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U.S. Department of Health and Human Services

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Enforcement Actions

AloeScience Labs, Inc. 11/14/12

  

Department of Health and Human Services' logoDepartment of Health and Human Services

Public Health Service
Food and Drug Administration
 

Dallas District
4040 North Central Expressway
Dallas, Texas 75204-3128

November 14, 2012

2013-DAL-WL-013

WARNING LETTER

UPS OVERNIGHT

Thomas A. Cottrell, President
AloeScience Labs, Inc.
3740 Marquis Drive
Garland, Texas 75042

Dear Mr. Cottrell,
 
The U.S. Food and Drug Administration (FDA) inspected your facility located at 3740 Marquis Drive, Garland, Texas, from February 27 through March 9, 2012. During our inspection, we evaluated the manufacturing of several of the dietary supplement products you produce, including (b)(4). During the inspection, our investigators found a number of violations of the dietary supplement Current Good Manufacturing Practice (CGMP) regulations, found in Title 21 of the Code of Federal Regulations, Part 111 (21 CFR Part 111). These violations cause your products 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 they have been prepared, packed, or held under conditions that do not meet CGMP regulations for dietary supplements. These inspectional observations were provided to you on the FDA-483 form issued at the conclusion of our inspection on March 9, 2012.

You can find the Act and FDA regulations through links at FDA’s home page at http://www.fda.gov.

Our FDA investigator observed the following violations during the inspection:

1. Your firm failed to provide records to show that you had established product specifications, as required by 21 CFR 111.95(b)(1), for the identity, purity, strength, and composition of the finished batch of each dietary supplement, and for limits on those types of contamination that may adulterate, or that may lead to adulteration of, the finished batch of dietary supplement to ensure the quality of the dietary supplement that you manufacture, as required by 21 CFR 111.70(e). For example, you were not able to provide any records to show that you established product specifications for the identity, purity, strength, and composition of the finished batch of (b)(4).

Further, your firm failed to provide records, as required by 21 CFR 111.95(b)(1) to show that you had established specifications for each component necessary to ensure that specifications for the purity, strength, and composition of the dietary supplements manufactured using the components are met, as required by 21 CFR 111.70(b)(2).  For example, your firm uses Aloe, Grapeseed (b)(4)%, Chamomile, Goldenseal, Wild Yam, Citric Acid, Sea Weed, Sodium Benzoate or Potassium Sorbate in your Liquid Dietary Supplement products, but you failed to provide records to show that you established component specifications for each of these components.
 
 Your April 12, 2012 dated response was reviewed and determined to be inadequate.  Your response does not address whether you will commit to establishing specifications for your components and finished batches of all dietary supplements.  Moreover, though your letter commits to conducting testing at an independent laboratory, you have provided no documentation to show that you established the necessary specifications that you indicate will be tested by an independent laboratory. 

2. You failed to conduct at least one appropriate test or examination to verify the identity of any component that is a dietary ingredient, as required by 21 CFR 111.75(a)(1)(i). Specifically, you provided no documentation of testing or examination results to verify the identities of any dietary ingredients used in the manufacture of the following finished batches of dietary supplements:

• (b)(4)
• (b)(4)
• (b)(4)
• (b)(4) 

Your April 12, 2012 dated response was reviewed and determined to be inadequate.  Your response states that suppliers’ certificates of assay are received and reviewed, and testing will be conducted by an independent laboratory. However, your response does not provide documentation to show that you have implemented identity testing on any components, and you have not indicated whether you have made changes to your procedures that will ensure that all components will be tested to verify identity before use in the manufacture of your dietary supplement products.

3. Your firm failed to include documentation, at the time of performance, in the batch production record (BPR), that quality control personnel approved and released, or rejected, the batch for distribution, including any reprocessed batch, to comply with 21 CFR 111.260(l)(3) and 21 CFR 111.123(a)(8). Specifically, our review of the following batch records indicate that your quality personnel did not document approval and release, or rejection, of the batch for distribution prior to release of the product for distribution:

• (b)(4) lot #(b)(4), manufactured on 1/13/12 and shipped on (b)(4)
• (b)(4) lot #(b)(4), manufactured on 8/16/11 and shipped on (b)(4).
• (b)(4) lot #(b)(4), manufactured on 9/20/11 and shipped on (b)(4).
• (b)(4) lot #(b)(4), manufactured on 9/21/11 and shipped on (b)(4)
• (b)(4) lot #(b)(4), manufactured on 9/26/11 and 9/29/11 and shipped on (b)(4).
• (b)(4) lot #(b)(4), manufactured on 10/18/11 and invoiced on (b)(4).
• (b)(4) lot #(b)(4), manufactured on 10/31/11 and shipped on (b)(4).

Your April 12, 2012 dated response was reviewed and determined to be inadequate.   Your response states that your Vice President has the authority and responsibility for record review and approvals and rejections, and that you are also training employees. However, you have not committed any quality control personnel to comply with this requirement.  Instead, your response provides details about employee training and states that because you are a small business, you cannot “budget, equip and staff a functional quality control unit.” 

4. Your firm does not have quality control operations for components, packaging and labels before use in the manufacture of a dietary supplement, including approving, and releasing from quarantine, all components, packaging, and labels before they are used, as required by 21 CFR 111.120(e).  Specifically, you failed to identify to our investigator during the inspection the quality control personnel responsible for approving, rejecting, or releasing the dietary supplement components.  You must approve and release from quarantine all components, packaging, and labels before they are used.  Our investigator observed that you have no quality control operations for approving and releasing components.

Your April 12, 2012 dated response was reviewed and determined to be inadequate.  Your response states that your Vice President has the authority and responsibility for record review and approvals and rejections, and that you are also training employees. However, you have not provided specific details about employee training, whether the training involves quality control functions, or whether you are conducting the required quality control reviews.  Neither have you provided documentation that all components are approved and released by your quality control operations prior to use.

5. Your firm’s master manufacturing records (MMR) for the dietary supplement products (b)(4) failed to identify specifications for the points, steps, or stages in the manufacturing process where control is necessary to ensure the quality of the dietary supplements and that the dietary supplements are packaged and labeled as specified in your MMR, as required by 21 CFR 111.205(b)(1). Your firm’s MMRs for these products failed to establish controls and procedures to ensure that each batch of dietary supplements that you manufacture meets the specifications identified, as required by 21 CFR 111.205(b)(2). Your firm’s MMRs for these dietary supplement products failed to include the following information required by 21 CFR 111.210:

• A complete list of components to be used, as required by 21 CFR 111.210(b). For example, the proprietary blend components that are listed in the product label for the (b)(4) dietary supplement are not listed in the MMR;

• The identity and weight or measure of each dietary ingredient that will be declared on the Supplement Facts label, as required by 21 CFR 111.210(d). For example, the identity and weight of each dietary ingredient was not listed for Vitamin C and (b)(4) Proprietary Blend in your (b)(4) Dietary Supplement;

• A statement of theoretical yield of a manufactured dietary supplement expected at each point, step, or stage of the manufacturing process where control is needed to ensure the quality of the dietary supplement, and the expected yield when you finished 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, as required by 21 CFR 111.210(f);

• A description of packaging and a representative label, or a cross-reference to the physical location of the actual or representative label, as required by 21 CFR 111.210(g);

• Written instructions, including specifications for each point, step, or stage in the manufacturing process where control is necessary to ensure the quality of the dietary supplement and that the dietary supplement is packaged and labeled as specified in the MMR, as required by 21 CFR 111.210(h)(1);

• Procedures for sampling in the MMRs, as required by 21 CFR 111.210(h)(2);

• Written instructions for your manual operations, as follows:

o one person to weigh or measure components and another person to verify the weight or measurement of the components, as required by 21 CFR 111.210(h)(3)(ii)(A);

o one person adding the component and another person verifying the addition, as required by 21 CFR 111.210(h)(3)(ii)(B).

• The written instructions in your MMRs did not include corrective action plans to use when a specification is not met, as required by 21 CFR 111.210(h)(5).

• Written instructions for verifying the weight or measure of any component and verifying the addition of any component, in accordance with 21 CFR 111.210(h)(3)(i).

Your April 12, 2012 dated response was reviewed and determined to be inadequate.   Your response states that you have Batch Reconciliation forms, Packaging Specification and Work-Order forms, SOPs with Corrective Action Plans, and Compounding Procedures that document the required information, as well as sampling and cross-reference procedures. Your response is inadequate because you have not provided documentation of MMRs that include each ingredient; each manufacturing step, specification, and its ranges; theoretical yields; and written instructions as described in the above deviations.  Your response does not provided any MMRs to address these deviations pointed out during the inspection for our review. 

Additionally, your letter states that the product (b)(4) is a small-volume run and explains that current sampling and cross-reference procedures for this product are adequate for quality assurance purposes. This understanding of the regulations is incorrect. The size of the batch of a dietary supplement product does not exempt it or any other dietary supplement product from the requirements  concerning the contents of the MMR. Procedures for sampling and a cross-reference for tests and examinations are required elements of the MMR, regardless of the size of the batch.

Additionally, your response states that your product formula specifies the exact amounts of ingredients to be weighed and incorporated into a batch. While we agree that the regulation requires that this information be included in the MMR, the regulation also requires that the MMR list the identity and weight or measure of each dietary ingredient declared on the Supplement Facts label and the identity of each ingredient on the ingredient lists of the dietary supplement [21 CFR 111.210(d)].

6. Your firm’s BPR did not include complete information relating to the production and control of each batch and the requirements to be included in a batch record, as required by 21 CFR 111.255(b) and 111.260. Specifically, your firm’s BPR for the (b)(4) dietary supplements did not include the following required information:

• The identity of equipment and processing lines used in producing the batch [21 CFR 111.260(b)].

• 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 where this information is kept) [21 CFR 111.260(c)].

• A unique identifier for components used [21 CFR 111.260(d)]. Specifically, the BPR for (b)(4) lot #9432 fails to list a unique identifier for the “viburnum et al blend”; the BPRs for (b)(4) (b)(4) lots #9333 and #9335 fail to list a unique identifier for the citric acid used; and the (b)(4) lots #9240 and #9242 fails to list a unique identifier for the peppermint used.

• The weight or measure of each component used [21 CFR 111.260(e)]. Specifically, batch records for (b)(4) lot #9432; (b)(4) lot #9306; (b)(4) lots #9333, #9335, and #9343; and (b)(4) lots #9359 and #9367 do not document the actual weight or measure of each ingredient added to the batch.

• A statement of the actual yield and a statement of the percentage of theoretical yield at appropriate phases of processing [21 CFR 111.260(f)].

• The results of any testing or examination performed during the batch production [21 CFR 111.260(h)]. Specifically, the BPR for (b)(4) (b)(4) lot #9359 does not list an initial (b)(4) reading for the batch, and the BPRs for (b)(4) lots 9240 and 9242 fail to list any (b)(4) test results.

• Documentation that the finished dietary supplement meets specifications established in accordance with 21 CFR 111.70(e) and (g) [21 CFR 111.260(i)].

 • Documentation, at the time of performance, of the manufacture of the batch, including the date on which each step of the MMR was performed [21 CFR 111.260(j)(1)]. Specifically, although the MMRs for (b)(4) instruct that the honey and (b)(4) slurries be heated to (b)(4) and held for (b)(4) minutes, the BPRs for (b)(4) lot #9306 and (b)(4) lots #9359 and #9367 do not contain documentation that this step was performed.

• Documentation, at the time of performance, of the manufacture of the batch of the initials of the person who weighed or measured each component used in the batch, and the initials of the person who verified the weight or measure of each component used in the batch, and the initials of the person who added the component to the batch, and the initials of the person who verified the addition of components to the batch [21 CFR 111.260(j)(2)].

• Documentation of the following, at the time of performance of packaging and labeling operations:

1. The unique identifier that you assigned to packaging and labels used, the quantity of the packaging and labels used, and reconciliation of any discrepancies between issuance and use of labels [21 CFR 111.260(k)(1)].

2. An actual or representative label, or a cross-reference to the physical location of the actual or representative label [21 CFR 111.260(k)(2)].

• Documentation at the time of performance that quality control reviewed the BPR, including any monitoring operation and the results of any tests and examinations on the finished batches of dietary supplements, and approved and released the batch and the packaged and labeled dietary supplements [21 CFR 111.260(1)].  Specifically, of ten batch records reviewed during the inspection, none had documentation of review and release for packaging or distribution by quality control personnel.

Your April 12, 2012 dated response was reviewed and determined to be inadequate.  You did not provide any current batch records for the (b)(4) dietary supplements to show that you have complied with the applicable requirements. 

7. You failed to quarantine components before you used them in the manufacture of a dietary supplement, as required by 21 CFR 111.155(c).  Prior to using any components in the manufacture of a dietary supplement, you must quarantine the components until:

o you collect representative samples of each unique lot of components (and, for components that you receive, of each unique shipment, and of each unique lot within each unique shipment) [21 CFR 111.115(c)(1)];

o quality control personnel review and approve the results of any tests or examinations conducted on components [21 CFR 111.115(c)(2)]; and

o quality control personnel approve the components for use in the manufacture of a dietary supplement, including approval of any treatment (including in-process adjustments) of components to make them suitable for use in the manufacture of a dietary supplement, and releases them from quarantine [21 CFR 111.155(c)(3)].

Your April 12, 2012 dated response was reviewed and determined to be inadequate.  Your response states that your procedure and forms are being reviewed and will be updated, if necessary, and incorporated into the batch module, when required.  Your response, however, does not commit to quarantining components prior to their use, and the response provides no documentation to show that you have complied with this requirement under 21 CFR 111.180(b)(3). 

8. Your firm failed to make and keep documentation of calibrations for instruments you use in manufacturing or testing a component or dietary supplements, as required by 21 CFR 111.35(b)(3). Among other requirements, your documentation must identify the instrument or control calibrated; provide the date of calibration; identify the reference standard used; identify the calibration method used, including appropriate limits for accuracy and precision; and provide the calibration reading or readings found [21 CFR 111.35(b)(3)(i)-(v)].

 Your April 12, 2012 dated response was reviewed and determined to be inadequate.   Your response states that you have replaced your pH meter, that you are reviewing and updating your calibration procedure, that you are using an NIST thermometer to calibrate your thermometers, and that you will document calibration activities. However, your response does not provide us with any calibration records for our review to determine that you meet this requirement. 

Comments

1. Drug Manufacturing: Our inspector observed that you have manufactured several drug products including, but not limited to, (b)(4). In your April 12, 2012 response you state that you have discontinued drug products and are notifying your customers that you are no longer producing drug products. Please be advised that under sections 201(g)(1)(B) and (C) of the Act [21 U.S.C. §§ 321(g)(1)(B) and (C)], products (other than foods) that are intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease, or to affect the structure or function of the body, are defined as drugs. The intended use of a product may be determined by, among other things, its labeling, advertising, and the circumstances surrounding its distribution [21 C.F.R. § 201.128]. You may have produced products other than those listed above that meet the definition of a drug. It is your responsibility to comply with the Act and FDA’s implementing regulations for all products you produce.

Under section 510(i)(1) of the Act (21 U.S.C. § 360(i)(1)), you are required to submit registration information annually by electronic means for each foreign establishment you own or operate that is engaged in the manufacture, preparation, propagation, compounding, or processing of a drug that is imported or offered for import into the United States.  The failure to register in accordance with this provision is a prohibited act under section 301(p) of the Act (21 U.S.C. § 331(p)).  

In addition, a drug offered for import may be refused admission under section 801(a)(3) of the Act (21 U.S.C. § 381(a)(3)), if the drug appears to be adulterated or misbranded.  Under section 502(o) of the Act (21 U.S.C. § 352(o)), the failure to register a drug as required by section 510, to list a drug as required under section 510(j), or to supply certain notice or information about the drug required under section 510 renders a drug misbranded. FDA regulations in 21 CFR part 207 specify the requirements for registering and listing drugs.

FDA no longer accepts paper submissions for Registration and Listing.  Establishment registration and drug listing information should be submitted via Structured Product Labeling (SPL) using the electronic system.  For information on how to use the electronic system visit http://www.fda.gov/eDRLS.

2. (b)(3)(A)

This letter is not an all-inclusive list of violations at your facility. It is your responsibility to ensure that your products comply with the Act and FDA’s 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.

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 re-inspection-related costs.  A re-inspection 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.  Re-inspection-related costs means all expenses, including administrative expenses, incurred in connection with FDA’s arranging, conducting, and evaluating the results of the re-inspection and assessing and collecting the re-inspection fees (21 U.S.C. 379j-31(a)(2)(B)).

For a domestic facility, FDA will assess and collect fees for re-inspection-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 re-inspection-related costs.

Please advise this office in writing within fifteen (15) working 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: Seri L. Essary, Compliance Officer, at the above letterhead address. If you have any questions regarding any issue in this letter, please contact Seri Essary at (214) 253-5335.

Sincerely,

/S/ 

Reynaldo R. Rodriguez, Jr.
Dallas District Director