Editor's Note
FDA issued this warning letter to Hawaii Pharm LLC alleging multiple violations of cGMP regulations, including failure to establish identity specifications for each component or product specifications for each dietary supplement. The warning letter notes that several products declare the ingredient Asarum Splendens, a potential source of aristolochic acid. FDA considers aristolochic acid to be a potent carcinogen and nephrotoxin that has been associated with permanent kidney damage. FDA reminds the company that it should ensure that products do not contain aristolochic acid. The letter also notes that some product labels declare Sida cordifolia , a source of ephedrine alkaloids, which FDA has determined presents an unreasonable risk of illness or injury and cause the products to be adulterated. FDA acknowledges the company's responses to alleged violations, but the agency says it is unable to evaluate the adequacy of the responses due to a lack of documentation.
April 24, 2020
Food and Drug Administration

The United States Food and Drug Administration (FDA) inspected your facility located at 6162 Kalanianaole Hwy, Honolulu, HI 96821-2371 from October 30, 2019 through November 7, 2019. Based on the inspectional findings, a subsequent review of your product labels collected during the inspection and your website, www.hawaiipharm.com, we have identified serious violations of the Federal Food, Drug, and Cosmetic Act (the Act) and applicable regulations. You may find the Act and FDA regulations through links on FDA’s website at  www.fda.gov .

Dietary Supplement Adulteration (CGMP)

The inspection revealed the following significant violations of the FDA’s regulations for Current Good Manufacturing Practice (CGMP) in Manufacturing, Packaging, Labeling, or Holding Operations for Dietary Supplements, under Title 21, Code of Federal Regulations (CFR), Part 111 (21 CFR Part 111). These violations cause your dietary supplement products to be adulterated under section 402(g)(1) of the Act [21 U.S.C. § 342(g)(1)] in that they have been prepared, packed, or held under conditions that do not meet the CGMP regulations for dietary supplements. We have received your written response dated November 20, 2019, concerning our investigator’s observations noted on the Form FDA 483, Inspectional Observations, which was issued to you on November 7, 2019; we address your response for the specific violations discussed below.

1. You failed to establish identity specifications for each component that you use in the manufacture of a dietary supplement, as required by 21 CFR 111.70(b)(1). Specifically, you have not established identity specifications for any incoming herbal ingredients that you receive and subsequently use to manufacture your dietary supplement products.

Once you have established component specifications and before using a component, you must conduct at least one appropriate test or examination to verify the identity of any component that is a dietary ingredient, as required by 21 CFR 111.75(a)(1)(i), unless you petition the agency under 21 CFR 111.75(a)(1)(ii) and the agency exempts you from such testing. You must also confirm the identity of other components and determine whether other applicable component specifications established in accordance with 21 CFR 111.70(b) are met, as required by 21 CFR 111.75(a)(2).

We have reviewed your November 20, 2019 response. In your response, you stated  (b)(4) . You stated to our investigator  (b)(4) , and your response states  (b)(4) . Your response also states  (b)(4) . We are unable to evaluate the adequacy of your response because you did not provide any copies of the component specifications that you have established thus far.

2. You failed to establish product specifications for each dietary supplement that you manufacture for the identity, purity, strength, and composition of the finished batch of the dietary supplement, and for limits on those types of contamination that may adulterate, or that may lead to adulteration of the finished batch of the dietary supplement to ensure the quality of the dietary supplement, as required by 21 CFR 111.70(e). Specifically, you have not established finished product specifications for any of dietary supplements that you manufacture and distribute.

We have reviewed your November 20, 2019 response. In your response you stated  (b)(4) . Your response states  (b)(4) . The response also states  (b)(4) . We are unable to evaluate the adequacy of your response because you did not provide copies of any of your finished product specifications completed thus far.

3. You failed to prepare and follow a written master manufacturing record (MMR) for each unique formulation of dietary supplement that you manufacture, and for each batch size, to ensure uniformity in the finished batch from batch to batch, as required by 21 CFR 111.205(a). Specifically, during the inspection you stated to our investigator  (b)(4) .

We have reviewed your November 20, 2019 response. In your response you stated (b)(4). You also state  (b)(4) . You also stated  (b)(4)  the MMRs  (b)(4) . We are unable to evaluate the adequacy of your response because you did not provide copies of MMRs.

4. You failed to prepare a batch production record (BPR) every time you manufacture a batch of a dietary supplement, as required by 21 CFR 111.255(a). Specifically, during the inspection, you stated to our investigator  (b)(4) .

We have reviewed your November 20, 2019 response. In your response, you stated  (b)(4) . You state  (b)(4) . We are unable to evaluate the adequacy of your response because you did not provide any copies of batch production records.

5. You failed to make and keep written procedures to fulfill the requirements that apply to the review and investigation of a product complaint, as required by 21 CFR 111.570(b)(1). Specifically, your firm does not have written procedures for product complaints.

We have reviewed your November 20, 2019 response. In your response, you stated  (b)(4) . You also stated  (b)(4) . We are unable to evaluate the adequacy of your response because you did not provide your written complaints procedure.

6. You failed to collect and hold reserve samples of each lot of packaged and labeled dietary supplements that you distributed, as required by 21 CFR 111.83(a). Specifically, your firm does not have a written procedure for maintaining reserve samples, and you do not maintain reserve samples of any of the dietary supplement products your firm has manufactured.

We have reviewed your November 20, 2019 response. In your response, you stated  (b)(4) . You stated  (b)(4) . We are unable to evaluate the adequacy of your response because you did not provide the written procedure. You referenced a document called  (b)(4) , Reserve Samples Record, but your response did not include this attachment. Furthermore, reserve samples are required to be retained for 1 year past the shelf life date (if shelf life dating is used) or for 2 years from the date of distribution of the last batch of dietary supplements associated with the reserve sample, for use in appropriate investigations. 21 CFR 111.83(b)(3).

Dietary Supplement Adulteration (non-CGMP)

The dietary supplement products discussed below are adulterated within the meaning of section 402(f) of the Act [21 U.S.C. § 342(f)] in that they are or contain a dietary ingredient that presents a significant or unreasonable risk of illness or injury.

1. The Non-Alcohol Bala (Sida Cordifolia), 4 fl. oz., and Bala (Sida Cordifolia), 4 fl. oz., products listed on your website, www.hawaiipharm.com, are adulterated within the meaning of section 402(f)(1)(A) of the Act [21 U.S.C. § 342(f)(1)(A)] in that each product label declares Sida cordifolia, a source of ephedrine alkaloids, which presents an unreasonable risk of illness or injury under the conditions of use recommended or suggested in the labeling, or if no conditions of use are recommended or suggested in the labeling, under ordinary conditions of use. [21 CFR 119.1; see Final Rule Declaring Dietary Supplements Containing Ephedrine Alkaloids Adulterated Because They Present an Unreasonable Risk, 69 FR 6788, 6793 (Feb. 11, 2004).]

Dietary Supplement Misbranding

The dietary supplement products discussed below are misbranded within the meaning of section 403 [21 U.S.C. § 343] of the Act and/or fail to comply with the regulations implementing the food labeling requirements of the Act, which are found in 21 CFR Part 101.

1. Your Hawaii Pharm brand Cat’s Claw, Fo-Ti Root, and Frankincense products are misbranded within the meaning of section 403(y) of the Act [21 U.S.C. § 343(y)] in that the label fails to bear a domestic address or domestic phone number through which the responsible person (as described in section 761) may receive a report of a serious adverse event with such dietary supplement.

2. Your Hawaii Pharm brand Cat’s Claw, Fo-Ti Root, and Frankincense products are misbranded within the meaning of section 403(i)(2) of the Act in that the product label fails to list other ingredients immediately following the supplement facts label required by 21 CFR 101.4(g).

3. Your Hawaii Pharm brand Cat’s Claw, Fo-Ti Root, and Frankincense products are misbranded within the meaning of section 403(q)(5)(F) of the Act [U.S.C. § 343(q)(5)(F)] because the Supplement Facts label is not in accordance with 21 CFR 101.36. For example, the products bear the following statement: “Percent Daily Values based on a 2,000 calorie diet.” This statement is only permitted when the percent of Daily Value is declared for total fat, saturated fat, total carbohydrate, dietary fiber, or protein as required by 21 CFR 101.9(c) and 21 CFR 101.36(b)(2)(iii)(D).

4. Your Hawaii Pharm brand Cat’s Claw is misbranded within the meaning of section 403(s)(2)(C) of the Act [21 U.S.C. § 343(s)(2)(C)] because the label fails to identify within the Supplement Facts label the part of the plant (e.g., root, leaves) from which each botanical dietary ingredient in the “proprietary blend” is derived, as required by 21 CFR 101.4(h)(1).

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

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

In addition, we offer the following comments:

• We note that the Wild Ginger (Asarum Splendens), 4 fl. oz., and Non-Alcohol Wild Ginger (Asarum Splendens), 4 fl. oz., products listed on your website, www.hawaiipharm.com, declare the ingredient Asarum Splendens. Asarum Splendens is a potential source of aristolochic acid, which is a potent carcinogen and nephrotoxin. Consumption of products containing aristolochic acid has been associated with permanent kidney damage, sometimes resulting in kidney failure that has required kidney dialysis or kidney transplantation. You should ensure that your product does not contain aristolochic acid.

• In your November 20, 2019 response,  (b)(4)  electronic records for several of your corrective actions. FDA has provided Guidance for Industry regarding the scope and application of the requirements for Electronic Records and Electronic Signatures in 21 CFR Part 11 at https://www.fda.gov/media/75414/download. We note that FDA does not consider the use of computer systems in the generation of paper records to trigger 21 CFR Part 11 under the circumstances described in the guidance.

Within fifteen working days of receipt of this letter, please notify this office in writing of the specific steps that you have taken to correct violations. Include an explanation of each step being taken to prevent the recurrence of violations, as well as copies of related documentation, such as photographs, corrective actions taken to date, or other useful information that would assist us in evaluating your corrections. If you do not believe that your products are in violation of the Act, include your reasoning and any supporting information for our consideration. If you cannot complete corrective action within fifteen working days, state the reason for the delay and the time within which you will complete the correction.

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