Mfg News: Novartis, FDA, Intas and Xellia 

A roundup of manufacturing news from Novartis, the US Food and Drug Administration, Intas Pharmaceuticals, and Xellia. Highlights below. 

* Novartis Investing $85 M for New Radiotherapy Mfg Plant in China  
* Intas Receives FDA Warning Letter for Drug-Product Mfg Facility
* Novartis Recalls Two Lots of Organ Transplantation Drug Due to Crystallization Issues 
* FDA Issues Safety Notice for Syringes Manufactured in China
* Xellia Starts Premix Bag Mfg at Cleveland Site

Novartis Investing $85 M for New Radiotherapy Mfg Plant in China 
Novartis has announced a RMB 600 million ($85 million) investment to build a new radiopharmaceutical manufacturing plant in Haiyan County, Zhejiang Province, China. Once the relevant drugs receive regulatory approval, production is expected to start by the end of 2026. 

Source: Novartis 

Intas Receives FDA Warning Letter for Drug-Product Mfg Facility 
The US Food and Drug Administration (FDA) has issued Intas Pharmaceuticals, an Ahmedabad, Gujarat, India-based bio/pharmaceutical company and CDMO, a Warning Letter for several GMP violations at its drug-product manufacturing plant in Gujarat, India. The Warning Letter follows the FDA’s inspection of the facility from May 1 to May 12, 2023.  

The FDA cited the company for its quality assurance and production departments for failing to provide adequate oversight and ensure the reliability of data related to the quality of finished drug products manufactured at the facility. The FDA said that visual inspectors manipulated particles and other defect counts on manual visual inspection records, in many instances, in order to keep the finished product batches within rejection limits. 

The FDA also cited the company for failure to initiate or conduct adequate investigations into significant deviations in its aseptic processing manufacturing operations, The agency said that the company did not adequately investigate visual inspection failures and non-viable particulates exceeding the company’s action levels. 

The agency also said that the company’s personnel qualification for the visual inspection of injectable products was deficient by not providing adequate challenge test set vials to qualify its operators to perform the visual inspection of the company’s drug products. 

In addition, the FDA said the firm failed to establish and follow appropriate written procedures designed to prevent microbiological contamination of drug products, noting that the company’s procedures did not include a requirement for smoke studies to be performed in dynamic conditions in classified critical areas. 

Overall, the agency said that the company’s quality system does not adequately ensure the accuracy and integrity of data to support the safety, effectiveness, and quality of the drugs manufactured by the company. The FDA acknowledged that the company is using a consultant to audit its operation and assist in meeting FDA requirements. The Warning Letter outlined the steps the company is to take to address the violations cited by the FDA.  

Source: US Food and Drug Administration 

Novartis Recalls Two Lots of Organ-Transplantation Drug Due to Crystallization Issues  
Novartis is conducting a voluntary nationwide recall at the consumer level in the US of two lots of Sandimmune Oral Solution (cyclosporine oral solution, USP), 100 mg/mL, an organ-transplant drug, in the US due to crystal formation observed in some bottles, which could potentially result in incorrect dosing.  

The issue was identified during an investigation of crystallization in a different lot of Sandimmune. No other Sandimmune formulations are impacted. 

Sandimmune, packaged in 50-mL bottles, is indicated for the prophylaxis of organ rejection in kidney, liver, and heart allogeneic transplants. 

Source: US Food and Drug Administration 

FDA Issues Safety Notice for Syringes Manufactured in China 
The US Food and Drug Administration (FDA) released a safety notice regarding the potential for device failures (such as leaks, breakage, and other problems) with plastic syringes manufactured in China.  

The FDA is collecting and analyzing data to evaluate plastic syringes made in China used for injecting fluids into, or withdrawing fluids from, the body. At the time of the November 30, 2023, communication by the FDA, the issue does not include glass syringes, pre-filled syringes, or syringes used for oral or topical purposes. 

To date (November 30, 2023), the FDA said it is aware of quality issues from recent syringe recalls, medical device reports, and additional complaints about syringes made at various manufacturing sites in China. Quality issues reported have included leaks, breakage, and other problems after manufacturers made changes to the syringe dimensions. 

The FDA says it is working with federal partners to further test syringes manufactured in China. The FDA says it plans to work with manufacturers to ensure adequate corrective actions are taken, and, as necessary, may prevent syringes made in China from entering the US. 

Source: US Food and Drug Administration 

Xellia Starts Premix Bag Mfg at Cleveland Site 
Xellia Pharmaceuticals has received approval by the US Food and Drug Administration for the manufacture of premix bag products at its facility in Cleveland, Ohio. Production has commenced and the first commercial batches have been released. 

Xellia has worked with the FDA to bring the Cleveland facility into operation and gained approval for the commercial manufacturing of its first injectable drug products at the Cleveland facility in March 2020 and now for its first premix bags. The approval from the FDA means that Xellia can now produce its first premix bags at its site in the US for the US market. 

Source: Xellia