingredients contaminated with DEG or EG has resulted in various lethal poisoning incidents in humans worldwide. See FDA’s guidance document
Testing of Glycerin, Propylene Glycol, Maltitol Solution, Hydrogenated Starch Hydrolysate, Sorbitol Solution, and Other High-Risk Drug Components for Diethylene Glycol and Ethylene Glycol
to help you meet the CGMP requirements when manufacturing drugs containing ingredients at high-risk for DEG or EG contamination at https://www.fda.gov/media/167974/download.
In response to our request for additional information, you committed to test all incoming and reserve samples of glycerin used in the manufacture of drug products (within expiry) for DEG/EG.
Without adequate testing, you do not have scientific evidence that the components conform to appropriate specifications prior to use in the manufacture of your drug products. As a manufacturer, you have a responsibility to sample, test, and examine drug components before use in production to assure adequate quality.
In response to this letter, provide:
• A commitment to provide DEG and EG test results, no later than 30 calendar days from the date of this letter, from testing retains for all lots of high-risk drug components used in the manufacture of drug products. Alternatively, if a retain of a component lot is unavailable, perform retain sample testing of all implicated finished drug product batches for the presence of DEG and EG.
• A full risk assessment for drug products that are within expiry which contain any ingredient at risk for DEG or EG contamination (including, but not limited to, glycerin). Take prompt and appropriate actions to determine the safety of all lots of the component(s) and any related drug product that could contain DEG or EG, including customer notifications and product recalls for any contaminated lots. Identify additional appropriate corrective action and preventive action (CAPA) that secure supply chains in the future, including, but not limited to, ensuring that all incoming raw material lots are from fully qualified manufacturers and free from unsafe impurities. Detail these actions in your response to this letter.
• A description of how you will test each component lot for conformity with all appropriate specifications for identity, strength, quality, and purity. If you intend to accept any results from your supplier’s COA instead of testing each component lot for strength, quality, and purity, specify how you will robustly establish the reliability of your supplier’s results through initial validation as well as periodic revalidation. In addition, include a commitment to always conduct at least one specific identity test for each incoming component lot. In the case of glycerin, propylene glycol, and certain additional high-risk components we note that this includes the performance of parts A, B, and C of the USP monograph.
• The chemical quality control specifications you use to test each incoming lot of high-risk drug components to determine acceptability for use in manufacturing.
• A comprehensive, independent review of your material system to determine whether all suppliers of components, containers, and closures, are each qualified and the materials are assigned appropriate expiration or retest dates. The review should also determine whether incoming material controls are adequate to prevent use of unsuitable components, containers, and closures.
• A summary of results obtained from testing all components to evaluate the reliability of the COA from each component manufacturer. Include your standard operating procedure that describes this COA validation program.
• A summary of your program for qualifying and overseeing contract facilities that test the drug products you manufacture.
2. Your firm failed to have, for each batch of drug product, appropriate laboratory determination of satisfactory conformance to final specifications for the drug product, including the identity and strength of each active ingredient, prior to release. Your firm also failed to conduct, for each batch of drug product, appropriate laboratory testing, as necessary, required to be free of objectionable microorganisms (21 CFR 211.165(a) and 211.165(b)).
Your firm failed to conduct adequate finished product release testing for each batch of your oral drug products and hand sanitizer drug products, including but not limited to, testing the identity and strength of active ingredients, and testing for objectionable microorganisms.
Without adequate finished product release testing, you do not have scientific evidence that each batch of drug product conforms to appropriate specifications before release.
In response to this letter, provide a list of chemical and microbial test methods and specifications used to analyze each batch of your drug products before making a batch disposition decision, and the associated written procedures.
3. Your firm’s quality control unit failed to exercise its responsibility to ensure drug products manufactured are in compliance with CGMP, and meet established specifications for identity, strength, quality, and purity (21 CFR 211.22).
Your firm failed to establish an adequate quality unit (QU) with responsibilities to ensure adequate oversight for the manufacture of your drug products. For example, your QU failed to ensure:
• Appropriate production and process controls designed to assure drug products manufactured have the identity, strength, quality, and purity they are purported or represented to possess (21 CFR 211.100(a)).
• Establishment of an adequate stability program (21 CFR 211.137(a)).
• Batch production records were maintained (21 CFR 211.188).
• Adequate training for employees engaged in the manufacture, processing, packing, or holding of drug products (21 CFR 211.25(a)).
Your firm’s quality systems are inadequate. See FDA’s guidance document
Quality Systems Approach to Pharmaceutical CGMP Regulations
for help implementing quality systems and risk management approaches to meet the requirements of CGMP regulations 21 CFR, parts 210 and 211 at https://www.fda.gov/media/71023/download.
In response to this letter, provide 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:
• A determination of whether procedures used by your firm are robust and appropriate.
• Provisions for QU oversight throughout your operations to evaluate adherence to appropriate practices.
• A complete and final review of each batch and its related information before the QU disposition decision.
• Oversight and approval of investigations and discharging of all other QU duties to ensure identity, strength, quality, and purity of all products.
• Describe how top management supports quality assurance and reliable operations, including but not limited to, timely provision of resources to proactively address emerging manufacturing/quality issues and to assure a continuing state of control.
Unapproved New Drug and Misbranded Drug Violations
“Dr. Brite® Kids Anti-Plaque Toothpaste, Hydroxyapatite, Berrylicious”, “Dr. Brite® Extreme Whitening Toothpaste, Hydroxyapatite, Fresh Mint,” “Dr. Brite® Healthy Gums Toothpaste, Vitamin C, Hydrating Mint,” “Dr. Brite® Kids Anti-Plaque Mouth Spray, Hydroxyapatite, Berrylicious,” “Dr. Brite® Kids Mineral Mouth Spray, Hydroxyapatite, Strawberry Sky,” “Dr. Brite® Hand Sanitizer Spray, Citrus, 70% Isopropyl Alcohol,” “Dr. Brite® Hand Sanitizer Spray, Unscented, 70% Isopropyl Alcohol,” “Dr. Brite® Hand Sanitizer Spray, Eucalyptus, 70% Isopropyl Alcohol,” “Dr. Brite® Unscented Hand Wipes, 70% Isopropyl Alcohol,” “Dr. Brite® Citrus Hand Wipes, 70% Isopropyl Alcohol,” and “Dr. Brite® Eucalyptus Hand Wipes, 70% Isopropyl Alcohol” products 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.
Examples from product labeling, including on product labels and labeling from your website, www.drbrite.com, that provide evidence of intended use (as defined in 21 CFR 201.128) for these products include, but may not be limited to, the following:
All Dr. Brite® Oral Healthcare and Toothpaste Products containing Hydroxyapatite
“
Clinically Proven
Based on a study conducted by University of California, Irvine, Dr. Brite oral care is clinically-proven to better reduce plaque, gum inflammation, and gum bleeding than leading conventional oral care products.” [from your website at www.drbrite.com under Clinical Study tab on corresponding website pages for all Dr. Brite® oral healthcare products]
“Our star ingredient
HYDROXYAPATITE
! Hydroxyapatite is a naturally occurring mineral that makes up 97% of our tooth enamel and has been scientifically-proven to whiten, strengthen, and protect your teeth without fluoride. Our oral care features a 10% hydroxyapatite that is naturally-derived, vegan, and free of nano particles.” [from your website at www.drbrite.com under Key Ingredients tab on corresponding website pages for all Dr. Brite® oral healthcare products]
“Dr. Brite® Kids Anti-Plaque Toothpaste, Hydroxyapatite, Berrylicious”
“▪ Powerful & effective anti-plaque solution.” [from product label]
“Naturally derived calcium and hydroxyapatite gently polish away plaque and stains
to help keep your smile radiant and free of cavities…” [from product label]
“With Hydroxyapatite…Kids Anti-Plaque Toothpaste – Berrylicious…Our award-winning kid’s mineral toothpaste is specially made to strengthen and fight cavities, all without iffy ingredients. Our gentle formula is fluoride-free, …”  [from your website at https://www.drbrite.com/collections/toothpaste/products/kids-anti-plaque-toothpasteberrylicious?variant=41271826677820]
“Dr. Brite® Extreme Whitening Toothpaste, Hydroxyapatite, Fresh Mint”
“▪ Freshens breath and fights bacteria.”  [from product label]
“▪ Promotes oral health & remineralizes enamel.” [from product label]
“Dr. Brite® Healthy Gums Toothpaste, Vitamin C, Hydrating Mint”
“▪ Powerful & effective gum healing solution.” [from product label]
“…With our Healthy Gums Toothpaste you’ll kill all the bacteria that leads to gum disease and keep your gums looking healthy for a bright smile…” [from your website at https://www.drbrite.com/collections/toothpaste/products/healthy-gums-toothpastemint?variant=41271825989692]
“Dr. Brite® Kids Mineral Mouth Spray, Hydroxyapatite, Strawberry Sky”
“▪ Powerful & effective fluoride alternative.” [from product label]
“Remineralize teeth naturally with a healthy fluoride alternative that your kids will love. Hydroxyapatite helps restore and strengthen the tooth enamel and fight plaque while preventing cavities.” [from product label]
“Dr. Brite® Hand Sanitizer Spray, Citrus, 70% Isopropyl Alcohol”
[product name from principal display panel on product label]
“Dr. Brite® Hand Sanitizer Spray, Unscented, 70% Isopropyl Alcohol”
[product name from principal display panel on product label]
“Dr. Brite® Hand Sanitizer Spray, Eucalyptus, 70% Isopropyl Alcohol”
[product name from principal display panel on product label]
“Dr. Brite® Unscented Hand Wipes, 70% Isopropyl Alcohol,” “Dr. Brite® Citrus Hand Wipes, 70% Isopropyl Alcohol,” and “Dr. Brite® Eucalyptus Hand Wipes, 70% Isopropyl Alcohol”
“Dr. Brite Hand Sanitizer, Hand Sanitizer Spray, and Alcohol Wipes all contain 70% isopropyl alcohol (The CDC Recommended amount). Isopropyl can kill bacterial and viral cells at 70% strength. This is the perfect concentration level because it doesn’t evaporate too quickly and is very effective. Even though isopropyl is harsh on the bacteria, it remains soft on your skin and can even work as an antiseptic. IPA is also the common type of alcohol used by hospitals.” [from your website at https://www.drbrite.com/collections/hand-wipes/products/3-packunscented-alcohol-wipes?variant=32515477307452, under FAQs: What kind of alcohol is in your Hand Sanitizer, Hand Sanitizer Spray, and Alcohol Wipes?]
Unapproved New Drug Violations
Oral Healthcare Drug Products
Based on the above labeling evidence, your “Dr. Brite® Kids Anti-Plaque Toothpaste, Hydroxyapatite, Berrylicious,” “Dr. Brite® Extreme Whitening Toothpaste, Hydroxyapatite, Fresh Mint,” “Dr. Brite® Healthy Gums Toothpaste, Vitamin C, Hydrating Mint,” “Dr. Brite® Kids Anti-Plaque Mouth Spray, Hydroxyapatite, Berrylicious,” and “Dr. Brite® Kids Mineral Mouth Spray, Hydroxyapatite, Strawberry Sky” products are intended for use as over-the-counter (OTC) anticaries drug products and OTC antigingivitis/antiplaque drug products.
1
As described below, these drug 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).
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), unless it is lawfully marketed under section 505G of the FD&C Act. No FDA-approved applications pursuant to section 505 of the FD&C Act, 21 U.S.C. 355, are in effect for any of the drug products identified above.
As discussed above, some of the claims for your products are for anticaries use and others are for antigingivitis/antiplaque use. Because it is unclear whether you intend for your products to be used as an anticaries or an antigingivitis/antiplaque oral healthcare drug product, we address both below.
Under section 505G of the FD&C Act, certain nonprescription drugs marketed without an approved application —commonly referred to as "OTC monograph drugs"—may be legally marketed if they meet applicable requirements. With respect to nonprescription (OTC) anticaries drug products, in order to be GRASE and not new drugs, the product must, among other things, conform to the conditions of use set forth in the applicable OTC monograph(s). Anticaries drug products are addressed in the “Anticaries Drug Products for Over-the-Counter Human Use” (“M021").
2
However, the oral healthcare drug products identified above do not comply with the applicable conditions specified in MO21. Specifically, these products contain the active ingredient hydroxyapatite, which is not a permitted active ingredient under M021. 21 CFR 201.66(b)(2) defines “active ingredient” to mean “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 humans.” Although your firm does not specifically list hydroxyapatite as an active ingredient, your labeling for your oral healthcare drug products, such as your website, includes statements that claim hydroxyapatite is intended for the reduction or prevention against caries. Such statements demonstrate that hydroxyapatite is an “active ingredient” in your oral healthcare drug products because it is intended to furnish pharmacological activity in the diagnosis, cure mitigation, treatment, or prevention of disease. Thus, your oral healthcare drug products identified above do not comply with the conditions set forth in M021.
Antigingivitis/antiplaque oral healthcare drug products for OTC use are also subject to section 505G of the FD&C Act, 21 U.S.C. 355h. Under section 505G(a)(3) of the FD&C Act,
3
antigingitivits/antiplaque oral healthcare drug products for OTC use are not required to have an approved application in order to be marketed, as long as they conform to the conditions set forth in the 2003 advanced notice of proposed rulemaking (ANPR) entitled “Oral Health Care Drug Products for Over-the-Counter Human Use; Antigingivitis/Antiplaque Drug Products; Establishment of a Monograph”, 68 FR 32232 (May 29, 2003) (hereinafter “2003 ANPR”),
4
and comply with all other applicable requirements.
However, the oral healthcare drug products identified above do not conform with the conditions described in the 2003 ANPR, including acceptable active ingredients for antigingivitis/antiplaque drug products.
5
Specifically, as described above, hydroxyapatite is an active ingredient in the oral healthcare drug products identified above, based on the definition of “active ingredient” in 21 CFR 201.66(b)(2). However, hydroxyapatite is not a permitted active ingredient, by itself or in combination, under the 2003 ANPR for OTC antigingivitis/antiplaque drug products. Therefore, your oral healthcare drug products do not conform with the 2003 ANPR.
Thus, “Dr. Brite® Kids Anti-Plaque Toothpaste, Hydroxyapatite, Berrylicious,” “Dr. Brite® Extreme Whitening Toothpaste, Hydroxyapatite, Fresh Mint,” “Dr. Brite® Healthy Gums Toothpaste, Vitamin C, Hydrating Mint,” “Dr. Brite® Kids Anti-Plaque Mouth Spray, Hydroxyapatite, Berrylicious,” and “Dr. Brite® Kids Mineral Mouth Spray, Hydroxyapatite, Strawberry Sky” do not comply with the applicable conditions specified in M021 and have not otherwise been found GRASE.
6
Such products also do not meet the conditions described in the 2003 ANPR nor any other final order or proposed rulemaking. 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 of unapproved new drug products into interstate commerce violates sections 505(a) and 301(d) of the FD&C Act, 21 U.S.C. 355(a) and 331(d).
Misbranded Drug Violations
Oral Healthcare Drug Products
Additionally “Dr. Brite® Kids Anti-Plaque Toothpaste, Hydroxyapatite, Berrylicious,” “Dr. Brite® Extreme Whitening Toothpaste, Hydroxyapatite, Fresh Mint,” “Dr. Brite® Healthy Gums Toothpaste, Vitamin C, Hydrating Mint,” “Dr. Brite® Kids Anti-Plaque Mouth Spray, Hydroxyapatite, Berrylicious,” and “Dr. Brite® Kids Mineral Mouth Spray, Hydroxyapatite, Strawberry Sky” are misbranded under section 502(ee) of the FD&C Act, 21 U.S.C. 352(ee), because these 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.
Consumer Antiseptic Hand Rub Drug Products
Based on the above labeling evidence, your “Dr. Brite® Hand Sanitizer Spray, Citrus, 70% Isopropyl Alcohol,” “Dr. Brite® Hand Sanitizer Spray, Eucalyptus, 70% Isopropyl Alcohol,” “Dr. Brite® Hand Sanitizer Spray, Unscented, 70% Isopropyl Alcohol,” “Dr. Brite®, Citrus Hand Wipes, 70% Isopropyl Alcohol,” “Dr. Brite® Eucalyptus Hand Wipes, 70% Isopropyl Alcohol,” and “Dr. Brite® Unscented Hand Wipes, 70% Isopropyl Alcohol” products are intended for use as consumer antiseptic hand rub drug products. These products are misbranded under section 502 of the FD&C Act because the products are not labeled in accordance with the “Drug Facts” labeling requirements described in 21 CFR 201.66. Specifically, the labels for these products fail to include a Drug Facts panel. Therefore, these products are misbranded under section 502(c) of the FD&C Act, 21 U.S.C. 352(c).
The introduction or delivery for introduction of a misbranded drug into interstate commerce violates section 301(a) of the FD&C Act, 21 U.S.C. 331(a).
Establishment Registration and Drug Listing Violations
Dr. Brite, LLC manufactures drug products as detailed in an FDA inspection conducted during April 2-5, 2024. Under section 510(b) of the FD&C Act, 21 U.S.C. 360(b), and 21 CFR 207.17(a), all manufacturers must register each domestic establishment. Additionally, under 21 CFR 207.29, firms must review and update registration information annually or certify that there are no changes.
Dr. Brite, LLC (FEI: 3016665985) has not fulfilled its establishment registration obligations and its registration expired on December 31, 2023. Dr. Brite, LLC (FEI: 3016665985) is required to submit registration information annually by electronic means for each establishment it owns or operates that is engaged in the manufacture, preparation, propagation, compounding, or processing of a drug that is in commercial distribution in the United States. As a result, all drugs manufactured in this establishment, including but not limited to, Dr. Brite Hand Sanitizer Spray, Dr. Brite Extreme Whitening Toothpaste, Dr. Brite Healthy Gums Toothpaste, Dr. Brite Kids Anti-plaque Toothpaste, Dr. Brite Hand Wipes, Dr. Brite Kids Anti-plaque Mouth Spray, and Dr. Brite Kids Mineral Mouth Spray are misbranded under Section 502(o) of the FD&C Act, 21 U.S.C. 352(o).
In addition, every person who is required to register must, at the time of initial registration, list all drugs manufactured, prepared, propagated, compounded, or processed for commercial distribution under section 510(j)(1) of the FD&C Act, 21 U.S.C. 360(j)(1). Dr. Brite Hand Sanitizer Spray, Dr. Brite Extreme Whitening Toothpaste, Dr. Brite Healthy Gums Toothpaste, Dr. Brite Kids Anti-plaque Toothpaste, Dr. Brite Hand Wipes, Dr. Brite Kids Anti-plaque Mouth Spray, and Dr. Brite Kids Mineral Mouth Spray are not duly listed with FDA but remain in U.S. commercial distribution.
We note that your firm previously listed two drugs, Dr. Brite, LLC’s Protect Hand Sanitizer (NDC 74110-001) and Eucalyptus Hand Wipes (NDC 74110-002), that were not certified as required and therefore were inactivated as of January 31st, 2024. In accordance with section 510(j)(2) of the FD&C Act, 21 U.S.C. section 360(j)(2), and 21 CFR 207.57(b), registrants are required to submit updated drug listing information to FDA twice each year, in June and December, notifying FDA if this information has changed. Under 21 CFR 207.57(b)(2) registrants may satisfy the listing update requirement with respect to unchanged listing information by making a single no change certification during the October 1st through December 31st annual registration period. If the drug listing data is not updated or certified through the no change certification, the product’s status becomes uncertified, and the listing data will get inactivated at the next scheduled FDA inactivation period (see 84 FR 404171
7
).
Failure to register in accordance with section 510 of the FD&C Act and failure to provide listing information in accordance with 510(j) of the FD&C Act are prohibited under section 301(p) of the FD&C Act, 21 U.S.C. 331(p), and will render a drug misbranded under section 502(o) of the FD&C Act, 21 U.S.C. 352(o). 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).
It is your responsibility to ensure that your establishment remains registered if you are manufacturing drug product for U.S. commercial distribution and all products manufactured at your establishments comply with all registration and listing requirements under section 510 of the FD&C Act, 21 U.S.C. 360, and 21 CFR Part 207 of FDA regulations. Registration and listing information and instructions on how to properly register an establishment or submit drug listings can be found at Electronic Drug Registration and Listing Instructions.
Cosmetics Manufactured for Distribution in the United States
In addition, some of the products you manufacture may be regulated as cosmetics, as defined in section 201(i) of the FD&C Act. Any cosmetics you manufacture must comply with applicable statutory and regulatory requirements, including the FD&C Act. Under section 301(a) of the FD&C Act [21 U.S.C. 331(a)], it is a prohibited act to introduce or deliver for introduction into interstate commerce a cosmetic that is adulterated or misbranded.
Further, your facility may be subject to requirements under the Modernization of Cosmetic Regulations Act of 2022 (MoCRA). Information on MoCRA requirements may be found at https://www.fda.gov/cosmetics/cosmetics-laws-regulations/modernization-cosmetics-regulation-act-2022-mocra.
CGMP Consultant Recommended
We note that during the inspection, you indicated that
(b)(4)
. In response to this letter, clarify whether you intend to continue manufacturing drugs at this or any other facility.
Based upon the nature of the violations we identified at your firm, you should engage a consultant qualified as set forth in 21 CFR 211.34 to evaluate your operations and to assist your firm in meeting CGMP requirements. The qualified consultant should also perform a comprehensive six-system audit of your entire operation for CGMP compliance and evaluate the completion and efficacy of your CAPA before you pursue resolution of your firm’s compliance status with FDA.
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.
Conclusion
The violations cited in this letter are not intended to be an all-inclusive list of violations that exist at your facility. You are responsible for investigating and determining the causes of any violations and for preventing their recurrence or the occurrence of other violations.
Correct any violations promptly. Failure to promptly and adequately address this matter may result in regulatory or legal action without further notice including, without limitation, seizure and injunction. Unresolved violations may also prevent other Federal agencies from awarding contracts.
Failure to address violations may also cause FDA to withhold issuance of Export Certificates. FDA may withhold approval of new applications or supplements listing your firm as a drug manufacturer until any violations are completely addressed and we confirm your compliance with CGMP. We may re-inspect to verify that you have completed corrective actions to address any violations.
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 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 complete corrective actions within 15 working days, state your reasons for delay and your schedule for completion.
Send your electronic reply to CDER-OC-OMQ-Communications@fda.hhs.gov. Identify your response with FEI 3016665985 and ATTN: Joel Hustedt.
Sincerely,
/S/
_/Francis Godwin/____________________________
Francis Godwin
Director
Office of Manufacturing Quality
Office of Compliance
Center for Drug Evaluation and Research
__/Tina R. Smith/____________________________
Tina Smith, M.S.
Captain, U.S. Public Health Service
Director
Office of Unapproved Drugs & Labeling Compliance
Office of Compliance
Center for Drug Evaluation and Research
1
We need not address in this letter whether it is permissible to market a product as both an anticaries and antigingivitis/antiplaque drug product; as discussed below, your “Dr. Brite® Kids Anti-Plaque Toothpaste, Hydroxyapatite, Berrylicious,” “Dr. Brite® Extreme Whitening Toothpaste, Hydroxyapatite, Fresh Mint,” “Dr. Brite® Healthy Gums Toothpaste, Vitamin C, Hydrating Mint,” “Dr. Brite® Kids Anti-Plaque Mouth Spray, Hydroxyapatite, Berrylicious,” and “Dr. Brite® Kids Mineral Mouth Spray, Hydroxyapatite, Strawberry Sky” drug products do not comply with the relevant conditions in the applicable OTC monograph for anticaries or antigingivitis/antiplaque nonprescription drug products.
2
M021, in the final administrative order, Over-the-Counter Monograph M021: Anticaries Drug Products for OTC Human Use, reflects the conditions in the relevant final order established and in effect under section 505G. See Order ID OTC000034, available at FDA’s website OTC Monographs@FDA, https://www.accessdata.fda.gov/scripts/cder/omuf/.)
3
Under section 505G(a)(3) of the FD&C Act, drugs that were classified as Category I for safety and effectiveness in an advanced notice of proposed rulemaking (ANPR) that is the most recently applicable proposal or determination issued under 21 CFR Part 330 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 ANPR, including labeling conditions, and comply with all other applicable requirements.
4
We note that OTC antigingivitis/antiplaque oral healthcare drug products were addressed in an ANPR entitled “Oral Health Care Drug Products for Over-the-Counter Human Use; Antigingivitis/Antiplaque Drug Products; Establishment of a Monograph,” (68 FR 32232, May 29, 2003) (hereinafter “2003 ANPR”).
5
ANPR for Oral Health Care Drug Products for OTC Human Use; Antigingivitis/Antiplaque Drug Products; Establishment of a Monograph. 68 FR 32232.
6
FDA is not aware of any adequate and well-controlled clinical trials in the published literature that support a determination that the above referenced non-fluorinated toothpaste and mouth spray products are GRASE for use under the conditions prescribed, recommended, or suggested in its labeling.
7
https://www.regulations.gov/document/FDA-2019-N-2374-0001
Content current as of:
12/10/2024
Regulated Product(s)
Drugs