Inspections, Compliance, Enforcement, and Criminal Investigations
Exclusive Supplements, Inc. 1/31/14
Department of Health and Human Services
|Public Health Service|
Food and Drug Administration
900 U.S. Customhouse
2nd and Chestnut Streets
Philadelphia, PA 19106
RETURN RECEIPT REQUESTED
January 31, 2014
Mark A. Mangieri, President
Exclusive Supplements Inc.
3000 Casteel Drive
Coraopolis, PA 15108
Dear Mr. Mangieri:
The U.S. Food and Drug Administration (FDA) conducted an inspection at your firm located at 3000 Casteel Drive, Coraopolis, PA from March 7, 2013 to March 21, 2013. During the inspection, our investigators collected labeling for your products, including your BioRhythm Advanced brand products. In addition, we reviewed your website at Internet address http://biorhythm-ads.com/index.cfm in January 2014. During the inspection, you informed our investigators that your firm distributes and packages your BioRhythm Advanced brand products and that you have entered into agreements with contract manufacturers to manufacture these products.
Based on our review, we found serious violations of the Federal Food, Drug, and Cosmetic Act (the Act) and applicable regulations. In addition, we received your letter, dated April 10, 2013, and address it below.
You may find the Act and its implementing regulations through links on FDA’s home page at www.fda.gov.
Unapproved New Drugs
We reviewed your website at the Internet address http://biorhythm-ads.com/index.cfm in January 2014. and we have determined that you take orders there for your BioRhythm Olio and ReGenerate products, which the website promotes 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 on your website 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.
Examples of some of the website claims that provide evidence that your products are intended for use as drugs include:
BioRhythm Olio product, under the Quick Facts tab:
- “Supports reduction of ‘bad’ cholesterol”
BioRhythm Olio product, under the Description tab:
- “Research indicates a diet that includes olive oil yields less overall disease and lower mortality rates”
- “Supports reduction of “bad” cholesterol”
BioRhythm ReGenerate product, under the Quick Facts tab:
- “Decrease bone fracture healing time and lessen joint pain”
BioRhythm ReGenerate product, under the Ingredients tab:
- “Cissus Quadrangularis [an ingredient in the product] … has already proven to be an excellent healing aid by significantly reducing the average recovery time in major injuries as well as reducing the pain associated with minor tears or inflammation”
Your BioRhythm Olio and ReGenerate products are not generally recognized as safe and effective for the above referenced uses and, therefore, the products are “new drugs” under section 201(p)(1) of the Act [21 U.S.C. §321(p)(1)]. 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 BioRhythm Olio product is 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 the drug safely for its intended purposes. Thus, your BioRhythm Olio product is misbranded within the meaning of section 502(f)(1) of the Act [21 U.S.C. §352(f)(1)], in that its 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)].
New Dietary Ingredient
During the inspection, our investigators collected labeling for your BioRhythm Androbolix product, which you market as a dietary supplement. The labeling for this product declares 4-etioallocholen-3,6,17-trione as a dietary ingredient. The term “dietary supplement” is defined in section 201(ff) of the FD&C Act [21 U.S.C. § 321(ff)]. Assuming that 4-etioallocholen-3,6,17-trione is a dietary ingredient under section 201(ff)(1) of the Act, it would also be a “new dietary ingredient” for which a notification is required under section 413(a)(2) of the Act [21 U.S.C. § 350b(a)(2)] and 21 CFR 190.6.
Under section 413 of the Act, a dietary supplement that contains a new dietary ingredient (i.e., a dietary ingredient not marketed in the United States before October 15, 1994) shall be deemed adulterated under section 402(f) of the Act [21 U.S.C. § 342(f)] unless it meets one of two requirements:
1. The dietary supplement contains only dietary ingredients that have been present in the food supply as an article used for food in a form in which the food has not been chemically altered; or
2. There is a history of use or other evidence of safety establishing that the dietary ingredient, when used under the conditions recommended or suggested in the labeling of the dietary supplement, will reasonably be expected to be safe and, at least 75 days before being introduced or delivered for introduction into interstate commerce, the manufacturer or distributor of the dietary ingredient or dietary supplement provides FDA with information, including any citation to published articles, which is the basis on which the manufacturer or distributor has concluded that a dietary supplement containing such dietary ingredient will reasonably be expected to be safe.
FDA is not aware of any information demonstrating that 4-etioallocholen-3,6,17-trione was lawfully marketed as a dietary ingredient in the United States before October 15, 1994, nor is FDA aware of any information demonstrating that this dietary ingredient has been present in the food supply as an article used for food in a form in which the food has not been chemically altered. In the absence of such information, 4-etioallocholen-3,6,17-trione is subject to the notification requirement for a new dietary ingredient in section 413(a)(2) of the Act [21 U.S.C. § 350b(a)(2)] and 21 CFR 190.6. Because the required notification has not been submitted, your BioRhythm Androbolix product is adulterated under sections 402(f)(1)(B) and 413(a) of the Act.
Dietary Supplement CGMP Violations
Even if your BioRhythm Olio and ReGenerate products did not have therapeutic claims which make them unapproved new and misbranded drugs, these products would be adulterated dietary supplements within the meaning of section 402(g)(1) of the Act [21 U.S.C. § 342(g)(1)] because the products have been prepared, packed, or held under conditions that do not meet the Current Good Manufacturing Practice (CGMP) regulations for dietary supplements, Title 21, Code of Federal Regulations, Part 111 (21 CFR Part 111) these . In addition, your BioRhythm Androbolix 300, Androbolix, Whole Gains Mango, Olio, and ReGenerate products are adulterated dietary supplements within the meaning of section 402(g)(1) of the Act for the same reason.
As a distributor that contracts with other manufacturers to manufacture dietary supplements that your firm releases for distribution under your firm’s name, your firm has an obligation to know what and how these activities are performed so that you can make decisions related to whether the products conform to established specifications and whether to approve and release the products for distribution [72 Fed. Reg. 34752, 34790 (June 25, 2007)]. Your firm introduces or delivers, or causes the introduction or delivery, of dietary supplements into interstate commerce for distribution to consumers. As such, your firm has an overarching and ultimate responsibility to ensure that all phases of the production of that product are in compliance with dietary supplement CGMP requirements.
Although your firm may contract out certain dietary supplement manufacturing operations, it cannot, by the same token, 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 with other firms to conduct certain dietary supplement manufacturing, packaging, and labeling operations for it is responsible for ensuring that the product is not adulterated for failure to comply with dietary supplement CGMP requirements, regardless of who actually performs the dietary supplement CGMP operations.
Specifically, during the inspection, our investigators observed the following violations:
1. You did not establish product specifications for the identity, purity, strength, and composition of your finished dietary supplements, and for limits on those types of contamination that may adulterate, or that may lead to adulteration of, the finished batch of dietary supplements, as required by 21 CFR 111.70(e). Specifically, during the inspection, you stated that you create and approve product formulations, which you provide to other manufacturers for the manufacture of your products in bulk. You also stated that you do not provide any additional specifications for the products. Further, in your response letter, dated April 10, 2013, you provided a Standard Operating Procedure (SOP) entitled “Specifications Setting Policy,” which specifies that “Exclusive Supplements must establish specifications for the finished batch of the dietary supplement.” While you stated that your firm will review the specifications that you have in place for finished products and establish finished product specifications where necessary, you failed to provide documentation of such finished product specifications. As such, we are unable to determine the adequacy of your proposed corrective actions at this time.
2. You did not prepare a written Master Manufacturing Record (MMR) related to your packaging and labeling operations, as required by 21 CFR 111.205. An MMR must include, among other things, the identity and weight or measure of each dietary ingredient that will be declared on the Supplement Facts label and the identity of each ingredient that will be declared on the ingredients list of the dietary supplement and a description of packaging and a representative label, or cross-references to the physical location of the actual or representative label (21 CFR 111.210). However, your firm did not prepare an MMR for the packaging and labeling operations conducted at your firm. We note the records provided as part of your firm response, dated April 10, 2013, are Batch Product Records and not MMRs. You must prepare MMRs for each of your products for the operations you perform.
3. You did not establish specifications to sufficiently assure that the product you receive for packaging and labeling as a dietary supplement is adequately identified and is consistent with your purchase order, as required by 21 CFR 111.70(f). Specifically, you stated during the inspection that you do you do not have written specifications for the packaging and labeling of your dietary supplement products, packaging, or labels that you receive for packaging and labeling. You also stated that you perform a visual examination of incoming products, but you stated that you do not document the visual examination you perform of incoming products. We note that a visual examination generally cannot sufficiently assure that dietary supplement products are adequately identified and consistent with your purchase order as a visual examination only provides information about the appearance of a product and such information alone generally cannot be used to verify the identity of product, particularly a product in capsule or tablet form.
We have reviewed your response letter, dated April 10, 2013, and determined your response to be inadequate. Your response states that you “will review the specifications [you] have in place for product [you] receive for packaging and labeling as a dietary supplement. Where necessary, these will be revised, approved and implemented.” However, you have not provided FDA with any documentation of such specifications, including those you have in place. As such, we are unable to determine the adequacy of your proposed corrective actions at this time.
4. Your quality control personnel approved and released for distribution product received from a supplier for packaging and labeling as a dietary supplement for which sufficient assurance was not provided to adequately identify the product to determine that the product is consistent with your purchase order, as required by 21 CFR 111.123(b)(4). Specifically, two products that you receive from a supplier for packaging and labeling are similar in name: BioRhythm Androbolix 300 capsules and BioRhythm Androbolix capsules. Your quality control personnel approved and released for distribution your BioRhythm Androbolix 300 capsules, lot# (b)(4), which you received from your contract manufacturer on 8/20/11. However, the Certificate of Analysis (COA) for this product lists ingredients that are not listed in your Androbolix 300 product Master Formula or product label. Rather, the ingredients listed on this COA are the ingredients listed in the Master Formula and product label for the other product, BioRhythm Androbolix capsules. Lot # (b)(4) was used to repack and label a total of (b)(4) – 120 capsule bottles of Androbolix 300 with finished product lot # (b)(4) and lot # (b)(4).
We note your firm’s response, dated April 10, 2013, concludes that the product received for packaging and labeling as Androbolix 300 was, indeed, Androbolix 300; your conclusion is that the COA included typographical errors. You base this conclusion on the fact that the product you received had the appropriate visual characteristics, namely color. You also submitted documentation in the form of a Master Batch Record from your contract manufacturer for your Androbolix 300 product. However, the listing of ingredients in this batch record further calls into question the identity of the product in that the ingredients are not consistent with either the Androbolix 300 Master Formula or the product label. Further, you did not submit the complete Batch Product Record, and there is no information as to how this product was manufactured or any other information that would assist in determining the identity of this product, such as results of identity testing. Reliance upon visual characteristics is not adequate to verify the identity and ensure quality of a dietary supplement product.
Furthermore, we note that the violations described above with respect to not preparing MMRs for your packaging and labeling operations under 21 CFR 111.205, not establishing specifications under 21 CFR 111.70(f), and the failures in your quality control operations under 21 CFR 111.123(b)(4) to ensure the products you receive from contract manufacturer(s) are consistent with your purchase order demonstrate a pervasive problem with your facility’s operations. It is critical that your firm have a system of production and process controls in place along with sufficient quality control operations to ensure the quality of your dietary supplements and that the dietary supplements are packaged and labeled as specified in the MMR (21 CFR 111.55 and 111.65). MMRs, applicable specifications, and quality control measures that relate specifically to your packaging, labeling and distribution operations are necessary to ensure the quality of your dietary supplement products, and to be compliant with the regulations under 21 CFR Part 111.
5. A qualified person did not investigate product complaints that involved possible failures of dietary supplements to meet specifications, or other requirements as required by 21 CFR 111.560(a)(2). Specifically, you did not investigate several complaints, including, but not limited to the following;
- A serious adverse event, dated 2/19/13, regarding BioRhythm brand Whole Gains Protein Watermelon in which the complainant experienced a rapid heart rate and dizziness after using the product.
- A serious adverse event, dated 4/5/11, regarding BioRhythm brand Olio softgels in which the complainant experienced rectal bleeding.
Furthermore, you failed to make and keep records related to product complaints, as required by 21 CFR 111.570. Specifically, you stated during the inspection that you remembered investigating two complaints related to your BioRhythm brand product, AfterGlow, in which the complainants stated that the product did not mix, and that the product tasted like sour milk; however, you did not document the investigation. You must investigate product complaints and document the investigation in order to comply with 21 CFR 111 Subpart O – Product Complaints.
6. You did not make and keep documentation of calibrations for instruments or controls that you use in manufacturing or testing a component or dietary supplement as required by 21 CFR 111.35(b)(3). Specifically, you do not document that your scales have been calibrated.
We have reviewed your response letter, dated April 10, 2013, and determined your response to be inadequate. Your response states that you will establish a more detailed written procedure for Calibration of Scales and will complete the implementation by May 13, 2013. However, you failed to provide documentation of such procedures. As such, we are unable to determine the adequacy of your proposed corrective actions at this time. We note that your scales should be calibrated as often as specified by the manufacturer of these scales.
Misbranded Dietary Supplements
Your BioRhythm brand Androbolix 300, Androbolix, and Whole Gains Mango dietary supplement products are misbranded under section 403 of the Act [21 U.S.C. § 343] in that the labeling for these products does not comply with labeling requirements for dietary supplements, including FDA’s regulations under 21 CFR Part 101. In addition, even if your BioRhythm Olio and ReGenerate products did not have therapeutic claims, which make these products unapproved and new misbranded drugs, they would also be misbranded for the same reason.
1. Your BioRhythm brand Androbolix 300, Androbolix, Whole Gains Mango, Olio, and ReGenerate dietary supplement 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 nutrition information does not comply with 21 CFR 101.36. For example,
- Your BioRhythm brand Androbolix 300 label does not list zinc, niacin and Vitamin B6 in the correct order. Niacin, vitamin B6 and zinc should be listed in that order before the other dietary ingredients in accordance with 21 CFR 101.36(b)(2) and 101.36(b)(3).
- In accordance with 21 CFR 101.36(b)(2)(ii)(B), your Whole Grains Protein label fails to include the total quantitative amount by weight per serving for dietary ingredients declared under 21 CFR 101.36(b)(2)(i)(B) using the units of measurement and the levels of significance given in § 101.9(c)(8)(iv). Furthermore, the enzymes declared on the label should not be listed after the terms “Ingredients” or “Other Ingredients”. The enzymes Pancreatin, amylase, protease, and lipase should be declared using their common or usual name and listed with their quantitative amount by weight per serving in metric units in the nutrition information within the Supplement Facts panel in accordance with 101.36(b)(3).
- Your Whole Grains Protein label fails to declare the dietary ingredients iodide, chloride, and potassium, their amounts in one serving of the product, and the percent of the daily value. Vitamins or minerals listed in 101.9(c)(8)(iv) shall be declared when they are added to the product for purposes of supplementation, or when a claim is made about them. Your label makes the claim to contain potassium iodide and potassium chloride.
In addition, the listing for “Other ingredients” on the labels of your BioRhythm brand Androbolix 300, Androbolix, Whole Gains Protein, Olio, and ReGenerate products must be listed outside of the Supplement Facts box in accordance with 21 CFR 101.4(g).
2. Your BioRhythm brand Androbolix and Androbolix 300 products are misbranded within the meaning of section 403(s)(2)(C) because the label fails to identify the part of the plant from which the ingredients are derived in accordance with 21 CFR 101.4(h). For example,
- Your Androbolix and Androbolix 300 labels fail to include the part of the plant from which Tribulus is derived.
- Your Androbolix 300 label fails to include the part of the plants from which Eurycoma longifolia and Cimicifuga racemosa are derived.
Adverse Event Reporting Violations
1. You failed to submit a Serious Adverse Event Report (SAER) for a dietary supplement within 15 business days after receiving a report about the adverse event, as required by section 761(c) of the Act [21 U.S.C. §§ 379aa-1(c)]. Specifically you did not submit an SAER for the following serious adverse events until April 11, 2013:
- A serious adverse event, dated 2/19/13, regarding BioRhythm brand Whole Gains Protein Watermelon in which the complainant experienced a rapid heart rate and dizziness after using the product.
- A serious adverse event, dated 4/5/11, regarding BioRhythm brand Olio softgels in which the complainant experience rectal bleeding.
This letter is not intended to be an all-inclusive list of violations that may exist at your facility. You are responsible for ensuring that your firm is operating in compliance with the Act and applicable FDA regulations, including dietary supplement CGMP regulations (21 CFR Part 111).
You should take prompt action to correct the violations noted in this letter and establish and implement procedures that will prevent these and other violations in the future. Failure to promptly correct these violations may result in enforcement action, such as seizure or injunction, without further notice.
Additionally, we have the following comment:
1. You state on page (b)(4) of your Standard Operating Procedures Manual (under the subheading 4. EXPIRATION DATING:
“The expiration date is the recommended shelf life date of the product as provided by the vendor/manufacturer of the bulk product. This information provided by the manufacturer is entered on the original receiving report for raw materials and must always be listed on the bulk containers as received by the manufacturer. If bulk materials are received by any vendor without the expiration date the bulk material will be refused by the shipping/receiving personnel and returned to the vendor.”
Please note that the term “shelf life date” includes expiration dating and “best if used by” dating [See 72 Fed. Reg. 34912, 34856 (Jun. 25, 2007)]. Any expiration, shelf life, or “best if used by” date you place on a product label should be supported by stability data [See 72 Fed. Reg. 34752, 34856 (Jun. 25, 2007)].
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 reinspection-related costs. A reinspection 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. Reinspection-related costs means all expenses, including administrative expenses, incurred in connection with FDA’s arranging, conducting, and evaluating the results of the reinspection 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 reinspection-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 reinspection-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.
Your response should be sent to Lynn S. Bonner, Compliance Officer at the address noted above.
If you have any questions with regard to this letter, Ms. Bonner can be reached at 215-717-3074 or Lynn.Bonner@fda.hhs.gov.
Anne E. Johnson
Acting District Director