Most of the time, manufacturers are concerned with keeping potential contaminants, including things that might casually be found in a forest, out of the drug production process. But a new Warning Letter sent to pharmaceutical manufacturer Keystone Laboratories by the US Food and Drug Administration (FDA) shows that the company allegedly thought differently, going as far as to use wooden sticks in its manufacturing process, earning the ire of FDA inspectors.
Wooden Sticks, Cardboard, and Water-Catching Buckets
The 18 March 2013 letter references an August 2012 inspection by FDA at the company's Memphis, Tennessee manufacturing facility. While there, FDA wrote that its investigators uncovered a host of violations unusual in both their severity and rarity.
[Editor's Note: A previous iteration of this article said the company's plant was located in Bozeman, Montana. The company's headquarters is there. We regret the error.]
For example, the company used wooden sticks and cardboard covers on production equipment. It is unclear how the sticks were used, but FDA noted they came into direct contact with drug products, while the cardboard was used to cover the products during processing. Neither are appropriate for pharmaceutical production due to their physical properties, which make them difficult to sanitize.
But just as troubling to investigators were other repeat observations, such as condensation seen leaking into a bucket. Elsewhere, vessels used to measure and mix drug products were observed to have deep, "rust-like stains," while other equipment was observed to have "visible build-up and filth."
These same observations had been made in 2009 and 2011, FDA claimed.
Neither did the company conduct adequate testing on released products as required by regulations.
"For example, the water you use in your drug products is a component with the potential for microbiological contamination which is objectionable in view of the component's intended use," FDA explained to the company in its Warning Letter. "Notwithstanding this, your firm failed to subject the water to routine microbiological testing. Furthermore, your firm failed to validate the water system to ensure consistent water quality for drug production and implement procedures for maintaining or monitoring the quality of the water produced.
Other Allegations
Keystone also exhibited a number of non-manufacturing violations, FDA alleged. Several products, including the company's Long Aid Medicated Hair Revitalizer Anti-Itch Formula, ULTRA GLOW Fade Creams, and BETTER BRAIDS Hair Care Products were all observed to be misbranded under federal law due to their lack of conformity with monographs for labeling.
Further, FDA claimed that the company failed to register with the agency as required by law, rendering all products manufactured by it misbranded by default. This, too, is a repeat observation from 2011.
In light of multiple and repeat offenses, FDA said it had significant concerns about the company's quality operations.
"Repeat citations from prior inspections indicate your quality control unit is not exercising its responsibilities, and may not have the appropriate authority to carry out its responsibilities," FDA wrote. "Due to continuing CGMP issues at your firm, we recommend you engage a third party consultant with appropriate CGMP expertise to assess your firm's facility, procedures, processes, and systems to ensure the drugs you manufacture have their appropriate identity, strength, quality, and purity."
The company has 15 working days to respond to the letter.