Warning Letter – Ltd. Novacyl Wuxi Pharmaceutical Co.

Novacyl Wuxi Pharmaceutical Co., Ltd. .
Product: pharmaceutical manufacturing facility
Date: 12/19/2014

1. Failure to manage laboratory systems with sufficient controls to ensure conformance to established specifications and prevent omission of data.
Our inspection revealed serious deficiencies related to your documentation practices, including missing raw data. It is a basic responsibility of your quality unit to ensure that your firm retains the supporting raw data that demonstrates your APIs meet specifications that they are purported to possess.

For example, during the inspection, our investigator found a chromatogram related to (b)(4), API in the trash, dated October 15, 2013, which reported an additional chromatographic peak when compared to the standard. During the inspection, your firm stated that the analyst discarded the chromatogram because it was present in the blank injection. However, the analyst was unable to retrieve the blank chromatogram from the system because it was overwritten by a subsequent injection.

In addition, the inspection documented that your firm made changes to integration parameters for the impurities test without appropriate documentation or justification. Your firm relied upon hand written notes on a chromatogram discovered in a drawer at the laboratory as the documentation for this change. Furthermore, your firm implemented this change without an audit trail that would have captured the date of the change and who made the change.

Other significant deficiencies noted in your laboratory system include:

a) Failure to have a written procedure for manual integration despite its prevalence.
b) Failure to use separate passwords for each analyst?s access to the laboratory systems.
c) Use of uncontrolled worksheets for raw analytical data in your laboratory.
d) Presence of many uncontrolled chromatograms, spreadsheets and notes of unknown origin found in a drawer.

The lack of controls on method performance and inadequate controls on the integrity of the data collected raise questions as to the authenticity and reliability of your data and the quality of the APIs you produce.

Your firm?s response, dated November 06, 2013, stated that your firm will create a validation program for all uncontrolled computer systems, create a new standard operating procedure (SOP), and retrain all analysts performing analytical tests. However, observations found during the most recent inspection regarding the inadequacy of your HPLC system raises questions regarding your ability to implement sustainable corrective and preventive actions, as previous commitments made to the agency were not fulfilled. Please provide specific milestones and your detailed plan on how you intend to implement the appropriate corrective actions. We will also encourage you to submit monthly reports to the agency of your progress.

As part of your response, provide a complete validation plan for your laboratory computerized systems. This plan should include an audit trail component and other appropriate controls to prevent deletion and overwriting of data. In addition, include a retrospective review of the analytical data and batch records for all of the APIs distributed that remain within expiration, along with an evaluation of data that may have been generated to support a drug application, including any Drug Master File. This investigation should include a review of all APIs manufactured at your site. Furthermore, provide details of the systemic corrective actions taken to prevent recurrence of these deficiencies. .

FDA District Office: CDRH

About the author

Amy enjoys researching and writing about developments in medical technology and how that intersects with US law. She received her J.D. from the University of Florida Levin College of Law in 2020 and now works as a Regulatory Associate for SoftwareCPR®, a general-purpose regulatory consulting firm that is recognized globally for their expertise with standards and national regulations pertaining to medical device, mobile medical app, and HealthIT software.

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