FDA 483 - Shima Laboratories Co., Ltd. - June 21, 2023

An FDA inspection conducted from June 6-9, 2023, at Shima Laboratories Co. Ltd., a medical device contract manufacturer in Tokyo, Japan, revealed significant quality system deficiencies. The FDA Form 483 listed four key observations. The company failed to adequately establish procedures for corrective and preventive actions, evidenced by the use of an unaccepted in-process product without proper documentation and resolution. Control of non-conforming products was also inadequate; the company's standard operating procedure lacked provisions for recording non-conforming quantities, and several instances showed products accepted despite deviations (e.g., excessive agitation, out-of-specification test results) without sufficient explanation or documented testing of affected batches. Furthermore, process validation for a critical manufacturing step was deficient, lacking clear acceptance criteria, with multiple revalidations revealing inconsistencies that were accepted based on unclear explanations of "errors." Lastly, production processes were not adequately controlled, as demonstrated by the formulation of a standard that involved adjustments outside its specified concentration range. These observations indicate non-compliance with medical device quality system regulations, requiring Shima Laboratories to implement comprehensive corrective actions to address each identified issue and prevent recurrence.