Inspections, Compliance, Enforcement, and Criminal Investigations

Threshold Enterprises Ltd 10/12/16

  

Department of Health and Human Services logo

 
San Francisco District
Pacific Region
1431 Harbor Bay Parkway
Alameda, CA 94502-7070
Telephone:    510-337-6700
FAX:    510-337-6701 

 

WARNING LETTER
 
Via UPS
Delivery Signature Requested
                                                     
October 12, 2016
 
Ira L. Goldberg, President
Threshold Enterprises, Ltd.
23 Janis Way
Scotts Valley, CA 95066
 
 
Dear Mr. Goldberg;
 
The U.S. Food and Drug Administration (FDA or we) conducted an inspection of your dietary supplement facility located at 23 Janis Way, Scotts Valley, California, from March 21, 2016, through April 20, 2016. The inspection found that your facility has significant violations of the Current Good Manufacturing Practice (CGMP) regulations for dietary supplements, Title 21, Code of Federal Regulations (CFR), Part 111 (21 CFR Part 111). These violations cause your 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 products have been prepared, packed, or held under conditions that do not meet CGMP requirements for dietary supplements. 
 
In addition, we have reviewed your product labeling collected during the inspection and have evaluated your website at Internet address www.sourcenaturals.com.  We have determined that certain claims and intended use statements cause your sublingual melatonin and topical progesterone cream product to be new drugs as defined by section 201(p) of the Act [21 U.S.C. § 321(p)] because they are not generally recognized as safe and effective for use under the conditions, prescribed, recommended, or suggested in the labeling, and are in violation of section 505(a) of the Act [21 U.S.C. § 355(a)] because a new drug application has not received approval prior to commercial marketing.   
 
You may find the Act and FDA’s implementing regulations through links on FDA’s home page at www.fda.gov.
 
Unapproved New Drugs
 
Your firm’s sublingual Source Naturals® Melatonin products and Source Naturals® Progesterone Cream are unapproved drugs under the Act.
 
Your sublingual Melatonin and Progesterone Cream products include labeling claims such as the following:
 
Source Naturals® Melatonin Products
  • “…it governs the body’s circadian rhythms, helping the body ease into restful sleep.”
  • “Suggested Use: 1 tablet at bedtime; ½ tablet may be sufficient for sample people. Do not take more than 1 tablet daily. Place tablet under the tongue and allow to dissolve slowly, altering the position of the tablet to avoid prolonged contact with the same area.”
  • “The sublingual form is absorbed directly into the bloodstream, via the blood vessels under the tongue and in the cheeks, bypassing the liver and allowing for quick entry into the system.”
  • “Melatonin is necessary for healthy sleep.”
Source Naturals® Progesterone Cream
  • “Progesterone cream is a topical application of natural progesterone USP from soy, with additional key ingredients to help women who seek relief from the normal discomforts of menopause, such as hot flashes, night sweats, and occasional sleeplessness.”
  • “This product uses liposome delivery technology for topical penetration and absorption of the ingredients. Liposomes are tiny lecithin spheres that surround the progesterone so it can deliver its benefits to the body.”
  • “The formula includes ingredients like yam root extract with phytoestrogens to support women through the hormonal transition during menopause.”
Under section 201(g)(1)(C) of the Act [21 U.S.C. § 321(g)(1)(C)] products (other than foods) that are intended to affect the structure or function of the body are defined as drugs. The claims listed above make clear that your Source Naturals® Melatonin products and Source Naturals® Progesterone Cream are intended to affect the structure or function of the human body. 
 
Your firm markets Source Naturals® Melatonin products as dietary supplements. However, the Act defines the term “dietary supplement” in section 201(ff)(2)(A)(i) of the Act [1 U.S.C. § 321(ff)(2)(A)(i)], as a product that is “intended for ingestion.” Because sublingual products are intended to enter the body directly through the skin or mucosal tissues, they are not dietary supplements and are not foods. Therefore, your firm’s Source Naturals® Melatonin products are drugs under section 201 (g)(1)(C) of the Act [21 U.S.C. § 321(g)(1)(C)].
 
Moreover, your Source Naturals® Melatonin products and Source Naturals® Progesterone Cream are “new drugs,” as defined by section 201(p) of the Act [21 U.S.C. § 321(p)], because they are not generally recognized as safe and effective for use under the conditions prescribed, recommended, or suggested in their labeling.
 
Under sections 301(d) and 505(a) of the Act [21 U.S.C. §§ 331(d) and 355(a)], a new drug may not be introduced or delivered for introduction into interstate commerce unless an FDA-approved application is in effect for it. Your sale of Source Naturals® Melatonin products and Source Naturals® Progesterone Cream without approved applications violates these provisions of the Act.
 
Over-the-counter (OTC) topical hormone containing products promoted for use as a drug are subject to final rule 21 CFR 310.530(b). The rule states that any OTC drug product other than hydrocortisone and hydrocortisone acetate that is labeled as a topically applied hormone-containing product for drug use is regarded as a new drug. Your product Source Naturals® Progesterone Cream falls within this rule because it is labeled as a topical hormone product for drug use.
 
Adulterated Dietary Supplements
 
The inspection 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 [21 U.S.C. § 342(g)(1)] in that they have been prepared, packed, or held under conditions which do not meet the CGMP regulations for dietary supplements.
 
1.    You failed to establish finished product specifications for each dietary supplement that you manufacture 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).
 
Once you have established the finished product specifications, you must verify that the specifications are met in accordance with 21 CFR 111.75(c), and you must make and keep records in accordance with 21 CFR 111.95(b).
 
We acknowledge your response, dated May 11, 2016; however, we find your response to be inadequate in that Forms QC-233g.4, QC-232a.4, QC- 232b.4, and QC-233b.4 fail to include numerical limits, ranges or other criteria for the tests described, and the specification section is identified as Bulk Product Specification.  Additionally, you state that many of the specifications, tests, and examinations occur at in-process steps or at finished batch stages and are designed to ensure the final bottles package meets all specifications.  For those in-process specifications intended to support finished product specifications, you must provide adequate documentation of the basis for why meeting the in-process specifications, in combination with meeting component specifications, will ensure the specifications for identity, purity, strength, composition, and limits of contaminants for the finished dietary supplement are met, as required by 21 CFR 111.70(c)(2).  These specifications must first be established in order to have criteria by which to test.
 
2.    You failed to establish the required specifications, as required by 21 CFR 111.70(b) for the following components: Passionflower Aerial Parts, Lemon Balm Leaf Extract, Chamomile Flower Extract 4:1, and Magnesium Chelate 30%.
 
Component specifications for each component used in the manufacture of a dietary supplement are to include:
 
i.    Identity specifications [21 CFR 111.70(b)(1)];
 
ii.    Specifications to ensure the purity, strength, and composition of dietary supplements manufactured using the components are met [21 CFR 111.70(b)(2)]; 
 
iii.    Specifications that establish the limits on those types of contamination that may adulterate or may lead to adulteration of the finished batch of the dietary supplement to ensure the quality of the dietary supplement [21 CFR 111.70(b)(3)];
 
Once you have established the above specifications, you must verify that the specifications are met in accordance with 21 CFR 111.73, and you must make and keep records in accordance with 21 CFR 111.95(b).
 
We acknowledge your response, dated May 11, 2016; however, we find your response to be inadequate in that you provided a testing grid for Passionflower Aerial Parts, Lemon Balm Leaf Extract, Chamomile Flower Extract, Bitter Melon 500mg CAP 1C, 3 and Bitter Melon Fruit Extract.  We have determined that these grids are insufficient information of having established component specifications.  Specifications may include a list of tests, references to analytical procedures, along with appropriate acceptance criteria that are numerical limits, ranges, or other criteria for the tests described.  Additionally, you state, ‘there is no scientifically valid method for determining strength of a botanical material in a raw herb form or extract form or in a blended product” as with Passionflower Aerial Parts, Lemon Balm Leaf Extract, Chamomile Flower Extract, Bitter Melon 500mg CAP 1C, and Bitter Melon Fruit Extract.  An exemption to having strength specifications for these ingredients would be inappropriate because it appears these components have a strength claim associated with them for the finished products, (e.g. 4:1 and 500 mg) so a strength specification must be established and documented in order to ensure the correct amount of the ingredient is added and the strength of the ingredient meets the label claim in the final products.
 
Misbranded Dietary Supplements
 
The review of your product labels for B-50 Complex, Melatonin Orange Flavored Sublingual, and Bitter Melon determined they are misbranded dietary supplements under Section 403 of the Act because they do not comply with the labeling requirements for dietary supplements. Specifically:
 
1.    Your B-50 Complex product is 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 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.  The directions of use suggest the consumer take 1 to 2 tablets daily.  The serving size listed should be two tablets.
 
2.    Your Bitter Melon and B-50 Complex products are misbranded within the meaning of section 403(i)(2) of the Act [21 U.S.C. § 343 (i)(2)] in that each product label fails to declare the common or usual name of each ingredient used as required by 21 CFR 101.4(a), 21 CFR 101.4(g) and 21 CFR 101.4(h).  For example, the source of the thiamine is not declared in the supplement facts label of the B-50 Complex product.  In addition, the standardized common name as noted in Herbs of Commerce or the Latin binomial name of the botanical is not declared in the supplement facts label of the Bitter Melon product.
 
The violations cited in this letter are not intended to be an all-inclusive statement of violations that exist 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 firm complies with all requirements of federal law, including FDA 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 and injunction. 
 
We offer the following cGMP comment:
 
The “purity” of a dietary supplement refers to that portion or percentage of a dietary supplement that represents the intended product.  “Impurity” refers to the identity and amount of a dietary supplement that is not the desired product.  You have identified impurities as heavy metals (assay for lead, arsenic, cadmium, mercury) pg. 7 in your response.  FDA refers to these as a type of contamination that may adulterate or that may lead to adulteration of the finished dietary supplement, not “impurities.”
 
We offer the following labeling comment:
 
The name “Supplement Facts” doesn’t extend the full width of the panel for all products.
 
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 reinspection 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.
 
Within fifteen (15) 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 documentations. 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.
 
Your written response should be sent to Lawton W. Lum, Director of Compliance, at the address noted below and should reference unique identifier 499200.
 
U.S. Food and Drug Administration
San Francisco District
1431 Harbor Bay Parkway
Alameda, CA  94502
 
If you have any questions regarding any issue in this letter, please contact William V. Millar, Compliance Officer, at (510) 337-6896 or by fax at (510) 337-6703.
 
Sincerely,
/S/ 
Kathleen M. Lewis, J.D.
District Director
San Francisco District

Page Last Updated: 10/21/2016
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