Inspections, Compliance, Enforcement, and Criminal Investigations

Techni Med, Inc. dba The Compounder 7/29/16

  

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

Public Health Service
Food and Drug Administration
 
Chicago District Office
550 W. Jackson Blvd., 15th Floor
Chicago, IL 60661
Telephone: (312) 353-5863
Fax: (312) 596-4187 

July 29, 2016

WARNING LETTER

CHI-10-16

 

VIA UPS OVERNIGHT DELIVERY
SIGNATURE REQUIRED
 
Lawrence J. Frieders, R.Ph., Owner
Techni-Med Inc., dba The Compounder
340 Marshall Avenue, Unit 100
Aurora, IL 60506-5649
 
 
Dear Mr. Frieders:
 
From May 6, 2015, to July 9, 2015, a U.S. Food and Drug Administration (FDA) investigator conducted an inspection of your facility, Techni-Med Inc., dba The Compounder, located at 340 Marshall Avenue, Unit 100, Aurora, IL 60506-5649. 
 
During the inspection, the investigator noted that you were not receiving valid prescriptions for individually-identified patients for a portion of the drug products you were producing. The investigator also noted that your firm produced domperidone drug products until May 12, 2015. Domperidone is not the subject of an applicable United States Pharmacopeia (USP) or National Formulary (NF) monograph, nor is it a component of an FDA-approved human drug product, and it does not appear on a list developed by the Secretary under section 503A(b)(1)(A)(i)(III) of the Federal Food Drug, and Cosmetic Act (FDCA) [21 U.S.C. § 353a(b)(1)(A)(i)(III)]. In addition, the investigator observed serious deficiencies in your practices for producing sterile drug products, which put patients at risk. For example, our investigator noted that your firm does not include the sampling of personnel gloves involved in aseptic processing as part of your environmental monitoring program. Furthermore, your firm failed to demonstrate through appropriate studies that your hoods are able to provide adequate protection of the ISO 5 areas in which sterile products are processed. Therefore, your products may be produced in an environment that poses a significant contamination risk.
 
FDA issued a Form FDA 483 and an amended Form FDA 483 to your firm on July 9, 2015, and August 12, 2015, respectively. FDA acknowledges receipt of your firm’s response to the Form FDA 483, dated July 29, 2015. 
 
Based on this inspection, it appears that you are producing drugs that violate the FDCA. 
 
A. Compounded Drugs under the FDCA
 
Section 503A of the FDCA [21 U.S.C. § 353a] describes the conditions under which certain compounded human drug products may qualify for exemptions from three sections of the FDCA: compliance with current good manufacturing practice (CGMP) requirements, section 501(a)(2)(B) of the FDCA; labeling with adequate directions for use, section 502(f)(1) of the FDCA; and FDA approval prior to marketing, section 505 of the FDCA [21 U.S.C. §§ 351(a)(2)(B), 352(f)(1) and 355(a)]. Receipt of valid prescriptions for individually-identified patients is one of the conditions that must be met to quality for the exemptions under section 503A.
 
During the FDA inspection, the investigator observed that your firm does not receive valid prescriptions for individually-identified patients for a portion of the drug products you produce, and that you produce drug products containing domperidone.
 
Another condition that must be met for a compounded drug to qualify for the exemptions under section 503A is that it is compounded from bulk drug substances that: (I) comply with the standards of an applicable United States Pharmacopeia (USP) or National Formulary (NF) monograph, if a monograph exists, and the USP chapter on pharmacy compounding; (II) if such a monograph does not exist, are components of drugs approved by the Secretary; or (III) if such a monograph does not exist and the drug substance is not a component of a drug approved by the Secretary, that appear on a list developed by the Secretary through regulation (section 503A(b)(1)(A)(i)).
 
Compounded drug products containing domperidone are not eligible for the exemptions provided by subsection (a) of 503A of the FDCA, because domperidone is not the subject of an applicable USP or NF monograph, is not a component of an FDA-approved human drug, and does not appear on a list of bulk drug substances that may be used for compounding developed by the Secretary.[1]
 
Accordingly, the drugs you compound without valid prescriptions for individually-identified patients and any drug products you compound using domperidone are not entitled to the exemptions in section 503A.
 
In addition, we remind you that there are a number of other conditions that must be satisfied to qualify for the exemptions in section 503A of the FDCA.[2] 
 
B. Violations of the FDCA
 
Because the drug products that you manufacture and distribute without valid prescriptions for individually-identified patients and the domperidone drug products you manufacture are not the subject of approved applications, they are unapproved new drugs and misbranded drugs in violation of sections 505(a) and 502(f)(1) of the FDCA, respectively.
 
In addition, drug products that are intended or expected to be sterile were prepared, packed, or held under insanitary conditions whereby they may have been contaminated with filth, or rendered injurious to health, causing them to be adulterated within the meaning of section 501(a)(2)(A) of the FDCA [21 U.S.C. § 351(a)(2)(A)]. Furthermore, because you manufacture and distribute a portion of your drugs without valid prescriptions for individually-identified patients, the manufacture of those drugs is also subject to FDA’s CGMP regulations for Finished Pharmaceuticals, Title 21, Code of Federal Regulations (CFR), Parts 210 and 211. The FDA investigator observed significant CGMP violations at your facility, causing such drug products to be adulterated within the meaning of section 501(a)(2)(B) of the FDCA. 
 
Unapproved New Drug Products
 
You do not have any FDA-approved applications on file for the drug products for which you have not obtained valid prescriptions for individually-identified patients and the domperidone products you manufacture. [3] Under sections 301(d) [21 U.S.C. § 331(d)] and 505(a) of the FDCA, a new drug may not be introduced into or delivered for introduction into interstate commerce unless an application approved by FDA under section 505 of the FDCA is in effect for the drug. Your marketing of these products, or other applicable products, without an approved application violates these provisions of the FDCA.
 
Misbranded Drug Products
 
You compound drug products, for which you have not obtained valid prescriptions for individually-identified patients and you manufacture and distribute domperidone drug products, that are intended for conditions that are not amenable to self-diagnosis and treatment by individuals who are not medical practitioners; therefore adequate directions for use cannot be written so that a layman can use these products safely for their intended uses. Consequently, their labeling fails to bear adequate directions for their intended uses, causing them to be misbranded under section 502(f)(1) of the FDCA, and they are not exempt from the requirements of section 502(f)(1) (see, e.g., 21 CFR § 201.115). The introduction or delivery for introduction into interstate commerce of these products therefore violates sections 301(a) of the FDCA [21 U.S.C. § 331(a)]. 
 
Further, it is a prohibited act under section 301(k) of the FDCA [21 U.S.C. § 331(k)] to do any act with respect to a drug, if such act is done while the drug is held for sale after shipment in interstate commerce and results in the drug being misbranded.
 
Adulterated Drug Products
 
Additionally, the FDA investigator observed that drug products in your facility that were intended or expected to be sterile were prepared, packed, or held under insanitary conditions, whereby they may have become contaminated with filth or rendered injurious to health, causing your drug products to be adulterated under section 501(a)(2)(A) of the FDCA. For example, the investigator noted that your firm does not include sampling of personnel gloves involved in aseptic processing as part of your environmental monitoring program. Furthermore, your firm failed to demonstrate through appropriate studies that your hoods are able to provide adequate protection of the ISO 5 areas in which sterile products are processed. Therefore, your products may be produced in an environment that poses a significant contamination risk.
 
The FDA investigator also noted CGMP violations at your facility, causing the drug products for which you have not obtained valid prescriptions for individually-identified patients to be adulterated under section 501(a)(2)(B) of the FDCA. The violations include, for example:
 
1.    Your firm failed to establish an adequate system for monitoring environmental conditions in aseptic processing areas [21 CFR 211.42(c)(10)(iv)].
 
2.    Your firm failed to ensure that manufacturing personnel wear clothing appropriate to protect drug products from contamination [21 CFR 211.28(a)].
 
3.    Your firm failed to establish and follow appropriate written procedures that are designed to prevent microbiological contamination of drug products purporting to be sterile, and that include validation of all aseptic and sterilization processes [21 CFR 211.113(b)].
 
4.    Your firm failed to ensure air supply that is filtered through high-efficiency particulate air filters under positive pressure for aseptic processing areas [21 CFR 211.42(c)(10)(iii)].
 
5.    Your firm does not have, for each batch of drug product purporting to be sterile and/or pyrogen-free, appropriate laboratory determination of satisfactory conformance to final specifications for the drug product [21 CFR 211.167(a)].
 
6.    Your firm failed to establish an adequate system for cleaning and disinfecting the room and equipment to produce aseptic conditions [21 CFR 211.42(c)(10)(v)].
 
Under Section 301(a) of the FDCA, the introduction or delivery for introduction into interstate commerce of any drug that is adulterated is a prohibited act. Further, it is a prohibited act under section 301(k) of the FDCA to do any act with respect to a drug, if such act is done while the drug is held for sale after shipment in interstate commerce and results in the drug being adulterated.
 
C. Corrective Actions
 
We have reviewed your firm’s planned corrective actions, as documented in your July 29, 2015, response to the Form FDA 483 inspectional observations issued at the close of the inspection. We also note that you informed the investigator during the inspection that you have ceased compounding and distributing products containing domperidone. Several of your proposed corrective actions appear adequate. However, some of the corrective actions described in your response are deficient to correct the insanitary conditions noted at your facility. For example, your firm committed to complete certification with dynamic unidirectional airflow studies on or before December 31, 2016. However, your response does not address any interim actions to be put into place prior to the completed certification. In addition, it is not clear based on your response how your firm will ensure the (b)(4) is adequate to sterilize and depyrogenate items. Moreover, your response did not include an evaluation of products previously produced under the observed inadequate conditions.
 
FDA strongly recommends that your management immediately undertake a comprehensive assessment of your operations, including facility design, procedures, personnel, processes, materials, and systems. In particular, this review should assess your aseptic processing operations. A third party consultant with relevant sterile drug processing expertise could be useful in conducting this comprehensive evaluation.
 
Please be aware that section 501(a)(2)(A) of the FDCA concerning insanitary conditions applies regardless of whether the drugs are compounded and distributed after receipt of a valid prescription for an identified-individual patient.
 
In addition, if you continue to manufacture and distribute drug products without valid prescriptions for individually-identified patients, the manufacture of such drugs would be subject to FDA's drug CGMP regulations (21 CFR Parts 210 and 211), among other requirements, and, before doing so, you should fully implement corrections that meet the minimum requirements of 21 CFR Part 211 in order to provide assurance that the drug products produced by your firm conform to the basic quality standards that ensure safety, identity, strength, quality, and purity. You should also correct the violations of sections 505(a) and 502(f)(1) of the FDCA.
 
D. Conclusion
 
The violations cited in this letter are not intended to be an all-inclusive statement of violations at your facility. 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, including 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. 
 
Within fifteen (15) working days of receipt of this letter, please notify this office in writing of the specific steps that you have taken to correct violations. Please include an explanation of each step being taken to prevent the recurrence of violations, as well as copies of related documentation. If you do not believe that the products discussed above are in violation of the FDCA, include your reasoning and any supporting information for our consideration. If you cannot complete corrective action within 15 working days, state the reason for the delay and the time within which you will complete the correction. Your written notification should be addressed to:
 
Russell Riley, Compliance Officer
Food and Drug Administration
Chicago District
Central Region
550 W. Jackson Blvd., Suite 1500
Chicago, IL 60661
 
Refer to the Unique Identification Number (CMS# 493750) when replying. If you have questions regarding the content of this letter, please contact Mr. Riley via email at Russell.riley@fda.hhs.gov or by phone at (312) 596-4219.
 
 
Sincerely,
/S/
William R. Weissinger
District Director
 

[1] Domperidone was nominated for inclusion on the list of bulk drug substances that can be used in compounding that must be developed through regulation pursuant to section 503A(b)(1)(A)(i)(III) of the FDCA (503A bulks list). See section 503A(b)(1)(A)(i)(III).   On June 9, 2016, FDA issued a final guidance titled, Interim Policy on Compounding Using Bulk Drug Substances Under Section 503A of the Federal Food, Drug, and Cosmetic Act. This guidance describes FDA’s regulatory policy for State licensed pharmacies, Federal facilities, and licensed physicians that compound human drug products using bulk drug substances that do not otherwise meet the conditions of 503A(b)(1)(A)(i) while the 503A bulks list is being developed. Specifically, the guidance sets out the conditions under which FDA does not intend to take action against a State licensed pharmacy, Federal facility, or licensed physician for compounding a drug product using a bulk drug substance that is not the subject of an applicable USP or NF monograph or a component of an FDA-approved drug, until the substance is identified in a final rule as being included or not included on the 503A bulks list. These conditions include that the substance may be eligible for inclusion on the 503A bulks list, was nominated with sufficient supporting information for FDA to evaluate it, and that it has not been identified by FDA as a substance that appears to present significant safety risks pending further evaluation. Domperidone has been identified as a substance that appears to present significant safety risks. For additional information, see the guidance at http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM469120.pdf.
[2] For example, section 503A also addresses anticipatory compounding, which includes compounding (not distribution) before receipt of a valid prescription order for an individual patient. We are not addressing anticipatory compounding here.
[3] The specific products made by your firm are drugs within the meaning of section 201(g) [21 U.S. C. § 321(g)] of the FDCA because they are intended for use in the diagnosis, cure, mitigation, treatment, or prevention of diseases and/or because they are intended to affect the structure or any function of the body. Further, they are “new drugs” within the meaning of section 201(p) of the FDCA [21 U.S.C. §321(p)] because they are not generally recognized as safe and effective for their labeled uses.


 

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