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U.S. Department of Health and Human Services

Animal & Veterinary

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Untitled Letter - ProCore Laboratories, LLC

September 25, 2012


2012-DAL-UTL-019


CERTIFIED MAIL
RETURN RECEIPT REQUESTED


Mr. James D. Tehan
President
ProCore Laboratories, LLC
1025 S. Beltline Road, Suite 100
Coppell, TX, 75019


Dear Mr. Tehan:

During our August 30 through September 8, 2011 inspection of your pharmaceutical manufacturing facility, ProCore Laboratories, LLC, located at 1025 S. Beltline Road, Suite 100, Coppell, TX investigators from the Food and Drug Administration (FDA) identified violations of the Current Good Manufacturing Practice (CGMP) regulations for Finished Pharmaceuticals, Title 21, Code of Federal Regulations (CFR), Parts 210 and 211. These violations cause your drug products to be adulterated within the meaning of Section of 501 (a)(2)(8) of the Federal Food, Drug, and Cosmetic Act (the Act) [21 U.S.C. § 351 (a)(2)(8)] in that the methods used in, or the facilities or controls used for, their manufacturing, processing, packing, or holding do not conform to or are operated or administered in conformity with, CGMP.

In addition, investigators from the Food and Drug Administration (FDA) identified significant violations of the Current Good Manufacturing Practice (CGMP) regulations for Dietary Supplements, Title 21, Code of Federal Regulations (CFR), Part 111. These violations cause your dietary supplement products to be adulterated within the meaning of Section of 402(g)(1) of the Act [21 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 in 21 CFR Part 111.

Also, several of the over-the-counter (OTC) drug products that you manufacture and/or distribute are in violation of sections 301(d), 505(a), 503(b) and 502(f)(1) of the Act, [21 U.S.C. §§ 331(d), 355(a) 353(b) and 352(f)(1)]. As described below, these drugs are misbranded and/or unapproved new drugs and by introducing them into interstate commerce, you are in violation of sections 301 (d) and 505(a) of the Act [21 U.S.C. § 331 (d) and 355(a)].

Finally, your veterinary drug product violates sections 512(a) and 501 (a)(5) of the Act [21 U.S. C. §§360b(a) and§ 351(a)(5)].

We have reviewed your firm's response of September 20, 2011, and note that it lacks sufficient corrective actions.

Specific violations observed during the inspection include, but are not limited, to the following:

Drug CGMP Violations:

1.  Your firm has not followed written procedures for cleaning and maintenance of equipment [21 CFR § 211.67(b)].

In addition, your response is inadequate because you have not explained if and how your cleaning/sanitization procedures were revised. The procedures in use at the time of the inspection (PCL-PR 001.7.1 and PCL-PR 001.7.2) did not include a step wherein the operator visually inspects the vessel that has been cleaned/sanitized to ensure there is no visible residue. In your response to this letter please provide the specific actions that you have taken with timeframes including a detailed description of the revisions to your cleaning procedures to ensure adequate cleaning of your non-dedicated manufacturing equipment.

This is a repeat observation from the May 2009 inspection.

It is also unclear whether you implemented corrective actions to address (b)(4)’s concern about (b)(4) effectiveness and recommendations about cleaning/sanitizing parameters (e.g., solution concentrations and temperature) in their May 19, 2011 service report. If you did implement corrective actions, please summarize these corrective actions. Please provide your scientific rationale if you did not implement corrective actions.

2.  Your firm has failed to maintain written records which were readily available, or which could be immediately retrieved electronically, for authorized inspection during the retention period at the establishment where the activities described in such records occurred [21 CFR § 211.180(c)].

For example, you were not able to provide stability data for the (b)(4) sunscreen products manufactured by your firm for your customer (b)(4).

In your response, your firm provided the stability data obtained from (b)(4) for (b)(4) SPF (b)(4) and states you are obtaining quotes from third party laboratories to conduct stability testing on your customer's products for those customers that do not perform their own stability testing. Your response is inadequate because you have not provided the stability data for the other sunscreen products manufactured for (b)(4). Your response is also inadequate because you have not provided your corrective action plan to ensure stability data is readily available for all of the products you manufacture.

This is a repeat observation from the May 2009 inspection.

3.  Your firm failed to withhold each lot of components, drug product containers and closures from use until the lot has been sampled, tested or examined as appropriate and released for use by the quality control unit [21 CFR § 211.84(d)(2)].

For example, your firm failed to test your purified water system for (b)(4) (b)(4) to determine conformance with compendial Standards for Purified Water.

In your response, your firm committed to initiate (b)(4) analysis of the water system. However, your response is inadequate in that your firm failed to identify the (b)(4) process control limit you plan to implement and provide a scientific rationale for the monitoring frequency of your water system (i.e., (b)(4)).

Dietary Supplement CGMP Violations:

1.  Your firm failed to establish product specifications for each dietary supplement you manufacture (21 CFR § 111.70(e)), and determine whether these specifications are met (21 CFR § 111. 73) by testing the finished batch of dietary supplement in accordance with testing requirements in 21 CFR § 111.75(c).

We have reviewed your response dated September 20, 2011 and have determined it to be inadequate. Specifically, you state that your firm has issued a purchase order for an (b)(4) machine and that the equipment company will help you calibrate it and then you will establish specifications for the raw materials. Your response does not address how the (b)(4) instrument will be used to establish product specifications for each dietary supplement product you manufacture. You did not provide documentation that dietary supplement product specifications have been established.

2.  Your firm failed to establish component identity specifications for each component used in the manufacture of your dietary supplement, as required by 21 CFR § 111.70(b)(1).
Specifically, your firm did not establish identity specifications for each component used in the manufacture of the following dietary supplements:

  • Vitamin B12 in (b)(4) (batch no. 11158) and (b)(4) B12 (b)(4) (batch no. 11158A)
  • (b)(4) in (b)(4) (Lot # 11164 and 11164C)
  • Amino acids in (b)(4) (Lot # 11173 and 11173A)

We have reviewed your response dated September 20, 2011 and determined it to be inadequate. Specifically, you stated that your firm issued a purchase order for a (b)(4) machine and that the equipment company will help you calibrate it and then you will establish specifications for the raw materials. Your response does not address why you cannot develop component specifications for the raw materials independent of the (b)(4) machine. You provided no documentation to show that these specifications were developed.

3.  Your firm failed to establish written procedures for the responsibilities of the quality control operations to include procedures for conducting a material review, making a disposition decision, and rejecting or approving any reprocessing, as required by 21 § CFR 111.103.

Specifically, our review of your Standard Operation Procedure (SOP), PCL-QC 001.10.3 revealed that this SOP addressed out of specification (OOS) batches, but the SOP did not provide written procedures for conducting a material review, making a disposition decision, and rejecting or approving any reprocessing.

We have reviewed your response dated September 20, 2011 and determined it to be inadequate. Your response did not indicate you would establish written procedures for these function in your current quality written procedure. You also did not provide any supporting documents to meet this requirement.

4.  Your firm failed to qualify the suppliers of components other than dietary ingredients by establishing the reliability of the suppliers' certificates of analysis through confirmation of the results of the suppliers' tests or examinations, before using those components, as required by 21 CFR § 111.75(a)(2)(ii)(A), and failed to maintain documentation of how the supplier was qualified, as required by 21 CFR § 111.75(a)(2)(ii)(C). Under 21 CFR § 111.75(a)(2), a certificate of analysis may be relied upon to confirm the identity of a component that is not a dietary ingredient and to determine whether applicable component specifications established in accordance with 21 CFR § 111.70(b) are met. In order to rely on a certificate of analysis from a supplier of the component, the following requirements of 21 CFR § 111.75(a)(2)(ii) must be met (A) qualify the supplier by establishing the reliability of the supplier's certificate of analysis through confirmation of the results of the supplier's tests or examinations; (B) the certificate of analysis must include a description of the test or examination method(s) used, limits of the test or examinations, and actual results of the tests or examinations; (C) maintain documentation of how the supplier was qualified; (D) periodically re-confirm the supplier's certificate of analysis; and (E) the documentation setting forth the basis for qualification (and re-qualification) of any supplier must be reviewed and approved by quality control personnel.

We have reviewed your response dated September 20, 2011 and determined it to be inadequate. Your response committed to finalize the Purchasing Controls SOP to include the supplier's qualification process, however, the response did not include a copy of the finalized procedure, did not address training on the procedure, and did not provide an expected implementation date.

Unapproved and Misbranded Over-the-Counter (OTC) Drugs:

In addition to the cGMP violations, your firm also manufactures (b)(4) (b)(4) -Cream (b)(4) Topical Analgesic for over-the-counter (OTC) use that violates sections 301(d), 505(a), and 502(f)(1) of the Federal Food, Drug, and Cosmetic Act (the Act) [21 U.S.C. §§ 331 (d), 355(a), and 352(f)(1 )].

Based on a review of the product labeling, which was collected during the inspection of your facility, and includes the website (b)(4) where (b)(4) Cream (b)(4) Topical Analgesic is promoted by one of your distributors, (b)(4) Cream (b)(4) Topical Analgesic is a drug, as defined in section 201(g) of the Act, [21 U.S.C. § 321 (g)], because it is intended for use in the cure, mitigation, treatment, or prevention of disease, and/or because it is intended to affect the structure or any function of the body of man.

Drug products intended for topical administration for OTC indications related to pain are being evaluated under the OTC Drug Review. The Tentative Final Monograph (TFM) issued on February 8, 1983 for OTC External Analgesics (48 Fed. Reg. 5852) is part of this evaluation.

(b)(4) Cream (b)(4) Topical Analgesic is a product that is marketed for use as an external analgesic. The External Analgesics TFM does not include indications specific to tendonitis and cramps. Additionally, we are not aware of an OTC product for topical application to treat these conditions having been available in the U.S. market as an OTC drug at the inception of the OTC Drug Review. Therefore, this product is not eligible for the OTC Review. Thus the current marketing of (b)(4) Cream (b)(4) Topical Analgesic violates sections 301(d) and 505(a) of the Act [21 U.S.C. §§ 331 (d) and 355(a)] because it is a new drug and it is not the subject of an approved new drug application.

In addition, labeling found on your distributor’s website, (b)(4) offers (b)(4) Cream (b)(4) Topical Analgesic for prescription on uses that include diabetic neuropathy, fibromyalgia, migraines and gout which are conditions that are not amenable to self-diagnosis and treatment by individuals who are not medical practitioners. Thus, adequate directions cannot be written for these conditions so that a layman can uses this product safely for its intended uses, causing it to be misbranded under section 502(f)(1) of the Act, [21 U.S.C. § 352(f)(1)]. Because (b)(4) Cream (b)(4) Topical Analgesic lacks an approved application, it is not exempt under 21 C.F.R. § 201.115 from the requirements of section 502(f)(1) of the Act. Prescription drugs can only be used safely at the direction, and under the supervision of, a licensed practitioner. Therefore, it is impossible to write "adequate directions for use" for prescription drugs. FDA-approved drugs which bear their FDA-approved labeling are exempt from the requirement that they bear adequate directions for use by a layperson. But otherwise, all prescription drugs by definition lack adequate directions for use by a layperson.

Your firm also manufactures (b)(4) Hand Sanitizer which is an OTC product that violates section 503(b)(4)B) of the Act (21 U.S.C. § 353(b)(4)(B)]. The product labeling for (b)(4) Hand Sanitizer" represents the product as an OTC topical antimicrobial cleanser and its active ingredient is benzalkonium chloride at (b)(4)%. The product's uses are described in its name and the following statements on its label:

“Kills 99.9% of bacteria"
"For hand sanitizing to decrease bacteria on the skin"

The above statements demonstrate that (b)(4) Hand Sanitizer" is a "drug" as defined by Section 201(g)(1) of the Act [21 U.S.C. § 321(g)(1)] because it is intended to prevent disease or to affect the structure or any function of the body of man.

However, the labeling for (b)(4) Hand Sanitizer” includes the prescription drug symbol “Rx” even though the product is marketed as an OTC drug product and for OTC indications. Therefore, (b)(4) Hand Sanitizer” is misbranded within the meaning of section 503(b)(4)(B) of the Act [21 U.S.C. § 353(b)(4)(B)].

Unapproved Veterinary Drug:

In addition, your firm also manufactures (b)(4) a topical antimicrobial for use in treating skin conditions in dogs and cats. We have determined this product violates sections 512(a) and 501(a)(5) of the Act [21 U.S.C. §§360b(a) and§ 351 (a)(5)].

Product labeling identifies (b)(4) as a (b)(4) of (b)(4) and (b)(4) surface active agents. This product is a drug within the meaning of section 201(g)(1) of the Act [21 U.S.C. § 321 (g)(1)] because it is intended for use in the cure, mitigation, treatment, or prevention of disease in animals or to affect the structure or function of the of animals. Specifically, the package labeling for (b)(4) identifies its intended uses as follows: "USES: dogs and cats-to be used in the management of superficial and severe skin conditions that are responsive to chlorhexidine…” In addition, you manufacture this product for (b))(4) which makes statements about this product on its website, (b)(4) that further show the product's intended uses as an antimicrobial and for treatment of skin disorders. Examples of these statements include:

  • "***Antiseptic solution with (b)(4)***”
  • "***PROPERTIES has a strong bactericidal and bacteriostatic activity on the Gram positive and Gram negative bacteria.
  • (b)(4) is a (b)(4) that helps restore the skin barrier, and also has anti-inflammatory properties. (b)(4) is a moisturizing agent; it helps restore the damaged skin. It possesses also antibacterial and antifungal properties which complement those of (b)(4).
  • (b)(4). Active ingredients fact list “*** (b)(4) effect against (b)(4)***”

Based on these uses, (b)(4) is a drug as defined by section 201(g)(1) of the Act.


Further, (b)(4) is considered a "new animal drug” under section 201(v) of the Act [21 U.S.C. § 321 (v)] because the composition of the veterinary drug product is such that the drug is not generally recognized, among experts qualified by scientific training and experience to evaluate the safety and effectiveness of animal drugs, as safe and effective for use under the conditions prescribed, recommended, or suggested in the labeling thereof.

To be legally marketed, a new animal drug must have an approved new animal drug application, conditionally approved new animal drug application, or index listing under sections 512, 571 and 572 of the Act [21 U.S.C. §§ 360b, 360ccc, and 360ccc-l]. (b)(4) is not approved or index listed by the FDA, and therefore the product is considered unsafe under section 512(a) of the Act and adulterated under section 501(a)(5) of the Act.

The violations cited in this letter are not intended to be an all-inclusive statement of the violations that exist at your facility. You are responsible for investigating and determining the causes of the violations identified above and for preventing their recurrence and the occurrence of other violations. It is your responsibility to assure compliance with all requirements of federal law and FDA regulations.

Please respond in writing within thirty working days from your receipt of this letter. You should include in your response an explanation of each step being taken to prevent the recurrence of violations, as well as copies of related documentation. Your response should be sent to the Food and Drug Administration, 4040 North Central Expressway, Suite 300, Dallas, Texas 75204, Attention: Rose Ashley, Compliance Officer. If you have any questions about the content of this letter please contact: Rose Ashley at (210) 308-1407.


Sincerely,

/s/
Reynaldo R. Rodriguez, Jr.
Dallas District Director


RRR/rma


(b)(4)
(b)(4)