Regulatory Focus™ > News Articles > 2020 > 6 > FDA warns Takeda over aseptic processing, inadequate investigations

FDA warns Takeda over aseptic processing, inadequate investigations

Posted 16 June 2020 | By Michael Mezher 

FDA warns Takeda over aseptic processing, inadequate investigations

The US Food and Drug Administration (FDA) last week warned Japanese drugmaker Takeda Pharmaceutical over good manufacturing practice (GMP) violations observed during an inspection of its Hikari, Yamaguchi facility last November.
Specifically, the warning letter cites the firm for three violations relating to its procedures for aseptic manufacturing and investigations into unexplained discrepancies and equipment malfunctions.
“Our inspection found that your Quality Unit (QU) did not take appropriate steps prior to resumption of aseptic manufacturing after a shutdown that included multiple significant activities that compromised your cleanroom control,” FDA writes.
FDA says the company allowed manufacturing operations to resume without performing media fills as required in its procedures and shipped multiple batches of affected products to the US.
While Takeda committed to performing aseptic process simulation for the affected manufacturing line, it stated that, “There was no adverse impact to product because [its] procedure for restarting production requires that environmental monitoring data and utility results are available before product release.”
However, FDA says this is inadequate, “Because you failed to adequately assess the impact of sterility assurance of the products manufactured in a facility after a shutdown in which cleanroom control was compromised.”
In addition to a risk assessment for the products distributed without adequate assurance of aseptic processing conditions, FDA says it wants Takeda to provide a “comprehensive assessment and remediation plan” to ensure its QU has the authority and resources to function effectively, as well as a “description of how top management supports quality assurance and reliable operations.
The warning letter also notes that Takeda “failed to establish and follow appropriate written procedures that are designed to prevent microbial contamination of drug products purporting to be sterile.”
Additionally, FDA says its investigators observed poor aseptic behavior at the facility, including staff failing to “sanitize gloved hands after touching surfaces such as curtains and computer touchscreens,” and performing manipulations with “rapid movements, rather than slow and deliberate aseptic technique.”
Lastly, the warning letter says Takeda, “Lacked adequate investigations into equipment malfunctions. Several investigations were concluded without sufficiently addressing root causes or ensuring adequate scope, allowing manufacturing risks to persist for extended periods.”
In one case, FDA says Takeda did not adequately investigate the occurrence of “black particles” in multiple batches of vials for one of its products. In another, the agency says the company used malfunctioning equipment “for a protracted period to sterilize components of [its] injectable product.”


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