- Issuing Office:
- Denver District Office
| || |
Department of Health and Human Services
|Public Health Service|
Food and Drug Administration
| ||Denver District Office|
Building 20-Denver Federal Center
P.O. Box 25087
Denver, Colorado 80225-0087
February 26, 2015
VIA UPS Overnight Mail
Ref: DEN-15-07 WL
Ellen Troyer, Co-Owner
Dr. Spencer Thornton, Co-Owner
4740 Farthing Drive
Colorado Springs, CO 80906
Dear Ms. Troyer and Dr. Thornton:
The U.S. Food and Drug Administration (FDA) conducted an inspection of your facility, Biosyntrx® located at 4740 Farthing Drive, Colorado Springs, Colorado, on September 4 and 5, 2014. During our inspection, you informed our investigator that your firm holds and distributes dietary supplements for which you have entered into agreements with contract manufacturers to manufacture, package, and label under your own firm’s name. Based on our inspection, we found serious violations of the Current Good Manufacturing Practice (CGMP) regulations for Manufacturing, Packaging, Labeling, or Holding Operations for Dietary Supplements, Title 21, Code of Federal Regulations (CFR), Part 111 (21 CFR Part 111). These violations cause your BioTears® Oral Gel Caps, ZoOmega-3 Concentrated Pharmaceutical-Grade Fish Oil, EpiCor™ A Nutrient-dense High Metabolite Immunogen, Sight C+™ Mineral Buffered Vitamin C, Oculair® Multiple Nutrients for Your Eyes and Body, and Eye & Body Complete® Multiple Nutrients for Optimal Eye and Body Health (formerly Macula Complete®) dietary supplement products 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 the dietary supplement products have been prepared, packed or held under conditions that do not meet CGMP requirements for dietary supplements. Our investigator’s observations were noted on form FDA-483, Inspectional Observations, which was issued to you on September 5, 2014.
In addition, FDA reviewed your product brochures and price list that are shipped with your products, as well as your website at the Internet address www.biosyntrx.com in February 2015, where you take orders for your Oculair®, Macula Complete® (currently Eye & Body Complete), and Sight C+™ products. From the review of your product brochures, price list, and website, FDA has determined that your Biosyntrx® BioTears®, Oculair®, Macula Complete® (currently Eye and Body Complete®), Sight C+™, ZōOmega-3, EpiCor™, and Zeaxanthin-4™ products are being promoted for conditions that cause the products to be drugs under section 201(g)(1)(B) of the Act [21 U.S.C. § 321(g)(1)(B)]. The therapeutic claims in your product labeling establish that the products are drugs because they are intended for use in the cure, mitigation, treatment, or prevention of disease. As explained further below, introducing or delivering these products for introduction into interstate commerce for such uses violates the Act.
FDA has also reviewed the labels for your Oculair Full-Spectrum Multiple Support and ZōOmega-3 products and has determined that these products are misbranded dietary supplements under section 403(q)(1)(A) of the Act [21 U.S.C. §343(q)(1)(A)].
We received your written response letter, dated September 24th, 2014. We have reviewed your responses, and we address your proposed corrective actions below.
You may find the Act and FDA regulations through links on FDA’s home page at www.fda.gov
Unapproved New Drugs
Examples of some of the “Price list” claims that provide evidence that your Biosyntrx® products, including BioTears®, Oculair®, Macula Complete® (currently Eye and Body Complete®), Sight C+™, ZōOmega-3, EpiCor™, and Zeaxanthin-4™, are intended for use as drugs include:
- “BioTears® has been clinically suggested to decrease inflammatory markers, interleukin-1 (IL-1) and IL-6 in tear film.”
- “EpiCor™ has been clinically suggested to appropriately modulate expression of NK cells, T cells, B cells and dentrite cells.”
- “Scientific research has established that dietary zeaxanthin plays an essential role in protecting the retina of the eye from the damaging effects of light.”
In addition, when scientific publications are used commercially by the seller of a product to promote the product to consumers, such publications may become evidence of the product's intended use. For example, under 21 CFR 101.93(g)(2)(iv)(C), a citation of a publication or reference in the labeling of a product is considered to be a claim about disease treatment or prevention if the citation refers to a disease use and if, in the context of the labeling as a whole, the citation implies treatment or prevention of a disease. The following are examples of reference citations used to market your products for disease treatment and prevention on your website and are thus evidence of your products' intended use as drugs:
- “Oculair® is a potent, bio-chemically balanced, full-body, Full spectrum multiple that contains the nutrients included in the LUTEIN Antioxidant Supplementation Trial (LAST) and the Age Related Eye Disease (ARED) study in amounts that reflect current published science.” Under this statement you include the reference to a study called “A Randomized, Placebo-Controlled, Clinical Trial of High Dose Supplementation with vitamins C and E, Beta Carotene, and Zinc for Age-Related Macular Degeneration and Vision Loss. Arch Ophthalmol 2001; 119:1417-1436”
- Macula Complete® (currently Eye & Body Complete)- “Designed for the person who desires optimal health, plus superior macula and mitochondrial protection.”
“Feher J Kovacsw B, et al. Improvement of visual functions and fundus alterations in early age-related macular degeneration treated with a combination of acetyl-l-carnitine, n-3 fatty acids, and coenzyme Q10. Ophthalmologica 2005 May-June; 219(3); 154-66.”
- Sight C+™- “A study titled “Toshida M, Takashima Y, Inoue M, et al. Prospective study showing that dietary vitamin C reduces the risk of age-related cataracts in a middle-aged Japanese population. EUR J Nutr; 2007; 46(2); 118-124.”
Examples of some of the brochure claims that provide evidence that your Biosyntrx® products, including BioTears®, ZōOmega-3, and Eye & Body Complete®, are intended for use as drugs include:
- “BioTears® uses Black Currant Seed Oil as a source of Omega 6 Essential Fatty Acids (EFAs) because it is the most biochemically stable source of linoleic acid (LA), and it also contains 18% gamma-linolenic acid (GLA), which, with the aid of specific nutrient co-factors, consistently converts to the series E1 prostaglandin (PGE1) anti-inflammatory…”
- “Safer small amounts of Omega-3 fatty acids, EPA and DHA, like the amount included in BioTears®, are proven capable of…preventing ocular surface inflammatory response when presented with nutrient co-factors that enhance…modulate the fatty acid-based inflammatory response.”
- “BioTears® a U.S. patent protected formulation from the scientists at Biosyntrx, is the eye care professional’s standard-of-care for dry eyes. It is an oral capsule, taken by mouth, to systemically address the root cause of Dry Eye Syndrome.”
- ZōOmega-3- “The research also strongly suggests that the active ingredients in ZoOmega-3, the long chain polyunsaturated acids EPA and DHA, may act in a retinal disease preventive role.”
- “Eye & Body Complete® is the only product in the eye care market that provides extra-strength, biochemically balanced, safe and convenient, full-spectrum range of active ingredients for the diagnosed macular degeneration patient and the consumer who wants to protect his or her eyes and entire body from nutrient deficiencies associated with increased risk of all age-related degenerative diseases.”
Your brochures for BioTears® and Eye & Body Complete® also contain evidence of intended use in the form of personal testimonials recommending or describing the use of BioTears® and Eye & Body Complete® for the cure, mitigation, treatment, or prevention of disease. Examples of such testimonials include:
- “The cornea is two thirds of refractive power of the eye. If you don’t have a good initial refracting surface it increases the high order aberrations and increases the symptoms that the patients will get superimposed on their lens multifocality. So a good dry eye oral supplement is very helpful. I really liked the oral supplement BioTears®. I think that it’s very effective”
- “My dry eye pain became unbearable after moving from San Francisco to Denver. Four oral capsules a day of BioTears allows me to hike or ski all day without having to use eye drops every hour.”
- “As a practice, I avoid making product recommendations. Having recently reviewed all of the supplements designed for MD patients, one stands out as probably the most effective and economical. The product is Eye & Body Complete®. It is the more all-inclusive nutritional formula available to AMD patients.”
Your products are not generally recognized as safe and effective for the above referenced uses, and, therefore, your Biosyntrx® BioTears®, Oculair®, Macula Complete® (currently Eye and Body Complete®), Sight C+™, ZōOmega-3, EpiCor™, and Zeaxanthin-4™ products are new drugs under section 201(p) of the Act [21 U.S.C. § 321(p)]. New drugs may not be legally introduced or delivered for introduction into interstate commerce without prior approval from FDA, as described in section 505(a) of the Act [21 U.S.C. § 355(a)]; see also section 301(d) of the Act [21 U.S.C. § 331(d)]. FDA approves a new drug on the basis of scientific data submitted by a drug sponsor to demonstrate that the drug is safe and effective.
Furthermore, your Biosyntrx® Oculair®, Macula Complete® (currently Eye & Body Complete®), Sight C+™, ZōOmega-3, and BioTears®products are offered for conditions that are not amenable to self-diagnosis and treatment by individuals who are not medical practitioners; therefore, adequate directions for use cannot be written so that a layperson can use these drugs safely for their intended purposes. Thus, these drugs are misbranded within the meaning of section 502(f)(1) of the Act [21 U.S.C. § 352(f)(1)], in that their labeling fails to bear adequate directions for use. The introduction of a misbranded drug into interstate commerce is a violation of section 301(a) of the Act [21 U.S.C. § 331(a)].
Dietary Supplements CGMP Violations
Even if your Biosyntrx® BioTears®, and Eye and Body Complete® products were not unapproved new drugs, they are adulterated dietary supplements within the meaning of section 402(g)(1) of the Act. FDA observed violations that cause your BioTears® Oral Gel Caps, ZoOmega-3 Concentrated Pharmaceutical-Grade Fish Oil, EpiCor™ A Nutrient-dense High Metabolite Immunogen, Sight C+™ Mineral Buffered Vitamin C, Oculair® Multiple Nutrients for Your Eyes and Body, and Eye & Body Complete® Multiple Nutrients for Optimal Eye and Body Health (formerly Macula Complete®) products to be adulterated dietary supplements within the meaning of section 402(g)(1) of the Act, because the products have been prepared, packed, or held under conditions that do not meet the CGMP regulations for dietary supplements.
Specifically, the following violations were observed:
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, as required by 21 CFR 111.103 and 21 CFR 111.140(b). Your firm’s quality control personnel must approve for release, or reject, any packaged and labeled dietary supplement (including a repackaged or relabeled dietary supplement) for distribution, as required by 21 CFR 111.127(h). During our inspection, you stated that you do not ask for any documentation for the products manufactured and distributed into interstate commerce, nor do you review the quality control practices at the contract manufacturer. You also stated that you do not review or sign off for finished product released prior to shipment and that you do not have a quality agreement with your contact manufactures outlining responsibilities.
To the extent you contract with other manufacturers to manufacture, package, or label dietary supplements 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 your 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)].
During the inspection, you stated that your firm holds and distributes dietary supplement products that are manufactured elsewhere. 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).
Whether you receive product from a supplier or from a contract manufacturer, you must have documentation of the quality control personnel review and approval for release of any packaged or labeled dietary supplement (21 CFR 111.127(h) and 111.140(b)). In addition, you must establish and follow written procedures for the responsibilities of the quality control operations (21 CFR 111.103). As noted above, you provided no documentation to meet these requirements.
We acknowledge your response, dated September 24, 2014, to the Form FDA 483, Inspectional Observations issued at the close of the inspection. We find your response to be inadequate in that you stated that you have signed a contract with (b)(4); however, you did not include any written procedures or supporting documentation regarding your new process.
2. Your firm failed to make and keep a written record of every product complaint that is related to good manufacturing practice as required by 21 CFR 111.570(b)(2). Specifically, you stated that you had received several complaints regarding the products you distribute; however, no complaint log and record of the findings of any investigation or follow up action, when such activities are performed, is kept.
We acknowledge your response, dated September 26, 2014, to the Form FDA 483, Inspectional Observations issued at the close of the inspection. In your response, you provided a standard operating procedure for the handling of product complaints to fulfill the requirements that apply to the review and investigation of the product complaint. We will verify the adequacy of this correction during any future inspection.
3. You failed to establish and follow written procedures for returned dietary supplements as required by 21 CFR 111.503. Specifically, during the inspection you stated that you have received returns for auto shipment errors (b)(4); however, when asked for written procedures for returns you stated that you do not have any procedures.
We acknowledge your response, dated September 26, 2014, to the Form FDA 483, Inspectional Observations issued at the close of the inspection. Your response stated that your product return policy has been documented and is kept on file for all employees to source if necessary; however, you failed to include any supporting documentation of this policy. As such, we are unable to evaluate the adequacy of your response.
4. You failed to establish and follow written procedures for holding and distributing operations as required by 21 CFR 111.453. You receive packaged and labeled dietary supplements from your contract manufacturers which you further distribute to customers through online sales or to wholesale accounts who distribute them in retail establishments; however, you stated during the inspection that you do not have any written procedures for these operations which you perform.
We acknowledge your response, dated September 26, 2014, to the Form FDA 483, Inspectional Observations issued at the close of the inspection. Your response stated that your holding and distributing procedure documents are now in your files; however, you failed to include any supporting documentation. As such, we are unable to evaluate the adequacy of your response.
5. You failed to establish finished product specifications for the identity, purity, strength, composition, and limits on contaminants for finished product batches, as required by 21 CFR 111.70(e). Additionally once specifications are established the finished product ability to meet the specifications must be verified as required by 21 CFR 111.75(c). Specifically, the BioTears® product has no established specifications, and there is no data available to confirm the composition, quantity, or strength of the ingredients contained in the product.
6. You failed to keep employee documentation of training, including the date of the training, the type of training, and the person(s) trained, as required by 21 CFR 111.14(b)(2).
Misbranded Dietary Supplements
1. Your Oculair Full-Spectrum Multiple Support and ZōOmega-3 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 the labels is incorrect. The terms “serving” or “serving size” for a dietary supplement are defined in 21 CFR 101.9(b) and 101.12, Table 2, as the maximum amount recommended on the label for consumption per eating occasion. For example:
- The directions on the Oculair Full-Spectrum Multiple Support product label suggest take two capsules with each morning and evening meal; however, the serving size states: 4 Capsules.
- The directions on the ZōOmega-3 product label suggest take one or two softgel caps daily with meals; however, the serving size states: 1 Softgel.
The violations described above are not meant to be an all-inclusive list of violations at your facility or that exist in connection with your products or 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 the Act and applicable FDA regulations. You should take prompt action to correct the violations cited in this letter. Failure to promptly correct these violations may result in enforcement action without further notice, including, without limitation, injunction and seizure under sections 302 and 304 of the Act [21 U.S.C. §§ 332 and 334].
We offer the following comment:
Any expiration date, shelf life, or “Best by” date you place on a product label should be supported by stability data [See 72 Fed. Reg. 34752, 34856 (Jun. 25, 2007)]. The term ‘shelf life dating” includes expiration dating and “best if used by” dating [See 72 Fed. Reg. 34752, 34912 (Jun. 25, 2007)]. You informed our investigator that you use a (b)(4) expiration date on your finished product labels; however you do not have stability testing data to support this date.
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.
Please respond to this office in writing within fifteen (15) working days from your receipt of this letter. In your response, identify the steps you have taken or will take to correct the above noted violations and prevent similar ones. In your response, please include the timeframe in which the corrections will be completed and provide any documentation that will effectively assist us in evaluating whether the corrective actions have been made and the adequacy of such. If you are unable to complete the corrective actions within fifteen (15) working days, identify the reason for the delay and the time within which you will complete the corrections. Please send your reply to the U. S. Food and Drug Administration, Attention: Nancy Schmidt, Compliance Officer, Denver Federal Center 6th and Kipling Building 20, Denver, CO 80225.
If you have any questions regarding any issues in the letter, please contact Compliance Officer Nancy Schmidt at (303)236-3046.
LaTonya M. Mitchell
Denver District Director