The Italian Medicines Agency on Wednesday released two statements of non-compliance with regard to good manufacturing practices (GMPs) for Visakhapatnam, India-based Krebs Biochemicals & Industries and Daund, India-based JP Laboratories.
At the Krebs facility, the Italian regulators uncovered 24 deficiencies, five of which were classified as major.
“The combination of the findings demonstrated a critical risk to public health, as the weaknesses of the company’s quality management system and the approach in several GMP areas such as facilities, material management, quality of the water used in the production and QC [quality control] tests, were not robust enough to sustain a GMP compliant level,” the inspection report says, noting the Krebs “should not be approved in any new/ongoing application.”
The five major deficiencies were identified in deviation management, personnel training, facilities, finished product storage management and production and monitoring of purified water.
The Italian Medicines Agency said each national competent authority in the EU should evaluate, following assessment conducted in conjunction with marketing authorization holders, if a recall of medicinal product is needed.
“Given the nature of non-compliance, assessment should include a complete retest of all imported batches of active substance,” the report says. “Prohibition of supply is recommended, unless there are not alternative suppliers and there is a risk of shortage.”
For JP, 28 deficiencies were raised by the Italian inspectors, nine of them classified as major, with regard to quality management (integrity and security of data in the quality system); Two for personnel; Building and facilities; Materials management; Production and In-Process control; Laboratory control (integrity and security of analytical data); Validation (equipment qualification); and change control.
The observed deficiencies are considered to apply to all other active substances manufactured at the same site, including ingredients used in chest pain drugs, such as Isosorbide Mononitrate Pure, Isosorbide Mononitrate Diluted 90%, Isosorbide Mononitrate Diluted 70%, Isosorbide Mononitrate Diluted 60%, Isosorbide Mononitrate Diluted 50%, Isosorbide Mononitrate Diluted 40% , Isosorbide Mononitrate Diluted 20%, Isosorbide Mononitrate Diluted 25%, Isosorbide Dinitrate Diluted 40% and Isosorbide Dinitrate Diluted 25%.
Similarly to the Krebs inspection, the regulators said the extent and severity of the findings “constitutes a critical risk for public health.”
“Given the nature of non-compliance, assessment should include a complete retest of all imported batches of active substance,” the agency said. “Prohibition of supply is recommended, unless there are not alternative suppliers and there is a risk of shortage.”
EudraGMDP Inspection Reports