Further Warning Letter with multiple Deviations to a Korean Company

On 16 April, the FDA published another Warning Letter to a Korean manufacturer of over-the-counter topical medicines. Similar deficiencies had already been observed at this manufacturer during an inspection in July 2017. The current Warning Letter lists the following deficiencies:


1. A product manufactured by the company is a healing ointment for dry skin. However, the ingredients and raw materials used in its manufacture were insufficiently tested for their content and possible contamination. Some of the components with a risk of contamination with ethylene or diethylene glycol were not tested on a batch basis. This includes the testing of glycerol and certain other high risk drug ingredient for which a United States Pharmacopeia (USP) limit test is required to ensure that these ingredients meet the relevant safety limits for DEG or EC levels. In its Warning Letter, the FDAS points out that the use of ingredients contaminated with DEG or EG has led to several fatal cases of poisoning in humans worldwide. Therefore, the FDA had recently updated its guidance "Testing of Glycerin, Propylene Glycol, Maltitol Solution, Hydrogenated Starch Hydrolysate, Sorbitol Solution, and Other High-Risk Drug Components for Diethylene Glycol and Ethylene Glycol".

2. In addition, C&T Dream had failed to implement adequate written procedures for production and process controls designed to ensure the identity, strength, quality, and purity of the products manufactured. The production and process controls in place were not validated, making it impossible to demonstrate that they were capable of consistently producing an OTC drug product with defined quality characteristics. The FDA assumes that without process validation, the soundness of the design and the state of control of a process throughout its life cycle cannot be assessed. The FDA states at this point: "Each key stage of a manufacturing process must be adequately designed and ensure the quality of raw materials, in-process materials, and finished drug products. Process qualification studies include intensive monitoring and testing during each major process step to characterise variations within a batch and evaluate batches to determine whether an initial control condition has been achieved. Successful process qualification studies are required prior to commercial distribution. Thereafter, continuous, vigilant monitoring of process performance and product quality is required to ensure stable manufacturing operations throughout the product life cycle."

3. A third deficiency concerned the buildings used for the manufacture, processing, packaging or storage of medicinal products, which were not in an appropriate condition or were not maintained in an appropriate condition. In addition to water damage and mould-like substances in the entrance area of the R&D centre, the inspectors also discovered a leaking ceiling in the area of the floor storage in the R&D centre. Plastic sheeting was simply attached to the ceiling to contain the leak.  In its letter, the FDA emphasises that the facility and buildings are in good condition and that hygienic conditions must be maintained in order to protect the drugs from possible contamination.

Current status

Although the company had proposed specific corrective actions after the previous inspection, the repeated failures show that the management's supervision and control over the manufacture of medicines is inadequate.
Currently, the manufacturer has probably stopped production for the US market, but it is also on the FDA's list for import warnings. The FDA points out that the deficiencies must be remedied before products can be resupplied to the USA and that the FDA must be notified in advance of any desired resumption of imports.

Further details can be found directly in the FDA's Warning Letter.

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