WARNING LETTER

Mariposa Labs, LLC MARCS-CMS 558110 — March 14, 2019

Product:: Drugs

Recipient:: Recipient Name

Mr. Claude M. Gillespie lll; Recipient Title

Owner and President; Mariposa Labs, LLC; 270 E 50th Street
Boise, ID 83714
United States

Issuing Office:: Division of Pharmaceutical Quality Operations IV; 19701 Fairchild
Irvine, CA 92612-2506
United States; (949) 608-2900

WARNING LETTER

VIA SIGNATURE CONFIRMED DELIVERY

March 14, 2019

Mr. Claude M. Gillespie III
Owner and President
Mariposa Labs, LLC
270 E 50th Street
Boise, ID 83714

Dear Mr. Gillespie:

The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, Mariposa Labs, LLC (FEI 3004003370), at 270 E 50th Street, Boise, Idaho, from March 19 to 30, 2018.

This warning letter summarizes significant violations of current good manufacturing practice (CGMP) regulations for finished pharmaceuticals. See 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 to the CGMP violations, your firm manufactures unapproved and misbranded drug products. Specifically, as formulated and labeled, “(b)(4),” “(b)(4),” (b)(4) OINTMENT (3.5 FL OZ), (b)(4) OINTMENT (2 OZ 57 ML), and (b)(4) CREAM are unapproved new drugs in violation of section 505(a) of the FD&C Act, 21 U.S.C. 355(a). “(b)(4)” is misbranded under 502(f)(1) of the Act, 21 U.S.C. 352(f)(1), and “(b)(4) OINTMENT” (3.5 FL OZ), “(b)(4) OINTMENT” (2 OZ 57 ML), and “(b)(4) CREAM”, are misbranded under section 502(c) of the FD&C Act, 21 U.S.C. 352(c). Introduction of such products into interstate commerce is prohibited under 301(a) and (d) of the FD&C Act, 21 U.S.C. 331(a) and (d).

We reviewed your April 15, 2018, response in detail and acknowledge receipt of your subsequent correspondence.

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

CGMP Violations

1. Your firm’s quality control unit failed to approve or reject all procedures or specifications impacting on the identity, strength, quality, and purity of the drug product (21 CFR 211.22(c)).

Your quality unit (QU) failed to ensure that adequate specifications were established for the over-the-counter (OTC) human drug products you manufacture. Your QU failed to meet its responsibility to ensure each batch was tested for, and conformed to, all appropriate attributes before distribution.

An effective pharmaceutical quality system ensures that each drug product batch released for distribution meets all appropriate manufacturing standards and test specifications.

Your response stated that you have stopped production of drug products and describes how your firm establishes specifications. Your response is inadequate because you did not evaluate whether distributed batches meet all appropriate specifications.

In response to this letter:

 Provide complete and appropriate specifications (each attribute and its acceptance limits) for each of your drug products.
 Conduct a risk assessment of the batches of your drug products within expiry which were manufactured and released to the market without complete testing for conformance with all appropriate specifications (such as assay, microbial limits, etc.). Commit to promptly test each batch in distribution for each of these quality attributes, and include a timeline for completion of all of these tests. If you do not intend to fully test all batches, or if testing reveals that a batch fails a specification, take appropriate market action including customer notifications and recalls.
 Provide a comprehensive assessment with corrective and preventive actions (CAPA) to ensure that your QU has the needed authority and resources to effectively discharge its functions. 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 provisions for QU oversight throughout your operations to evaluate adherence to appropriate practices
o complete and final review of each batch and its related information prior to the QU disposition decision
o oversight and approval of investigations, and discharging of all other QU duties to assure identity, strength, quality and purity of all products.

2. Your firm failed to follow written procedures describing the handling of all written and oral complaints regarding a drug product (21 CFR 211.198).

You did not adequately document multiple complaints of mold, chemical smell, and stinging for the (b)(4) creams, a drug with labeled indications including use on “newborns” and on broken skin. For example, you received a complaint for mold contamination in (b)(4) Cream (lot #5589). You recalled lot #5589 from your customer, and your investigation found 36 containers in that lot contaminated with mold.

Your microbiological test results confirmed the mold to be (b)(4). Your investigation suspected (b)(4) as a potential root cause. However, you lacked sufficient evidence to support this conclusion. You did not extend your investigation to determine if additional lots of (b)(4) Cream or any of your other topical products may have been contaminated.

You told our investigator that you did not use the customer complaint log form to document complaints consistently, as required by your complaint handling procedure, SOP QAA-008.

In your response, you stated that you will revise your complaint handling procedure and document each complaint you receive. Your response is inadequate because it lacked sufficient details of your planned SOP revisions and a retrospective review of all complaints.

In response to this letter, provide the following:
 A retrospective, independent review of all complaints received since February 1, 2017 to determine if you thoroughly investigated complaints and implemented appropriate CAPA. Provide a risk assessment of all drugs that were the subject of product quality complaints, and justify the scope of the investigation and sufficiency of the CAPA taken to prevent recurrence.
 A comprehensive, independent review of your material system to determine whether all containers, closures, and ingredients from each supplier are qualified and assigned appropriate expiration or retest dates. The review should also determine whether incoming material controls are adequate to prevent using unsuitable containers, closures, and components.
 A comprehensive, independent assessment of your overall system for investigating deviations, atypical events, complaints, out-of-specification results, and failures. Your CAPA should include but not be limited to improvements in investigation competencies, root cause analysis, written procedures, and quality unit oversight. Also include your process for evaluating CAPA effectiveness.
 A complete assessment of documentation systems used throughout your manufacturing and laboratory operations to determine where documentation practices are insufficient. Include a detailed CAPA plan that comprehensively remediates documentation practices and ensures you retain complete and accurate records.

3. Your firm failed to establish adequate 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)).

You have not validated the processes you used to manufacture your drug products.

During this inspection, you stated to our investigator that it was difficult to determine manufacturing parameters for your drug products. Production records for (b)(4) and (b)(4) drug products show that you have not sufficiently identified critical manufacturing variables, including but not limited to mixing speed and time. Your firm does not appear to have appropriate controls to ensure stable manufacturing operations and consistent drug quality.

Your response is inadequate because you have not evaluated the effect of manufacturing products using processes that were not adequately validated.

In response to this letter, conduct a prompt risk assessment for batches manufactured and released to the market with processes that were not validated. The risk assessment should address product quality and patient safety risks for all drugs still in distribution. Specify actions you will take as a result of the risk assessment, such as customer notification and product recalls. The risk assessment should include results of retrospective testing by your firm, or an independent laboratory, of all distributed batches that are within expiration date for all appropriate chemical and microbiological attributes.

FDA cited similar CGMP observations at your facility during our previous inspection. These repeated failures demonstrate that your company’s oversight and control over the manufacture of drugs is inadequate.

We acknowledge your decision to cease manufacturing and distributing drugs. If you no longer manufacture the drugs, specify the date you made this decision for each drug and the reasons your firm ceased manufacturing. If your firm is no longer manufacturing drug products for the U.S. market, FDA asks that you cancel your firm’s registration. Please contact FDA in advance if you are considering resuming drug manufacturing operations in the future.

If you resume production of drug products, your firm must first ensure that you fully comply with all CGMP requirements.

Unapproved New Drug and Misbranding Violations

Your products “(b)(4),” “(b)(4),” (b)(4) OINTMENT (3.5 FL OZ), (b)(4) OINTMENT (2 OZ 57 ML ), and (b)(4) CREAM 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 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 intended as skin protectants.

Examples of claims observed on your products’ labels include the following claims that demonstrate the intended uses for “(b)(4),” “(b)(4),” (b)(4) OINTMENT (3.5 FL OZ), (b)(4) OINTMENT (2 OZ 57 ML), and (b)(4) CREAM. This list is not inclusive of all claims demonstrating the products’ intended uses.

“(b)(4)”
 The product name, “(b)(4)”
“(b)(4)”
 The product name, “(b)(4)”
(b)(4) OINTMENT (3.5 FL OZ)
Statements that appear on the product label:
 “HEALS AND CALMS IRRITATED SKIN! . . . can be used to soothe rough patches, cradle cap, burns, cuts, scrapes, and diaper rash.”
“(b)(4) OINTMENT” (2 OZ 57 ML)
Statements that appear on the product label:
 “… can be used to soothe rough patches, cradle cap, burns, cuts, scrapes, and diaper rash.”

Additionally, your product label includes the URL, (b)(4). This is considered to be part of the labeling, and claims available on this website demostate the following intended uses of the product:

 “protects and nourishes your family’s driest, itchiest skin . . . Use all-natural All Over Ointment on eczema, psoriasis, rashes, dry skin, “chicken skin”, mysterious bumps, cuts and scrapes, windburn, baby and toddler cradle cap, diaper rash, c-section scars, razor burn, cracked heels and knuckles, and even your face.”
“(b)(4) CREAM”
Statements that appear on the product label:
 “moisturize, heal, and protect irritated skin from the elements (sun, wind, cold).”

 “soothes rashes, itchy spots, and dry patches . . . protects skin from harsh elements (sun, wind, cold)”

OTC drug products intended as skin protectants, such as (b)(4) OINTMENT (3.5 FL OZ), (b)(4) OINTMENT (2 OZ 57 ML), and (b)(4) CREAM, are subject to the Final Rule for Skin Protectant Drug Products for Over-the-Counter Use. See 21 CFR Part 347. However, these products are not formulated or labeled in accordance with this final rule for the reasons explained below.

The formulation and labeling for (b)(4) OINTMENT (3.5 FL OZ), (b)(4) OINTMENT (2 OZ 57 ML), and (b)(4) CREAM are not consistent with the conditions of the final rule referenced above. According to 21 CFR 201.66(b)(2), an active ingredient means 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.

The (b)(4) OINTMENT (3.5 FL OZ), (b)(4) OINTMENT (2 OZ 57 ML), and (b)(4) CREAM labels fail to declare active and inactive ingredients. As listed below, the ingredients for each product are promoted on your product labels in such a manner as to suggest that they are all active ingredients, as described in 21 CFR 201.66(b)(2). Furthermore, the ingredients listed below are not permitted active ingredients under the final rule for OTC skin protectant products (21 CFR 347).

(b)(4) OINTMENT (3.5 FL OZ)

Ingredients: Water, Glycerin, Stearic Acid, Propanediol, Caprylic/Capric Triglyceride, Cetyl Alcohol, Saccaromyces Ferment Filtrate, Jojoba Esters, Stearyl Alcohol, Beeswax, Lonicera Caprifolium (Honeysuckle) Flower Extract, Lonicera Japonica (Honeysuckle) Flower Extract, Camellia Sinensis Leaf Extract *, Cucumis Sativus (Cucumber) Fruit Extract *, Mangifera Indica (Mango) Fruit Extract *, Persea Gratissima (Avocado) Fruit Extract* *100% organic ingredient

(b)(4) OINTMENT (2 OZ 57 ML)
Ingredients: Water, Glycerin, Stearic Acid, Propanediol, Caprylic/Capric Triglyceride, Cetyl Alcohol, Saccaromyces Ferment Filtrate, Jojoba Esters, Stearyl Alcohol, Beeswax, Lonicera Caprifolium (Honeysuckle) Flower Extract, Lonicera Japonica (Honeysuckle) Flower Extract, Camellia Sinensis Leaf Extract*, Cucumis Sativus (Cucumber) Fruit Extract*, Mangifera Indica (Mango) Fruit Extract*, Persea Gratissima (Avocado) Fruit Extract* *100% organic ingredient

(b)(4) CREAM

Ingredients: Water, Carthamus Tinctorius (Safflower) Seed Oil, Prunus Amygdalus Dulcis (Sweet Almond) Oil, Diheptyl Succinate, Butyrospermum Parkii (Shea) Butter, Glyceryl Stearate, Glycerin, Cetearyl Alcohol, Stearic Acid, Sorbitol, Cetearyl Olivate, Citrus Aurantifolia (Lime) Peel Oil, Citrus Aurantium Dulcis (Orange) Peel Oil, Mentha Piperita (Peppermint) Oil, Mentha Viridis (Spearmint) Leaf Oil, Aloe Barbadensis Leaf Juice*, Argania Spinosa Kernal Oil, Macadamia Ternifolia Seed Oil, Lonicera Japonica (Honeysuckle) Flower Extract, Cinnamomum Camphora (Camphor) Leaf Oil, Lonicera Caprifolium (Honeysuckle) Flower Extract, Theobroma Cacao (Cocoa) Seed Butter, Sorbitan Olivate, Capryloyl Glycerin/Sebacic Acid Copolymer, Tocopheryl Acetate, Xanthan Gum, Citric Acid, Sodium Phytate, Potassium Sorbate, Persea Gratissima (Avocado) Fruit Extract*, Cucumis Sativus (Cucumber) Fruit Extract*, Mangifera Indica (Mango) Fruit Extract*, Camellia Sinensis Leaf Extract*, *100% organic ingredient

(b)(4) OINTMENT (3.5 FL OZ) and (b)(4) CREAM are also labeled for the healing of irritated skin. Healing is not a condition that is included in the OTC Drug Review.

Furthermore, drug products, such as (b)(4) OINTMENT (3.5 FL OZ) and (b)(4) OINTMENT (2 OZ 57 ML) that are also intended to treat diaper rash are being evaluated as part of the OTC Drug Review. They have been proposed to be classified as generally recognized as safe and effective and not misbranded under the Tentative Final Monograph (TFM) for Diaper Rash Drug Products for Over-the-Counter (OTC) Human Use, published on June 20, 1990 (55 FR 25204), if they meet each condition in the TFM and each general condition in 21 CFR 330.1.

Pending a final rule, FDA does not intend to pursue regulatory action against products marketed in conformance with the conditions proposed in the TFM and each general condition in 21 CFR 330.1. Such marketing, however, is subject to the risk that a final rule may require reformulation and/or relabeling or FDA approval through the new drug procedures of the FD&C Act (section 505). The labeling for such drugs, like all OTC drugs, must comply with all of the requirements of section 502 of the FD&C Act and all pertinent regulations found in 21 CFR. However, these products are not labeled or formulated in accordance with this TFM for the reasons explained below.

The formulation and labeling for (b)(4) OINTMENT (3.5 FL OZ) and (b)(4) OINTMENT (2 OZ 57 ML) are not consistent with the conditions proposed in the TFM for Diaper Rash Drug Products (55 FR 25204). The formulations for these two products as described above are not proposed in the TFM for Diaper Rash Drug Products.

Thus, as formulated and labeled, (b)(4) OINTMENT (3.5 FL OZ), (b)(4) OINTMENT (2 OZ 57 ML) and (b)(4) CREAM do not comply with the final rule described above. Furthermore, we are not aware of sufficient evidence to show (b)(4) OINTMENT (3.5 FL OZ), (b)(4) OINTMENT (2 OZ 57 ML), and (b)(4) CREAM as formulated and labeled, are generally recognized as safe and effective.

In addition, there is no evidence that “(b)(4)” and “(b)(4)” are generally recognized as safe and effective for their labeled uses. Therefore, these products are new drugs within the meaning of Section 201(p) of the FD&C Act 21 U.S.C. 321(p). As new drugs, “(b)(4),” “(b)(4),” (b)(4) OINTMENT (3.5 FL OZ), (b)(4) OINTMENT (2 OZ 57 ML), and (b)(4) CREAM may not be legally marketed in the United States absent approval of an application filed in accordance with section 505 of the FD&C Act 21 U.S.C. 355(a). “(b)(4),” “(b)(4),” (b)(4) OINTMENT (3.5 FL OZ), (b)(4) OINTMENT (2 OZ 57 ML), and (b)(4) CREAM are not the subject of FDA-approved applications, and therefore, the current marketing of these products violates section 505(a) of the FD&C Act, 21 U.S.C. 355(a). Introduction of such products into interstate commerce is prohibited under Section 301(d) of the FD&C Act, 21 U.S.C. 331(d).

(b)(4) OINTMENT (3.5 FL OZ), (b)(4) OINTMENT (2 OZ 57 ML), and (b)(4) CREAM are not labeled in accordance with the Drug Facts labeling requirements described in 21 CFR 201.66 because Drug Facts do not appear on the product labels Therefore, these products are misbranded under section 502(c) of the FD&C Act, 21 U.S.C. 352(c), because the information that is required to appear on the labeling is not prominently placed thereon with such conspicuousness and in such terms as to render it likely to be read and understood by the ordinary individual under customary conditions of purchase and use.

In addition, a drug is misbranded under 502(f)(1) of the FD&C Act, 21 U.S.C. 352(f)(1), if the drug 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 section 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.

(b)(4) is intended for treatment of one or more diseases that are not amenable to self-diagnosis or treatment without the supervision of a licensed practitioner. Therefore, it is impossible to write adequate directions for a layperson to use this product safely for its intended purposes. Thus, (b)(4) fails to bear adequate directions for its intended uses and, therefore, is misbranded within the meaning of section 502(f)(1) of the FD&C Act, 21 U.S.C. 352(f)(1).

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). Therefore, the marketing of “(b)(4),” (b)(4) OINTMENT (3.5 FL OZ), (b)(4) OINTMENT (2 OZ 57 ML), and (b)(4) CREAM violates this provision of the FD&C Act.

Conclusion

Violations cited in this letter are not intended as an all-inclusive list. You are responsible for investigating these violations, for determining the causes, for preventing their recurrence, and for preventing other violations.

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. Unresolved violations in this warning letter may also prevent other Federal agencies from awarding contracts.

Until these CGMP violations are corrected, we may withhold approval of pending drug applications listing your facility. We may re-inspect to verify that you have completed your corrective actions. We may also refuse your requests for export certificates.

After you receive this letter, respond to this office in writing within 15 working days. Specify what you have done since our inspection to correct your violations and to prevent their recurrence. 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 ORAPharm4_responses@fda.hhs.gov or mail your reply to:

CDR Steven E. Porter, Jr.
Director, Division of Pharmaceutical Quality Operations IV
19701 Fairchild Road
Irvine, CA 92612-2506

Please identify your response with unique identifier 558110.

If you have questions regarding any issues in this letter, please contact Ms. Maria P. Kelly-Doggett, Compliance Officer via email to maria.kelly-doggett@fda.hhs.gov or by phone at (425)-302-0427 and reference unique identifier 558110.

Sincerely,
/S/

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