Inspections, Compliance, Enforcement, and Criminal Investigations

PI Pharma Inc 10/30/14

  

Department of Health and Human Services logoDepartment of Health and Human Services

Public Health Service
Food and Drug Administration
 
Cincinnati District Office
Central Region
6751 Steger Drive
Cincinnati, OH 45237-3097
Telephone: (513) 679-2700
FAX: (513) 679-2761 

 

October 30, 2014
WARNING LETTER
WL-15-422732-05
Via United Parcel Service
 
Donald W. Jessup, Owner
PI Pharma Inc. also dba Nature’s Extra 
198 Twin Branch Road
Campton, KY 41301
 
Dear Mr. Jessup:
 
The United States Food and Drug Administration (FDA) conducted an inspection of your facility, located at 198 Twin Branch Road, Campton, KY from February 10, 2014 to February 19, 2014.  Based on our inspection and review of your product labeling, we found serious violations of the Federal Food, Drug and Cosmetic Act (the Act) and applicable regulations. You can find the Act and its implementing regulations through links on FDA’s home page at http://www.fda.gov.
 
Unapproved New Drugs
 
Based on our review of the product labels obtained during the inspection of your facility, and of the website (b)(4), which is listed on the (b)(4) product label, we have determined that the claims on the product labels and on the website provide evidence that the products “Argentia Silver Cream” and (b)(4) are intended for use in the diagnosis, cure, mitigation, treatment or prevention of disease and/or intended to affect the structure or any function of the body, and are therefore drugs within the meaning of section 201(g)(1) of the Act [21 U.S.C.§ 321(g)(1)]. 
 
Examples of the claims that provide evidence that your products are intended for use as drugs include:
 
Argentia Silver Cream
 
  • “Wound Healing… Pain Relief & Burn Therapy…”
  • “Directions: apply topically as needed to open wounds, scratches, bites, burns, abrasions, or inflamed areas of the skin.”
  • “ANTIBACTERIAL… ANTIFUNGAL… ANTIVIRAL… ANTI-INFLAMMATORY”
(b)(4) 
  • “Genital Wart Treatment”
  • (b)(4) gently delivers the combination of Melaleuca, Prunella Vulgaris, Vitamin E, and Aloe, along with the 5% salicylic acid solution deep into the skin tissue, assisting the body’s own immune system to regain control, naturally. . . . Prunella Vulgaris has been shown to be an extremely effective anti-viral agent.”
 
It is clear from the above-mentioned claims that these products, “Argentia Silver Cream” and (b)(4) are intended for use as drugs. Because “Argentia Silver Cream” and (b)(4) are not generally recognized as safe and effective for use under conditions prescribed, recommended, or suggested in their labeling, they are also “new drugs” under section 201(p) of the Act [21 U.S.C. § 321(p)].  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 distribution of “Argentia Silver Cream” and (b)(4) without approved applications violates these provisions of the Act.
 
(b)(4) is also misbranded under section 502(f)(1) of the Act [21 U.S.C. § 352(f)(1)], because its labeling fails to bear adequate directions for use. “Adequate directions for use” means directions under which a layman can use a drug safely and for the purposes for which it is intended [21 CFR § 201.5]. (b)(4) is offered for genital warts, a condition which is not amenable to self-diagnosis and treatment by individuals who are not medical practitioners. Therefore, adequate directions cannot be written so that a layman can use this product safely for its intended use. (b)(4) is not exempt from the requirement that its labeling bear adequate directions for use under 21 CFR §§ 201.100(c)(2) and 201.115 because no FDA-approved application is in effect for it. For these reasons, (b)(4) is misbranded under section 502(f)(1) of the Act [21 U.S.C. § 352(f)(1)]. The introduction or delivery for introduction of a misbranded drug into interstate commerce violates section 301(a) of the Act [21 U.S.C. § 331(a)].
 
We reviewed your March 10, 2014 response letter and determined your response to be inadequate. You state in your response that “[t]he label for Argentia Silver Cream is being revised to remove all references to health benefits that may be considered a drug product claim” and as of the date of your response, “[t]he corrective actions have been made…” You also state that you “will no longer produce (b)(4) with label content that appears to make drug claims.” However, you have not provided FDA any detail on the specific changes made or any updated product labeling to evaluate those revisions.   
 
Dietary Supplement CGMP Violations
 
In addition, our inspection revealed that you have significant violations of the Current Good Manufacturing Practice (CGMP) regulations for dietary supplements, Title 21, Code of Federal Regulations, Part 111 (21 CFR 111). These violations cause your (b)(4) dietary supplements 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 they have been prepared, packed, or held under conditions that do not meet the CGMP regulations for dietary supplements.
 
We have received and reviewed your written response dated March 10, 2014 concerning our investigator’s observations noted on the Form FDA 483, List of Inspectional Observations that was issued to you. We address this response below, in relation to each of the noted violations. Your significant violations are as follows:
 
1.    You failed to establish product specifications 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 for each dietary supplement that you manufacture, as required by 21 CFR 111.70(e). Specifically, our investigator asked to review finished product specifications for your (b)(4) dietary supplement product. However, you were unable to provide such specifications to us for review.
 
Further, you failed to verify that your finished batch of dietary supplements meets product specifications for identity, purity, strength, and composition, and for limits on those types of contamination that may adulterate or that may lead to adulteration of the finished batch of the dietary supplements, for a subset of finished dietary supplement batches that you identify through a sound statistical sampling plan (or for every finished batch), as required by 21 CFR 111.75(c).  Specifically, you informed our investigator that you were not conducting any finished product testing, but instead were relying on your established written procedures “Release of Finished Goods,” SOP No.:RFG-6-0, to allow for finished goods to be conditionally released by Quality Control based upon prior history of product.
 
We reviewed your response letter, dated March 10, 2014, and find your response to be inadequate. Your response states that you have acquired an FTIR and will use it in conjunction with your HPLC unit to assay product mixtures, use the FT-IR for identity testing, revise finished product and raw material specifications and analytical data sheets, and develop methods. Your response states that you intend to start this “immediately” and will start with your largest selling products. 
 
However, your response does not define a time frame of when you plan to have specifications established and testing methods in place to verify that the finished batch of dietary supplement products meet its specifications and your response does not provide documentation for us to determine the adequacy of your proposed corrective actions.
 
2.    You failed to establish specifications for a product you receive from a supplier for packaging and labeling as a dietary supplement (and for distribution rather than for return to the supplier) to provide sufficient assurance that the product you receive is adequately identified and is consistent with your purchase order, as required by 21 CFR 111.70(f). Specifically, our investigator asked to review your product specifications for your (b)(4) dietary supplements. However, you were unable to provide such specifications to us for review.
 
3.    You failed to determine whether the specifications you establish under 21 CFR 111.70(b) are met, as required by 21 CFR 111.73. Specifically, your firm does not conduct any raw material testing on components that are used in the finished dietary supplements manufactured by your firm. Before you use a component, you must conduct at least one appropriate test or examination to verify the identity of a component that is a dietary ingredient, as required by 21 CFR 111.75(a)(1)(i). You must confirm the identity of other components that are not dietary ingredients and determine whether other applicable component specifications established in accordance with 21 CFR 111.70(b) are met, as required by 21 CFR 111.75(a)(2). 
 
We reviewed your response letter, dated March 10, 2014, and find your response to be inadequate. Your response states that you have acquired an FTIR for identity testing; that you will revise finished product and raw material specifications and analytical data sheets; and develop analytical methods.
 
You intend to start this “immediately” and will start with your largest selling products. Your response also states that you will be revising the applicable SOP’s and analytical methods. 
 
However, your response does not define a time frame for when you plan to have your testing methods implemented and revisions in place and it does not give a plan for when you expect to have such corrections in place for all components used in the manufacture of your dietary supplement products. Your response also does not provide documentation for us to determine the adequacy of your proposed corrective actions. 
 
4.    Your batch production records failed to include complete information relating to the production and control of each batch, as required by 21 CFR 111.255(b). The batch records that you provided to our investigators at the time of inspection did not include complete information related to production and in-process controls used during production. Specifically, the batch records used by your firm to document the production of your (b)(4) dietary supplement (lots 4006 and 4012) were missing the following information:
           
a.    The identity of equipment and processing lines used in producing the batch, as required by 21 CFR 111.260(b). For example, the packaging record associated with the batch records for (b)(4) does not list the processing line used to package this product.
 
b.    The date and time of maintenance, cleaning and sanitizing of the equipment used during production of the batch, as required by 21 CFR 111.260(c).
 
c.    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). Specifically, your batch production records did not include documentation that your finished products meet labeling and packaging specifications.
 
d.    Documentation, at the time of performance, of packaging and labeling operations, as required by 21 CFR 111.260(k). Specifically, you failed to include:
 
i.    The unique identifier that you assigned to packaging and labels used, the quantity of the packaging and labels used, and when label reconciliation is required, reconciliation of any discrepancies between issuance and use of labels, as required by 21 CFR 111.260(k)(1);
 
ii.    The results of any tests or examinations conducted on packaged and labeled dietary supplements (including repackaged or relabeled dietary supplements), or a cross-reference to the physical location of such results as required by 21 CFR 111.260(k)(3).
 
e.    Documentation at the time of performance that quality control personnel approved and released, or rejected, the packaged and labeled dietary supplement, including any repackaged or relabeled dietary supplement, as required by 21 CFR 111.260(l)(4).
 
This letter is not an all-inclusive list of the 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. You are responsible for ensuring 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, such as seizure and injunction.
 
During the inspection, our investigator also observed deviations from current good manufacturing practice (CGMP) regulations in the manufacture of drug products, including Argentia Silver Cream and (b)(4), at your facility. As a manufacturer of human drugs it is your responsibility to assure that any drug products are manufactured in conformance with CGMP as delineated in 21 CFR Parts 210 and 211. 
 
For example, your firm has not performed appropriate laboratory testing to determine if finished drug product meets final specifications, including the identity and strength of each active ingredient, prior to release, as required by 21 CFR 211.165(a). Our inspection showed that your firm does not conduct any finished product testing on the drug products manufactured by your firm. In addition, your firm has neither performed at least one identity test on incoming components, including Salicylic Acid USP and Colloidal Silver, as required by 21 CFR 211.84(d)(1), nor established the reliability of your component supplier’s analyses through appropriate validation of the supplier’s test results at appropriate intervals, as required by 21 CFR 211.84(d)(2). Your firm failed to maintain equipment by not sanitizing and changing filters for your water purification system according to the manufacturer’s directions and at appropriate intervals in order to prevent contamination, as required by 21 CFR 211.67(a). Also, your firm failed to establish written procedures for production and process control designed to assure that the drug products have the identity, strength, quality and purity they purport or are represented to possess, as required by 21 CFR 211.100(a). Specifically, your firm has failed to establish process parameters for adequate mixing of your drug products, including mixing times, speeds, and temperatures. All the observations listed above were repeat deficiencies from the previous inspection.
 
We acknowledge your responses dated March 6, 2013 and March 10, 2014. Your responses did not include corrective actions for the human drug observations in the Form FDA 483 (items five through nine). Please provide your proposed corrective actions, or evidence that items five through nine have been corrected.
 
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 non-compliance 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 non-compliance materially related to a food safety requirement of the Act.  Accordingly, FDA may assess fees to cover any costs related to reinspection.
 
You should respond in writing within fifteen (15) working days from your receipt of this letter. Your reply should include the specific steps that you are taking to correct the violations cited in this letter and documented evidence of your corrective actions. 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.
 
Your response should be sent to the U.S. Food and Drug Administration, 6751 Steger Dr., Cincinnati, OH 45237, Attention: Mark E. Parmon, Compliance officer. If you have questions regarding the content of this letter, please contact Mark E. Parmon, Compliance Officer, at (513) 679-2700 extension 2162.
 
 
Sincerely,
/S/ 
Paul J. Teitell
District Director
Cincinnati District

Page Last Updated: 11/03/2014
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