| Public Health Service Food and Drug Administration |
| Central Region Waterview Corporate Center 10 Waterview Blvd., 3rd Floor Parsippany, NJ 07054 Telephone (973)331-4904 |
Department of Health and Human Services
April 15, 2011
WARNING LETTER
VIA OVERNIGHT MAIL
Mr. Hans Lindgren
Senior Vice President of Operations
Nutro Laboratories, a div of NBTY, Inc.
650 Hadley Road
South Plainfield, New Jersey 07080-2404
File # 11-NWJ-16
Dear Mr. Lindgren:
On October 13, 2010 through October 29, 2010 investigators from the U.S. Food and Drug Administration (FDA) conducted an inspection of your dietary supplement manufacturing facility located at 650 Hadley Road, South Plainfield, New Jersey. During the inspection we found violations of the Federal Food, Drug, and Cosmetic Act (the Act) and FDA regulations pertaining to dietary supplements. You may find copies of the Act and these regulations through links on FDA's Internet home page at http://www.fda.gov.
Our investigators documented 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 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 the products have been prepared, packed, or held under conditions that do not meet CGMP regulations for dietary supplements. These observations were presented to you in an FDA 483 form at the conclusion of our inspection on October 29, 2010. We received your November 22, 2010 response to the FDA 483 and we have addressed your response below.
The CGMP violations observed at your facility include:
1. Failure to establish component specifications to ensure purity, strength, and composition of your dietary supplements. [21 CFR 111.70(b)(2)].
Component specifications are required whenever their use is necessary to ensure the purity, strength, and composition of the final dietary supplement product. Specifically, you did not establish a purity specification for the component Crospovidone. You were notified on September 16, 2010, by your supplier that the component Crospovidone, lot# PKVX09126031 contained high levels of peroxide, an impurity. However, even after being notified about the high levels of peroxide, you did not establish a purity specification for peroxide for this lot of Crospovidione.
We have reviewed your response to Observation 1 and determined that it is inadequate. In your response, you indicated that you updated your specification for Crospovidone to include a test for peroxide with a specification of <400 ppm, as per the European Pharmacopoeia, and that this was completed on October 20, 2010. Your response is inadequate because you did not provide any documentation to show that you have updated the purity specification for this component. Under 21 CFR 111.95(b)(1), you must maintain a record of the specifications you have established for Crospovidone, including the purity specification you indicated in your response. Further, the response indicated that you performed stability testing on the Crospovidone lot# PKVX09126031 and placed all dietary supplements containing Crospovidone lot# PKVX09126031 on hold while you wait for the results of your stability program, which were due in December of 2010. However, you did not indicate your actions for products that were manufactured with Crospovidone lot# PKVX091027006. Our investigators collected a sample of Crospovidone lot# PKVX091027006 from your inventory and the sample results revealed levels of peroxide greater than 400 ppm.
2. Failure to qualify your supplier of a component by establishing the reliability of the Certificate of Analysis (COA) through confirmation of the supplier’s test results. [21 CFR 111.75(a)(2)(ii)(A)].
Specifically, you received a (b)(4) for Crospovidone, lot PKVX090802168. According to your Raw Material Specification and Evaluation Report, dated February 16, 2010, you did not establish the reliability of the supplier COA through confirmation of the results of the supplier’s tests or examinations. For example, the supplier’s COA listed the following tests that were not confirmed by you for their reliability, as documented on your Raw Material Specification and Evaluation Report: pH <791> (USP30), Water-soluble substances test (USP30), Residue on Ignition % <281> (USP30), and Assay (on dried basis) <461> (USP30).
We have reviewed your response to Observation 2 and determined that it is inadequate. Your response did not clearly indicate what specifications were updated and if they were part of your supplier qualification program.
We acknowledged that your response to Observation 4 appears to be adequate in that you replaced the “unreliable” data logger and created a new SOP for your employees to follow regarding temperature monitoring. We will review the adequacy of this corrective action during our next inspection.
The above violations are not intended to be an all-inclusive list of violations at your facility. It is your responsibility to ensure that all of your firm’s products are in compliance with the Act, and all applicable federal laws and regulations. You should take prompt action to correct the violation cited in this letter. Failure to promptly correct the violation may result in legal action without further notice including seizure and/or injunction.
We also note the following with regard to your use of Crospovidone. First, we note that your firm used multiple lots of the component Crospovidone that were tested by FDA and found to contain high levels of peroxide, an impurity that can cause a finished product to be sub-potent. The peroxide limit in the U.S. Pharamacopeia 32-NF27 S2 monograph for the related substance, Copovidone, is 400 ppm. Similarly, the European Pharmacopeia monograph for Crospovidone (Type A) specifies a peroxide limit of 400 ppm. The 400 ppm limit corresponds to 0.35 absorbance units (AU) and is the level considered consistent with good manufacturing practices. We are not aware of any information regarding the safety of using Crospovidone with levels of peroxide above 400ppm. You have not furnished documentation of any stability testing of finished dietary supplements that you may have conducted, as indicated in your response.
Further, we note that you stated to FDA investigators that you calculated the amount of peroxide in the finished dietary supplements that had been produced with the lots of Crospovidone containing excess peroxide and determined that there was no health risk (i.e., the level of peroxides in the finished product had no detrimental effect on product quality). However, you did not provide documentation to our investigators to support that the finished product did not contain high levels of peroxide and did not provide documentation to support how your in-process specifications may reduced the detrimental effect of hydrogen peroxide on finished products. If in-process specifications are necessary to ensure that finished product specifications are met, they must be documented in accordance with 21 CFR 111.70(c).
You should respond 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 the violations, including an explanation of each step taken to prevent the recurrence of violations and copies of supporting documentation. If you cannot complete corrective action 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 Andrew Ciaccia, Compliance Officer at the following address: U.S. Food and Drug Administration, 10 Waterview Blvd., Parsippany, New Jersey 07054. If you should have any questions regarding any issue in this letter, you may contact Andrew Ciaccia, Compliance Officer.
Sincerely,
/S/
Diana Amador-Toro
District Director
New Jersey District
-
No comments:
Post a Comment