Professional Plan and Execution Results in On-Time IND Submission and Clinical Program Initiation


PROJECT BACKGROUND

A mid-size biotechnology company with multiple development candidates in their pipeline lacked an overarching strategy for moving a lead compound from selection to Investigational New Drug (IND) application filing and subsequent Phase I clinical trial initiation. Specifically, the definition of clinical requirements, including form, dose, and quantity, were not coordinated with activities associated with developing and manufacturing the clinical trial material, thereby creating unpredictable schedule constraints and missed commitments.

Compounding the issue of not having an integrated development framework, the organization lacked standard policies, procedures, and methodologies for drug development and basic project management tools, such as a cross-functional schedule and associated risk mitigation plan. Myriad third-party relationships that created virtual late stage development and manufacturing capabilities for the primarily discovery-focused company further punctuated the criticality of a well-orchestrated approach.

Despite these challenges, Senior Management established a very aggressive timeline (7 months) to file the IND application with supporting documentation; develop, manufacture, and release the clinical trial material; and start Phase I clinical trials. Since the company was driving toward their Initial Public Offering (IPO), Senior Management also acknowledged the significant negative ramifications associated with failing to meet the First-In-Man (FIM) target within the 7 month commitment. To maximize the potential for success, the Senior Management team sought assistance from Integrated Project Management Company, Inc. (IPM) to work shoulder-to-shoulder with the team leader and functional representatives through planning and execution of the aggressive schedule.

IPM’S SOLUTION

Using its core tenets of process, discipline, and leadership, IPM applied a multi-pronged approach to proactively manage activities, resolve issues, and ultimately ensure the on-time initiation of Phase I clinical trials.

Immediately upon being engaged by the client, IPM instituted a Strategy Review Board (SRB) comprised of seasoned senior management members from the company’s Technical Operations functional area to provide high-level guidance and strategic endorsement. The SRB then chartered the Project Leader, assisted by the IPM project manager and in collaboration with all his functional areas’ sub-team members, to develop and present an overall strategy for the development candidate. The strategy included the intended clinical use for the compound, results from IND enabling studies, and the recommended drug product (DP) formulation for the Phase I trials.

In determining the DP formulation recommendation, close coordination between the Clinical and Non-Clinical teams was critical. Without a constructive exchange of requirements and constraints, identification of the form, dose strengths, and quantities required for Phase I trials would have been impossible. This information was vital for empowering productive contract negotiations with the supporting CMO. After in-depth discussions of the overall strategy and identification of potential risks and corresponding risk mitigation plans, the SRB approved the strategy for the development candidate. Each functional area now had a clear understanding of the level of effort and required timing to successfully file the IND and achieve FIM within 7 months.

Armed with the development candidate’s strategy, the IPM project manager subsequently created an aggressive Project Plan and Schedule (PP&S) that delineated an appropriate level of task decomposition and integrated resource allocation estimates. The project manager facilitated separate sessions with each functional area and then rolled the individual timelines into an interdependent PP&S. The risk mitigation plans identified at the SRB were directly incorporated into the Work Breakdown Structure for each significant task in the PP&S. Last, the project manager conducted an overall PP&S review with the team to confirm all critical project activities, logical task interdependencies, and accurate task durations.

With an integrated timeline now established, proper organizational oversight was critical for success. A Core Team was established for overall supervision of the project with Clinical, Non-Clinical, and Chemical Manufacturing Controls (CMC) sub-teams established to manage their respective areas. The IPM project manager set up weekly sub-team meetings to manage daily activities and provide inter-team communications. Timelines and risk identification drove agenda topics for each sub-team meeting, and action items from each team meeting were captured in an Action Item Database and aggressively managed until closed.

Guided by a well-defined critical path, IPM placed particular emphasis on tracking activities related to manufacturing clinical supplies. The formulation selection influenced CMO selection, so IPM coordinated the organization’s internal proposal and contract negotiation process and reached contract agreement with the CMO in just two weeks, a benchmark time for the company. The IPM project manager established initial contact with the CMO’s project manager and, after agreement on how best to manage the relationship, the IPM project manager planned and conducted the kick-off meeting that formally initiated the working relationship between the two organizations. Following the kick-off, the project manager led the collaboration by coordinating the development and management of a common timeline and conducted weekly conference calls to review accomplishments, highlight issues, and monitor upcoming tasks.

In parallel with developing and manufacturing clinical trial material, the IPM project manager organized and facilitated the initial meeting to compile information for the IND filing. Since several team members possessed little experience with filing an IND, the project manager assigned an “expert” from each functional area to provide guidance on required information expected from each group. Specific sections, with required completion dates, were assigned to team members based on individual expertise. During the facilitated discussions, it became clear that existing data and reports lacked organization and, in several instances, reports did not exist on completed studies. The project manager conducted a separate facilitated session to identify reports that needed to be written and worked directly with the QA representative to establish a comprehensive file management plan so team members could easily access and store files, reports, and laboratory notes as the IND was being compiled.

After filing the IND, the project manager facilitated a Lessons Learned session involving all team members to identify areas that were managed well and areas for improvement. With input from the Clinical, Non-Clinical, CMC, and Regulatory sub-teams, a formal methodology for filing an IND application was created which is now considered a best practice within the company.

PROJECT RESULTS

The project resulted in on-time filing of the IND and successful manufacture and release of Phase I supplies two weeks ahead of the aggressive, best-case schedule. Through IPM’s leadership and project management expertise, the following value was delivered:

  • An overarching strategy that moved an identified development candidate to FIM in minimum time.
  • A robust integrated project plan that detailed the execution strategy, correct sequencing of activities, interdependencies between functional activities, and completion of an accurate risk assessment.
  • A proactive and aggressive project management mindset instilled within the organization.
  • A proven methodology for management of CMO’s relationships.
  • A “best practice” process for the organizing and filing of IND documents.


Through daily collaboration with the project team and by proactively applying good project management fundamentals, the first patient was dosed two weeks in advance of what was originally thought to be the best case timeline. IPM continues to work with the team to manage ongoing Phase II activities.