Receive two warning letters in a year? Compliance issues at KVK-Tech, a U.S. generic drugmaker

For any company, receiving a warning letter from the FDA is a disaster and a wake-up call to passively improve quality compliance, and receiving two warning letters in a year is a disaster.
, KVK-Tech, a U.S. generic drugmaker, received warning letters from the FDA in February and October about its production controls, respectively.
a warning letter issued in February against the company's factory in Terry Drive, and FDA inspectors found three violations during inspections from April 9 to 16, 2019.
1, violation of 21 CFR 211.165 (e): Failure to establish and document the accuracy, sensitivity, specificity and reproducibility of its test methods.
FDA inspectors found that the plant did not properly integrate co-enchantment peaks and failed to detect excess results (OOS) when testing impurities on fentanine hydrochloride capsules, a weight-loss drug.
problem was actually discovered in 2016, when a deviation report at the plant recorded "analysts using the XX method to score, and the reported levels of impurities may not reflect the true concentration of the drug."
training on May 24, 2016, to educate analysts to properly integrate and measure co-cleansing peaks during drug impurity analysis.
However, in December 2016, pharmaceutical analysts performed XX integrals to calculate the peak area of a batch of stability impurities tested in fentanine hydrochloride capsules, which, if properly integrated, would exceed the impurity specification limit.
the product remained on the market until the XX stability impurity test failed on June 20, 2017.
inspection, it was observed that there were many times when the close co-wastation peak was not properly integrated.
2, Violation 21 CFR 211.192: Unexplained differences or faults in any batch or its composition, whether or not the batch has been distributed, have not been thoroughly investigated.
pharmaceutical plant in the filling process found 5 mg/5 mL of methyl acetate oral liquid in a batch of foreign particles, but only filtered out foreign particles, visual inspection after release.
the source and nature of particulates and their impact on the quality of medicines have not been adequately investigated.
fda has called for a recall of the batch.
3, Violation 21 CFR 211.68 (b): No appropriate controls have been put in place on the computer or related systems to ensure that only authorized personnel can change master production, control records, or other records.
fda strongly recommends that the drug company hire a qualified consultant to assist with remediation.
a) a comprehensive investigation of the extent of inaction in data records and reports, b) a current risk assessment of the potential impact of observed failures on the quality of the drug, and c) management strategies, including details of corrective and preventive action plans.
February 4 to March 13 this year, the FDA inspected the company's plant in Campus Drive and found three violations, leading to a warning letter in October.
1, violation of 21 CFR 211.67 (b): Proper written equipment cleaning and maintenance procedures have not been established and followed.
the plant performs packaging operations for a wide range of solid oral dosage forms, but does not verify the process for cleaning non-specialized packaging equipment, such as tablet counters, as required by the standard operating procedures for cleaning, which can lead to cross contamination.
2, violation of 21 CFR 211.188: The batch production and control records for the production and control of each batch of drugs are incomplete.
During the packaging of a batch of hydroxyl hydroxyl hydrochloride tablets, FDA inspectors observed that the air pressure meter reading was outside the acceptable range of the cap press, although a passing value (of the air pressure meter) was recorded in the batch record.
, the actual air pressure reading of the packaging equipment is not recorded in the batch records of isopropyl hydrochloride tablets.
3, record authenticity issues: Sample logs a clean verification sample received at 10:50 p.m. on September 24, 2019.
, according to the log, the chromatography of the sample was completed around 5:50 p.m. on September 24, 5 hours before the sample was received.
the building's access card reader records show that at around 10:50 p.m. that day, the analyst who registered the samples was not in the building.
analysts gave conflicting explanations for the problem, eventually admitting that incorrect information had been entered into the log.
KVK-Tech is currently shut down at the request of the FDA.
Because of similar CGMP violations at both production sites, the FDA believes that this demonstrates inadequate oversight and control of drug production by company management and that a comprehensive assessment should be conducted immediately to ensure that production systems, processes and products comply with FDA requirements, and strongly recommends that the company hire a CGMP consultant who meets the requirements of 21 CFR 211.34, to assist in conducting a comprehensive audit of the company's CGMP compliance and assessing the completion and effectiveness of corrective actions and preventive measures.
consultants providing advisory services on the manufacture, processing, packaging or storage of medicines should have adequate education, training and experience.
keep a record of the consultant's name, address, and qualifications, as well as the type of service they provide.
Quality Compliance Expert Opinion: It can be seen that the FDA is aware of the current market for the establishment of a "mature quality system" of production enterprises lack of recognition and incentives, to put it speaking, quality management does not mean that manufacturers can earn money, so easy to appear "bad currency expulsion of good money" phenomenon, so regulators need to assume the role of consumer control, through the use and integration of regulatory tools, such as drug sampling inspection, regular inspection of production facilities, public warning, recall, etc., to ensure the provision of safe, effective and high-quality drugs for patients.
two warning letters to U.S. generic drug companies, the FDA also treats domestic companies equally, meticulously and strictly.
Production enterprises must start from the source, establish a good quality management system, and establish quality compliance assurance mechanisms, such as from the company or board of directors to hire independent, professional third parties, and constantly improve the level and ability of their own quality system, quality compliance risk to a minimum.
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