- PreMark Health Science, Inc.
- Issuing Office:
- Dallas District Office
Department of Health and Human Services
|Public Health Service|
Food and Drug Administration
4040 North Central Expressway
Dallas, Texas 75204-3128
December 18, 2014
UPS OVERNIGHT MAIL
William David Palmer, J.D., MBA
President and CEO
PreMark Health Science, Inc.
3200 West Story Rd
Irving, Texas 75038
Dear Mr. Palmer:
The U.S. Food and Drug Administration (FDA or we) inspected your facility, located at 3200 W. Story Rd, Irving, Texas, from April 15 through 24, 2014. During the inspection, our investigators identified significant violations of FDA's Current Good Manufacturing Practice (CGMP) regulations for dietary supplements, found in 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 Federal Food, Drug, and Cosmetic Act (the Act) [Title 21, United States Code (U.S.C.) § 342(g)(1)] in that they have been prepared, packed, or held under conditions that do not meet the CGMP regulations for dietary supplements.
We acknowledge receipt of your written response with attachments, dated May 30, 2014, to the Form FDA 483 (inspectional observations) that was issued to your firm at the conclusion of the inspection on April 24, 2014. We address your written response below.
The inspection revealed the following significant violations:
1. You failed to conduct at least one appropriate test or examination to verify the identity of a component that is a dietary ingredient, prior to its use, as required by 21 CFR 111.75(a)(1)(i) (except in situations where a firm successfully petitions FDA for an exemption from this requirement, pursuant to 21 CFR 111.75(a)(1)(ii)).
Specifically, you failed to conduct identity testing on Soy lsoflavones (b)(4) (Lot #(b)(4) and (b)(4)) and Zinc Citrate (Lot #(b)(4)), used in the manufacture of Batch #(b)(4) of your (b)(4) product on March 27, 2014. Before using a component that is a dietary ingredient, you must conduct at least one appropriate test or examination to verify the identity of the dietary ingredient, unless you have petitioned FDA for an exemption from such testing, consistent with the requirements of 21 CFR 111.75(a)(1)(ii), and FDA exempts you from such testing. Your firm has not petitioned FDA for such an exemption.
We received your written response with attachments, dated May 30, 2014, but your response cannot be evaluated because of the lack of supporting documentation. You submitted a revised SOP for (b)(4), which is designed to ensure that all incoming raw materials, including dietary ingredients, will be tested by the (b)(4) equipment for acceptance. However, the revised SOP for (b)(4) does not identify or reference a list of the specific dietary ingredients that can be accurately tested by (b)(4) and how the (b)(4) are compared to the reference standards for acceptance or rejection. Further, (b)(4) may not have the ability to provide details in the identification of complex components, such as Soy lsoflavones (b)(4). Note that you must 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, in accordance with 21 CFR 111.320(b). The supporting documentation you provided does not include scientific evidence that the (b)(4) is an appropriate test method, as required under 21 CFR 111.320(b).
Finally, no documentation was provided to demonstrate that an investigation was conducted into any potentially impacted product not subjected to (b)(4) testing between October 23 to November 15, 2013, when your (b)(4) was inoperable.
2. You failed to establish laboratory control processes that are reviewed and approved by quality control personnel, including the use of criteria for selecting reference materials used in performing tests and examination, as required by 21 CFR 111.315(d).
Specifically, you indicated to our investigators during the inspection that your non-compendia reference standard materials (i.e., (b)(4)) for the (b)(4) are selected from (b)(4) component shipments received and analyzed by your (b)(4) equipment. However, you failed to establish any criteria (i.e., characterization) to establish a reference standard. Non-compendia reference standard materials should be of the highest purity by reasonable effort and should be thoroughly characterized to ensure the identity, purity, quality, and strength of the product.
We received your written response with attachments, dated May 30, 2014, but your response cannot be evaluated because of the lack of supporting documentation. You submitted a revised SOP for (b)(4) to ensure that all incoming raw materials will be tested by the (b)(4) equipment for acceptance prior to release into production. However, the revised SOP for (b)(4) does not identify or reference a list of the specific dietary ingredients that can be accurately tested by (b)(4) and how the (b)(4) are compared to the reference standards for acceptance or rejection. You have not confirmed your criteria for selecting reference standards by either purchasing known reference standards, if available, or using an outside laboratory to assist you in characterizing the dietary ingredients for use as (b)(4) reference standards.
3. You failed to establish specifications for any point, step, or stage in the manufacturing process where control is necessary to ensure the quality of your dietary supplements and that your dietary supplements are packaged and labeled as specified in the master manufacturing record, as required by 21 CFR 111.70(a).
Specifically, you do not have established specifications for each component you use in the manufacture of your (b)(4)[21 CFR 111.70(b)], for your (b)(4) labels [21 CFR 111.70(d)], or for the packaging and labeling of your (b)(4) [21 CFR 111.70(g)).
We received your written response with attachments, dated May 30, 2014, and found your response to be inadequate. The response cannot be evaluated because no evidence was provided to demonstrate that you have established the required specifications.
4. You failed to prepare and follow a written master manufacturing record (MMR) for each unique formulation of dietary supplement that you manufacture, and for each batch size, to ensure uniformity in the finished batch from batch to batch, as required by 21 CFR 111.205(a).
Specifically, you failed to create an MMR for any of the dietary supplement products you have manufactured since (b)(4). You must create an MMR that satisfies the requirements of 21 CFR 111.210.
We received your written response with attachments, dated May 30, 2014, but your response cannot be evaluated because of the lack of supporting documentation. Your response (Exhibit C) provided a blank MMR template that lists the name of the finished product but does not include the specific information required under 21 CFR 111.210. For example, it does not list the strength, concentration, weight, or measure of each dietary ingredient for each batch size [21 CFR 111.210(a)] or a complete list of components to be used [21 CFR 111.210(b)]. Additionally, you have not provided a timeframe for establishing an MMR for each unique formulation of dietary supplement you manufacture.
5. You failed to create batch production records (BPR) that satisfy the requirements of 21 CFR 111.260.
Specifically, your BPRs for your (b)(4) do not include the following information:
a) 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)]. You also did not make and keep documentation in individual equipment logs of the date of the use, maintenance, cleaning, and sanitizing of equipment, as is permitted as an alternative to including such information in the BPR under 21 CFR 111.35(b)(2);
b) The initials of the person responsible for adding a component to the batch [21 CFR 111.260(j)(2)(iii)];
c) The initials of the person responsible for verifying the addition of components to the batch [21 CFR 111.260(j)(2)(iv)];
d) The unique identifier assigned to the packaging and labels used and when label reconciliation is required, reconciliation of any discrepancies between issuance and use of labels [21 CFR 111.260(k)(1)]; and,
e) An actual or representative label, or a cross-reference to the physical location of the actual or representative label specified in the MMR [21 CFR 111.260(k)(2)].
We received your written response with attachments, dated May 30, 2014, but your response cannot be evaluated because of the lack of supporting documentation. Although you state that you have created new templates for BPRs, you have not provided evidence demonstrating that you have implemented the changes for each unique formulation.
6. You failed to establish and follow written procedures for the responsibility of quality control operations, including written procedures for conducting a material review and making a disposition decision, as required by 21 CFR 111.103.
Specifically, you have not established written procedures for quality control operations. Once you have established such written procedures, your quality control personnel must ensure that your manufacturing, packaging, labeling, and holding operations ensure the quality of the dietary supplement and that the dietary supplement is packaged and labeled as specified in the master manufacturing record, in accordance with 21 CFR 111.105.
The violations cited in this letter are not intended to be an all-inclusive statement of violations that exist in connection with your products. You are responsible for investigating and determining the causes of the violations identified above and for preventing their recurrence or the occurrence of other violations. It is your responsibility to ensure that your firm complies with all requirements of federal law and FDA regulations.
You should take prompt action to correct the violations cited in this letter. Failure to promptly correct these violations may result in legal action without further notice, including, without limitation, seizure and injunction.
Additionally, we have the following comment. Under 21 CFR 111 .35(b)(1)(i), your firm must make and keep written procedures for calibrating instruments and controls that you use in manufacturing or testing a component or dietary supplement. We note that your firm does not currently have such procedures. Your written response with attachments, dated May 30, 2014, states that you have modified your SOPs for (b)(4) and (b)(4) to document (b)(4) calibration checks of all balances and thermometers and (b)(4) third-party calibration of scales and testing of all test equipment. The two SOPs attached in Exhibit G of your response, however, do not include a list of equipment and the frequency with which they are calibrated. Additionally, the scale calibration record provided in your response as Exhibit H is not current as of the date of your response letter, and the scale is not identified.
Within fifteen working days of receipt of this letter, please notify this office in writing of the specific steps that you have taken to correct violations. Include an explanation of each step being taken to prevent the recurrence of violations, as well as copies of related documentation. If you cannot complete corrective action within fifteen working days, state the reason for the delay and the time within which you will complete the correction.
Section 743 of the Act (21 U.S.C. 379j-31) authorizes FDA to assess and collect fees to cover FDA's costs for certain activities, including reinspection-related costs. A reinspection is one or more inspections conducted subsequent to an inspection that identified noncompliance materially related to a food safety requirement of the Act, specifically to determine whether compliance has been achieved. Reinspection-related costs means all expenses, including administrative expenses, incurred in connection with FDA's arranging, conducting, and evaluating the results of the reinspection and assessing and collecting the reinspection fees (21 U.S.C. 379j-31(a)(2)(8)). For a domestic facility, FDA will assess and collect fees for reinspection-related costs from the responsible party for the domestic facility. The inspection noted in this letter identified noncompliance materially related to a food safety requirement of the Act. Accordingly, FDA may assess fees to cover any reinspection-related costs.
Your written response should be sent to Thao Ta, Compliance Officer, U.S. Food and Drug Administration, 4040 North Central Expressway, Suite 300, Dallas, TX, 75204. If you have questions regarding any issues in this letter, please contact Thao Ta at (214) 253-5217.
Reynaldo R. Rodriguez, Jr.
Dallas District Director