FDA Warning Letter Breakdown: High-Risk Component Testing, Toxic Ingredients and Water System Failures at a Homeopathic Oral Liquid Manufacturer
CDER cites missing DEG/EG and methanol testing, unvalidated suppliers and an uncontrolled water system at a homeopathic firm.
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On October 10, the FDA’s CDER issued a warning letter to a homeopathic drug manufacturer in Chelan, Washington, following an inspection from April 9–11, 2025. It’s a good candidate for a breakdown as it offers quite a few Part 211 lessons for drug firms.
Here’s a quick rundown of the deficiencies cited:
Failure to test components for identity, purity, strength, quality and to validate supplier test data.
Failure to perform required testing for high-risk ingredients at risk of diethylene glycol (DEG) or ethylene glycol (EG) contamination.
Inadequate testing of ethanol for impurities like benzene and methanol.
Lack of identification and quality testing for potentially toxic or biologically risky ingredients, including animal venoms and botanicals.
Use of an uncontrolled, unvalidated water system as a major drug component.
Inadequate process validation for dilution control despite ingredients with potentially dangerous effects, including products marketed for children.
As of the letter’s date, the firm had not responded to the Form FDA 483 or to two subsequent FDA inquiries about its intentions to respond—an early signal of how seriously the FDA views the situation.
Let’s run through it.
High-risk component testing was missing, and supplier COAs were never validated
The first and most substantial finding is a 21 CFR 211.84 failure we see all the time in our audit work: components were not tested for identity, purity, strength and quality, and supplier certificates of analysis were accepted without establishing their reliability.
The firm manufactures oral liquid homeopathic drug products, including products intended for children. Investigators found:
No adequate testing for purity, strength, quality or identity of components used in the oral drug products
Reliance on supplier COAs without validating the suppliers’ test methods or data at appropriate intervals
From there, the FDA drills into three particularly serious risk areas:
Components were at risk for DEG/EG contamination. The firm used glycerin and other high-risk components without performing appropriate identity testing for DEG and EG. The FDA notes that glycerin identity testing under the USP monograph includes a limit test designed to ensure levels of DEG and EG remain within safety limits. FDA explicitly reminded the firm that:
DEG and EG contamination of drug ingredients has caused lethal poisoning incidents worldwide
Guidance is available on testing glycerin, propylene glycol, maltitol solution, hydrogenated starch hydrolysate, sorbitol solution and other high-risk components for DEG and EG. (Despite that, the firm did not perform the required identity testing for glycerin and other high-risk components before use.)
Ethanol products were not tested for benzene or methanol. The firm used ethanol as an inactive ingredient in its homeopathic formulations and relied on supplier COAs without adequately testing incoming ethanol for impurities such as benzene or performing adequate identity testing for methanol. Ethanol used in drug products must meet the USP monograph for alcohol, which includes impurity limits for methanol, acetaldehyde and acetal, benzene and the sum of other impurities. The monograph also requires a methanol limit test to prevent methanol contamination. Ethanol that does not meet the USP monograph is adulterated. The warning letter notes that the firm’s finished products contain a stated percentage of alcohol in their formulations, making the lack of appropriate testing even more serious.
Potentially toxic or harmful ingredients were not appropriately tested. Beyond solvent risks, the FDA describes a broader pattern: the firm failed to adequately test incoming components to confirm identification, purity, strength (including dilution level) and quality. Specific examples include:
No appropriate testing on a substance more commonly known as a particular toxic material, where testing should have focused on a highly toxic impurity also used as a rodenticide.
Use of one ingredient in a named homeopathic product and another ingredient in a different product, again without appropriate impurity testing.
No testing at all on mother tinctures used as homeopathic active pharmaceutical ingredients.
Ask yourself:
For every high-risk excipient (glycerin, propylene glycol, certain sugar alcohols, ethanol), can you show specific, documented tests for identity and relevant toxic impurities like DEG, EG and methanol on each lot?
Are supplier COAs ever accepted without an initial validation and periodic revalidation of test methods and reliability?
Do you always perform at least one specific identity test per incoming lot—even when dealing with “low dose” homeopathic or natural products?
For ingredients known to have highly toxic impurities or biologic risks, do your specifications and test panels reflect that risk in a traceable, risk-based way?
Water system design and control fell far short of basic expectations
Water is described as the major component of the firm’s drug products. Yet the water system itself, as described in the letter, does not resemble a qualified pharmaceutical utility.
Investigators found that the water system consists of a unit located underneath a sink. That system was not continuously circulating, increasing the risk of biofilm development. Water was dispensed into separate storage containers, each assigned a lot number for future use. The firm did not monitor water quality at the point of use or from individual containers for chemical or microbiological quality over time.
Critically, the firm did not demonstrate that the water met the relevant USP monograph (described in the letter as a specific water type) nor appropriate chemical and microbiological limits, including microbial enumeration and checks for objectionable microorganisms.
The FDA uses the letter to restate fundamental expectations here:
A well-designed, controlled and maintained water system is essential when water is a component in drug manufacturing.
Water must be suitable for its intended use and routinely tested for chemical and microbiological attributes.
Ongoing monitoring is critical to ensure microbial counts are below limits and the water is free from objectionable organisms.
Identifying contamination in the system is integral to maintaining a state of control and suitability for manufacturing.
Ask yourself:
Is your water system design (physical layout, circulation, storage) defensible under inspection, or is it essentially a collection of ad hoc fixes?
Do you monitor water at relevant points of use with defined action and alert limits tied to product risk?
Can you show a complete validation package for your water system, including ongoing performance data, not just an installation check?
If you had to perform a lot-by-lot risk assessment on all batches made with a suspect water system, do you have the historical data to do it today?
Dilution control and process validation for potentially dangerous ingredients
The FDA also flagged “Concerns Regarding Process Validation” as a distinct issue. Investigators documented that the firm uses ingredients with potentially dangerous effects, yet some products are marketed for use in children. One product contains minute levels of ethylene glycol, identified in the letter by another name, and is labeled to assist with detoxification.