Inspections, Compliance, Enforcement, and Criminal Investigations
Venus Pharmaceuticals International, Inc. 5/4/11
Department of Health and Human Services
|Public Health Service|
Food and Drug Administration
New York District
WARNING LETTER NYK-2011-10
May 4, 2011
Mr. Bharat Kakumanu, CEO
Venus Pharmaceuticals International, Inc.
55-A Kennedy Drive
Hauppauge, NY 11788
Dear Mr. Kakumanu:
On August 16-19, 2010, the U.S. Food and Drug Administration (FDA) inspected your dietary supplement manufacturing and repacking facility located at 55-A Kennedy Drive, Hauppauge, New York. Our investigators found serious violations of the Current Good Manufacturing Practice (CGMP) regulation for dietary supplements, Title 21, Code of Federal Regulations, Part 111 (21 CFR Part 111).
These violations cause your dietary supplements identified below 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. § 343(g)(1)] because the dietary supplements have been prepared, packed or held under conditions that do not meet the CGMP regulations for dietary supplements in 21 CFR Part 111. You may find the Act and the CFR through links in FDA's home page at www.fda.gov.
Your significant violations are as follows:
1. Your firm 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 of each finished batch, as required by 21 CFR 111.205(a).
For example, you did not have master manufacturing records for the following dietary supplements manufactured by your firm: Miracle Reds Blend, Batch #1007004, Super Fruits and Green, Batch #1006011, and Superior Joint Powder, Batch #1005016 [21 CFR 111.205(a)].
We received your response to the FDA-483 on September 21, 2010. Your response included what your firm now maintains as Master Manufacturing Records for the Venus Pharmaceuticals dietary supplements listed above. However, your response is inadequate because your Master Manufacturing Records lack the following information required by 21 CFR 111.210:
• A complete list of components to be used [21 CFR 111.210(b)];
• An accurate statement of the weight or measure of each component to be used [21 CFR 111.210(c)];
• The identity and weight or measure of each dietary ingredient that will be declared on the Supplement Facts Panel and the identity of each ingredient that will be declared on the ingredient list of the dietary supplement [21 CFR 111.210(d)];
• The expected yield when you finish manufacturing the dietary supplement, including the maximum and minimum percentages of theoretical yield beyond which a deviation investigation of a batch is necessary and material review is conducted and disposition decision is made [21 CFR 11.210(f)]; and
• A description of packaging and a representative label or a cross-reference of the physical location of the actual or representative label [21 CFR 111.210(g)].
2. Your firm's batch production records do not include complete information relating to the production and control of each batch, as required by 21 CFR 111.255(b). For example, the batch record for our Miracle Reds Blend, Batch # 1007004 lacks the following information, which is required by 21 CFR 111.260:
• The identity of equipment and processing lines used in producing the batch [21 CFR 111.260(b)];
• The unique identifier assigned to each component used in the manufacturing of the dietary supplement; and the unique identifier assigned to the packaging and label used for repacking product received by your supplier [21 CFR 111.260(d)];
• Documentation at the time of performance of packaging and labeling operations [21 CFR 111.260(k)]; and reviewed the batch production record [21 CFR 111.260(k)(1)(1)].
Your September 21, 2010 response included documentation of what you now use for your batch production records; however the batch production records you provided are still inadequate. In addition to failing to include the above mentioned information, which is required to be included in your batch production records, such records are not specific to any product. While you have the fields for information, the fields must be filled in with all the necessary information for the specific production batch that is being manufactured.
3. Your firm failed to verify that your finished batch of dietary supplements meet product specifications for 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, as required by 21 CFR 111.75(c). Specifically, your firm did not verify that such finished product specifications were met for the Miracle Reds Blend, Batch # 1007004,
Super Fruits and Greens, Batch #1006011, and Superior Joint Powder, Batch #1005016. You may verify that these specifications are met by testing or examining every finished batch or a subset of finished batches for each of the dietary supplements you manufacture [21 CFR 111.75(c)]. However, your firm did not conduct finished product testing to verify that established product specifications were met for these finished dietary supplement products.
Your September 21, 2010 response states that your firm has implemented "finished product testing procedures" for your dietary supplements and included a blank form labeled "Finished Product QC Report." Your response is inadequate because the documentation that you provided does not outline the actual test that you will perform or the specifications that the finished products will need to meet.
4. Your firm did not 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). Specifically, your firm did not conduct identification testing for the dietary ingredients used in the Miracle Reds Blend Batch # 1007004, the Miracle Reds Blend, Batch #1007004, Super Fruits and Greens, Batch #1006011, and Superior Joint Powder, Batch #1005016. Before using a component that is a dietary ingredient, you must conduct at least one appropriate test or examination to verify the identity of any component that is a dietary ingredient, unless you have petitioned FDA for an exemption from such testing, consistent with the requirements in 21 CFR 111.75(a)(1)(ii), and FDA has granted such petition. As of April 8, 2011, your firm has not petitioned FDA for such an exemption.
Your September 21, 2010 response states that you have implemented procedures to test the raw materials used in your dietary supplement products and included a blank form labeled "Raw Material Identification QC Report." However, your response is inadequate because your documentation fails to show the testing that your firm has implemented. Submitting just the form that you intend to use does not adequately address the violation.
5. Your firm did not establish written procedures for laboratory operations, as required by 21 CFR 111.303. More specifically, you have not established written procedures for the tests and examinations conducted to determine whether component, in-process and finished dietary supplement specifications are met.
Your September 21, 2010 response states that your firm has established "written procedures for tests and examinations conducted to determine whether the specifications were met," and it references SOP No. QMS-035. But, it appears that this SOP was submitted in error because this SOP describes your "Deviation Report System" and not your written procedures for laboratory operations. It appears that SOP No. LAB-065 would be more appropriate to address the above violation; however, this SOP is lacking because it fails to outline the specific laboratory tests that you plan to conduct, and how those tests demonstrate that specifications have been met.
6. Your firm did not establish written procedures for the responsibilities of your firm's quality control operations, as required by 21 CFR 111.103.
Your September 21, 2010 response states that you have established written procedures for quality control operations; however your response is inadequate. The SOPs provided in support of your response fail to provide detailed actions for which the quality control unit will be responsible.
This letter is not an all-inclusive list of violations at your facility. It is your responsibility to ensure that your firm and the products you market comply with the Act and its implementing regulations.
Failure to promptly correct the violations specified above may result in enforcement action without further notice. Enforcement action may include seize of violative products and/or injunction against the manufacturers and distributors of violative products.
In addition, we note:
1. Your firm failed to establish 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).
Your September 21, 2010 response, which states that your firm has established written procedures for calibration of measuring scales, references SOP No. MAN-100; however that SOP is inadequate. While the SOP addresses when the instruments should be calibrated, it does not provide specific instructions on how to perform the calibrations.
2. You firm failed to make and keep records of the written procedures for packaging and labeling operations, as required by 21 CFR 111.430(b).
Your September 21, 2010 response, which states that your firm has established written procedures for packaging and labeling, references SOP No. Man-055; however there is nothing in the SOP that actually addresses the packaging and labeling process for your dietary supplements. Instead, that SOP covers procedures for line clearance, line opening, and line cleaning.
3. Your firm failed to make and keep written procedures to ensure that each person engaged in the 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, as required by 21 CFR 111.14(b)(1) and 111.12(c). Specifically, your firm has not developed written training procedures for personnel engaged in manufacturing, packaging, and labeling your dietary supplements.
Your September 21, 2010 response, which states that your firm has established written training procedures, references SOP No. Man-095; however your response is inadequate. That SOP only addresses some GMP training. It fails to outline all other trainings necessary for your operation as well as the documentation you will use to keep track of the employees that have completed their training.
Please advise this office in writing within 15 days from your receipt of this letter of the specific steps you have taken to correct the violations noted above and to ensure that similar violations do not occur. Your response should include any documentation necessary to show that correction has been achieved. If you cannot complete all corrections before you respond, state the reason for the delay and the date by which you will complete the corrections.
Please send your reply to the Food and Drug Administration, Attention: Kristen C. Jackson. If you have questions regarding any issues in this letter, please contact Kristen Jackson at 718-662-5711.
New York District