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U.S. Department of Health and Human Services

Inspections, Compliance, Enforcement, and Criminal Investigations

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Klein Laboratories, Inc. 7/17/14

  

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

Public Health Service
Food and Drug Administration
 New England District Office
One Montvale Avenue, 4th floor
Stoneham, MA 02180
Phone 781.587.7500
Fax 781.587.7556 

WARNING LETTER
CMS # 416436


VIA UNITED PARCEL SERVICE


July 17, 2014


Mr. Peter D. Klein
Owner/President
Klein Laboratories, Inc.
55 Middletown Ave (Rear)
North Haven, CT 06473-3936


Dear Mr. Klein:


The U.S. Food and Drug Administration (FDA) inspected your dietary supplement manufacturing firm located at 55 Middletown Ave (Rear), North Haven, Connecticut, on August 22, 2013- November 12, 2013. During the inspection, our investigators collected labeling samples, including a sample of the label for your Osteojuv product. The inspection and review of the product label for your Osteojuv product revealed serious violations of the Federal Food, Drug, and Cosmetic Act (the Act) and applicable regulations. You may find the Act and FDA's implementing regulations through links on FDA's home page at http://www.fda.gov.


We have received your response, dated November 18, 2013, to the Form FDA 483, Inspectional Observations, which was issued to you on November 12, 2013, at the conclusion of the inspection. We have incorporated comments on the adequacy of your response below.


Unapproved New Drug Violations


Based on our review of the label for your Osteojuv product, we have determined that Osteojuv is promoted for conditions that cause it to be a drug within the meaning of
section 201(g)(1)(B) of the Act [21 U.S.C. § 321(g)(1)(B)]. The therapeutic claims on your product label establish that the product is a drug because it is intended for use in the
cure, mitigation, treatment, or prevention of disease. As explained further below, introducing or delivering this product for introduction into interstate commerce for such
uses violates the Act.


Examples of some of the claims on the label of your Osteojuv product that provide evidence that Osteojuv is intended for use as a drug include:


• "Aggressively Target: ... Pain"


• "Aggressively Target: ... Inflammation"


Your product is not generally recognized as safe and effective for the above referenced uses and therefore, the product is a "new drug" under section 201 (p) of the Act [21
U.S.C. §321(p)]. 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.


Dietary Supplement CGMP Violations:


Even if your Osteojuv product was not an unapproved new drug, it would still be an adulterated dietary supplement under section 402(g)(1) of the Act [21 U.S.C. § 342(g)(1)]
in that it has been prepared, packed, or held under conditions that do not meet the Current Good Manufacturing (CGMP) regulations for dietary supplements, Title 21, Code of
Federal Regulations, Part 111 (21 CFR Part 111).


During the inspection of your facility, the following significant violations of the dietary supplement CGMP regulations were observed:


1. Your firm failed to conduct at least one appropriate test or examination to verify the identity of a component that is a dietary ingredient prior to using the component in the manufacture of your dietary supplements, as required by 21 CFR 111.75(a)(1)(i). Specifically, your firm did not conduct an identification test or examination for dietary ingredients prior to using such ingredients in the manufacture of the dietary supplement product Osteojuv, (b)(4) Instead, your firm relies upon certificates of analysis from your suppliers to verify the identity of dietary ingredients used as components in the manufacture of your dietary supplements. You may rely on a certificate of analysis from a supplier, consistent with the requirements in 21 CFR 111.75(a)(2)(ii), to confirm the identity of components that are not dietary ingredients and to determine whether other applicable component specifications established in accordance with 21 CFR 111.70(b) are met. However, you may not rely on a certificate of analysis from your supplier to confirm the identity of a component that is a dietary ingredient. You must conduct at least one appropriate test or examination to verify the identity of a component that is a dietary ingredient, unless you successfully petition FDA for an exemption from such testing requirements [21 CFR 111.75(a)(1)].


We have received your response letter, dated November 18, 2013, and have determined your response to be inadequate. You state that "[I]ingredients listed in this observation has been identified by three independent methods. Color Identity, Mesh of ingredient identity, Specific PH identity and comparison with certificate of analysis supplied by ingredient manufacturer." None of the methods, which you list, color, "mesh" or pH, is an appropriate test or examination to verify the identity of a dietary ingredient. Color, "mesh" or pH cannot inform you of whether the dietary ingredient you receive is what it purports to be (what you ordered), because it is not possible to verify the identity of the dietary ingredient by any of these methods, as explained below.


While color is an intrinsic property of an article, it is not exclusive to the article: many articles (or compounds) have the same color. Furthermore, a food color may be added to the article. Therefore, while an incoming dietary ingredient of the wrong color could be excluded, an article of the same color is not substantiation of the identity, because as stated, many articles have the same color. Moreover, an article could have the same color and still be rejected, if, for example, its spectroscopic data were not identical to a reference standard. Color cannot, therefore, be used as positive evidence of identity.


We understand "Mesh of ingredient identity," as stated in your response, to mean a certain mesh size that determines the particle size distribution, or to express it more precisely, sieve analysis, where a powder is separated on sieves of different sizes. However, particle size distribution, which is determined by sieve analysis is a function of the milling process. It is not an intrinsic property of the material or article. While particle size distribution is important in tablet and capsule manufacture, it cannot be used as a defining identity characteristic, since almost any powder can be milled to a particular particle size distribution.


Finally, pH is a value used as a measure of the acidity or alkalinity (basicity) of an aqueous solution. It is not clear what you mean by "Specific PH identity" for your powders, since you did not provide any information on how the pH of the dietary ingredient solid is measured. However, even if the incoming solid dietary ingredient powder was soluble in water, and its pH could be measured in aqueous solution, it would still not be a valid identity test, because pH it is not exclusive to the article. Many articles (or compounds) have the same pH.


2. Your firm failed to establish identity specifications for each component that you use in the manufacture of your dietary supplement products, as required by 21 CFR 111.70(b)(1). Specifically, your firm failed to provide any documentation showing that your firm has established identity specifications for the components Glucosamine Sulfate 90% (b)(4) Chondroitin Sulfate 90% (b)(4) and Hyaluronic Acid (b)(4) used to manufacture the dietary supplement product Osteojuv, (b)(4)

 

We have received your response letter, dated November 18, 2013, and have determined your response to be inadequate. You state that "Ingredients listed in this observation has been identified by three independent methods. Color Identity, Mesh of ingredient identity, Specific PH identity and comparison with certificate of analysis supplied by ingredient manufacturer." This response does not state what you have established as your identity specifications for each component. Further, as explained above, your listed methods of "color," "mesh of ingredient," and "specific pH" are not appropriate tests or examinations to verify the identity of a dietary ingredient.


3. Your firm 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, as required by 21 CFR 111.70(e). Specifically, your firm was unable to provide specifications for finished batches of Ostejov, (b)(4). Once you have established dietary supplement product specifications, you must verify that finished batches of your product meet the specifications you have established (see 21 CFR 111.75(c)).


We have received your response letter, dated November 18, 2013, and have determined your response to be inadequate. You state that "Identity is performed as stated in our response to investigators observation #3. Color, Mesh, PH Identity verification to Certificate of Analysis provided by supplier." This response does not address whether you have established specifications for the purity, strength, or composition of Osteojuv. Your response also does not address whether you have established limits on those types of contamination that may adulterate, or that may lead to adulteration of, the finished batch of the dietary supplement, as required under 21 CFR 111.70(e).


4. Your firm failed to prepare and follow a written master manufacturing record (MMR) for each unique formulation of dietary supplement that you manufacture, and for each batch size, in accordance with 21 CFR 111.205(a). Specifically, the MMR you provided during the inspection for the dietary supplement product Osteojuv does not match the unique formulation listed in the batch record for Osteojuv (b)(4).

 

Your firm's November 18, 2013 response is inadequate as it did not provide evidence that your firm has established or is utilizing MMRs in the manufacturing of dietary supplement products.
 

 

5. Your firm failed to include complete information relating to the production and control of each batch on the batch production record, as required by 21 CFR 111.255(b). Specifically, your firm's batch production record for Osteojuv, lot (b)(4) did not include any of the required information in a batch production record required under 21 CFR 111.260 except the identity and weight or measure of each component used, which are required under 21 CFR 111.260(e).


Your firm's November 18, 2013 response is inadequate. You stated that you have completed a training program for all manufacturing staff to assure that the batch and production record requirements are maintained and in compliance; however, you did not provide evidence that your firm is preparing batch production records with complete information relating to the production and control of each batch of dietary supplements.


6. Your firm did not establish and follow written procedures regarding the responsibilities for quality control operations, as required by 21 CFR 111.103. Specifically, during the inspection you stated to investigators that you did not know what the investigators were referring to when they requested a copy of your firm's written procedures for quality control operations.


Although your firm's November 18, 2013 response did include a copy of written procedures for quality control personnel, your response did not state whether these procedures were implemented and are being followed. We will verify the adequacy of this correction during any future inspection.


7. Your firm failed to establish and follow written procedures to review and investigate dietary supplement product complaints, as required by 21 CFR 111.553. Specifically, you stated during the inspection your firm did not have written procedures for handling dietary supplement product complaints.


Your firm's November 18, 2013 response is inadequate. This response includes documentation related to the handling of drug product complaints. Your response does not include complaint processing procedures or related documentation for dietary supplement products.


8. Your firm failed to hold dietary supplement components under conditions that would prevent their mixup, contamination, or deterioration, as required by 21 CFR 111.455(c) and 21 CFR 111.460(a). Specifically, our investigators observed components stored without labeling and/or other means of identification that would prevent their mix-up, contamination, or deterioration. In addition, when asked what the identity of a white powdered substance inside several unlabeled, unidentified fifty five (55) gallon drums was, you responded by stating you did not know.


Your firm's November 18, 2013 response is inadequate. Although your response states that all of the materials referred to above were discarded and destroyed, your firm is responsible for maintaining control of these types of materials. Your response did not include any evidence or documentation to show your firm has implemented controls to prevent the further mix-up, contamination, or deterioration of components.


Your firm failed to quarantine components before using them in the manufacture of dietary supplement products by your firm, as required by 21 CFR 111.155(c). Specifically, your employee stated that your firm does not quarantine any components before using them to manufacture dietary supplements. Further, our investigator did not quarantine the components Glucosamine Sulfate 90% (b)(4) Chondroitin Sulfate 90% (b)(4) and Hyaluronic Acid (b)(4) before you used them to manufacture (b)(4)

 

Although your November 18, 2013 response provides written procedures entitled, (b)(4) and (b)(4) your response did not state whether these procedures were implemented and are being followed. We will verify the adequacy of this correction during any future inspection.


9. Your firm failed to make and keep records of the written procedures for packaging and labeling operations, as required by 21 CFR 111.430(b). Specifically, you stated to our investigator that your firm did not have written procedures for labeling operations.


Although your November 18, 2013 response provides written procedures for labeling operations, your response did not state whether these procedures were implemented and are being followed. We will verify the adequacy of this correction during any future inspection.


10. Your firm did not collect and hold reserve samples of each lot of packaged and labeled dietary supplements that you distribute, as required by 21 CFR 111.83(a). Specifically, your employee informed our investigator that you do not have or keep reserve samples for any dietary supplement product your firm manufactures.


Although your November 18, 2013 response provided written procedures entitled, (b)(4) and (b)(4) your response did not state whether these procedures were implemented and are being followed. We will verify the adequacy of this correction during any future inspection.


This letter is not intended to be an all-inclusive list of violations at your facility or that exist in connection with your products or their labeling. It is your responsibility to ensure that all products marketed by your firm comply with the Act and its implementing regulations.


You should take prompt action to correct the violations and prevent their future recurrence. Failure to do so may result in enforcement action, without further notice, including seizure and/or injunction.


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 re-inspection-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. Re-inspection-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.


Please notify this office in writing within fifteen working days of receipt of this letter as to the specific steps that you have taken to correct the above-listed violations and to ensure that similar violations will not occur. Your response should include any documentation necessary to show that corrections have been achieved. If corrective action cannot be completed within fifteen working days, state the reason for the delay and the time frame within which the corrections will be made.


Please direct your written reply to the U.S. Food and Drug Administration, One Montvale Avenue, Stoneham, MA 02180, Attention: Todd Maushmi, Compliance Officer. If you have any questions about the content of this letter please contact: Todd Maushart at (781) 587-7578.


Sincerely,
/S/
Mutahar S. Shamsi
District Director
New England District