| Public Health Service Food and Drug Administration |
Florida District |
Department of Health and Human ServicesCERTIFIED MAIL
RETURN RECEIPT REQUESTED
WARNING LETTER
FLA-12-08
November 1, 2011
Mr. Carlos J. Alvarez
President
CJ Labs, Inc.
12245 SW 128th St. Unit 301
Miami, FL 33186
Dear Mr. Alvarez:
On May 25 - June 24, 2011, the U.S. Food and Drug Administration (FDA) conducted an inspection of your facility, located at 12245 SW 128th St. Unit 301, Miami, Florida. The inspection revealed serious violations of FDA's Current Good Manufacturing Practice (CGMP) in Manufacturing, Packaging, Labeling, or Holding Operations for Dietary Supplements, Title 21, Code of Federal Regulations, Part 111 (21 CFR Part 111). At the conclusion of the inspection, you were issued a Form FDA 483, List of Inspectional Observations, which listed a number of the violations that cause your dietary supplement products, Milk Thistle and L-Carnitine, 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 products have been prepared, packed, or held under conditions that do not meet CGMP requirements for dietary supplements.
In addition, FDA collected and reviewed samples of the labeling of your dietary supplement and cosmetic products during the inspection of your facility. Based on our review of your product labels, we have determined that your products, Nutra Stress Tablets, Tri-flex Capsules, Noni Juice, Arthritis Formula Capsules, and Prostaguard Capsules, are promoted for conditions that cause them to be drugs 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 labels establish that the products are drugs because they are intended for use in the cure, mitigation, treatment, or prevention of disease.
Furthermore, your products, Cardispan Levocarnitina and Collagen Cream With Dribble of the Snail, are cosmetics within the meaning of section 201(i) of the Act [21 U.S.C. 321(i)] because they are intended to be applied to the human body for cleansing, beautifying, promoting attractiveness, or altering the appearance. As such, FDA has determined that these cosmetic products are misbranded within the meaning of section 602(a) of the Act [21 U.S.C. § 362(a)] because the ingredients in each product are not listed on the label in accordance with 21 CFR 701.3.
You can find the Act and its implementing regulations through links on FDA's home page at http://www.fda.gov.
The significant violations are the following:
Adulterated Dietary Supplements
1. You failed to verify that a subset of your finished batches of dietary supplements that you identify through a sound statistical sampling plan, or every finished batch, meet finished product specifications for identity, purity, strength, composition, as required by 21 CFR 111.75(c).
Specifically, during the inspection you stated that you do not perform any finished product testing to verify the identity, purity, strength and composition of your dietary supplement products. Furthermore, your batch records for the following released finished products lacked finished product testing to verify the identity, purity, strength, and composition:
• Milk Thistle batches 3827 dated 9/20/10, 3827 dated 9/23/10, 3652 dated 7/13/10, and 4295 dated 6/3/11;
• L - Carnitine batches 4174 dated 3/11/11, 4182 dated 3/16/11, 4188 dated 3/22/11, 4201 dated 3/30/11, and 4300 dated 5/24/11.
In your response letter dated July 12, 2011, you stated you have hired a second consultant to develop raw material specifications and that you will send raw materials to a contract laboratory for identity testing with a completion time of six months. We find this response inadequate in that you have not addressed finished product testing or the development of specifications of finished products, as required by 21 CFR 111.70(e).
2. You failed to confirm the identity of other components (not including dietary ingredients) and determine whether other applicable component specifications established in accordance with 21 CFR 111.70(b) are met by either conducting appropriate tests or examinations; or relying on a certificate of analysis (COA) from the supplier of the component that you receive, as required by 21 CFR 111.75(a)(2). In order to rely on your suppliers' COAs you must, among other requirements, first qualify the suppliers COAs through confirmation of the results of the supplier's tests or examinations, as required by 21 CFR 111.75(a)(2)(ii)(A).
Specifically, during the inspection it was determined that you do not conduct any testing of raw materials upon receipt.
In your response letter dated July 12,2011, you stated that your consultant will qualify each of your suppliers per COA with an expected completion time of six months. We find this response to be inadequate in that you do not address the products going to be produced in the next six months prior to your estimated time of completion for the correction.
3. Your quality control unit failed to perform the operations required by 21 CFR 111.105.
Specifically, your written standard operating procedures (SOP) version #1 is not approved by the quality control unit [21 CFR 111.105(a)].
4. Your quality control operations for you master manufacturing record, the batch production record, and manufacturing operations failed to approve and release, or eject, each finished batch for distribution, as required by 21 CFR 111.123(a)(8). Specifically, Milk Thistle batches (3827 dated 9/20/10,3827 dated 9/23/10,3652 dated 7/13/10, and 4295 dated 6/3/11) were released without the approval of the Quality Control Unit to ensure that the dietary supplement met specifications of identity, purity, strength, and composition.
5. Your firm's quality control operation failed to approve and release from quarantine all components, packaging, and labeling before they were used, as required by 21 CFR 111.120(e). Specifically, labels and dietary supplement components were released for use by the office manager rather than the Quality Control Personnel. Additionally, during the inspection it was indicated that the packaging manager completes the Labeling, Receiving and Inspection Report which is then signed on the "tested by" line and circle "approved" by the office manager.
In your response letter dated July 12, 2011, you stated you have now designated individuals (one QC Manager and two QC personnel) to perform the functions of the Quality Control Unit. You also state your new SOP system is going to be approved by the QC personnel, which we will verify at our next inspection.
6. Your batch production records (BPR) failed to include complete information relating to the production and control of each batch of dietary supplement product you manufacture, as required by 21 CFR 111.255(b). Specifically, your BPR's did not include the following required information:
• Milk Thistle batches (3827 dated 9/20/10, 3827 dated 9/23/10, 3652 dated 7/13/10, 4295 dated 6/3/11) and L-Carnitine batches (4174 dated 3/11/11, 4182 dated 3/16/11, 4188 dated 3/22/11, 4201 dated 3/30/11, 4300 dated 5/24/11) did not include the identity of equipment and processing lines used in producing the batch [21 CFR 111.260(b)];
• Milk Thistle batches (3827 dated 9/20/10, 3827 dated 9/23/10, 3652 dated 7/13/10, 4295 dated 6/3/11) and L-Carnitine batches (4174 dated 3/11/11, 4182 dated 3/16/11, 4188 dated 3/22/11, 4201 dated 3/30/11, 4300 dated 5/24/11) did not include the date and time of the maintenance, cleaning, and sanitizing of the equipment and processing lines used in producing the batch, or a cross-reference to records, such as individual equipment logs, where this information is retained [21 CFR 111.260(c)];
• Milk Thistle batches (3827 dated 9/20/10, 3827 dated 9/23/10, 3652 dated 7/13/10) did not include the unique identifier (lot #) that you assigned for each component [21 CFR 111.260(d)];
• Milk Thistle batches (3827 dated 9/20/10,3827 dated 9/23/10, 3652 dated 7/13/10) and L- Carnitine batches (4174 dated 3/11/11, 4182 dated 3/16/11, 4188 dated 3/22/11, 4201 dated 3/30/11, 4300 dated 5/24/11) did not include the unique identifier (lot #) that you assigned for the packaging and label used [21 CFR 111.260(d)];
• Milk Thistle batches (3827 dated 9/20/10, 3827 dated 9/23/10, 3652 dated 7/13/10) and L- Carnitine batches (4174 dated 3/11/11, 4182 dated 3/16/11, 4188 dated 3/22/11, 4201 dated 3/30/11, 4300 dated 5/24/11) did not include a statement of the actual yield [21 CFR 111.260(f)];
• Milk Thistle batches (3827 dated 9/20/10, 3827 dated 9/23/10, 3652 dated 7/13/10, 4295 dated 6/3/11) and L-Carnitine batches (4174 dated 3/11/11, 4182 dated 3/16/11, 4188 dated 3/22/11, 4201 dated 3/30/11, 4300 dated 5/24/11) did not include documentation that the finished dietary supplement meets established specifications in accordance with 21 CFR 111.70(e) and (g) [21 CFR 111.260(i)];
• L-Carnitine batch (4300 dated 5/24/11) and Cardispan tablets (batch 4301 dated 5/26/11) were not completed at the time of performance in that weight and lot number verification initials were not added concurrent with the steps of weighing and lot number documentation [21 CFR 111.2600)];
• L-Carnitine batch (4300 dated 5/24/11) did not include the date on which each step was performed to produce the batch, and did not include the initials of the person(s) performing each step [21 CFR 111.2600)(1) and (2)];
• Milk Thistle batches (3827 dated 9/20/10, 3827 dated 9/23/10, 3652 dated 7/13/10, 4295 dated 6/3/11) and L-Carnitine batches (4174 dated 3/11/11, 4182 dated 3/16/11, 4188 dated 3/22/11, 4201 dated 3/30/11, 4300 dated 5/24/11) when label reconciliation is required, did not include reconciliation of any discrepancies between issuance and use of labels [21 CFR 111.260(k)(1)]. Label reconciliation is required for cut or rolled labels if a 100-percent examination for correct labels is not performed by appropriate electronic or electro mechanical equipment during or after completion of finishing operations (72 FR 34752 at 34889, June 25, 2007);
• L-Carnitine batches (4174 dated 3/11/11, 4182 dated 3/16/11, 4188 dated 3/22/11, 4201 dated 3/30/11, and 4300 dated 5/24/11) did not include an actual label or representative label, or a cross-reference to the physical location of the actual or representative label specified in the master manufacturing record [21 CFR 111.260(k)(2)];
• Milk Thistle batches (3827 dated 9/20/10, 3827 dated 9/23/10, 3652 dated 7/13/10, 4295 dated 6/3/11) and L-Carnitine batches (4174 dated 3/11/11, 4182 dated 3/16/11, 4188 dated 3/22/11, 4201 dated 3/30/11, 4300 dated 5/24/11) did not include documentation that quality control personnel reviewed the batch production record [21 CFR 111.260(1)(1)].
In your response letter dated July 12, 2011, you state that you have created "Master Records;" however this letter does not address the lack of pertinent control data, which is missing for the above noted batches.
7. Your firm failed to make and keep written master manufacturing records (MMRs) for each unique formulation of a dietary supplement that you manufacture, and for each batch size, in accordance with 21 CFR Part 111, Subpart P, as required by 21 CFR 111.205(c). During the inspection you could not produce an MMR for the following products:
• L-Carnitine
• Milk Thistle
In your response letter dated July 12, 2011, you state that you have created "Master Records" and they are going to be kept separate from your "Production Batch Records." We will verify your new "Master Records" at our next inspection.
8. Your reserve sample failed to consist of at least twice the quantity necessary for all tests or examinations to determine whether or not the dietary supplement meets product specifications, as required by 21 CFR 111.83. Specifically, your firm did not have reserve samples on hand for Vitamin E 1000 - lot #4025. You stated that the reserve sample for this particular lot was removed and provided to a customer. During the inspection, you also stated that the amount of all reserve samples collected are determined based on the size of the lot produced.
In your response letter dated July 12, 2011, you state that you are going to keep three samples of each batch record and the new batch number will show all the samples that are going to be kept for each product. We deem this response inadequate in that you did not state that the reserve samples would consist of at least twice the quantity necessary for all tests or examinations to meet product specifications as required.
9. You failed to make and keep documentation of the controls you use to ensure that equipment functions according to its intended use, as required by 21 CFR 111.35(b)(6). Furthermore, your improvised equipment arrangement is not of appropriate design, construction, and workmanship to enable the equipment to be suitable for its intended use and to be adequately cleaned and properly maintained, as required by 21 CFR 111.27(a). Specifically, you did not have documentation assessing the use of wooden sticks attached with masking tape to the inside of the tablet coater machine or the use of a commercial leaf blower and fan also used in the tablet coater machine. You stated to our investigator that you have not qualified this set-up of the equipment controls used in the manufacturing process for your dietary supplement products.
In your response letter dated July 12, 2011, you state that you will remove the "rubber" sticks, the leaf blower, and the fan within four months. We note that you have committed to purchasing (b)(4) bars and you will replace the leaf blower and fan with an oil free air compressor. You should send us documentation of this adjustment. You are also required to establish appropriate controls for your new equipment to ensure that the new equipment functions with regard to its intended use.
10. You failed to establish procedures for packaging and labeling operations, as required by 21 CFR 111.403. Specifically, the Standard Operation Procedure #QAL-17 "Dietary Supplement Labeling Version #1" does not establish detailed procedures for certain labeling operations as follows:
• Use and reconciliation of labels [21 CFR 111.410(b)];
• Examination of labels for each batch [21 CFR 111.410(c)];
• Manufacturing history of a dietary supplement through distribution [21 CFR 111.410(c)];
• Effective operations for filling, assembling, packaging, labeling, and performing other related operations in a way that ensures the quality of the dietary supplement [21 CFR 111.415];
• Repackaging and relabeling [21 CFR 111.420];
In your response letter dated July 12, 2011, you state that you are revising your SOP QAL #17 in order to be in compliance and that you will train the Quality Control personnel in labeling and receiving inspections within a four month time frame. We deem this response inadequate because you fail to take any immediate corrective action that addresses products you intend to manufacture prior to your stated completion time for correction.
11. You failed to make and keep written procedures for holding and distribution operations, as required by 21 CFR 111.475(b)(1). Specifically, you do not have written procedures for holding and distributing dietary supplements in your C. J. Labs Standard Operating Procedures manual.
In your response letter dated July 12, 2011, you state you will develop and implement these procedures within a time frame of three months. We deem this response to be inadequate because you have not addressed the products you intend to distribute in the next three months.
12. You failed to make and keep written procedures for maintaining, cleaning, and sanitizing, as necessary, all equipment, utensils, and any contact surfaces that are used to manufacture, package, label, or hold components or dietary supplements, as required by 21 CFR 111.35(b)(1)(iii). Specifically, you did not establish written procedures for maintaining, cleaning, and sanitizing the Small V mixer, Large V mixer, Tablet Coater, Tablet Press, Capsulation Machine, Foil Packet machine, Bottle Labeler/Filler line, the (b)(4) tank, and utensils.
In your response letter dated July 12, 2011, you state that your consultant is working to create new procedures and they are going to be completed within a six month time frame; however you failed to address the products you intend to manufacture and distribution within the next six months. We will verify your new procedures at our next inspection.
Unapproved New Drugs
Examples of some of the therapeutic claims observed on your product labels include:
Nutra Stress
• "Helpful for ... depression, insomnia.... Helps prevent heart and blood pressure disorders."
Tri-flex
• "Regenerates damaged cartilaginous joints. Relieves some discomfort associated with arthritis and rheumatism."
Noni Juice
• "[I]t may be used in the treatment of diabetes, ulcers, heart disease, high blood pressure as well as kidney and bladder disorder."
Arthritis Formula
• "Regenerates damaged cartilaginous joints. Relieves some discomfort associated with arthritis and rheumatism."
Prostaguard
• "Relieves the symptoms of enlarged prostate.... For prostate and urinary tract health."
Because your products, listed, above, are not generally recognized as safe and effective for the above referenced uses they are "new drugs" under section 201(p) of the Act [21 U.S.C. § 321(p)]. New drugs 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, because your products, listed above, are offered for conditions that are not amenable to self-diagnosis, and treatment by individuals who are not medical practitioners, adequate directions cannot be written so that a layperson can use the product safely for its intended uses. Thus, these products are also misbranded within the meaning of section 502(f)(1) of the Act, in that the labeling for these drugs fails to bear adequate directions for use [21 U.S.C. § 352(f)(1)].
Misbranded Cosmetics
Your "Collagen Cream with Dribble of the Snail" and "Cardispan Levocarnitin" products are misbranded within the meaning of section 602(a) of the Federal Food, Drug, and Cosmetic Act [21 U.S.C. § 362(a)] because the ingredients for these products are not declared in accordance with the cosmetic labeling requirements of 21 CFR 701.3.
The cosmetic labeling violations are as follows:
Cardispan Levocarnitina:
• White Petrolatum should be listed as Petrolatum (21 CFR 701.3(c));
• Ricinus comminus should be listed ·as either Castor Oil or Castor Seed Oil (Ricinus comminus) (21 CFR 701.3(c));
• "Osipropyl" myristate should be listed as Isopropyl myristate (21 CFR 701.3(c));
• Procol P is a trade name for a mixture of cetearyl alcohol, polysorbate 60, PEG-150 stearate, and steareth-20 (21 CFR 701.3(c)). Each of these ingredients must be listed
separately(21 CFR 701.3(a));
• Reocare ATH is a trade name mixture of sodium polyacrylate, ethylhexyl stearate and trideth 6) (21 CFR 701.3(c)). Each of these ingredients must be listed separately (21
CFR 701.3(a));
• Agua demineralisada should be listed as water (21 CFR 701.3(c)).
Collagen Cream with Dribble of the Snail:
• "Jeesic PS-VA" and Polawax are trade names and are not acceptable as cosmetic ingredient names (21 CFR 701.3(c)). All of the constituents of these materials must be listed separately (21 CFR 701.3(a));
• Purified water should be listed as water (21 CFR 701.3(c));
• Reocare ATH is a trade name mixture of sodium polyacrylate, ethylhexyl stearate and trideth 6) (21 CFR 701.3(c)). Each of these ingredients must be listed separately (21 CFR 701.3(a)).
The violations mentioned in this letter are not intended to be an all-inclusive list of violations at your facility. 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 described above and prevent their further recurrence. Failure to promptly correct these violations may result in legal action, without further notice, including, but not limited to, seizure and/or injunction against the manufacturers and distributors of violative products.
We also note the following:
• You did not make and keep records required for your physical plant and grounds for cleaning, as required by 21 CFR 111.23(b). Our investigators found that no such records exist, whereas your SOP Version #1 Section PRO-01 identifies the use of a cleaning and maintenance log.
• You did not establish written procedures for packaging operations, as required by 21 CFR 111.403. Specifically, your C. J. Labs Standard Operating Procedures for packaging apply to pharmaceutical products and not dietary supplements. In your response letter dated July 12, 2011, you state that your consultant will create a packaging SOP for dietary supplerp.ents within the time frame of five months. We will verify this correction at our next inspection.
• For each dietary supplement you manufacture, it is your firm's responsibility to establish product specifications for 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 by 21 CFR 111.70(e). As stated in the final rule (72 FR 34752 at 34837; June 25, 2007), "the manufacturer has the responsibility to determine what types of contamination are likely or certain to contaminate a given product and to determine what types of tests to conduct and when to test for such contamination." Our investigator noted that you had no specifications for any type of contamination for your finished batches of dietary supplements.
You should respond in writing within fifteen (15) working days from your receipt of this letter. Your response should outline the specific steps you are taking to correct the violations noted above. You should include in your response, documentation and any other useful information that would assist us in evaluating your corrections. If you cannot complete all corrections before you respond, you should explain the reason for your delay and state when you will correct any remaining violations.
Please send your written reply to the Food and Drug Administration, Attention: Carla A. Norris, Compliance Officer, 555 Winderley Place, Suite 200, Maitland, Florida, 32751. If you have questions regarding any issues in this letter, please contact Ms. Norris at (407) 475-4730.
Sincerely,
/S/
Emma R. Singleton
Director, Florida District
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