Inspections, Compliance, Enforcement, and Criminal Investigations
Dynamic Pharmaceuticals, Inc. 6/23/11
Department of Health and Human Services
|Public Health Service
Food and Drug Administration
555 Winderley Place, Ste. 200
RETURN RECEIPT REQUESTED
June 23, 2011
Christopher K. Reckner, President
Dynamic Pharmaceuticals, Inc.
15431 Flight Path Drive
Brooksville, Florida 34604
Dear Mr. Reckner:
On November 20, 2010 to December 3, 2010, the U.S. Food and Drug Administration (FDA) conducted an inspection of your dietary supplement manufacturing facility located at 15431 Flight Path Dr, Brookville, Florida. Our investigation revealed significant 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 lists a number of the violations that cause the following products manufactured in your facility, (b)(4) and (b)(4) dietary supplements, (b)(4) and (b)(4) 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 these dietary supplements have been prepared, packed, or held under conditions that do not meet current good manufacturing practice requirements for dietary supplements. You may find the Act and its implementing regulations through links on FDA's home page at www.fda.gov.
The inspection revealed the following violations:
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 product specifications for identity, purity, strength, and composition, as required by 21 CFR 111.75(c). Specifically, your finished product testing for all of the dietary supplement products you manufacture only includes testing for hardness, thickness, weight and/or dissolution. Your QC Final Release Testing Procedure, QC-024-06, dated 02/08/10, requires referring to the appropriate Master Product Specification to verify the testing requirements and requires testing for hardness, thickness, weight and/or dissolution. You did not test for or have procedures that require testing for product specifications for identity, purity, strength, and composition.
In your response letter dated December 14, 2010, you stated that you will update your SOP QC-024 to reflect that all final release testing for finished products will include but will not be limited to visual inspection, assay testing utilizing one or more of the following methods: (b)(4) Further, you state that you will train all employees involved in the release of dietary supplements. You also state that you will test all dietary supplements manufactured in the last 6 months to assure product quality. However, your response is inadequate because you have not provided documentation to indicate that you have completed any of these proposed corrective actions to date.
2. You failed to identify and use an appropriate scientifically valid method for each established specification for which testing or examination is required to determine whether the specification is met, as required by 21 CFR 111.320(b). Specifically, your in-process specification data at the Final Blending step for (b)(4) of your (b)(4) and (b)(4) dietary supplements were established using spectroscopy data collected from initial batches of the products. However, the initial batches of your product are not a recognized reference standard and are not part of a scientifically valid method. Nor have you verified that a test methodology that uses such batches in this way is appropriate for the intended use, as required by 21 CFR 111.320(a).
In your response letter dated December 14, 2010, you stated that you will update your SOP QC-025 and QC-026 to include established methods of introducing data into the NIR library that has been verified to meet 21 CFR Part 111, train employees involved in the testing of all dietary supplements, acquire 3 new samples of each dietary supplement blend and analyze all new samples for identity, purity, and composition by the use of assay and microbial testing, and upload results into the NIR library if acceptable. However, your response is inadequate because you failed to provide a copy of your updated SOPs for our review.
3. Your batch production record (BPR) for the Final Blending step for (b)(4) Batch # 10289, Batch 5 of 23, failed to contain the following information:
• The unique identifier assigned to each component used, as required by 21 CFR 111.260(d). Specifically, the BPR did not contain the lot number of the raw material Granulation L- Leucine, LIsoleucine, LValine.
• The identity and weight or measure of each component used, as required by 21 CFR 111.260(e). Specifically, the BPR did not include weights of the raw materials Granulation L-Leucine, LIsoleucine, LValine, Talc, Croscarmellose Sodium, and Magnesium Stearate.
• Documentation, at the time of performance of the manufacture of the batch, including initials of the person performing each step, as required by 21 CFR 111.260(j)(2). Specifically, on 11/29/10 our investigator observed that the production employee did not document at the time of performance, the addition of each component during the Final Blending step for (b)(4) Batch # 10289, Batch 5 of 23. The production employee responsible to verify addition of the components also did not document the activity at the time of performance. Further, the production employee responsible for verifying components weighed during this manufacturing step did not document verification of the activity at the time of performance for many components.
In your response dated December 14, 2010, you stated that all employees associated with the blending phase have been retrained on the proper documentation practices per CGMP and SOP BLN-009-00 and all dietary supplement blending records are being updated to reflect specific standards and instructions for each blend manufactured at your firm. However, you did not provide documentation of your training. We intend to verify your corrective actions at the time of the next inspection.
4. Your quality control personnel failed to conduct a material review and make a disposition decision if a specification established in accordance with 21 CFR 111.70 is not met, as required by 21 CFR 111.113(a)(1). Specifically, your procedure QC-025-00, dated 12/31/08, for use of the (b)(4) equipment for in-process testing following the Final Blending step, includes routine retesting of samples which fail this test without requiring your quality control personnel to conduct a material review and make a disposition decision.
In your response dated December 14, 2010, you stated that all affected SOPs will be updated to reflect that all failures during manufacturing of all dietary supplements will be properly identified, investigated and documented. However, your response is inadequate because you have not provided a copy of your revised SOPs for our review or indicated that you have completed your proposed corrective action to date.
5. You failed to meet the following requirements to establish a BPR:
• Your BPR does not include complete information relating to the production and control of each batch, as required by 21 CFR 111.255(b). Specifically you failed to record the blending times on the BPR for (b)(4) Batch # 10289, Batch 5 of 23.
• Your BPR does not accurately follow the appropriate master manufacturing record and you did not perform each step in the production of the batch, as required by 21 CFR 111.255(c). Specifically, your production employees did not follow the (b)(4) Dry Blending Instructions while manufacturing (b)(4) Batch # 10289, Batch 5 of 23. According to your production employee, the stage (b)(4) ingredient talc was (b)(4) ingredients which does not follow the blending instructions in the BPR.
In your response letter dated December 14, 2010, you stated that a new SOP BLN-009-00 was created to provide instructions on the proper procedure for blending and to assure that the written instructions within the specific batch record are followed and that all blending operators were trained regarding the new SOP. However, your response is inadequate because you have not submitted any documentation of this training or provided a copy of the SOP for our review.
6. You failed to use effective measures to protect against the inclusion of metals or other foreign material in components or dietary supplements as required by 21 CFR 111.365(i). Specifically, your firm's manufacturing processes for tablets and caplets do not include the use of filters or strainers, traps, magnets, electronic metal detectors, or any other comparable means to protect against the inclusion of metal or other foreign materials. Although your firm pours blended in-process product through a metal mesh screen when adding it to the encapsulation equipment, and allows compressed product to pass over a shaker unit, and inspects all equipment and tooling before and after each production run, these methods are not sufficient to ensure that metal and other foreign objects are not included in your dietary supplements because they were not specifically intended to prevent the inclusion of metal or other objects. For example, the (b)(4) Equipment Cleaning Check List does not specifically address checking the condition of metal surfaces or parts.
In your response letter dated December 14, 2010, you stated that you will identify all equipment that has a possible hazard for incorporating metal into a product, secure metal detection equipment, validate the effectiveness of installed magnetic separators, and train all employees involved in the specific manufacturing and quality inspection of the equipment identified. However, your response is inadequate because you have provided no documentation that you have implemented your corrective action plan.
This letter is not an all-inclusive list of violations at your facility. It is your responsibility to ensure that your establishment 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 seizure of violative products and/or injunction against the manufacturers and distributors of violative products.
In addition we have the following comments:
• 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.
• Our investigator found that your firm manufactures a variety of supplements intended for use in animals (or pets). We would encourage you to contact FDA's Center for Veterinary Medicine to discuss the regulatory status of these products and specific requirements that apply to such products.
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.
Your response should be sent to: Winston R. Alejo, Compliance Officer, 555 Winderley Place, Suite 200, Maitland, Florida, 32751. If you have any questions about the content of this letter please contact: Mr. Alejo at (407) 475-4731.
Emma R. Singleton
Director, Florida District