Pure Encapsulations, Inc. 12/23/11
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Department of Health and Human Services
|Public Health Service|
Food and Drug Administration
New England District
One Montvale Avenue
Stoneham, Massachusetts 02180
(781) 587-7500 FAX: (781) 587-7556
CMS # 222054
December 23, 2011
Mr. Kyle W. Bliffert
Pure Encapsulations, Inc.
490 Boston Post Road
Sudbury, MA 01776
Dear Mr. Bliffert:
The U.S. Food and Drug Administration (FDA) conducted an inspection of your dietary supplement manufacturing, packaging, labeling, and holding facility, Pure Encapsulations, Inc., located at 490 Boston Post Road, Sudbury, MA, on August 4-24, 2011. During the inspection, our investigators found serious 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 PhytoBalance 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 dietary supplements have been prepared, packed, or held under conditions that do not meet CGMP regulations for dietary supplements.
In addition, our review of your product labeling revealed that your PhytoBalance dietary supplements, as described further below, are in violation of the Act and regulations implementing the food labeling requirements of the Act, which are found in 21 CFR 101.
You can find the Act and FDA regulations through links on FDA’s home page at http://www.fda.gov
Dietary Supplement CGMP Violations
The inspection revealed the following violations:
1). You failed to reject a component that did not meet your identity specifications established under 21 CFR 111.70(b)(1), as required by 21 CFR 111.77(b). Specifically, your firm used the dietary ingredients (b)(4) and (b)(4) to manufacture the finished product PhytoBalance (Lot No. (b)(4)). However, these dietary ingredient components failed to meet identity specifications prior to their use in the manufacture of PhytoBalance (Lot No. (b)(4)).
Furthermore, you failed to document any material review and disposition decision and follow-up, as required by 21 CFR 111.140(b)(3). Specifically, your “Nonconforming Material Report” forms for (b)(4) and (b)(4) do not include final material disposition decisions and signatures of the individual(s) who conducted the material review and made the disposition decisions, as required by 21 CFR 111.140(b)(3)(vii).
We received your reply to the FDA-483 dated September 12, 2011. You stated that you have sent the three most recent lots of (b)(4) for TLC identity testing. Your response is inadequate because you did not indicate whether these lots include the same lot that failed the identity specification during our inspection, and you have not provided the results of this testing for verification. You also stated that you no longer use (b)(4) in the manufacture of PhytoBalance or any other product at your firm. While this may prevent future problems with the use of (b)(4), it does not address your use of (b)(4) that failed to meet your identity specifications in your existing product, PhytoBalance (Lot No. (b)(4)).
2. You failed to ensure that the tests and examinations that you use to determine whether the specifications are met are appropriate, scientifically valid methods, as required by 21 CFR 111.75(h)(1). Specifically, the following components were used as analytical standards in your FT-NIR library by authentication using organoleptic tests and review of certificates of analyses (CoA): (b)(4) The identity testing of components used to manufacture PhytoBalance (Lot No. (b)(4)) was based on organoleptic testing of the above ingredients and the use of such ingredients as standards to which components were compared. However, these ingredients, which are powders, cannot be identified through organoleptic testing. There is no ability to distinguish these ingredients from other powder ingredients through gross organoleptic analysis. Therefore, these ingredients can not be used as a standard on which a scientifically valid method for identity testing can be based.
In your September 12, 2011 response letter, you stated that you will update the FT-NIR analytical standards against which all new receptions of dietary ingredients are compared so that all are based on reference samples for which identity testing has been verified under the current CGMP regulations. You stated that updates will be completed by purchasing standards, sending lots to independent labs for TLC or HPLC identity tests, or consulting with experts. You estimated that you will need up to six months to update the FT-NIR analytical standards. You have also revised your SOP (b)(4), to require standards to be verified by scientific methods or reference standards, not reliance on the supplier’s CoA.
You stated that you will provide a written update on the progress of your corrections, confirm in writing when your updates are completed, keep records of the methods used to verify the analytical standards for each ingredient, and provide FDA with samples of these records. To the extent you hire an independent lab to perform certain manufacturing operations for your firm, such as TLC or HPLC identity testing, you are ultimately responsible for complying with the requirements related to such manufacturing operations, even though you have hired another person to perform that job task (72 Fed. Reg. 34753 at 34790, June 25, 2007). While your response appears to be adequate, your updates will be verified at our next inspection or by review of documentation provided by your firm.
Misbranded Dietary Supplements
Your PhytoBalance dietary supplement is misbranded within the meaning of section 403(i)(2) of the Act [21 U.S.C. § 343(i)(2)] because your product is fabricated from two or more ingredients but the label fails to declare the common or usual name of each ingredient. For example:
- Your label fails to declare the sub-ingredients of the vegetable capsules used to manufacture this product [21 CFR 101.4(b)(2)]. The requirement to list component ingredients (or “sub-ingredients”) may be met by either parenthetically listing the component ingredients after the common or usual name of the multi-component ingredient, or by listing the component ingredients without listing the multi-component ingredient itself. Under the first alternative, the component ingredients must be listed in descending order of predominance within the multi-component ingredient; and under the second alternative, the component ingredients must be listed in descending order of predominance in the finished food [21 CFR 101.4(b)(2)].
- Your label fails to declare the common or usual name of each botanical ingredient as required by 101.4(h). In accordance with 21 CFR 101.4(h), the common or usual name of ingredients of dietary supplements that are botanicals (including fungi and algae) shall be consistent with the names standardized in Herbs of Commerce, 1992 edition. Furthermore, the listing of these names on the label shall be followed by statements of the Latin binomial name of the plant, in parentheses, except that this name is not required when it is available in the reference entitled Herbs of Commerce, for the common or usual name listed on the label, and when required, the Latin binomial name may be listed before the part of the plant [21 CFR 101.4(h)(2)]. Specifically, your label lists the ingredients “dioscorea (wild yam) extract (root)” and “glycyrrhiza (licorice) extract (root).” “Dioscorea” and “glycyrrhiza” are not appropriate common or usual names. If a Latin binomial name is used, it should be listed parenthetically after the common or usual name. In addition, you parenthetically list the name “wild yam.” According to Herbs of Commerce, “wild yam” is the standardized common name for Dioscorea villosa L. However, based on your records, PhytoBalance is made using (b)(4)
The above violations are not intended to be an all-inclusive list of violations that exist in connection with your products and their labeling. It is your responsibility to ensure that your products meet all of the requirements of the Act and its implementing regulations. Failure to promptly correct the violations specified above may result in enforcement action without further notice. Such action may include, but is not limited to, seizure and injunction.
Please notify this office in writing within 15 working days from your receipt of this letter as to the steps you have taken to correct the above-listed violations and to prevent similar violations. Your response should include any documentation necessary to show that correction has been achieved. If you cannot complete all corrections within 15 working days, please state the reason for the delay and the date by which the corrections will be made.
Please address your reply to the U.S. Food and Drug Administration, One Montvale Avenue, Stoneham, MA 02180, Attention: Todd Maushart, Compliance Officer. If you have any questions about the content of this letter, please contact: Todd Maushart at (781) 587-7486.
Mutahar S. Shamsi
New England District
Mr. Pierre Fitzgibbon
Atrium Innovations, Inc.
1405 Boulevard du Parc-Technologique
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