The US Food and Drug Administration (FDA) recently issued warning letters over failures to conduct investigations into out-of-specification (OOS) results in laboratory testing, among other GMP violations, at drug manufacturing facilities in China, Ireland and Australia.
China-based Jilin Shulan Synthetic Pharmaceutical, Australia’s Jalco Cosmetics and Ireland-based Europharma Concepts were each placed on FDA import alert in March and February as a result.
Jilin Shulan Synthetic Pharmaceutical
GMP violations—flagged during a four-day FDA site inspection last November at Jilin Shulan Synthetic Pharmaceutical—include a lack of documentation for deviations in the firm's laboratory testing results, insufficient data-protection controls on its chromatography computer systems as well as record-keeping delays when performing manufacturing operations.
“Significant findings in this letter indicate that your quality unit is not able to fully exercise its authority and/or responsibilities,” FDA concluded in the warning letter, posted on Tuesday. “Your quality system does not adequately ensure the accuracy and integrity of data to support the safety, effectiveness, and quality of the drugs you manufacture.”
The firm attributed its failure to initiate investigations into batch records with results that had been OOS and out-of-trend to its “staff’s lack of cGMP knowledge,” according to the FDA warning letter. It also failed to provide a deviation report or justification on an operator that had violated manufacturing procedures, as revealed in a note FDA found in batch records.
On the cited failure to synchronize performance and documentation of manufacturing operations, the firm responded that “these deficiencies were due to the lack of oversight.”
Inadequate handling of data generated on the firm’s computerized systems, such as the use of a portable drive that was not password-protected, was cited as well. The FDA investigator found that “operators had full system permissions, including the ability to modify and delete files.”
For FDA to consider lifting the import alert placed on the firm earlier this year, the agency called for investigations into the extent of data and reporting inaccuracies, a risk assessment of the cited violations, such as the potential effects on patients, and details on a management-led global CAPA strategy, among other measures.
At least four significant GMP violations were revealed at Jalco Cosmetics drug manufacturing facility in Australia last December. These included a past contract manufacturer’s OOS results that showed “sub-potent...content at 24 months, and low viscosity at 36 months,” FDA said.
To address this issue, the firm reported in its December response letter to FDA its plans to conduct real-time stability studies for its next production batch. However, Jalco Cosmetics has yet to implement an adequate stability program, according to FDA.
“Without an adequate stability program, you cannot confirm your drug products continue to meet established specifications throughout their labeled shelf-life,” the agency's warning letter states.
A lack of written products to ensure quality control over production and processes—causing issues such as an unvalidated process for a cream distributed in the US in 2016—failure to test incoming material used for manufacturing cream, and released cream without testing are among the other violations outlined in the warning letter to Jalco Cosmetics.
Europharma Concepts’ facility in County Offaly, Ireland had failed to check for presence of diethylene glycol (DEG) or ethylene glycol (EG) in lots of glycerin raw material that had been used in its drug manufacturing at the time of the FDA’s investigation from October to November 2017.
“DEG contamination in glycerin has resulted in various lethal poisoning incidents in humans worldwide,” FDA said.
FDA also revealed a lack of testing on incoming active pharmaceutical ingredients the firm had been using in manufacturing its gel over-the-counter (OTC) drug product that should be conducted to ensure quality.
The firm’s response to these findings was deemed inadequate in that it did not address whether its materials had been analyzed for DEG or EG.
Another violation flagged at the Irish facility relates to a manufacturing process used on the gel OTC product that had yet to be validated as no process validation program was in place, according to FDA.
Jilin Shulan Synthetic Pharmaceutical