Bio-Thera Solutions, Ltd – FDA CRL

The U.S. Food and Drug Administration (FDA) issued a Complete Response Letter (CRL) to Bio-Thera Solutions Ltd. for its Biologics License Application (BLA) for BAT1706, a proposed biosimilar, submitted under section 351(k) of the Public Health Service Act. The FDA determined that the application cannot be approved in its current form due to several critical deficiencies.

A primary issue identified was in clinical pharmacology, where the bioanalytical method used to quantify BAT1706 and EU-Avastin concentrations failed selectivity acceptance criteria. This suggests potential interference, impacting the accuracy of pharmacokinetic (PK) measurements and the ability to demonstrate biosimilarity or establish a scientific bridge to the EU-Avastin comparator. Consequently, the FDA concluded there is insufficient PK data to confirm BAT1706 has no clinically meaningful differences from US-Avastin. Bio-Thera is required to repeat experiments to establish method selectivity.

Furthermore, a mandatory inspection of Bio-Thera Solutions' manufacturing facility in Guangzhou, China (FEI: 3017231337) could not be completed due to travel restrictions. This inspection is essential to assess compliance with Current Good Manufacturing Practices (CGMP) and must be conducted and its findings assessed before the application can be approved, regardless of whether other deficiencies are addressed.

The CRL also cited issues concerning product quality related to Drug Substance and Drug Product Manufacturing and Control Strategy. Bio-Thera must provide a comprehensive safety update, including new clinical data, a worldwide safety summary, and translations of foreign labeling. Additional recommendations included addressing microbiological issues related to shipping validation and low endotoxin recovery studies. The FDA reserved comments on labeling and the proprietary name until these core deficiencies are resolved.