USFDA 483 / IPCA Laboratories, Silvassa, India / FEI 3005977675/ USFDA Investigators: Rajiv Srivastava, Kellia Hicks  / Inspection dates April 18-26, 2023 / Observation 2 – Timely closure of Deviations and CAPAs

The responsibilities and procedures applicable to the quality control unit are not in writing and fully followed.

Specifically,

A. Failure to ensure deviation investigations and associated corrective and preventive actions (CAPAs) are timely, accurate, and documented contemporaneously.

a. A quality event of a tablet inspection system not working recorded on 20 July 2021; Steps in investigation was not documented and event was not closed for 10 months.

b. For a laboratory analysis related quality event recorded on 12 December 2020, CAPA was documented on 17th March 2021. (3+ months)

c. For another quality event, dated 3rd September 2019 associated CAPA is on 20th August 2021. (20+ months)

d. For a quality event of 17 December 2019, associated CAPA was dated 27th July 2021. (18+ months). The date remediation activities began is not captured, so it cannot be determined how long the Investigations remained open.

• • Another CAPA associated with a deviation for an adjustment to standard operating procedure, was not implemented and closed for seven months.
  • A deviation was recorded in Trackwise on 12 December 2020, but documentation began in Trackwise two weeks later, on 24th December 2020. And a new due date was documented without justification (which was beyond the time frame established for completing. Investigation without extension and justification)

B. For an OOS recorded on 29 Jan 2020 in a test of dissolution, root cause was human error – the analyst did not place the tablet in the respective dissolution vessel.

CAPAs were:

1. Training the analyst
2. SOP updation, which were made effective only in 2022

• • Operation and cleaning procedures for Cleaning apparatus (Effective on 9 February 22 & 2nd April 2022).
  • Procedure for performing dissolution profile study (Effective 6th April 2022)

In between, there was another similar OOS, recorded on 15 June 2021 with similar human error – analyst did not ensure tablet was placed in respective distribution vessels. This shows the CAPA and Training are not effective.

In Manufacturing, Quality and other technical operations, deviations, discrepancies do happen. But the key point is how comprehensively and timely Companies are addressing such Issues.

• Failures (deviations, OOS and so on) should be recorded promptly (many companies follow a time frame of not more than 24 hours). Failure investigations should be Initiated without delay.
• Failure investigations should be performed timely, assigning maximum priority. When there are different aspects, that need to be investigated, Develop & Document an investigation plan. As the investigation of each aspect gets completed, document the same rather than waiting for all investigations to complete. After all investigations are completed a summary report can be prepared, referencing the different aspects investigated. This convinces confidence about the investigation process and approach, that the investigations are happening In a dynamic fashion. This also helps companies to ensure Important aspects are not missed out in the investigation and documentation and channelise and guide the investigation in right direction.
• Another important aspect to be addressed, is the potential impact on other processes, products. batches. Potential for recurrence of similar deviation should be evaluated, remedial measures taken so that other processes, products are not affected. These actions should be promptly taken (during the preliminary investigation) and documented. Additional actions can be taken where necessary, during the progress of Investigation. After the investigation completion and conclusion of the actual root causes, a comprehensive impact analysis can be performed; and If some of these evaluations were already performed during the course of investigation, this can be cross referenced. This gives confidence on the Company’s intentions & and the robustness of the quality system to take prompt remediation actions with the focus on patient safety.
• Implement the corrective actions and preventive actions identified, promptly. A CAPA implementation time frame of say 3months, or 6months or more, for a major system correction or facility corrections can be understood (Provided adequate interim safeguards, like procedural controls are Implemented of course). But delaying actions like SOP correction, revision; documentation correction, Training personnel are hardly justified.

Quality & TechOps personnel of companies may well review whether they have similar situations in their sites, take measures to address the same:

• If there are past investigations and CAPAs with unreasonable delays. review and document the same, reason for the delays, how the firm will address / take actions to ensure such delays don’t happen further.
• Prepare an action plan for completing the long pending investigations and implementing CAPAs on priority. Document the plan and keep updating the progress.
• Evaluate whether there are impacts on other processes, products, batches due to the open deviations / CAPAs – document the same; take remediation actions where necessary (implementing immediate containment measures, procedural controls, market actions etc.).
• Implement a robust system for tracking open investigations and CAPAs, make it a part of Management review meetings involving Senior Management.