Inspections, Compliance, Enforcement, and Criminal Investigations
The Glutathione Corporation 4/5/13
Department of Health and Human Services
|Public Health Service|
Food and Drug Administration
New York District
Food & Drug Administration
158-15 Liberty Avenue
Jamaica, NY 11433
April 5, 2013
WARNING LETTER NYK-2013-11
VIA UNITED PARCEL SERVICE
Dr. Harry B. Demopoulos, Chief Executive Officer
The Glutathione Corporation
8 Westchester Plaza
Elmsford, NY 10523
Dear Dr. Demopoulos:
The U.S. Food and Drug Administration (FDA) inspected your dietary supplement manufacturing facility, located at 8 Westchester Plaza, Elmsford, New York on September 19, 2012 through October 1, 2012, and found that you have serious violations of FDA’s Current Good Manufacturing Practice (CGMP) in Manufacturing, Packaging, Labeling, or Holding Operations for Dietary Supplements regulation, Title 21, Code of Federal Regulations, Part 111 (21 CFR Part 111). These violations cause your dietary supplement products to be adulterated under 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 regulation for dietary supplements.
In addition, we have reviewed the labeling for your products and your website at www.glutathionescience.com. Based on our review, we have concluded that certain of your products identified below are in violation of sections 403, 505(a), and/or 502(f)(1) of the Act [21 U.S.C. §§ 343, 355(a), and/or 352(f)(1)] and the regulations implementing the food labeling requirements of the Act, which are found in Title 21, Code of Federal Regulations, Part 101 (21 CFR Part 101). You may find the Act and its implementing regulations through links on FDA’s home page at www.fda.gov.
Dietary Supplement cGMP Violations:
The inspection revealed the following violations:
- Your firm did not establish specifications for each component that you use in the manufacture of a dietary supplement as required by 21 CFR 111.70(b), and conduct at least one appropriate test or examination to verify the identity of a component that is a dietary ingredient, prior to its use, as required by 21 CFR 111.75(a)(1)(i). Specifically, your firm failed to establish an identity specification for L-Glutathione Reduced, which is a dietary supplement ingredient for most of your firm’s products. During the inspection you informed the Investigators that you perform a microscopic examination of incoming lots of L-Glutathione Reduced to verify that the ingredient has its “characteristic structure”; however, you have no written specification or description for this characteristic microscopic structure and you keep no documentation of any lot by lot microscopic examination of the incoming component. Furthermore, your firm lacks documentation of conducting identity tests of any of the other dietary ingredients contained in any of your dietary supplement formulas, and you have not received approval of a petition for exemption from identity testing, as provided for in 21 CFR 111.75(a)(1)(ii).
- You did not verify, for the finished batches of your dietary supplements identified below, that either every finished dietary supplement batch or a subset of the finished dietary supplement batches that you identify through a sound statistical sampling plan meets product specifications for identity, purity, strength, composition, and for limits on those types of contamination that may adulterate or that may lead to adulteration of the finished batch, as required in 21 CFR 111.75(c). Specifically, your firm does not perform any finished product testing for the dietary supplements manufactured by your firm, which include; Ultrathione 500 Glutathione, Ultrathione 1000 Sports Pack, Ultrathione Performance, Ultrathione Extreme Performance, Daily Essentials, Super Ascorbic-B Antioxidant Nutrients, Ultrathione Health Pack, Ophthalmic Nutrients 1500, Travel Smart & Strong, Ultimate Travel Smart & Strong, Arthro-Packs, Guardian, Guardian BCAA/B-12 (capsules), Ultrathione Extreme Performance Plus, and Guardian BCAA/B-12 (powder).
- You did not prepare a written master manufacturing record for each unique formulation of a dietary supplement that you manufactured, as required by 21 CFR 111.205(a). Specifically, you have no master manufacturing records for the dietary supplements manufactured by your firm.
- Your batch production record did not include complete information relating to the production and control of each batch, as required by 21 CFR 111.255(b). Specifically, batch records for four lots of Ultrathione 500 Glutathione (lot numbers 163, 164, 165, and 166) and two lots of Daily Essentials (without lot numbers but with expiration dates listed on the batch record as 8/6/14 and 8/20/14) manufactured by your firm did not include key information required by 21 CFR 111.260, such as:
- Documentation of the manufacture of the batch at the time of performance [21 CFR 111.260(j)];
- The date on which each step of the master manufacturing record was performed [21 CFR 111.260(j)(1)];
- The initials of the person performing each step [21 CFR 111.260(j)(2)];
- The initials of the person weighing out the ingredients/components [21 CFR 111.260(j)(2)(i)];
- The initials of the person responsible for verifying the weight or measure of each component [21 CFR 111.260(j)(2)(ii)];
- The date and time of the maintenance, cleaning and sanitizing of the equipment and processing lines used in producing the batch, or cross references to records, such as individual equipment logs, where this information is retained [21 CFR 111.260(c)];
- A statement of the actual yield and percentage of theoretical yield at appropriate phases of processing [21 CFR 111.260(f)].
- You did not establish and follow written procedures for the responsibilities of the quality control operations, as required by 21 CFR 111.103. Specifically, your firm has no written procedures for quality control or specified responsibilities of a quality control operation.
- You did not establish written procedures for the requirements to review and investigate a product complaint, as required by 21 CFR 111.553. Specifically, your firm has no written procedures for handling product complaints.
- You did not establish and follow written procedures for fulfilling the requirements of 21 CFR 111 Subpart G for components of dietary supplements that you receive for manufacturing, packaging or labeling, as required by 21 CFR 111.153. Specifically, your firm lacks written procedures for meeting these requirements for incoming ingredients/components used in the manufacturing of the dietary supplements by your firm.
Unapproved New Drugs:
Your product labels and website, www.glutathionescience.com, were reviewed in March 2013, and we have determined that your products, Ultrathione 500 Glutathione, Ultrathione 1000 Sports Pack, Ultrathione Performance, Ultrathione Extreme Performance, Ultrathione Health Pack, Ophthalmic Nutrients 1500, Ultimate Travel Smart & Strong, Guardian, and Ultrathione Extreme Performance Plus, are 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 on your website establish that the products are drugs because they are intended for use in the cure, mitigation, treatment or prevention of disease. The marketing of these products with these claims violates the Act.
Many of your product labels include the URL for your website where consumers can purchase your products. The home page for that website includes links to the following promotional materials which contain claims regarding an ingredient in each of these products (Glutathione, also referred to as L-glutathione and GSH). In addition, the individual product webpages for many of the products that consumers can purchase on the website include links to the same promotional materials. Examples of these claims on the promotional materials include:
The Health Full Regimen
- “…keep a box of Ultrathione 500’s available, and use them…if respiratory infections seem rampant around you…”
Holiday Beacon December
- “…people who use APC’s Glutathione products…have a significant reduction in Seasonal Respiratory Infections.”
Beacon Hypertension – Arthritis
- “…Glutathione, abbreviated as “GSH”…can … dismantle toxic fats that have become peroxidized (“rancid”) … When there is excessive, uncontrolled peroxidation of fats the following can occur in humans: … vision loss as in Macular Degeneration, and Alzheimer’s.”
The “Glutathione” Corporation L-gamma-“Glutathione”
- “…GSH corrects pathologic processes that are found…in…diseases such as Pulmonary Emphysema, Cystic Fibrosis, Pulmonary Hypertension, and Diabetic Vascular Complications.”
Your 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) of the Act [21 U.S.C. § 321(p)]. A new drug may not be legally marketed in the United States without prior approval from FDA as described in section 505(a) of the Act [21 U.S.C. § 355(a)]. 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.
Further, your 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 products safely for their intended uses. Thus, the labeling fails to bear adequate directions for the products’ intended uses, causing the products to be misbranded under section 502(f)(1) of the Act [21 U.S.C. § 352(f)(1)]. The introduction of misbranded drugs into interstate commerce is a violation of section 301(a) of the Act [21 U.S.C. § 331(a)].
Misbranding of Dietary Supplements:
Even if the labeling for your dietary supplement products did not contain claims that cause them to be an unapproved new and misbranded drug, they would still be misbranded dietary supplements under section 403 of the Act [21 U.S.C. § 343] in that the labeling does not comply with the food labeling requirements in 21 CFR Part 101, as follows:
- Your Ultrathione 500 Glutathione, Ultrathione 1000 Sports Pack, Ultrathione Performance, Ultrathione Extreme Performance, Daily Essentials, Super Ascorbic-B Antioxidant Nutrients, Ultrathione Health Pack, Ophthalmic Nutrients 1500, Travel Smart & Strong, Ultimate Travel Smart & Strong, Arthro-Packs, Guardian, Guardian BCAA/B-12 (capsules), Ultrathione Extreme Performance Plus, Guardian BCAA/B-12 (powder), and Pure-E 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 is not enclosed inside a “Supplement Facts” box, in accordance with 21 CFR 101.36.
- Your Ultrathione 500 Glutathione, Ultrathione 1000 Sports Pack, Ultrathione Performance, Ultrathione Extreme Performance, Daily Essentials, Super Ascorbic-B Antioxidant Nutrients, Ultrathione Health Pack, Ophthalmic Nutrients 1500, Travel Smart & Strong, Ultimate Travel Smart & Strong, Arthro-Packs, Guardian, Guardian BCAA/B-12 (capsules), Ultrathione Extreme Performance Plus, Guardian BCAA/B-12 (powder), and Pure-E dietary supplement products are misbranded within the meaning of section 403(q)(1)(A) of the Act [21 U.S.C. § 343(q)(1)(A)] in that the product labels fail to bear a Serving Size as required by 21 CFR 101.36(b)(1)(i) and 21 CFR 101.9(b).
- Your Ultrathione 500 Glutathione, Ultrathione 1000 Sports Pack, Ultrathione Performance, Ultrathione Extreme Performance, Super Ascorbic-B Antioxidant Nutrients, Ultrathione Health Pack, Ophthalmic Nutrients 1500, Travel Smart & Strong, Ultimate Travel Smart & Strong, Arthro-Packs, Guardian, Guardian BCAA/B-12 (capsules), Ultrathione Extreme Performance Plus, Guardian BCAA/B-12 (powder), and Pure-E dietary supplement products are misbranded within the meaning of section 403(s)(2)(B) of the Act [21 U.S.C. § 343(s)(2)(B)] in that the product labels fail to include the term “dietary supplement” as part of the statement of identity, except that the word “dietary” may be deleted and replaced by the name of the dietary ingredients in the product, in accordance with 21 CFR 101.3(g).
This letter may not list all the violations at your facility. You are responsible for ensuring that your facility operates in compliance with the Act and all applicable FDA regulations, including the CGMP regulation for dietary supplements.
You should take prompt action to correct the violations described above and prevent their future recurrence. We may take further action if you do not promptly correct these violations. For instance, we may take further action to seize your product(s) and/or enjoin your firm from operating.
In addition, we have the following comments:
- During the inspection, you stated that your firm does not assign lot numbers, per se, on finished batches of products. Rather, you assign an expiration date to your finished lots and print the expiration date on the label. Expiration dates are calculated 23 months from the month of manufacture of the finished batch of dietary supplement. For your dietary supplement, Daily Essentials, manufactured in August 2012, the expiration date was erroneously printed on your label as 08/2014; however, it should have been labeled 07/2014. You released eight units (which were stored in the finished product release area) with this incorrect label. Additionally, although you stated during the inspection that you do not manufacture more than (b)(4) in a month (which would cause confusion in relying on the expiration month and year as the “lot number”), we note that our investigator collected manufacturing records for at least two lots manufactured with expiration dates identified as “8/6/14” and “8/20/14.” Upon reducing these expiration dates to the date printed on your label, as is your firm’s custom, these two lots would both be reduced to 8/2014, causing mixing of the lots.
- We note that you are required by 21 CFR 111.15(b)(1) to maintain your physical plant in a clean and sanitary condition. In your firm’s mixing room, FDA Investigators observed: a) dust build-up on a ceiling pipe, which was approximately 12 ft. above the opening of the large mixer; and b) a white powder build-up on the base of a mechanical hopper, which was approximately 2 ft. above the opening of the small mixer.
- We note that you are required by 21 CFR 111.30(c) to routinely calibrate, inspect, and check the automated, mechanical, or electronic equipment to ensure proper performance. You informed FDA Investigators during the inspection that your firm had no calibration schedule, and does not routinely calibrate the following pieces of equipment which are used in the manufacturing and re-packing of dietary supplements by your firm: a) the (b)(4) used to weigh out the ingredients/components for each batch of product; and b) (b)(4) Model (b)(4) that is used to measure the mixing time for each batch of product.
You should respond in writing within fifteen (15) working days from your receipt of this letter. Your response should outline the specific steps you are taking to correct these violations. If you cannot complete all corrections before you respond, you should explain the reason for your delay and state when you will correct any remaining violations.
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 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.
Your written response should be sent the Food and Drug Administration; Attention:
LCDR Frank Verni
U. S. Food and Drug Administration
158-15 Liberty Avenue, Room 4050
Jamaica, NY 11433
If you have any questions about the content of this letter please contact: LCDR Verni at (718) 662-5702.
Ronald M. Pace
New York District