| || |
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
VIA UPS Overnight
JUL 19 2013
Mr. David LeBaron
Chief Executive Officer
ProNatural Nutrition, LLC
396 North 2150 West # B4
P.O. Box 2144
Cedar City, UT 84721
Ref: # DEN-13-18-WL
Dear Mr. LeBaron:
On October 25 through October 30, 2012, the U.S. Food and Drug Administration (FDA) conducted an inspection of your dietary supplement manufacturing facility located at 396 North 2150 West #B4, Cedar City, UT. During the inspection, you informed our investigator that you are a contract manufacturer that is manufacturing and packaging dietary supplements for contract customers who then distribute the dietary supplements. The inspection revealed that your firm is promoting its dietary supplements with claims that cause the products to be drugs under section 201(g)(1)(B) of the Federal Food, Drug, and Cosmetic Act (the Act) [21 U.S.C. § 321(g)(1)(B)]. The inspection also revealed serious violations of the Current Good Manufacturing Practice (CGMP) regulations for Dietary Supplements, Title 21, Code of Federal Regulations (CFR), Part 111. These violations cause your dietary supplement products to be adulterated within the meaning of 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 that do not meet current good manufacturing practice regulations for dietary supplements. Based on our inspection and subsequent review of your product labeling, we found serious violations of the Act and applicable regulations. You may find the Act and FDA regulations through links at FDA’s home page at http://www.fda.gov
We have received your correspondence dated November 14, 2012, submitted in response to the FDA-483, List of Inspectional Observations, issued to you at the close of the inspection. Overall, we cannot consider the response to be acceptable due to the lack of specificity of your response and lack of supporting documentation regarding your stated corrective actions. We have included some detailed comments below.
Your significant violations are as follows:
Unapproved New Drugs
The inspection revealed that your firm is promoting certain dietary supplements with claims that cause the products to be drugs under Section 201(g)(1)(B) of the Act [21 U.S.C. § 321(g)(1)(B)]. We have reviewed the labeling of your products collected at the inspection in October 2012 and determined that the (b)(4) products are promoted for conditions that cause the products to be drugs under Section 201(g)(1) of the Act [21 U.S.C. § 321(g)(1)]. The therapeutic claims on the labels 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 Section 505(a) of the Act.
Examples of some of the claims observed in the labeling for your products include:
- “[H]ealing to cells and tissue”
- “[H]ealing to cells and tissue”
- “Colds ... Sinus ... Sore Throat ... Fungus ... Ear Infections ... Allergies”
- “[N]on-Toxic Antibiotic”
Your products are not generally recognized as safe and effective for the above referenced uses; therefore, the products are “new drugs” as defined by 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.
Furthermore, the (b)(4) product is offered for a condition that is 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 this drug safely for its intended purpose. Thus, the (b)(4) product is misbranded under section 502(f)(1) of the Act [21 U.S.C. § 352(f)(1)], in that the labeling for this drug 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)].
Additionally, even if your (b)(4) products were not unapproved new drugs, they would be adulterated dietary supplements within the meaning of 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 that do not meet the CGMP regulations for dietary supplements.
Dietary Supplement CGMP Violations
The inspection revealed serious violations of the Current Good Manufacturing Practice (CGMP) regulations for Dietary Supplements, Title 21, Code of Federal Regulations (CFR), Part 111. These violations cause your dietary supplement products to be adulterated within the meaning of 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 that do not meet current good manufacturing practice regulations for dietary supplements.
Your significant violations of the dietary supplement CGMP requirements are as follows:
1. You failed to establish specifications as follows:
a. You did not establish a specification for any point, step, or stage in the manufacturing process where control is necessary 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 111.70(a)].
b. You did not establish specifications for each component that you use in the manufacture of a dietary supplement to include:
i. A specification for identity of each component [21 CFR 111.70(b)(1)];
ii. Specifications necessary to ensure that specifications for purity, strength and composition of dietary supplements manufactured using the components are met [21 CFR 111.70(b)(2)]; and
iii. Limits on those types of contamination that may lead to adulteration of the finished batch [21 CFR 111.70(b)(3)].
- You did not establish a specification for any point, step, or stage in the manufacturing process where control is necessary 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 111.70(a)].You did not establish labeling and packaging specifications for your dietary supplement [21 CFR 111.70(d)].
- You did not 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 [21 CFR 111.70(e)].
- You did not establish packaging and labeling specifications to ensure that you use the specified packaging and that you applied the specified label [21 CFR 111.70(g)].
Specifically, you provided no documentation of any of these required specifications for any of your dietary supplements.
Your November 14, 2012 response did not indicate how you are establishing appropriate specifications for raw materials, finished products, packaging components, labeling components, or packaging and labeling operations, or when you expect to complete this for all (b)(4) products on your current product list other than your general time frame of “3-6 months”. Your response also did not address how you will determine whether or not the specifications have been met.
2. Because you failed to establish component specifications, as required by 21 CFR 111.70(b), you failed to determine whether the component specifications were met, as required by 21 CFR 111.75(a)(2) and 21 CFR 111.325. You were not able to provide any written documentation for testing or examination on components and did not provide any component specifications.
If you would like to rely on a certificate of analysis from the supplier of the components you receive for use in your firm’s dietary supplements to confirm the identity of such components (other than for the identity of dietary ingredients which identity testing or examination must be conducted by your firm under 21 CFR 111.75(a)), and to confirm other component specifications are met, you must first qualify your suppliers by establishing the reliability of the suppliers’ certificates of analysis through confirmation of the results of the supplier's tests or examinations [21 CFR 111.75(a)(2)(ii)(A)].
Your November 14, 2012 response indicates that procedures are in the process of being created, to include the form of test carried out; however, you did not provide any draft procedures for our review. We also were not able to determine if you are conducting any testing to verify the identity of your dietary ingredients or components (other than dietary ingredients), prior to their use. Therefore, we find your response to be inadequate.
3. You failed to establish written procedures for the responsibilities of the quality control operations, including written procedures for conducting a material review and making a disposition decision, and for approving or rejecting any reprocessing as required by 21 CFR 111.103. You do not have written procedures for the responsibilities of your quality control operations pertaining to the following areas:
· Collection of representative samples and collection and holding of reserve samples [21 CFR 111.105(f) and (g)]
· Laboratory operations [21 CFR 111.110]
· Material review and disposition [21 CFR 111.113]
· Equipment, instruments and controls [21 CFR 111.117]
· Components, packaging and labeling [21 CFR 111.120]
· Master manufacturing record, batch production records and manufacturing operations [21 CFR 111.123]
· Release of packaged and labeled dietary supplements [21 CFR 111.123(a)(8)]
· Returned dietary supplements [21 CFR 111.130]
Although your November 14, 2012 response states that procedures for the above are being created, you did not provide any draft documents for our review; consequently we cannot determine whether your corrective actions are sufficient to meet all the applicable regulatory requirements. Therefore, we find your response to be inadequate.
4. You did not prepare and follow a written master manufacturing record for each unique formulation of dietary supplement that you manufacture, and for each batch size, to ensure uniformity in the finished batch from batch to batch as required by 21 CFR 111.205(a). We note that a master manufacturing record for each unique formulation of a dietary supplement must include the elements specified in 21 CFR 111.210.
Based on the information provided in your November 14, 2012 response, we have determined your response to be inadequate because you did not include any supporting documentation of your corrective action. If you have any examples of MMR’s already completed which contain all the required information, please provide an example for our review.
5. 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, your batch records for (b)(4) dated: 1/25/11, 10/11, 4/15/11, 1/4/11 and 6/15/10; (b)(4) dated: 11/15/11; 8/25/11; 1/24/11; and 4/13/12; and (b)(4), both dated 3/16/12 were missing the following information required under 21 CFR 111.260:
· the identity of equipment used during batch production [21 CFR 111.260(b)]
· the date and time of maintenance, cleaning and sanitizing of the equipment used during production of the batch [21 CFR 111.260(c)]
· the statement of the actual yield and a statement of the percentage of theoretical yield at appropriate phases of processing [21 CFR 111.260(f)]
· the actual results obtained during any monitoring operation [21 CFR 111.260(g)]
· the results of any testing or examination performed during the batch production [21 CFR 111.260(h)]
· the initials of the person performing each manufacturing step and the person responsible for verifying the weight or measure of each component used in the batch, and for verifying the addition of components to the batch [21 CFR 111.260(j)]
· documentation, at the time of performance, of packaging and labeling operations [21 CFR 111.260(k)]
In your November 14, 2012 response letter, you state “We will update the written checklist of what is required and what will be a part of every production Batch records.” Besides paraphrasing the deviations noted on the 483, to date, you have not provided any additional documentation so that we can ascertain the implementation of your proposed corrective actions; therefore, we deem your response unacceptable.
6. You did not establish and follow written procedures for manufacturing operations as required by 21 CFR 111.353. Specifically, our investigators found that you lack standard operating procedures for the weighing, blending and encapsulation processes for all of the dietary supplement products manufactured at your facility. In addition, we note that you must make and keep records of the written procedures for your manufacturing operations in accordance with 21 CFR 111.375(b).
Your November 14, 2012 response indicates your intent to establish written SOP’s for all processes performed from receipt to distribution. However, your response is inadequate because you did not provide any supporting documentation of your corrective action.
7. Your firm failed to establish and follow written procedures to fulfill the requirements related to packaging and labeling operations, as required by 21 CFR 111.403. For example, there is no written procedure for the receipt, quality approval, and use of labels and packaging materials. In addition, we note that you must make and keep records of the written procedures for your packaging and labeling operations in accordance with 21 CFR 111.430(b).
8. You failed to establish and follow written procedures for holding and distributing operations, as required by 21 CFR 111.453. Specifically, you did not provide documentation of written procedures for holding and distributing operations. In addition, we note that you must make and keep records of written procedures for your holding and distribution operations in accordance with 21 CFR 111.475(b).
This letter is not intended to be an all-inclusive list of violations which 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 and FDA regulations. You should take prompt action to correct the violations described above and prevent their further recurrence. Failure to promptly correct these violations may result in enforcement action, without further notice, including, without limitation, seizure and/or injunction.
In addition to the above violations, we have the following comments:
- Our investigation revealed that employees are provided on-the-job (OJT) training for their assigned tasks. However, there is no documentation of OJT trainings or any other records to demonstrate that your employees have been appropriately trained for their specific manufacturing operations, dietary supplement cGMPs, allergen identification and control, or quality control operations. Since you do not have an established training program, you have no assurance that employees have the education, training, or experience necessary to perform their assigned functions. You do not have any documentation of training, including the date of the training, the type of training, and the person(s) trained, Under 21 CFR 111.12(c), a manufacturer must ensure that each person engaged in manufacturing, packaging, labeling or holding, or in performing any quality control operations, must have the education, training, or experience to perform the person’s assigned functions. In addition, under 21 CFR 111.14(b)(2), a manufacturer must document the training, including the date of the training, the type of training, and the person(s) trained.
- Your firm is using a metal funnel to transfer raw materials to the (b)(4) blender for mixing. The funnel was observed to have a rough interior seam secured with rivets, not an easily cleanable surface. Powder residue was observed on the interior of the funnel. Additionally, this funnel was observed stored in direct contact with the floor. Under 21 CFR 111.27(a)(2), a manufacture must use equipment and utensils of appropriate design and construction so that use will not result in the contamination of components or dietary supplements. Under 111.27(a)(3)(v), a manufacturer must maintain all equipment and utensils used in order to protect components and dietary supplements from being contaminated by any source.
- There are no written procedures for calibrating instruments and controls that you use in manufacturing or testing a component or dietary supplement. In addition, at the time of our inspection, your electronic scales used to weigh in-process capsules and raw ingredients for dietary supplement production were last calibrated on 9/20/2010. Furthermore, there are no written procedures related to equipment and utensils. Under 21 CFR 111.25(a), a manufacturer must establish and follow written procedures for calibrating instruments and controls that you use in manufacturing or testing a component or dietary supplement, as required by 21 CFR 111.25(a). Under 21 CFR 111.35(b)(1), a manufacturer must make and keep written procedures for calibrating instruments and controls; calibrating, inspecting, and checking equipment, and maintaining, cleaning, and sanitizing equipment, utensils, and other contact surfaces.
- Some of your firm’s products labeled as dietary supplements are not solely intended for ingestion. For example, (b)(4) declares on the label, “May be used topically”. Another example, (b)(4) states, “[A]pply topically”. When intended for topical use, (b)(4) and (b)(4) are not dietary supplements because the Act defines the term “dietary supplement” in Section 201(ff)(2)(A)(i) of the Act [21 U.S.C. § 321(ff)(2)(A)(i)] as a product that is “intended for ingestion.” Topical products and products intended to enter the body directly through the skin or mucosal tissues are not dietary supplements. The labels suggesting that consumers use (b)(4) topically subject the products to regulation as drugs.
Furthermore, as drug products containing colloidal silver and with disease claims on their labeling, (b)(4) are subject to 21 CFR 310.548, which states in subsection (a) “[t]here is a lack of adequate data to establish general recognition of the safety and effectiveness of colloidal silver ingredients or silver salts for over-the-counter (OTC) use in the treatment or prevention of any disease.” Under 32 CFR 310.548(b), any OTC drug product containing colloidal silver ingredients or silver salts that is labeled, represented, or promoted for the treatment and/or prevention of any disease is regarded as a new drug 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.
Additionally, per 21 CFR 310.548(b), any product containing colloidal silver ingredients or silver salts which is labeled, represented, or promoted for the treatment and/or prevention of any disease, and is not the subject of an FDA-approved application is misbranded under Section 502 of the Act [21 U.S.C. § 352].
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 determining 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 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 in writing within fifteen working days from your receipt of this letter. Your response should outline the specific steps you are taking to correct the violations noted above and the steps you are taken to prevent their recurrence. You should include in your response documentation and any other useful information that would assist us in evaluating your corrections. If you cannot complete these corrective actions within fifteen working days, state the reason for the delay and the date by which you will have completed the correction.
Your response should be sent to the following address: U.S. Food and Drug Administration, Denver District, 6th Avenue & Kipling Street, Building 20 DFC, P.O. Box 25087, Denver, CO 80225-0087, Attn: Sarah A. Della Fave, Compliance Officer. If you have any questions regarding any issue in this letter, please contact Ms. Della Fave at (303) 236-3006.
Denver District Office
This page was posted on January 24, 2019.