Case Study #1
Clinical Quality Assessment & Corrective Action Initiatives
Clinical quality consulting services provided by Falcon GCP Solutions Practice (including Computer System Validation):
- Internal audits of Clinical Operations' processes and documentation;
- Audits of investigator sites and clinical trial master documentation and files;
- Audits of Serious Adverse Event tracking and files;
- Development of Clinical Trial Management System (CTMS) User Requirements Specifications;
- Corrective action activities for enhancement and implementation of improved GCP standards to support regulatory compliance.
Mid-size device company (Clinical R & D), a subsidiary of a top global pharmaceutical company, involved in the conduct of global clinical trials (under IND Submissions in the US) using an approved, commercially available device in combination with an FDA-approved drug.
Complex clinical studies were being conducted in complex therapeutic areas without a clinical trial infrastructure that could maintain expected GCP quality standards. Written procedures were deficient in some areas and clinical program growth was so rapid that compliance with requirements was compromised. Serious deficiencies in the management of the global clinical trials, as well as SAE tracking and follow-up were identified through internal audits and audits performed at clinical investigator sites. There was an immediate need for prioritized corrective action strategies.
Critical areas identified for improvement were prioritized by the client with Falcon guidance. Corrective action plans with Falcon evolved to a series of GCP improvement activities over a nine month period. Consulting services shifted to corrective action and improvement activities which involved the mapping of fourteen (14) key Clinical Operations and Clinical Trial Management Process areas, encompassing all relevant and adjacent functional areas and disciplines. Services also included detailed evaluation of written standards (SOP "Gap Analysis") and enhancement and/or development of new standards (n=30), followed by training on each new standard for all relevant personnel.
Case Study #2
Process Assessments Lead to a Successful Mock FDA Inspection
Falcon Consulting GCP Solutions Practice conducted a series of individual, yet synchronized, Process Assessments of:
- Clinical Operations, Clinical Trial Management, and Quality Management Practices;
- Pharmacovigilance and Drug Safety Surveillance;
Post implementation of Falcon Process Assessment recommendations, Falcon Consultants planned and conducted a Mock FDA Inspection, which incorporated several of the company's pivotal studies. Indirectly related, Falcon Consultants supported the implementation of a Clinical Trials Management System (CTMS) by assisting the client with Functional Specification Development, Software Vendor Selection, and Project Implementation Management.
Falcon GCP Solutions Practice (including the Computer Systems Validation) Consultants provided value-added services to this small Bio-Pharmaceutical company involved in the conduct of US-based clinical trials to support the filing of their first New Drug Application to the US Food and Drug Administration.
With several large clinical study programs being conducted simultaneously, client and client CRO partner's infrastructure and resources were being maximized. As this was the client's lead product candidate, management required assurances that study conduct was adequate and in compliance with regulatory requirements, risks were known and minimal, and process efficiency was optimal.
Falcon Consultants assessed processes in all identified critical areas, determined compliance with existing benchmarks, and provided useable guidances for improved compliance and efficiency. Assessment summaries were provided to the client in the form of presentations and reports for future consideration. Actionable items were identified and managed to completion with the assistance of Falcon personnel. This resulted in the client revising several procedures within the overall SOP portfolio, developing some new procedures as a result of the Gap Analysis, and implementing specific training initiatives; namely, an interactive training delivery system.
Case Study #3
Evaluation of Clinical Systems Requirements
The task was to conduct workshops, individual interviews, and review existing manual and automated process to determine the company's needs for new electronic systems and/or modifications to existing systems and/or processes. Additionally, the systems were reviewed to ascertain the current regulatory validation and to provide a remediation plan in the event that the systems had not been sufficiently validated.
Mid-size device company (Clinical R&D), a subsidiary of a top global pharmaceutical company, involved in the conduct of global clinical trials (under IND Submissions in the US) using an approved, commercially available device in combination with an FDA-approved drug.
The predominant issue with the company was the manner in which essential documentation, monitoring reports, SAEs, and other clinical documentation was flowing from the investigators' sites back to the sponsor and into the hands of the appropriate personnel and ultimately into the Master File. In addition to the documentation problem, Clinical Project Managers were experiencing difficulties with tracking investigator milestones and project deadlines due to the inefficiencies and unsophisticated tools.
Falcon Consulting Group conducted several workshops to determine the existing document workflows and lifecycles. Additionally, a document inventory was conducted to both determine the types and location of essential documentation.
Furthermore, a Clinical Trials Management System (CTMS) was proposed. The CTMS requirements were gathered (from individual interviews, workshops, etc.), and a Requirements document drafted. The Requirements were used in the production of an RFP to be sent to various CTMS vendors. Vendor responses were evaluated in conjunction with product presentations, and vendor audits. As a result, a product was chosen. The product is in the implementation phase with Falcon Consulting Group providing guidance and configuration consulting.
Case Study #4
Inventory, Quality Control and Scanning of Trial Master Files
The project tasks were to receive the Trial Master Files (TMFs) for two European studies from the Sponsor and two (2) CROs, consolidate each TMF into a separate file, inventory each file to ensure that all Essential and Regulatory Documents were present, scan each compiled TMF to a portable document format (pdf), and file documents electronically to replicate the hardcopy TMF. The TMFs included all documents as defined by ICH Topic E6 §8.0 (e.g. Protocols and Amendments, IVRS Files, Monitoring Files, Investigator Files, Data Management Files, etc.).
While the TMFs were in-house, Falcon also supported the compilation of CSR appendices by the CRO, provided Project Management expertise, tracked all activities, and provided updates to the Sponsor.
Small specialty biopharmaceutical company involved in the conduct of global clinical trials using an approved and commercially available product worldwide.
The Sponsor purchased the compound while multiple US and EU studies were in progress. Challenges arose with the oversight of the CROs as well as the maintenance of the previous Sponsor's TMFs. As the studies were being closed, the Client had concerns with the integrity of the previous TMFs and did not have internal knowledge of ex-US requirements. In addition, the Sponsor did not have the physical space or resources to complete the reconciliation of the files.
Falcon assigned dedicated inventory, scanning/electronic filing and Quality Control teams. A standardized TMF index and naming conventions were generated collaboratively with the Client. TMF sections were reviewed for completeness and re-filed according to the TMF index. The sections were scanned into an electronic format. The electronic documents were named according to the TMF naming conventions and electronically filed according to the TMF index. All electronically filed documents were entered into a Master Tracker with hyper-linking capabilities; the Tracker served as the TMF table of contents for the hardcopy and electronic TMF. Each scanned and tracked TMF section was boxed for archived off-site storage with complete inventory capabilities. Missing documents and/or deficient sections were listed and provided to the Client for follow-up with the CRO. As requested by the Client, documents were provided to the CRO for use in the CSR appendices. All activities were accomplished on-time and under budget.
A quality assurance sampling of documents and sections were reviewed to ensure that the selected document/section was reviewed, inventoried, scanned, and filed (electronically and hardcopy) according to the TMF index and naming conventions. After all activities were complete, the Master Tracker was updated with the appropriate box number, the boxes were sent off-site for archival, and the electronic files (including the Master Tracker) were copied to DVD and delivered to the Client, and the Master Tracker was also uploaded to the Client's server.