India-based Malladi Drugs & Pharmaceuticals and Labocont Industrial SRL’s drug manufacturing facility in the Dominican Republic drew US Food and Drug Administration (FDA) warning letters over failures to prevent or minimize the risk of contamination, among other violations revealed during 2017 site inspections.
The agency’s review of the responses from both of the foreign drugmakers found inadequacies in addressing the manufacturing nonconformities as initially identified in Form 483s, including a lack of risk assessments for all drugs manufactured within and distributed in the US.
Malladi Drugs & Pharmaceuticals and Labocont Industrial SRL were placed on import alerts in December 2017 and February 2018, respectively, in response to the violations.
GMP deviations for active pharmaceutical ingredients (API) at Malladi Drugs & Pharmaceuticals relate to conducting at least part of its API production in areas exposed to the outdoors, no justification for preventing contamination “from foreign matter and other impurities” due to inadequate processes for cleaning equipment, as well as an inadequately validated process.
“Our investigator observed vermin, such as birds and insects, in the facility near open equipment used for drug manufacturing,” FDA said. “Their presence puts your drugs at risk of contamination. You failed to take adequate precautions to prevent the risk of contamination while producing drugs using open equipment.”
Further, the agency’s inspection found that a process for API drug manufacturing — which the firm acknowledged had not been adequately validated — and a lack of appropriate control procedures resulted in 24 batches producing out-of-specification test results for about two years.
The firm was directed to provide a risk assessment for all drugs manufactured and distributed within the US, including for those that may have been vermin-contaminated, and to replace its equipment surfaces deemed “difficult to reproducibly clean.”
Labocont Industrial SRL
A July 2017 response to the GMP nonconformities flagged at Labocont Industrial SRL “failed to commit to specific and comprehensive actions to address the violations observed during the inspection,” FDA said.
The firm was cited over not separating the manufacturing its over-the counter drugs with that of its non-drug products. The failure to “completely and comprehensively separate” both production facilities “presents an unacceptable risk of...contamination in other drug products manufactured at your facility,” the agency added.
To address this issue, FDA gave the firm two options: Either dedicate separate manufacturing facilities for the different products and provide an implementation timeline, or conduct a full decontamination of the facility to continue production of a single product type and propose the plan for agency consideration prior to introducing products into the US supply chain.
Other GMP violations outlined in the warning letter include a lack of documented data obtained from assay analysis, invalidated analytical methods used for assay determinations, and uncalibrated and unverified instruments for performing laboratory tests.
Malladi Drugs & Pharmaceuticals
Labocont Industrial SRL