- Delivery Method:
- Via Overnight Delivery
- Food & Beverages
Recipient NameAna R. Marx
Recipient TitleManaging Member
- Marco Pharma International LLC
851 NW Highland Street
Roseburg, OR 97470
- Issuing Office:
- Division of Human and Animal Food Operations West VI
January 10, 2020
In reply, refer to: CMS 585324
Dear Ms. Marx:
The U.S. Food and Drug Administration conducted an inspection of your facility, located at 851 NW Highland Street, Roseburg, Oregon, on May 14, 2019, through May 22, 2019. Based on the inspectional findings, we have identified serious violations of the Federal Food, Drug, and Cosmetic Act (the Act) and applicable regulations. You can find the Act and FDA regulations through links on the FDA's home page at http://www.fda.gov.
Adulterated Dietary Supplements
The inspection of your facility revealed serious violations of 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, including your Absinthium Herbal Liquid Extract 100 ml (Absinthium), S21 Multi Somaplex 100 ml (Multi Somaplex), S9 Molybdenum Somaplex 30 ml (Molybdenum), and your S17 Manganese-Copper-Cobalt Somaplex 30 ml (Manganese-Copper-Cobalt) products, to be adulterated within the meaning of section 402(g)(1) of the Act [21 U.S.C. § 342(g)(1)] in that the dietary supplements have been prepared, packed, or held under conditions that do not meet CGMP requirements for dietary supplements.
The significant violations documented during the inspection include, but are not limited to, the following:
1. You failed to establish the required specifications for any point, step, or stage in the manufacturing process where control is necessary to ensure the quality of the dietary supplement and that the dietary supplement is packaged and labeled as specified in the master manufacturing record, as required by 21 CFR 111.70(a). Specifically, you failed to establish:
a. Specifications to provide sufficient assurance that the product you received for packaging and labeling as a dietary supplement (and for distribution rather than return to the supplier) is adequately identified and is consistent with the purchase order, as required by 21 CFR 111.70(f). For example, you failed to establish specifications to ensure that the bulk shipments of Multi Somaplex received for repackaging and labeling, and for distribution rather than return to the supplier, is adequately identified and consistent with the purchase order.
b. Specifications for the packaging and labeling of the finished packaged and labeled dietary supplements, including specifications that ensure that you used the specified packaging and that you applied the specified label, as required by 21 CFR 111.70(g), for the liquid dietary supplement products that you repackage, label, and distribute.
c. Specifications for dietary supplement labels (label specifications) and for packaging that may come in contact with dietary supplements (packaging specifications), as required by 21 CFR 111.70(d). For example, you have not established packaging and labeling specifications for your Multi Somaplex dietary supplement product.
Once you have established the specifications, as required by 21 CFR 111.70, you must take specific actions to determine whether the specifications are met, as required by 21 CFR 111.73. You must also ensure any tests and examinations you use to determine whether the specifications are met are appropriate, scientifically valid methods, as required by 21 CFR 111.75(h)(1), and you must make and keep records of all activities relating to such specifications, in accordance with 21 CFR 111.95(b)(1).
We have reviewed your June 14, 2019, August 8, 2019, and October 31, 2019, responses. Your June 14, 2019, response included a document titled "Product Specification Sheet" that purportedly provided specifications for only one product, a N11/AB Liquid 20 ml product. However, this document does not adequately address the requirements for identity, purity, strength, and composition specifications for this product. Moreover, your response did not include specifications for any of the other dietary supplements that your firm sells. You indicate that you have "begun building SPECS for all of our products" and that you expect to complete this process "no later than 8/31/19." However, you have failed to provide us documentation demonstrating that this process was completed. You did not provide any additional specifications in your August 8, 2019, and October 31, 2019, correspondence and therefore your responses are inadequate.
2. 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.
To the extent that you contract with other firms to manufacture your product 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 you can make decisions related to whether your dietary supplement products conform to established specifications and whether to approve and release the products for distribution [see 72 Fed. Reg. 34752, 34790 (Jun. 25, 2007)). Although a firm may contract out certain dietary supplement manufacturing 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). The quality control personnel must ensure that the manufacturing, packaging, labeling, and holding operations 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 111.105). Further you 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 June 14, 2019, August 8, 2019, and October 31, 2019, responses, but we are unable to evaluate the adequacy of your corrective actions. Your June 14, 2019, response states a quality control procedure was being created but this procedure was not included in this or the August 8, 2019, or October 31, 2019, response.
3. Your Master Manufacturing Records (MMRs) for your dietary supplement products that you package and label failed to include the information required by 21 CFR 111.210. For example, the MMRs for your Molybdenum, Manganese-Copper-Cobalt, and Multi Somaplex products you provided to our investigator failed to include the following information:
a. Written instructions, as required by 21 CFR 111.210(h), including the following:
i. Specifications for each point, step, or stage in the manufacturing process where control is necessary to ensure the quality of the dietary supplement and that the dietary supplement is packaged and labeled as specified in the master manufacturing record, as required by 21 CFR 111.210(h)(1).
ii. Procedures for sampling and a cross-reference to procedures for tests or examinations, as required by 21 CFR 111.210(h)(2).
iii. Specific actions necessary to perform and verify points, steps, or stages in the manufacturing process where control is necessary to ensure the quality of the dietary supplement and that the dietary supplement is packaged and labeled as specified in the master manufacturing record, as required by 21 CFR 111.210(h)(3).
iv. Special notations and precautions to be followed, as required by 21 CFR 111.210(h)(4).
v. Corrective action plans for use when a specification is not met, as required by 21 CFR 111.210(h)(5).
We have reviewed your June 14, 2019, August 8, 2019, and October 31, 2019, responses. The MMRs provided in your June 14, 2019, response continued to be deficient in the areas cited above. Although you state in your June 14, 2019, response that you have updated all of your MMRs, those MMRs still do not contain the information, as required above by 21 CFR 111.210. Those MMRs now contain representative labels but still do not contain the necessary information listed above. Additionally, you did not provide any further responses to this issue in your August 8, 2019, and October 31, 2019, correspondence and these responses do not address this issue. Therefore, your responses are inadequate.
4. Your batch production records (BPRs) failed to include the required information relating to the production and control of each batch, as required by 21 CFR 111.260. Specifically, your BPR for Multi Somaplex, Lot 136172 did not include the following information:
a. The date and time of the maintenance, cleaning, and sanitizing of the equipment and processing lines used in producing the batch, or a cross reference to records, such as individual equipment logs, where this information is retained, as required by 21 CFR 111.260(c).
b. Documentation that the finished dietary supplement meets specifications established in accordance with 21 CFR 111.70(e) and (g), as required by 21 CFR 111.260(i).
c. Documentation, at the time of performance, that quality control personnel:
i. Reviewed the batch production record, as required by 21 CFR 111.260(I)(1).
ii. Approved and released, or rejected, the batch for distribution, including any reprocessed batch, as required by 21 CFR 111.260(1)(3).
iii. Approved and released, or rejected, the packaged and labeled dietary supplement, as required by 21 CFR 111.260(1)(4).
You did not provide any completed BPRs or documentation of any corrective actions you have taken to address this issue in your June 14, 2019, August 8, 2019, or October 31, 2019, correspondence and therefore your responses are inadequate.
5. You failed to calibrate instruments and controls you use in manufacturing or testing a component or dietary supplement, as required by 21 CFR 111.27(b). Specifically, our investigator observed your (b)(4) model scale contained a calibration sticker stating the last calibration date was July 23, 2012, that expired on July 23, 2013, and you could not provide evidence this scale has been recalibrated since this date.
We have reviewed your June 14, 2019, August 8, 2019, and October 31, 2019, responses, but we are unable to evaluate the adequacy of your corrective actions. Your June 14, 2019, response states you have contacted a calibration company and included an invoice from this company but documentation was not provided to show your equipment was calibrated. You did not provide any further response or describe any corrective actions you have taken to address this issue in your August 8, 2019, or October 31, 2019, correspondence and therefore your responses are inadequate.
Misbranded Dietary Supplements
Your Para A Herbal Liquid Extract 59 mL (Para A), Absinthium Herbal Liquid Extract 100 mL (Absinthium), and S21 Multi Somaplex 100 ml (Multi Somaplex) products are misbranded dietary supplements under section 403 of the Act [21 U.S.C. § 343] because they do not comply with the labeling requirements for dietary supplements, as required by 21 CFR 101, as follows:
1. Your Para A 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. Specifically, your Para A label declares the dietary ingredient "Citrus seed extract" but this is not the common or usual name of a dietary ingredient.
2. Your Para A, Absinthium, and Multi Somaplex 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 does not comply with 21 CFR 101.36. For example:
a. Your Para A, Absinthium and Multi Somaplex products' Supplement Facts label fails to list the serving size for each of the age groups indicated on the label which include suggested use by both adults and children. If the product is represented for persons within more than one group, the quantitative amount and percent of Daily Value for each group shall be presented in separate columns in accordance with 21 CFR 101.36(b )(2)(iii)(E).
b. Your Multi Somaplex product label lists (b)(2)-dietary ingredients as components of the Proprietary Ionic Trace Element Blend whereas (b)(2)dietary ingredients must be declared in accordance with 21 CFR 101.36(b)(2).
3. Your Para A product is misbranded within the meaning of 403(s)(2)(B) of the Act [21 U.S.C. § 343(s)(2)(B)] because it does not include a statement of identity as a "dietary supplement", as required by 21 CFR 101.3(g). 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. Your Para A label includes a statement of identity as "Herbal Liquid Extract." While this is an appropriately descriptive term of the dietary ingredients, it fails to include the term "supplement", as required by 21 CFR 101.3(g).
4. Your Para A and Absinthium products are misbranded within the meaning of section 403(s)(2)(C) of the Act [U.S.C. § 343(s)(2)(C)] in that each label fails to identify the part of the plant (e.g., root, leaves) from which each botanical dietary ingredient in the product is derived, as required by 21 CFR 101.4(h)(1) and 101.36(d)(1). For example, your Para A and Absinthium product labels fail to declare the specific part of certain plants that use the term "aerial part" or "aerial portion".
The violations cited in this letter are not intended to be an all-inclusive statement of violations that exist at your facility or 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 that your products comply with the Act and FDA's implementing 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 of violative products and/or injunction.
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. If you believe that your products are not 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.
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 reply should be sent to the Food and Drug Administration, 22215 26th Avenue SE, Suite 210, Bothell, Washington, 98021, to the attention of Tracy K. Li, Compliance Officer. If you have any questions, please contact Compliance Officer Li at (425) 302-0428.
Miriam R. Burbach
Program Division Director
cc: Oregon Department of Agriculture
Food Safety Division
635 Capitol Street NE
Salem, Oregon 97301