- Heron Botanicals, Inc.
- Issuing Office:
- Seattle District Office
| || |
Department of Health and Human Services
|Public Health Service|
Food and Drug Administration
22215 26th Avenue SE, Suite 210
Bothell, WA 98021
May 28, 2015
In reply refer to Warning Letter SEA 15-17
Eric L. Yarnell, ND, President
Heron Botanicals, Inc.
26013 United Road NE, Suite 110
Kingston, Washington 98346
Dear Dr. Yarnell:
The United States Food and Drug Administration (FDA) conducted an inspection of your dietary supplement manufacturing facility located at 26013 United Road NE, Suite 110, Kingston, Washington, on September 2, 2014, through September 17, 2014. During our inspection, the investigators found significant violations of FDA’s Current Good Manufacturing Practice (CGMP) regulations for dietary supplements, Title 21, Code of Federal Regulations, Part 111 (21 CFR Part 111). These CGMP violations cause the dietary supplement products you manufacture to be adulterated within the meaning of section 402(g)(1) of the Federal Food, Drug, and Cosmetic Act (the Act) [21 U.S.C. § 342(g)(1)] in that these products have been prepared, packed, or held under conditions that do not meet CGMP requirements for dietary supplements. Our investigators’ observations were presented to you on Form FDA 483, Inspectional Observations, at the conclusion of the inspection on September 17, 2014.
Further, we have reviewed your dietary supplement product labeling, and have determined that your products are misbranded because they do not comply with FDA’s labeling regulations under section 403 [21 U.S.C. § 343] of the Act.
We have received your written response dated October 3, 2014, related to our investigators’ observations noted on the Form FDA 483, Inspectional Observations, and address your response to each observation below.
The significant violations documented during the inspection include, but are not limited to, the following:
Dietary Supplement CGMP
1. You failed to establish product specifications for the identity, purity, strength, and composition of the finished batch of the dietary supplements to ensure the quality of each dietary supplement, as required by 21 CFR 111.70(e). Specifically, our investigators observed that finished product specifications for identity, purity, strength, and composition were not established for your Echinacea angustifolia and Dipsacus sylvestris dietary supplement products.
We have reviewed your response and conclude that it is not adequate. Your written response stated your firm’s definitions for identity, purity, strength, and composition of the finished dietary supplement products, but definitions are different than specifications for identity, purity, strength, and composition. For example, your method for evaluating finished product purity does not ensure that the finished dietary supplement liquid extract is present in a certain percentage. On your label, you claim Echinacea angustifolia is extracted at 70%; however, there is no purity specification established for the dietary ingredient present in the finished product.
We note thatyour definition of strength is not a specification and that strength may be affected by differences in maceration times, or in raw material purity.
2. You failed to establish component specifications to ensure that the finished dietary supplement product specifications for purity, strength, and composition are met, as required by 21 CFR 111.70(b)(2). Specifically, our investigators observed that your dietary supplement raw material specifications for Echinacea angustifolia and Dipsacus sylvestris consist of identity testing by relevant botanical description, macroscopic description, microscopic description, and organoleptic evaluations for taste, odor, and color. However, your raw material specification for Echinacea angustifolia and Dipsacus sylvestris do not address specifications that will ensure that finished product specifications for purity, strength, or composition are met. We note that the testing you are doing is not adequate to evaluate for purity, strength, and composition because that evaluation can only be achieved by chemical analysis.
We have reviewed your response to this charge and conclude that it is not adequate. Your written response states that the intent of 21 CFR 111.70(b) is to require component specifications to ensure that the finished dietary supplement product manufactured using the component will meet the identity, purity, strength, and composition specifications of the dietary supplement, not that components themselves have specifications for purity, strength or composition. However, you did not submit finished product specifications for purity, strength, or composition, or component specifications that are necessary to ensure that the specifications for purity, strength, and composition of the finished product using the components are met.
3. You failed to establish in-process specifications for any point, step, or stage in the master manufacturing record (MMR) where control is necessary to ensure that specifications are met for the identity, purity, strength, and composition of the dietary supplement, as required by 21 CFR 111.70(c)(1). Specifically, our investigators observed that in-process specifications for purity and strength are not established to ensure consistent extraction of the dietary ingredient during the maceration process for your Echinacea angustifolia and Dipsacus sylvestris dietary supplement products.
We have reviewed your response and conclude that it is not adequate. Your written response states that your firm makes no claims to the amount of “active ingredient” extracted from raw materials during maceration that are present in your final product. As such, you assert, that you are not required to monitor any “active ingredients.” The minimum maceration time that you identify is not adequate because variations in maceration times may lead to greater concentrations or decomposition of the dietary ingredient(s). Therefore, assurance of batch-to-batch consistency of the dietary ingredient(s) in order to determine the purity, strength, and composition in your finished dietary supplement products, at a specific level or within a certain range, is not demonstrated.
4. You failed to reject a component that did not meet your identity specifications established under 21 CFR 111.70(b)(1), as required by 21 CFR 111.77(b). Specifically, your Quality Assurance/Quality Control (QA/QC) personnel did not reject raw materials received, nor were there any identified treatments, adjustments, or reprocessing for these materials in the following instances when deviations to your raw material specifications were observed during identification testing:
a. The Raw Material Specification (RMS) for Dipsacus sylvestris specifies its odor as “(b)(4).” The Lot Manufacturing Record (LMR) for Lot Number 2736 describes it as “non-descript, fresh, somewhat swampy” and the LMR for Lot Number 2747 describes it as “no distinct aroma.” Both lots of this raw material were approved for processing by QA/QC.
b. The RMS for Astragalus membranaceus lists a specification for taste, but not for odor, while the LMR for Lot Number 2653 of this material describes the scent of the material but not the taste. Additionally, none of the qualitative language in the microscopic description of the LMR meets the specifications listed on your RMS. This lot of raw material was approved for processing by QA/QC.
c. The RMS for Rheum palmatum specifies its taste as “(b)(4)” and the odor as “(b)(4),” while the LMR for Lot Number 2324 of this material describes the taste as “bitter” and the odor as “bitter, acrid.” Additionally, none of the qualitative language in the microscopic description of the LMR meets the specifications listed on your RMS. This lot of raw material was approved for processing by QA/QC.
Our investigators observed there were differences between the written specifications and the recorded results. They explained to you that these variations make it difficult to determine whether raw materials were being properly identified.
We have reviewed your response and conclude that it is not adequate. Your written response stated that the materials listed in the observation were all raw plant materials, which can have organoleptic variations between different batches of the same plant. You explained that you rely on the specifications listed in the RMS, prior personal knowledge and familiarity with species, botanical or taxonomic texts, plant monographs and Certificate of Analysis (COA) from qualified suppliers to approve or reject a batch of raw materials. You stated these materials were approved based upon this system. However, you must establish an identity specification [21 CFR 111.70(b)(1)] and determine whether the specification you establish under 21 CFR 111.70 is met (21 CFR 111.73). This verification is performed by conducting at least one test or examination to verify the identity specification is met [21 CFR 111.75(a)(1)]. Therefore, you failed to establish your specifications to account for variations in the raw plant materials to ensure accurate raw material evaluations and appropriate disposition decisions.
5. Your quality control failed to approve, or reject written procedures, tests, and deviations or modifications that may affect the identity, purity, strength, or composition of a dietary supplement, as required by 21 CFR 111.105(a). Specifically, your QA/QC department did not document approval of your MMRs [21 CFR 111.123(a)(1) and 21 CFR 111.140(b)(2)]. For example, MMRs were not approved for:
- Fresh Rheum palmatum root tincture product
- Fresh Urtica dioica seed tincture product
- Dry Lespedeza capitata aerial parts in flower tincture
We have reviewed your response. Your written response stated that the unsigned MMRs were used appropriately according to your internal procedures. You provided your revised procedure which shows that the President and the Chief Operation Officer may sign all procedures and processes as the QA/QC representative, so long as they did not personally complete the task. However, it is not clear that the individuals assigned the quality control function are qualified through training and/or experience to serve in a QA/QC role, as required by 21 CFR 111.12. Your firm’s corrective action will be evaluated during a future FDA inspection of your facility.
Your Echinacea Angustifolia, Teasel – Dipsacus Sylvestris, Chinese Rhubarb – Rheum palmatum, Stinging Nettle – Urtica dioica, Round-Head Lespedeza – Lespedeza capitata, and Ephedra – Ephedra sinica Herbal Dietary Supplement products are misbranded within the meaning of section 403(e)(1) of the Act [21 U.S.C. § 343(e)(1)] in that the labels fail to list the name and place of business of the manufacturer, packer, or distributor in accordance with 21 CFR 101.5.
The above violations are not intended to be an all-inclusive statement of violations that exist in connection with your products and their labeling. 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 that your firm complies with all requirements of the Act and FDA regulations.
We offer the following comment:
Your COA for the Fresh Echinacea angustifolia root glycerite and Dipsacus sylvestris finished products provided analytical results for the contaminants yeast and mold; however, you did not provide finished product specifications for either of these contaminants. Based on your evaluation and inclusion of these contaminants in your COAs, it appears that the presence of yeast and mold in the Echinacea angustifolia and Dipsacus sylvestris may adulterate or may lead to adulteration of the finished batch of dietary supplement. Under 21 CFR 111.70(b)(3), a firm must establish limits on those types of contaminants that may adulterate or may lead to adulteration of the finished dietary supplement to ensure the quality of the dietary supplement.
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.
Section 743 of the Act [21 U.S.C. § 379j-31] authorizes FDA to assess and collect fees to cover FDA’s costs for certain activities, including re-inspection-related costs. A re-inspection is one or more inspections conducted subsequent to an inspection that identified noncompliance materially related to a food safety requirement of the Act, specifically to determine whether compliance has been achieved. Re-inspection-related costs means all expenses, including administrative expenses, incurred in connection with FDA’s arranging, conducting, and evaluating the results of the re-inspection and assessing and collecting the re-inspection fees [21 U.S.C. § 379j-31(a)(2)(B)]. For a domestic facility, FDA will assess and collect fees for re-inspection-related costs from the responsible party for the domestic facility. The inspection noted in this letter identified noncompliance materially related to a food safety requirement of the Act. Accordingly, FDA may assess fees to cover any re-inspection-related costs.
Within 15 working days of your 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. If you cannot complete corrective action within 15 working days, state the reason for the delay and the time within which you will complete the action.
Your reply should be sent to the following address: U.S. Food and Drug Administration, 22215 26th Avenue SE, Suite 210, Bothell, Washington 98021 to the attention of Maria P. Kelly-Doggett, Compliance Officer. If you have any questions regarding any issues in this letter, please contact Compliance Officer Maria Kelly-Doggett by telephone at 425-302-0427.
Miriam R. Burbach
Washington State Department of Agriculture
Food Safety Program
P.O. Box 42560
Olympia, Washington 98504-2560