| Public Health Service Food and Drug Administration |
| Chicago District 550 West Jackson Blvd., 15th Floor Chicago, Illinois 60661 Telephone: 312-353-5863 |
Department of Health and Human Services
September 15, 2011
WARNING LETTER
CHI-18-11
CERTIFIED MAIL
RETURN RECEIPT REQUESTED
Stephen A. Erickson
President and Co-Owner
Dental Technologies, Inc.
6901 N. Hamlin Avenue
Lincolnwood, IL 60712
Dear Mr. Erickson:
During our March 16, 2011 through April 12, 2011 inspection of your contract drug manufacturing facility, Dental Technologies, Inc., located at 6901 N. Hamlin Avenue in Lincolnwood, Illinois, an investigator from the Food and Drug Administration (FDA) identified significant violations of Current Good Manufacturing Practice (CGMP) regulations for Finished Pharmaceuticals, Title 21, Code of Federal Regulations, Parts 210 and 211. These violations cause your drug product(s) to be adulterated within the meaning of Section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (the Act) [21 U.S.C. § 351(a)(2)(B)] in that the methods used in, or the facilities or controls used for, their manufacture, processing, packing, or holding do not conform to, or are not operated or administered in conformity with, CGMP.
In addition, you manufacture a number of prescription drugs without approved applications. As described below, these drugs are 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)].
We acknowledge your written response, dated March 2, 2011, and note that it lacks sufficient corrective actions.
Specific violations observed during the inspection include, but are not limited, to the following:
CGMP Violations
1. Your firm has not conducted at least one specific identity test and has not established the reliability of the supplier’s analyses through appropriate validation of the supplier’s test results at appropriate intervals [21 C.F.R. § 211.84(d)(2)].
For example, your firm has failed to perform the required identification tests for Glycerin USP (i.e., limit of Diethylene Glycol and Ethylene Glycol) as required by the USP monograph. Furthermore, our investigators confirmed that your employees failed to perform these critical identification tests for Glycerin USP as required by your specification. Diethylene Glycol and Ethylene Glycol are both dangerous contaminants that have been found in Glycerin raw materials.
In your response, your firm states that you are performing the test and submitted a copy of the specifications. Your response is inadequate because your firm has yet to provide actual identification test results for the presence of Diethylene Glycol and Ethylene Glycol in Glycerin USP, an ingredient in each of your drug product lots.
2. Your firm has not thoroughly investigated the failure of a batch or any of its components to meet its specifications whether or not the batch has already been distributed, or extend those investigations to other batches of drug product that may have been associated with the specific failure or discrepancy [21 C.F.R. § 211.192].
For example, your firm’s investigation into microbial testing for the presence of Pseudomonas aeruginosa identified in water samples collected on December 20, 2010, and December 27, 2010, was inadequate. Your investigation concluded that the microbial contamination occurred at the water delivery spigots. Your investigation, however, failed to include information regarding the swab tests results of the spigots and the test results of the spigots following sanitization. Further, your firm continued to manufacture drug products with purified water that may have failed to meet your specifications.
In your response, your firm states that you tested all drug product lots manufactured during this period and the test results were negative for Pseudomonas aeruginosa. Your response is inadequate because you did not include any information regarding how many samples of each lot were tested. Further, your response fails to include corrective actions regarding changes to the operation of your purified water system to assure that it will produce water that meets your company’s quality standards (e.g., frequency and method of water system sanitization, assessment of the microbial quality of the feed water, and SOP revisions).
3. Your firm has failed to follow written procedures describing the handling of all written and oral complaints regarding drug products [21 C.F.R. § 211.198(a)].
For example, your Quality Control Unit (QCU) failed to ensure consumer complaints were adequately investigated as required by your complaint handling procedure, QSP 14.02, “Customer Complaints.” Your firm evaluated (b)(4) patient complaints for nausea and vomiting and concluded that the patients were hypersensitive to fluoride. Subsequently, your firm’s corrective action included discontinuance of the Cherry flavor (b)(4) 2% NaF Rinse product and the destruction of the remaining lots. Your firm’s investigations, however, failed to evaluate the manufacturing process, raw materials, or packaging components that could have contributed to the patient reactions. Moreover, your investigations did not extend to similar patient illness complaints your firm has received regarding other sodium fluoride oral rinse products manufactured by your firm.
Your response is inadequate because it fails to address how you will investigate the patient illness complaints for your remaining sodium fluoride oral rinse products.
4. Your firm has not established scientifically sound and appropriate specifications designed to assure that components and drug products conform to appropriate standards of identity, strength, quality, and purity [21 C.F.R. § 211.160(b)].
For example, your firm uses a rapid diagnostic test method (i.e., (b)(4) to test water samples from your Purified Water system and your drug products. This culture media system has not been shown to be equivalent to current compendial microbiological test methods. Your firm lacked any studies to show fitness for use of these methods for your firm’s drug products. Furthermore, your firm does not perform growth promotion testing on the media systems utilized for purified water and finished drug product testing.
In your response, your firm proposes to develop new protocols at your contract laboratory with appropriate method validation. Your response, however, fails to provide the completion and/or implementation dates of the proposed protocols and method validation. In addition, your firm has yet to provide an update on the use and qualification of the current rapid diagnostic media test kit.
Unapproved New Drug Violations
In addition to violating CGMPs, you manufacture and market unapproved prescription drugs in violation of the Act.
In regard to your unapproved drugs, on June 8, 2006, FDA issued a guidance entitled “Marketed Unapproved Drugs—Compliance Policy Guide (CPG),” which explains FDA’s policies aimed at ensuring that all drugs marketed in the U.S., prescription and over-the-counter, have been shown to be safe and effective. This guidance can be found on FDA’s webpage at http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM070290.pdf. Other related information can be found on http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/EnforcementActivitiesbyFDA/SelectedEnforcementActionsonUnapprovedDrugs/ucm118990.htm.
The guidance clearly articulates FDA’s expectation that illegally marketed products, those products marketed without required FDA approval, be removed from the market. The guidance also outlines FDA’s enforcement policies aimed at efficiently and rationally bringing all drugs requiring approved applications into the approval process. As described in the CPG, all drugs marketed without required applications are subject to enforcement action at any time, without additional notice.
During the March 16 – April 12, 2011 inspection, we found that your firm is manufacturing the following prescription drugs:
- (b)(4) Acidulated Phosphate Fluoride Foam, 2.59% (1.23% Fluoride Ion) 250 mL
- (b)(4) Oral Solution, 2% (0.9% Fluoride Ion) 1853 mL
Based on information your firm submitted to FDA’s Drug Registration and Listing System and the information collected during the inspection, there are no FDA-approved applications on file for these drug products.
This letter is not intended to contain an all-inclusive list of your firm’s unapproved drugs. You are responsible for investigating and determining the complete status of all of the drugs manufactured by your firm.
Finally, we have concerns about your firm’s fundamental understanding of the regulatory expectations and requirements when conducing testing of Glycerin for Diethylene Glycol. Please review the FDA Guidance entitled, “Guidance for Industry Testing of Glycerin for Diethylene Glycol” which explains FDA’s policy on analytical testing procedures for all containers of all lots of glycerin under 21 CFR § 211.84(d)(1). This guidance can be found on FDA’s webpage at http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm070347.pdf
The violations cited in this letter are not intended to be an all-inclusive statement of 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.
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. Other federal agencies may take this Warning Letter into account when considering the award of contracts. Additionally, FDA may withhold approval of requests for export certificates, or approval of pending drug applications listing your facility, until the above violations are corrected. FDA may re-inspect to verify corrective actions have been completed.
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. Include an explanation of each step being taken to prevent the recurrence of violations and copies of supporting documentation. If you cannot complete corrective action within fifteen (15) working days, state the reason for the delay and the date by which you will have completed the correction. Additionally, your response should state if you no longer manufacture or distribute drug product(s), and provide the date(s) and reason(s) you ceased production.
Your reply should be sent to Carrie Ann Plucinski, Compliance Officer, Food and Drug Administration, 550 W. Jackson Blvd., 15th floor, Chicago, IL 60661. If you have any questions about the content of this letter, please contact Ms. Plucinski at 312-596-4224.
Sincerely,
/S/
Scott J. MacIntire
District Director
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