Warning Letters Week of 5/3/2020: 42 Concern COVID-19 Claims

FDA has issued 42 warning letters to firms and individuals who distribute unapproved new drugs to prevent or treat COVID-19 infections. This will continue.

FDA continues to issue untitled letters to firms that distribute products that should be regulated under the HCT/P requirements—we cover two this week. This week FDA also posted one letter to a contract testing laboratory, two to compounding pharmacies, one to a device manufacturer, and one to a non-clinical device testing laboratory after a BIMO inspection. 

HCT/P | Henry N. Small, MD, PA

Henry N. Small, MD, PA (Houston, TX) received an untitled letter from CBER based on the marketing of cord blood stem cells and stem cell therapy for a variety of diseases advertised on his website. These products should be regulated as HCT/P products. FDA notes that these products require FDA approval to be commercialized as a new drug. They also don’t meet the exceptions described in 21 CFR 1271.15. FDA also directs Dr. Small to the FDA’s HCT/P regenerative medicine policy and guidance.

HCT/P | BrioMD Lab LLC dba BrioMD

BrioMD Lab LLC dba BrioMD (Hattiesburg, MS) received an untitled letter from CBER based on a review of the information provided on their website.  The firm markets cell therapies to treat a broad range of diseases and conditions including Crohn’s disease, asthma, emphysema, degenerative disc disease, and traumatic brain injury to name just a few. FDA concludes that their product(s) should be regulated under theHCT/Pregulations and that they don’t qualify for exemptions. 

DRUGS | Shriram Institute for Industrial Research

Shriram Institute for Industrial Research (Delhi, India) received a warning letter on April 15, 2020, based on the outcome of an inspection ending October 22, 2019. The firm is a contract testing laboratory that tests both drug products and API.

The warning letter states that some of the deficiencies represent repeat observations identified during a 2016 inspection of the site and notes, “Repeated failures demonstrate that executive management oversight and control over the manufacture of drugs is inadequate.” FDA recommends the firm hire a qualified consultant(s) to assist them in coming into compliance.

And finally, FDA provides them with the extended boilerplate version of how they are to remediate their data integrity issues, noting that, “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.”

Deficiencies include but are not limited to:

• Failure to implement adequate controls over computer systems.  Specifically, the audit trail function on the HPLCs was not enabled until sometime in October 2019 when the inspection was announced.  This timing was confirmed by interviews with analysts. The firm committed to designate an engineer, “to perform the routine inspection to the proper performance of the equipment.” This was deemed an inadequate response because it did not address controls the firm would put in place to ensure that audit trails were enabled and remained enabled.
• The Quality Unit failed to ensure that laboratory staff followed written procedures as shown by the firm’s failure to investigate OOS events. The investigators were told that OOS investigations were performed only upon customer request. Also, the firm failed to follow procedures for review of logbooks and review of laboratory results.  For example, test results were not documented contemporaneously with their performance; documentation errors are obscured; electronic data supporting analytical laboratory data were not reviewed before releasing final lab results. FDA deemed the firm’s response inadequate because they failed to perform a risk assessment regarding their failure to follow OOS procedures and inadequate documentation practices on the commercially released product.
• USP labeled materials were tested without performing system suitability testing and represent a repeat problem identified during the 2016 inspection. Further, the firm failed to document the test method used before issuing a CoA. The response was inadequate because it did not include interim measures and did not include an evaluation of the consequences for releasing products when system suitability was not performed as required by USP methods.

DEVICE | Bedfont Scientific, Ltd.

Bedfont Scientific, Ltd. (Kent, UK) received a warning letter on February 12, 2020, based on the outcome of an inspection ending October 31, 2019. The firm manufactures carbon monoxide gas analyzers.

Deficiencies include but are not limited to:

• Design validation was not performed on units from the initial production run, but rather prior to a variety of changes that had been made for the production runs. Software and firmware changes were not documented within the change control quality system.
• The CAPA system is not adequate because the firm cannot adequately analyze their quality data.  
• The firm has not developed and implemented procedures for controlling product that does not meet specified requirements.  
• The firm has not ensured that all measuring and test equipment is suitable for its intended use. For example, the firm has not implemented a calibration program to periodically evaluate the performance of the flow meters. 
• The firm has not adequately implemented its own internal audit program.  

BIMO | Joseph B. Zwischengerber M.D.

Joseph B. Zwischengerber M.D. at the University of Kentucky (Lexington, KY) received a warning letter on March 26, 2020, based on the outcome of a BIMO inspection ending November 21, 2019. The inspection evaluated non-clinical laboratory studies for the Novalung System.

Deficiencies include but are not limited to:

• The study director did not fulfill their responsibilities. For example, the study director did not ensure that protocols were followed, that all data were collected accurately and verified, and ensure raw data were archived at the end of the study. Further, the “returned Goods Authorization forms” were missing important information/data. 
• The laboratory failed to monitor studies to ensure they conformed to GLP regulations. For example, data in the final report did not accurately reflect the animals from which the data came. Data in the final report did not reflect the raw data. 

COMPOUNDING PHARMACIES

• Tailor Made Compounding LLC (Nicholasville, KY) received a warning letter on April 1, 2020, based on the outcome of an inspection ending October 14, 2018. The warning letter notes that the firm recalled one group of products because the by-use date was incorrect. In addition to adulteration deficiencies, the FDA also notes the firm manufactures unapproved new drug products, which are also misbranded.
• Medlife Pharmacy and Compounding, Inc (Irvine, CA) received a warning letter on April 24, 2020, based on the outcome of an inspection ending April 18, 2018 (yes, two years ago).