U.S. flag An official website of the United States government
  1. Home
  2. Inspections, Compliance, Enforcement, and Criminal Investigations
  3. Compliance Actions and Activities
  4. Warning Letters
  5. Pharmaceutical Laboratories and Consultants, Inc. - 540675 - 08/29/2018
  1. Warning Letters


Pharmaceutical Laboratories and Consultants, Inc. MARCS-CMS 540675 —

Recipient Name
Mr. James R. Stephen
Pharmaceutical Laboratories and Consultants, Inc.

1010 W. Fullerton Avenue, Suite H
Addison, IL 60101-4333
United States

Issuing Office:
Detroit District Office

United States



Black HHS-Blue FDA Logo



Division of Pharmaceutical Quality Operations III
300 River Place, Suite 5900
Detroit, MI 48207
Telephone: (313) 393-8100
Fax: (313) 393-8139 


August 29, 2018
Case# 540675
Mr. James R. Stephen
President and Owner
Pharmaceutical Laboratories and Consultants, Inc.
1010 W. Fullerton Avenue, Suite H
Addison, IL 60101-4333
Dear Mr. Stephen:
The U.S. Food and Drug Administration (FDA) inspected your contract testing laboratory, Pharmaceutical Laboratories and Consultants, Inc. at 1010 W. Fullerton Avenue, Suite H, Addison, IL, from September 18 to October 10, 2017.
This warning letter summarizes significant violations of current good manufacturing practice (CGMP) regulations for finished pharmaceuticals. See 21 CFR, parts 210 and 211.
Because your methods, facilities, or controls for manufacturing, processing, packing, or holding do not conform to CGMP, your drug products are adulterated within the meaning of section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 351(a)(2)(B).
We have not received a response from your firm with corrective actions to the violations identified during the inspection.
FDA cited similar CGMP deficiencies during inspections in May 2007, May 2009, December 2012, and March 2014; and in Warning Letter CHI-6-07, issued on July 25, 2007. Your firm also failed to respond to these deficiencies. These repeated failures demonstrate that management oversight and control over the testing of over-the-counter (OTC) drugs and components is inadequate.
We request that you contact Russell Riley, by e-mail at ORAPHARM3_RESPONSES@fda.hhs.gov within five (5) days of receipt of this letter to schedule a regulatory meeting to discuss these significant violations and the corrective actions and preventive actions you intend to implement. FDA will send a separate letter with details including meeting logistics.
During our 2017 inspection, our investigators observed specific violations including, but not limited to, the following.
1.      Your firm failed to establish laboratory controls that include scientifically sound and appropriate specifications, standards, sampling plans, and test procedures designed to assure that components, drug product containers, closures, in-process materials, labeling, and drug products conform to appropriate standards of identity, strength, quality, and purity (21 CFR 211.160(b)). 
Inadequate method validation
You lacked scientific data to demonstrate that the microbial limits procedure and test methods you use to test customers’ finished OTC drug products and components are suitable and reliable. For example, you did not validate your methods to ensure reproducibility. In addition, your test methods did not follow United States Pharmacopeia (USP) Chapters and , and you did not provide data to show that your methods are equivalent to or better than the USP methods.62>
In addition, your firm did not have adequate test methods to detect objectionable microorganisms, including P. aeruginosa, E. coli, S. aureus, C. albicans, Clostridium sp., Salmonella sp., and bile-tolerant Gram-negative bacteria. These organisms are known to cause infections or produce toxins that can cause serious harm to patients. Also, although you tested for the presence of Clostridia, you did not incubate the inoculated sample under anaerobic conditions as is necessary to support the growth of Clostridia. Further, your firm also did not have all the necessary media, buffers, and environmental conditions needed to conduct microbiological testing.
Unsuitable media 
Your firm did not have suitability studies that demonstrated that your media procedures and practices were acceptable for microbiological testing of your customers’ OTC drug products and components. For example:
  • Your firm did not perform quality control testing on (b)(4) prepared media to ensure the media support growth and acceptable recovery during testing. You lacked a program that includes quality control testing of all prepared media for its quality attributes, such as pH, and growth promotion prior to use in testing customers’ OTC drug products and components. Our investigators observed that you did not have any microorganisms stored at your facility and did not have the test strains and specified microorganisms for completing microbiological testing. You were not able to provide purchasing records for any reference microorganisms or test strains. 
  • Our investigators observed dried and cracked test plates in your incubators. Their condition would prevent detection of microorganisms present in the product. Your firm uses (b)(4) of media per plate for pour plate preparation. USP typically requires 15-20 ml of media per plate to provide sufficient nutrients and moisture to promote microbial growth. 
Lack of positive controls
Your firm did not use positive controls during microbiological testing to ensure the reliability of your test results. When a positive control is not used during testing, test results cannot be considered valid because the absence of microbial growth could be due to media lacking the appropriate nutrient composition, water content, purity, or incubation conditions necessary to support growth of the microorganisms that may be present in the OTC drug product or component tested.
In response to this letter, provide a comprehensive evaluation of the adequacy of your laboratory controls, including procedures, practices, testing, and staff competencies.
2.      Your firm failed to ensure that each person engaged in the manufacture, processing, packing, or holding of a drug product has the education, training, and experience, or any combination thereof, to enable that person to perform his or her assigned functions (21 CFR 211.25(a)).
You perform microbiological testing activities without qualified staff.
Your firm has (b)(4) employees. (b)(4) conducts microbiological testing, and (b)(4) reviews the test data. (b)(4) has appropriate qualifications to perform microbiology testing nor adequate training in CGMP regulations, as is evident by the deficiencies cited in this letter. This lack of staff qualification in microbiology was further demonstrated by your firm’s failure to use basic microbiological laboratory equipment such as an operational microscope and typical reagents used for Gram staining. You stated that you were not aware of the last time your firm conducted Gram stain testing for identification.
In response to this letter, provide an updated training plan describing how you will ensure that all employees are adequately qualified to perform laboratory testing. Provide documentation demonstrating that all employees are qualified to perform all microbiological testing.
3.      Your firm failed to use equipment in the manufacture, processing, packing, or holding of drug products that is of appropriate design, adequate size, and suitably located to facilitate operations for its intended use and for its cleaning and maintenance (21 CFR 211.63).
Your microbiological laboratory equipment was not suitable for use. For example, the (b)(4) you use to sterilize your microbiological media had not been qualified to ensure its performance. Also, it had a cracked door seal and broken temperature gauge. You informed our investigators that to sterilize media, your practice was to (b)(4). However, your (b)(4) had never been calibrated, and you (b)(4). You were not sure whether these parameters are maintained throughout the (b)(4) cycle because you only check them periodically during the cycle.
You also use (b)(4) unqualified incubators which are intended to grow and maintain microbiological cultures. You have not conducted mapping studies to ensure adequate temperature distribution for (b)(4) incubator. In addition, one incubator did not have an internal thermometer or a continuous monitoring device to monitor temperature and ensure it remains within (b)(4).
In response to this letter, provide a detailed plan for qualifying, maintaining, and monitoring all laboratory equipment. Also provide a comprehensive, independent review of your laboratory practices, methods, equipment, and analyst competencies. Based on this review, provide a detailed corrective action and preventive action (CAPA) plan to fully remediate your laboratory system. Your plan should also include the process you will use to evaluate the effectiveness of the implemented CAPA.
4.      Your firm failed to ensure that laboratory records included complete data derived from all tests necessary to assure compliance with established specifications and standards (21 CFR 211.194(a)).
You recorded results for tests you admitted that you did not conduct. Your worksheets for total aerobic microbial counts and total yeast and mold counts report results for (b)(4) per test, as your microbial limits test procedure requires. However, our investigators found that you used (b)(4) per test. You acknowledged to our investigator that you only use (b)(4) and that reporting (b)(4) results is a “habit” your firm needs to “break.”
Your firm also failed to document critical information on microbiological worksheets. You did not record details of preparing microorganism suspensions for growth promotion testing. You neglected to record incubation times, laboratory materials, and equipment numbers for sample preparation. You did not note how much (b)(4) water you used in your growth media or how many containers you sterilized in the (b)(4) during media preparation. 
Customers rely on your laboratory data for information about the quality of drugs and their components. Your data reporting and documentation practices compromise supply-chain accountability, and may put consumers at risk.
In response to this letter, provide a comprehensive investigation into your poor data, records, and reporting practices. Identify omissions, alterations, deletions, and other deficiencies. Provide a risk assessment summarizing the effect of incomplete and inaccurate data on assessing laboratory control and product quality. Also, provide a comprehensive corrective action plan, with target dates, to ensure that laboratory records are complete and reliable.
Responsibilities of contract testing lab
FDA considers contractors as extensions of the manufacturer’s own facility. Your failure to comply with CGMP may affect the quality, safety, and efficacy of the drugs you test for your clients. It is essential that you understand your responsibility to operate in full compliance with CGMP, and to inform all of your customers of significant problems encountered during the testing of these drugs.
CGMP consultant recommended
Based upon the nature of the violations we identified at your firm and because you failed to correct repeat violations, we strongly recommend engaging a consultant qualified as set forth in 21 CFR 211.34, to assist your firm in meeting CGMP requirements. We also recommend that the qualified consultant perform a comprehensive audit of your entire operation for CGMP compliance, and evaluate the completion and effectiveness of any corrective actions and preventive actions you have implemented.
Your use of a consultant does not relieve your firm’s obligation to comply with CGMP. Your firm’s executive management remains responsible for fully resolving all deficiencies and ongoing CGMP compliance.
Data Integrity Remediation
Your quality system does not adequately ensure the accuracy and integrity of data to support the safety, effectiveness, and quality of the drugs you manufacture. In response to this letter, provide the following:
A.    A comprehensive investigation into the extent of the inaccuracies in data, records, and reporting, including results of the data review for drugs distributed to the United States. Include a detailed description of the scope and root causes of your data integrity lapses.
B.    A current risk assessment of the potential effects of the observed failures on the quality of your drugs. Your assessment should include analyses of the risks to patients caused by the release of drugs affected by a lapse of data integrity, and risks posed by ongoing operations.
C    A management strategy for your firm that includes the details of your global corrective action and preventive action plan. The detailed CAPA plan should describe how you intend to ensure the reliability and completeness of all data generated by your firm, including all laboratory data, manufacturing records, and all data submitted to FDA.
Shared Space with Non-Drug Operations
In addition, our inspection revealed that you were operating a microbrewery in space shared with your contract testing laboratory where you test OTC drug products and components. You prepared and stored microbiology laboratory media in the same area you use to conduct brewery operations. 
For example, our investigators observed a full fermenter located approximately ten feet from the space where media is prepared, warmed, and stored. A brewery employee was also preparing beer kegs in this area. In addition, laboratory test media, open beer bottles, and brewing materials were co-mingled within the same refrigerator.
These facility conditions pose unacceptable risks, including contamination of media during its preparation and compromised sample analyses. Conducting your testing operations in a space shared with a microbrewery is inappropriate and does not comply with CGMP. Your testing must be performed using facilities that are designed and controlled for drug laboratory testing.
Violations cited in this letter are not intended as an all-inclusive list. You are responsible for investigating these violations, for determining the causes, for preventing their recurrence, and for preventing other violations in all your facilities.
Correct the violations cited in this letter promptly. Failure to promptly correct these violations may result in legal action without further notice including, without limitation, seizure and injunction. Unresolved violations in this warning letter may also prevent other Federal agencies from awarding contracts.
Until these violations are corrected, we may withhold approval of pending drug applications listing your facility. We may re-inspect to verify that you have completed your corrective actions. We may also refuse your requests for export certificates.
After you receive this letter, respond to this office in writing within fifteen (15) working days. Specify what you have done since our inspection to correct your violations and to prevent their recurrence. If you cannot complete corrective actions within 15 working days, state your reasons for delay and your schedule for completion.
Please send your electronic reply to: ORAPHARM3_RESPONSES@fda.hhs.gov.
Attn:    Russell K. Riley
Compliance Officer
U. S. Food and Drug Administration
Division of Pharmaceutical Quality Operations III
Refer to the Unique Identification Number (Case# 540675) when replying. If you have questions regarding the contents of this letter, please contact Mr. Riley by phone at (630) 323-2763 ext. 101.
Art O. Czabaniuk
Program Division Director
Division of Pharmaceutical Quality Operations III
Redacted cc:


Back to Top