K.C. Pharmaceuticals, Inc.
The FDA’s Warning Letter to K.C. Pharmaceuticals dated 8/3/2023 lays out in blistering detail the company’s persistent inability to design, build and operate a facility which is compliant with Current Good Manufacturing Practice (CGMP) for pharmaceuticals. In particular, the company failed to establish and follow required procedures to ensure product sterility. Nor had it addressed deficiencies in its manufacturing plant in Pomona, California that increase the risk of contamination.
As the FDA drily notes, “Your aseptic processing operation is inadequately designed to prevent contamination of your ophthalmic drug products.”
According to the Warning Letter, K.C. Pharmaceuticals also never fully investigated multiple failures of an essential assessment of sterile processing known as a media fill. In a media fill, a liquid that bacteria like to grow in (called media) is run through the entire manufacturing process on the same equipment that drug ingredients will pass through. This media is then observed for the growth of bacteria or fungus. If any growth develops, there is a failure of aseptic (sterile) manufacturing process and the company must exhaustively identify where this failure occurred – for example, on which piece of equipment – and why, and then make corrections and demonstrate that these corrections were effective by repeating the media fill.
K.C. Pharmaceuticals (FEI 2026940) has a long history of less-than-stellar FDA inspections. Read on.
PART 1
FDA Inspections of K.C. Pharmaceuticals from 2009 through 2023
The first electronically documented inspection in 2009 reported failures in many critical components of a drug manufacturing facility, including “validation lacking for sterile drug processing.”
In 2010: “Equipment and utensils are not cleaned, maintained, and sanitized as appropriate intervals to prevent contamination that would alter the safety, identify, strength, quality or purity of the drug product.”
The company received a Warning Letter dated 5/21/2010 which highlighted an inadequate response to failed media fills.
In 2013: “Procedures designed to prevent microbiological contamination of drug products purporting to be sterile are not established and followed.”
In 2014: “Procedures designed to prevent microbiological contamination of drug products purporting to be sterile do not include adequate validation of the sterilization process.”
In 2015: “Procedures designed to prevent microbiological contamination of drug products purporting to be sterile are not established and written.”
In 2017: “Procedures designed to prevent microbiological contamination of drug products purporting to be sterile are not followed.”
In 2020: “Procedures designed to prevent microbiological contamination of drug products purporting to be sterile are not established.”
The 2023 inspection report is not yet available on the data dashboard.
PART 2
Why did K.C. Pharmaceuticals have the same CGMP violations repeatedly?
K.C. Pharmaceuticals is a large manufacturer of “private label” eye drops for companies including but not necessarily limited to those listed below. Distributors are not required to provide manufacturer information.
Walmart (Equate)
Target
Generic pharmacy brands (CVS, Walgreens, Good Neighbor, Major Drug, Rugby Drug)
Grocery stores (HEB, Kroger, Meijer, Publix, Albertsons/Safeway/Vons (Signature Care), Winco)
Distributors (McKesson, Cardinal Health)
Low operating costs are essential to make a profit in this market space.
To correct the CGMP violations identified during multiple FDA inspections, K.C. Pharmaceuticals would need to make a substantial financial investment in its physical facility, manufacturing equipment and employee training.
An FDA inspection results in one of three global outcomes, described by acronyms: NAI (no action indicated), VAI (voluntary action indicated) and OAI (official action indicated). Of the 8 inspections of K.C. Pharmaceuticals related to drug manufacturing prior to 2023, two resulted in OAI (2010 and 2013) and 6 resulted in VAI.
Although ‘voluntary’ action does not mean ‘optional’ - K.C. Pharmaceuticals is required by law to comply with CGMP - the lack of stronger enforcement action after each inspection evidently allowed the company to continue with business as usual, thereby avoiding significant capital expenditures.
Until 2023, the FDA’s approach to K.C. Pharmaceuticals reads like a combination of “just try harder” and “everybody gets a trophy.”
The Warning Letter must have come as a shock.
PART 3
So why might the FDA be increasing pressure on K.C. Pharmaceuticals now?
Warning Letters are publicly viewable and mostly comprehensible to a determined lay reader. After 13 years of laconic “voluntary action indicated” inspections, the FDA pummeled K.C. Pharmaceuticals with two inspections and a Warning Letter. Why?
In a few words, EzriCare artificial tears.
Over-the-counter eye drops can blind you and kill you. Until 2023, nobody would have believed this.
To give the FDA some credit, the agency identified what appears to be the major manufacturer of nationally distributed, popular private label brands such as Walmart’s Equate artificial tears. This is called ‘going where the risk is.’
K.C. Pharmaceuticals was likely due for an inspection, but the FDA has a large COVID-related inspection backlog. Something sent them zipping out to Pomona CA in January and February 2023, and that something was possibly the CDC, which had the words “eye drops” and “genetically unique Pseudomonas aeruginosa” on its lips.
Where is the evidence that this company cares about patient safety? Or has it in effect played the odds on unreliable aseptic processing – for more than a decade – by depending on stronger preservatives such as benzalkonium chloride to kill microorganisms introduced during manufacture. [Note that EzriCare artificial tears did not contain an effective preservative.]
The FDA Warning Letters in 2010 and in 2023 both emphasize K.C. Pharmaceuticals’ lack of proper response to failed media fills, which is the end-of-grade report card on aseptic processing. Could somebody read a book?
PART 4
What should patients do?
Patients are in a tough spot. Numerous popular and affordable eye drops in many categories (lubricants, anti-allergy, redness relief) start their shelf life in Pomona.
Manufacturers are responsible for retaining bottles of each lot of each product and testing them periodically for bacterial and fungal growth. When you use an eye drop, you trust the manufacturer to do the sterility testing and to initiate a recall of lots which fail. But most importantly, you believe that the message will reach you to discard a bottle of artificial tears you purchased at the grocery store 8 months ago.
Manufacturers, not distributors, are responsible for initiating drug recalls. A June 15, 2023 recall for TopCare eye drops notes that the products contain benzalkonium chloride and that no adverse events were reported. This is a ‘class III’ recall because the product violates manufacturing laws but is considered unlikely to cause harm. [“Lack of documentation of the fill line” is FDA slang for inadequate management of aseptic processing.]
It is difficult to make comprehensive recommendations in this situation. Thousands of patients have used eye drops manufactured by K.C. Pharmaceuticals for years, seemingly without problems.
But what is the usual consumer response to an OTC eye drop that stings or smells strange? Throw it out. Before EzriCare, almost no one would consider reporting an OTC eye drop problem to the FDA, a frustrating and time intensive process. Thus, absence of evidence of contamination is not evidence of absence.
One recommendation is easy to make: for patients who customarily use non-preserved eye drops, consider staying with brand names.
Although K.C. Pharmaceuticals’ preservative-free vial eye drops may be manufactured on different equipment from their bottled eye drops, due to the extensive redactions in the FDA documents [anything (b)(4) is a redaction] it isn’t possible to determine which equipment was involved in the failed media fills. A preservative is the final defense that kills bacteria or other microorganisms introduced during manufacture.
The Dry Eye Foundation has compiled a list of ophthalmic products known to be manufactured by K.C. Pharmaceuticals. The Foundation cannot guarantee that every product is on the list.
PART 5
A final word to distributors
In my opinion, distributors have a duty to customers to ensure that their private label products are manufactured by CGMP-compliant companies.
How many times would you have to read “Procedures designed to prevent microbiological contamination of drug products purporting to be sterile are not...” before deciding to shop around for a new manufacturer?
If several major buyers such as Walmart and Target had pressured K.C. Pharmaceuticals to become GCMP-compliant or lose their contracts, I suspect the company would have complied.
Sandra Brown MD
Medical Advisor, The Dry Eye Foundation
