Do Not Panic: How to Achieve Inspection Readiness

pills-1569173_1920-copyInspection Readiness (IR) is a proactive process. It is a process of ‘getting ready’ for an inspection by a regulatory authority (such as FDA), which is conducting an official review of documents, facilities, records, and any other resources that are deemed by the authority to be related to the clinical trial.  Every pharma company is responsible for inspection readiness through providing the training to employees and ensuring their understanding and application of policies, standards, and procedures. Pharma organizations should allocate the right number of qualified resources to assure that inspection teams are in place to manage activities before, during, and after inspections. Clinical Operation Managers are traditionally driving the IR activities for the given clinical study with Quality Assurance (QA) support. Manufacturing/CMC Inspection Readiness is usually covered by separate QA GMP group. In both cases, IR is a cross-functional effort.

The article will discuss the practical aspects of inspection readiness and preparation, focusing on a role of the Inspection Readiness Tools and Inspection Planning Timeline.

  1. Inspection Readiness Tools

Every pharma organization should be inspection ready at all times. Day one of IR starts with first clinical protocol finalized and continues through finalization of the clinical study report. Many companies adopted the use of Inspection Readiness Tools as part of their IR processes. IR tools should undergo a regular review of the for accuracy and completion. Clinical Operation group should be in charge of maintaining those tools. IR tools have two primary objectives:

  • Inspection Readiness: to increases awareness of areas that can be covered during inspections and to consider implementation at early stages.
  • Inspection Preparation: To facilitate inspection preparation upon submission or following inspection announcement.

IR includes study personnel training and collection of all trial documents and information in advance and before inspection.

The IR tools & documentation usually include:

  • Study Team List: to document the start and end dates of personnel assignment. Note, once anybody is on the inspection readiness study team may be called upon during a future regulatory inspection, independently from other assignments (e.g. being transferred to another project).
  • Document Location Tracker: to identify the location of study documents to allow quick retrieval during inspection (including documents located in Trial Master File).
  • SOP Log: to demonstrate what SOPs were used during the study conduct (applicable when the sponsor company was acquired by another pharmaceutical company during the study conduct).
  • Clinical Trial Systems List: to demonstrate what IT systems were used during the study conduct.
  • Decision Log: to explain when, why and by whom decisions were made.
  • CRO List & CRO Oversight Plans: to demonstrate what CROs were utilized during the study conduct and how the CRO was overseen. Sponsor remains responsible for work outsourced to vendors (study conduct, the quality, and integrity).
  • CV, Training, Job Descriptions, Organizational Charts: to demonstrate relevant training and expertise of the dedicated personnel. Each line is responsible for providing those as needed, location of those documents should be known upfront before the inspection.
  1. Inspection Planning Timeline

To help to visualize the Inspection Planning Timeline process, I included the example of the possible planning schedule. As stated above, the inspection readiness is a cross-functional effort and should be proactive (light green color). Once the project team is closer to achieve the key study milestones, such as database lock/freeze (light orange color), the IR scrutiny should intensify, and quality of IR tools and documentation should be re-assessed. The TMF audit plan should also be prepared and implemented (dark orange color). It is recommended that IR/TMF assessment activities start at least 9-12 months before the planned NDA/BLA filing (light blue color). The mock inspections (GMP, ICH-GCP/GLP) completed by third party auditors are highly recommended and can increase overall quality and enable fixing a lot of issues ahead of the real inspection (dark blue color). Mock GMP inspections and ICH GCP inspections should happen anywhere between 3-6 months before the NDA/BLA submission when the team already achieved (at least in theory) full inspection readiness.

BLA Submisson Timeline mock.xlsxClick-here-to-upload-fda-inspection-planning-timeline (pdf).

References:

 

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