FDA warns Japanese firm for particle contamination, takes mask-maker to task — again

Regulatory NewsRegulatory News
| 26 August 2021 | By Joanne S. Eglovitch 

The US Food and Drug Administration (FDA) admonished Japanese pharmaceutical manufacturer Toyoba Co. in a recent warning letter for taking a lax approach to fixing microbiological contamination issues and resolving data integrity problems that included falsification of data.
The firm’s failure to report accurate data “compromised the sterility assurance of drug products released from the facility and may have increased risks to patients,” wrote FDA in the 19 August letter.
The company, a contract manufacturer of injectables located in Otsu, Shiga, also produces fibers and textiles. The firm was inspected by FDA from mid-to-late February 2021.
The agency said that between 2019 and 2020, multiple batches of an injection solution were found to have “significant particulate contamination” yet the firm failed to launch a timely investigation to uncover the root cause of the defects.
FDA said that “our review revealed that your in-process quality standards, limits, categories, and triggers for investigations do not sufficiently differentiate intrinsic from extrinsic particulate contamination.”
In a follow-up investigation, the company found that its procedures for performing supplier audits had improved and said it was “highly possible” that washing and sterilization processes could not remove certain particles attached to stoppers or vials. Yet FDA pointed out that the investigation “failed to adequately address the upstream root cause of the contamination and implement timely corrective action and preventive actions (CAPA).”
The firm was also taken to task for not adequately investigating “multiple instances” of an iron contaminant that were found in visible particle identification studies. This contaminant, said FDA, has the potential to “induce adverse events because of immunogenic response.”
A follow up investigation by the company found that the 12 batches cited during the inspection were found to have visible particles such as cellulose fibers, glass fibers, black and white particles and “stain” like particles of various colors.
FDA wants the firm to provide a comprehensive and independent assessment of their overall system for investigating deviations, complaints and out of specification results.
Data integrity failures
FDA also faulted the firm for not adequately investigating the extent of data integrity breaches, including what the agency termed falsification of airborne particle measurement records. This breach compromised the firm’s environmental monitoring data related to operators, equipment surfaces, and non-viable particulate monitoring.
Another data integrity breach involved operators manipulating contact plate measurements.
FDA told the firm that “accurate microbiological data is fundamental to evaluating and maintaining the state of control of an aseptic processing operation. Awareness of microbial excursions in an aseptic processing operation is essential to trigger prompt actions that maintain environmental controls …. Your failure to report accurate data compromised the sterility assurance of drug products released from the facility and may have increased risks to patients.”
The firm was advised to hire a consultant and has 15 days to resolve these problems.
Other firms have been taken to task for similar problems with particulate contamination. In June 2020, FDA warned Takeda over unexplained discrepancies; among other failings, the firm did not adequately investigate the occurrence of black particles in multiple batches of vials for one of its products (RELATED: FDA warns Takeda over aseptic processing, inadequate investigations, Regulatory Focus, 16 June 2020).
FDA tells UK company to stop distributing masks
In another recent warning letter, FDA’s Center for Devices and Radiological Health told a UK-based company, Invisi Smart Technologies, to stop distributing masks with unsubstantiated claims that they will prevent and treat COVID-19.
The company’s website claims that the technology used in the ISM30 Invisi Smart Masks had been tested against human coronavirus and were able to “kill viruses and bacteria as they come into contact with the mask allowing you to wear your mask with confidence all day…and for the next 30 days!”
The agency also objected to the firm’s unsubstantiated claims that the “self-disinfecting technology” in the masks allowed users to wear them without washing.
FDA said that “based on our review, your websites are offering for sale in the United States the above mentioned mask models without marketing approval, clearance, or authorization from the FDA. Accordingly, your devices are adulterated under section 501(f)(1)(B) of the Act … because your firm does not have an approved application for premarket approval (PMA) in effect.”
Further, FDA “requests that your firm immediately cease activities that result in the misbranding or adulteration of these devices.”
Toyobo warning letter
Invisi Smart Technologies warning letter


© 2022 Regulatory Affairs Professionals Society.

Discover more of what matters to you