Mr. Jaime Gonzalez Castrodad
- Lopez Gonzalez Santana Corporation dba Domel and dba Dermixx
# 488 (Altos) Calle de Diego
Rio Piedras 00924
- Issuing Office:
- San Juan District Office
| || |
Office of Human and Animal Food Operations
East Division IV
466 Avenida Fernández Juncos
San Juan, Puerto Rico 00901-3223
Tel: (787) 729-8500
July 16, 2018
AMENDED WARNING LETTER
17-OHAFOE4-WL-09 / CMS No. 524175
Mr. Jaime Gonzalez Castrodad, President
Lopez Gonzalez Santana Corporation (dba Domel and dba Dermixx)
Calle de Diego #488 Altos
Rio Piedras, Puerto Rico 00924
Dear Mr. Gonzalez:
During our January 31 through February 10, 2017, inspection of your firm located at Calle de Diego #488, Rio Piedras, PR 00924, an investigator from the Food and Drug Administration (FDA or we) identified significant violations of Current Good Manufacturing Practice (CGMP) in Manufacturing, Packaging, Labeling, or Holding Operations for Dietary Supplements, Title 21, Code of Federal Regulations, Part 111 (21 CFR Part 111). These violations cause your dietary supplement products ALZ, Calci-Max, Enzycap, Iro-Plex liquid, Iro-Plex caplets, and Maltaglobin 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)] because they have been prepared, packed, or held under conditions that do not meet the CGMP regulations for dietary supplements. In addition, we have reviewed the labeling for your ALZ, Calci-Max, and Iro–Plex Liquid dietary supplements and determined that it is misbranded within the meaning of Section 403 of the Act [21 U.S.C. § 343]. You can find the Act and FDA regulations through links in FDA’s website at www.fda.gov.
Adulterated Dietary Supplements
The January 31 through February 10, 2017, inspection of your firm revealed the following significant violations of the CGMP requirements for dietary supplements. These violations cause your dietary supplement products to be adulterated under section 402(g)(1) of the Act in that they have been prepared, packed, or held under conditions that do not meet the CGMP regulations for dietary supplements.
We understand that your firm receives your finished, packaged and labeled dietary supplements products from one or more co-manufacturers and that your firm holds and distributes these dietary supplement products. During the inspection, you told our investigator that your firm develops the formulas for each of your dietary supplement products with input from your co-manufacturer and that your firm specifies the container type, size, and quantity of the dietary supplement product. Additionally, you also told our investigator that your firm, in conjunction with your co-manufacturer, approves final artwork for each of your dietary supplement product labels.
The following CGMP violations were observed during the inspection:
1. You failed to establish and follow written procedures for the responsibilities of the quality control operations, including written procedures for conducting a material review and making a disposition decision, and for approving or rejecting any reprocessing, as required by 21 CFR 111.103. Specifically, you had no written procedures for the responsibilities of the quality control operations. You must implement quality control operations in accordance with 21 CFR 111.65 to ensure the quality of the dietary supplement and that the dietary supplement is packaged and labeled as specified in the master manufacturing record.
To the extent that another firm manufactures, packages, and/or labels your dietary supplements on your behalf that your firm releases for distribution under your firm’s name, your firm has an obligation to know what and how manufacturing activities are performed so that your firm can make decisions related to whether the packaged and labeled dietary supplement products conform to established specifications and whether to approve and release the products for distribution [See 72 Fed. Reg. 34752, 34790 (June 25, 2007)]. Although a firm may contract out certain dietary supplement manufacturing, packaging, and/or labeling operations, it cannot contract out its ultimate responsibility to ensure that the dietary supplement it places into commerce (or causes to be placed into commerce) is not adulterated for failure to comply with dietary supplement CGMP requirements (see United States v. Dotterweich, 320 U.S. 277, 284 (1943) (explaining that an offense can be committed under the Act by anyone who has “a responsible share in the furtherance of the transaction which the statute outlaws”); United States v. Park, 421 U.S. 658, 672 (1975) (holding that criminal liability under the Act does not turn on awareness of wrongdoing, and that “agents vested with the responsibility, and power commensurate with that responsibility, to devise whatever measures are necessary to ensure compliance with the Act” can be held accountable for violations of the Act). In particular, the Act prohibits a person from introducing or delivering for introduction, or causing the delivery or introduction, into interstate commerce a dietary supplement that is adulterated under section 402(g) for failure to comply with dietary supplement CGMP requirements (see 21 U.S.C. 342(g) and 331(a)). Thus, a firm that contracts out some or all of its operations must establish a system of production and process controls to ensure the quality of the dietary supplement and that the dietary supplement is packaged and labeled as specified in the master manufacturing record (21 CFR 111.55). Your firm’s quality control personnel must ensure that the manufacturing, packaging, labeling, and holding operations ensure the quality of your dietary supplements and that the dietary supplements are packaged and labeled as specified in the master manufacturing record, as required by 21 CFR 111.105. Further, your firm must have documentation of the quality control personnel review and approval for release of any packaged and labeled dietary supplement (21 CFR 111.127(h) and 21 CFR 111.140(b)(2).
We have reviewed your response dated February 16, 2017, and have determined that it is inadequate. You state that you visit the manufacturing facilities and evaluate them using a questionnaire identified as FMQE 1022-Supplier Quality Evaluation Questionnaire. Your response does not address whether your firm has established and followed written procedures for the responsibilities of the quality control operations.
2. You failed to establish and follow written procedures for how you review and investigate product complaints, as required by 21 CFR 111.553. Specifically, your firm does not have a written procedure detailing the steps to be taken in response to product complaints. Your written procedure must fulfill the requirements of 21 CFR 111.560, and you must make and keep records in accordance with 21 CFR 111.570.
3. You failed to establish and follow written procedures to fulfill the requirements for returned dietary supplements, as required by 21 CFR 111.503. Specifically, your firm does not have written procedures for returned dietary supplements.
4. Your firm did not collect and hold reserve samples of each lot of packaged and labeled dietary supplement that you distribute, as required by 21 CFR 111.83(a). Specifically, you have not collected and held reserve samples of the products distributed. For each lot of packaged and labeled supplement that you distribute, your firm must collect reserve samples and hold the samples in accordance with 21 CFR 111.83(b). Specifically, the reserve samples that you maintain must:
- Be held using the same container-closure system in which the packaged and labeled dietary supplements were distributed [21 CFR 111.83(b)(1)].
- Be identified with the appropriate batch, lot, or control number [21 CFR 111.83(b)(2)].
- Be retained for one year past the shelf life date (if shelf life dating is used), or for two years from the date of distribution of the last batch of dietary supplement associated with the reserve sample [21 CFR 111.83(b)(3)].
- Consist of at least twice the quantity necessary for all tests or examinations to determine whether or not the dietary supplement meets product specifications [21 CFR 111.83(b)(4)].
We have reviewed your response dated February 16, 2017, and are unable to evaluate the adequacy of your corrective actions. Your response states that you will retain two containers of each new product lot received and will store them in the warehouse in the area designated as “Sample of Packages Products”. The containers will be kept until they reach the expiration date. Additionally, you will also keep label specimens of the products at the facility. However, your response did not provide evidence to demonstrate how you will implement these activities. It also fails to explain how you intend to satisfy the requirements of 21 CFR 111.83(b)(3). We will evaluate the adequacy of your corrective actions at our next inspection.
Misbranded Dietary Supplements
1. Your ALZ and Iro-Plex Liquid dietary supplements products are misbranded within the meaning of 403(s)(2)(B) of the Act [21 U.S.C. § 343(s)(2)(B)] in that the label fails to identify the product by using the term “dietary supplement” as a part of the product’s statement of identity, as required by 21 CFR 101.3(g), except that the word "dietary" may be deleted and replaced by the name of the dietary ingredients in the product or an appropriately descriptive term indicating the type of dietary ingredients that are in the product.
2. Your Calci-Max and Iro-Plex Liquid products are misbranded within the meaning of section 403(q)(1)(A) of the Act [21 U.S.C. §§ 343(q)(1)(A)] because the serving size declared on each label is incorrect. Serving size for a dietary supplement is the maximum amount consumed per eating occasion as recommended on the product label as defined in 21 CFR 101.9(b) and 21 CFR 101.12(b) Table 2. For example:
o The Calci-Max directions of use suggest the consumer take one (1) or two (2) capsules daily, but the serving size lists 1 capsule. The serving size listed should be two capsules.
o The Iro-Plex Liquid serving size is not expressed in a common household measure. The directions of use suggest the consumer take a teaspoon (5ml) daily, but the serving size lists 5 ml. The serving size listed should be 1 teaspoon (5 ml).
3. Your Iro-Plex Liquid product label is misbranded within the meaning of Section 403(e)(1) of the Act [21 U.S.C. § 343 (e)(1)] in that it fails to list the name and place of business of the manufacturer, packer, or distributor in accordance with 21 CFR 101.5.
4. Your Calci-Max product is misbranded within the meaning of section 403(i)(2) of the Act [21 U.S.C. § 343(i)(2)] in that the product label fails to declare the common or usual names of each ingredient used as required by 21 CFR 101.36 and 21 CFR 101.4. For example, the label declares the ingredient K-2 (Menatetrenone), but this is not the common or usual name for vitamin K.
5. Your Iro-Plex Liquid product is misbranded within the meaning of Section 403(q)(1)(B) of the Act [21 U.S.C. § 343(q)(1)(B)] because it fails to declare the correct number of servings per container in accordance with 21 CFR 101.36(b)(1)(ii). The net weight (118 ml) divided by the serving size (5 ml) results in about 23 servings, but the label lists the servings per container as “about 6.” The servings per container should be listed as “about 23.”
6. Your ALZ, Iro-Plex Liquid, and Calci-Max products are misbranded within the meaning of section 403(q)(5)(F) of the Act [21 U.S.C. § 343 (q)(5)(F)] in that the presentation of the nutrition information on the labeling of your product does not comply with 21 CFR 101.36. For example:
o Your ALZ product label lists a %DV for N Acetyl Cisteine, but a Daily Value has not been established for that dietary ingredient.
o Your Iro-Plex Liquid product label declares incorrect %DV’s for iron and vitamin B-6 based on the amount per serving declared.
o Your Calci-Max product label fails to declare the %DV for zinc, magnesium, and selenium.
o Your Iro-Plex Liquid and Calci-Max product labels fail to list the dietary ingredients in the correct order in accordance with 21 CFR 101.36(b)(2)(i)(B) and 101.36(b)(3)(i).
o Your Iro-Plex Liquid and Calci-Max product labels fail to present the nutrition information in the correct format in accordance with 21 CFR 101.36(e), in that a heavy bar shall separate the (b)(2)- and (b)(3)-dietary ingredients, with the latter presented below the heavy bar.
o Your Iro-Plex Liquid product label fails to use the correct unit of measurement on the quantitative amount declared for vitamin B-12 and folic acid, and your Calci-Max product fails to use the correct unit for folate and selenium, in accordance with 21 101.9(c)(8) and 101.36(b)(2)(ii)(B).
7. Your Iro-Plex Liquid product is misbranded within the meaning of section 403(r)(1)(A) of the Act, 21 U.S.C. § 343(r)(1)(A), because its label contains a nutrient content claim, but the product does not meet the requirements to make such a claim. Under section 403(r)(1)(A) of the Act, a claim that characterizes the level of a nutrient which is of the type required to be in the label or labeling of food (e.g., sugar) must be made in accordance with a regulation authorizing the use of such a claim. Characterizing the level of a nutrient in the food labeling of a product without complying with the specific requirements pertaining to nutrient content claims for that nutrient misbrands the product under section 403(r)(1)(A) of the Act.
In accordance with 21 CFR 101.60(a), a claim about sugar content of a food may only be made on the label or labeling of a food if, among other requirements, the claim uses one of the terms defined in 21 CFR 101.60(c) in accordance with the definition of that term. Under 21 CFR 101.60(c)(1)(i), the term “sugar free” may be used only if the food contains less than 0.5g of sugars, as defined in 21 CFR 101.9(c)(6)(ii), per RACC and per labeled serving. Additionally, under 21 CFR 101.(c)(1)(ii), the food must contain no ingredient that is a sugar or that is generally understood by consumers to contain sugars unless the listing of the ingredient in the ingredient statement is followed by an asterisk that refers to the statement below the list of ingredients, which states “adds a trivial amount of sugar,” “adds a negligible amount of sugar,” or “adds a dietarily insignificant amount of sugar."
Specifically, your Iro-Plex Liquid product label bears the claim “sugar free,” but fails to meet the requirement under 21 CFR 101.60(c)(1)(ii) to bear that claim. Your product label lists corn syrup as an ingredient, and therefore, you must meet the requirements for sugar content claims in 21 CFR 101.60(c). Your product label, however, fails to state “adds a trivial amount of sugar,” “adds a negligible amount of sugar,” or “adds a dietarily insignificant amount of sugar."
8. Your Calci-Max product 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 the part of the plant (e.g., root, leaves) from which e each botanical dietary ingredient in the product is derived, as required by 21 CFR 101.4(h)(1).
This letter is not intended to be an all-inclusive list of the violations that exist at your facility or that exist in connection with your products. You are responsible for ensuring that your products are in compliance with the Act and all implementing regulations, including the CGMP regulation for dietary supplements. You should take prompt action to correct the violations cited in this letter and to prevent their recurrence. Failure to promptly correct these violations may result in enforcement action by FDA without further notice, including seizure and injunction.
We also have the following comments:
● During the inspection, you told our investigator that your firm provides manufacturers with the formulas for your dietary supplement products. Finished product specifications must be established 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). We are not aware of any finished product specifications established by your firm or your co-manufacturer for your finished dietary supplement products.
We have reviewed your response dated February 16, 2017. You state that you will request that all manufacturing firms attach a COA to the commercial invoice of each product. However, it is not clear what the finished product specifications for each of your dietary supplement products are, and what information your quality control unit is reviewing in order to approve a dietary supplement product for release for distribution. For example, we are not aware of any established finished product specifications that your co-manufacturer must meet, and for which the COA would verify are met, for each finished batch that your quality control unit must approve for release for distribution, as required by 21 CFR 111.127(h). We will evaluate the adequacy of your corrective actions at our next inspection.
- Your ALZ product label, it appears the dietary ingredient vinpocetine is misspelled as vipocesetin and huperzine is misspelled as hupersine. Your Calci-Max product label misspells the following terms: zinc chelate, selenium, and Rhodiola.
- Your Iro-Plex Liquid product declares the ingredient “butterscotch flavor” but fails to specify if the flavor is artificial or natural.
- Your Iro-Plex Liquid product label notes “Daily Value not established” but does not include a column for % Daily Value and does not include an “*” to designate that the Daily Value has not been established for the dietary ingredient. Your Calci-Max product does not indicate “Daily Value not established” for flaxseed oil cold pressed, black cohosh extract, or Rhodiola rosea extract.
- Your Calci-Max product declares the term “Lifenol” which is not a common or usual name of an ingredient. Furthermore, it appears by the listing of “Lifenol & Humulus lupulus” that these terms may be two separate ingredients. If this is not the case, then the names “Lifenol” and “Humulus lupulus” should be listed in such a way that the consumer is aware of the relationship between the “Lifenol” and the “Humulus lupulus.”
- Your Calci-Max product label claims “L-methylfolate” on the primary display panel, but the Supplement Facts label declares “methylfolate.”
You should notify this office in writing within fifteen (15) working days of receiving this letter of the steps you have taken to correct violations described above, including an explanation of each step taken to prevent the recurrence of violations. Your response should include copies of supporting documentation and any other useful information that would assist us in evaluating your corrections. If corrective action cannot be completed before you respond, you should state the reason for the delay and the time frame within which the corrections will be completed.
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 non-compliance 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 non-compliance materially related to a food safety requirement of the Act. Accordingly, FDA may assess fees to cover any re-inspection-related costs.
Your written response should be sent to Beira Montalvo, Compliance Officer, U.S. Food and Drug Administration, 466 Fernandez Juncos Avenue, San Juan, PR 00901-3223. If you have questions regarding this letter, please contact Ms. Montalvo at 561-416-1065 Ext 1108 or Edwin Ramos, DCB, at 787-729-8662.
Ramon A. Hernandez
Office of Human and Animal Foods D4E
San Juan District Director/Program