Our PROJECT & PROGRAM MANAGEMENT white paper mini-series continues with:
by Kevin Whittlesey, Ph.D., DHC
Effective project and program management will have a substantial positive impact on the quality, time, and cost of cell and gene therapy product development. Although the terms ‘program management’ and ‘project management’ are often used interchangeably, there are key differences between them, and appropriate expertise is required to fulfill each role. This article will address the differences between these two vital functional areas and how they can be applied to positively impact cell and gene therapy product development.
Project vs. Program Management
What is the distinction between project management and program management? Project management is the execution and operationalization of a particular aspect of an existing project plan. This is generally within a single functional area. Examples might include the management of one or more manufacturing campaigns or the entire set of IND-enabling nonclinical studies for a cell or gene therapy product. In the arena of regulatory affairs, project management would oversee the many contributors to and components of a complex regulatory submission, such as an IND, CTA, BLA, or MAA to ensure that authoring and review cycles remain on track for a targeted submission date.
Program management, by contrast, is a highly cross-disciplinary role and lies at the center of the hub-and-spoke model, drawing on and integrating different functional areas. This is a broader role and requires a strong understanding of each individual functional area to integrate how delays or changes in one functional area will affect others and the overall development program. This role requires a strong knowledge base in some or all of manufacturing, analytical development, nonclinical testing and development, and regulatory affairs. Additionally, the program management role is often highly strategic in nature, being called upon to balance resourcing, identify risks to program execution, and establish contingency plans to address items of greatest risk to program timelines.
While important distinctions can be drawn between project and program management, they share a critical similarity in that they are both vital to the success of cell and gene therapy product development.
CMC Project Management
The manufacturing of a cell or gene therapy product is a highly complex process in significant need of effective project management. Whether the work is performed at an in-house manufacturing facility or outsourced (or a combination of the two), there are requirements for raw material procurement and testing, vendor assurance, upstream and downstream processing, and extensive analytical testing and reporting, all of which need to be coordinated and sequenced in order to minimize risks, mitigate the possibility of delays, and limit the potential for additional cost. Issues associated with manufacturing are the most common cause for clinical holds or other regulatory problems for cell and gene therapy programs, so it’s vital that these activities are competently and effectively managed to limit the risk of gaps and deficiencies. If a product is not being manufactured in-house, it is then typically outsourced to a contract development and manufacturing organization (CDMO). CDMOs often have their own internal project management assigned to each particular manufacturing campaign, but in many cases a sponsor may have complex touchpoints between their own organization and a network of CDMOs, analytical CROs, and other internal and external stakeholders. Given the complexity of managing this network of relationships, it is often important to have a single internal point of contact to manage the touchpoints, ensure timely communication, keep close track of the deliverables and milestones, and proactively address project risks and/or manage delays. Manufacturing challenges are a common cause of project delays. A specialist resource such as a CMC project manager dedicated to managing these activities and timelines can help mitigate this risk.
Nonclinical Project Management
Nonclinical project management ensures the coordination of all IND-enabling studies and narrative associated with a particular therapeutic candidate. This is usually a combination of in-house and outsourced activities that typically require extensive liaisons between the internal project team and one or more outside contract research organizations (CROs), academic facilities and other external vendors, and other consultants. It is common for at least some aspects of the in vitro research and development activities to be conducted internally whereas in vivo animal studies, particularly GLP toxicology and safety studies, are often conducted at CROs. Activities at CROs, whether they be animal studies or development and execution of a particular assay, are critical to the IND-enabling package and require significant oversight and monitoring to ensure that studies are conducted as intended and designed and reported in a timely manner. Moreover, activities at a CRO often need to be closely coordinated with manufacturing and testing activities to ensure the necessary test article is provided to support nonclinical studies in the time window agreed to, sometimes many months in advance, with the CRO. Moreover, the nonclinical activities and timelines need to be integrated with regulatory project management to ensure a seamless and efficient progression to IND and/or other regulatory filings.
Regulatory Project Management
Strong project management of regulatory activities for a cell or gene therapy program is critical to ensure both preparation of a cogent submission aligned with the defined regulatory strategy and efficient and effective interactions with regulatory authorities. An IND/CTA or BLA/MAA application, for example, is comprised of CMC, nonclinical, and clinical sections in addition to administrative and other information. The information within each section is generated by diverse stakeholders, including a large number of study reports generated both internally and by CDMOs, CROs, and other external service providers. There are typically a constellation of contributors and often sub-teams of contributors to each section (or module) of an IND, which can easily extend to thousands of pages in size. Following initial drafting of each section, multiple rounds of review are common, to ensure input from all relevant stakeholders, and internal consistency of disparately authored parts of the filing. Keeping track of the status and readiness of all these components is a significant undertaking. Cell and gene therapy products are all unique and each has particular considerations and product-specific regulatory guidance received through prior regulatory correspondence that must all be thoroughly addressed. Regulatory project management is a critical part of that, requiring careful coordination and tracking to ensure that nothing gets missed or overlooked which could result in a clinical hold and project timeline delay.
Highlighting the Criticality of Program Management
Above we have offered just few examples of areas in cell and gene therapy in which highly effective project management is vital to successful product development. Program management requires the ability to integrate some or all of those areas and be able to quickly identify the ways in which the projects in different functional areas influence one another, as well as the strategic ability to ‘see around corners’ to identify key program risks and deploy resources proactively as appropriate to mitigate risk. At a minimum, for example, the program manager needs to be able to quickly assess the impacts of a manufacturing delay on the nonclinical development projects and the regulatory pathway plans, and rapidly deploy mitigation strategies to minimize the impact of such a delay. Ideally, the effective program manager will have proactively identified manufacturing delays as a key risk to program timelines and deployed effective mitigation strategies to minimize the probability and impact of such delays to the extent possible based on the particular program’s weighting of timeline and resource considerations. Effective program management requires not only the attention to detail required for project management, but a strong foundation in and understanding of all the key functional areas represented in the cell or gene therapy program and how they interact, as well as a strategic understanding of the business context of the program to rapidly determine which risk mitigation strategies make sense to deploy in the individual context of the program and sponsor in question. Projects of varying scale, scope, and timing may together comprise a single program.
Project and program management are both critical functional roles in the development of complex and often unique cell and gene therapy products which are time consuming and expensive to develop and manufacture. It is imperative to ensure that there are skilled and dedicated staff to monitor and ensure the successful execution of both project and program plans. While some companies may choose to bring any or all of these roles in-house, Dark Horse Consulting can provide these critical functions either on an interim basis while staffing up, or on a long-term basis, integrated as part of the crossfunctional product development teams.
by Phil Bowles, MSc., DHC Principal
"Successful delivery of a new Cell and Gene Therapy (CGT) facility relies on effective project management throughout its lifecycle to meet quality, financial and schedule goals. CGT capital projects require significant investment of money, time and human capital to construct or modify a clinical or commercial manufacturing facility. The new or expanded manufacturing capacity delivered by the project will inevitably be..."
by Heather Todd, M.S., DHC Senior Consultant
by Sara Masterson, MBA, DHC Principal
by Michael Kinzie, DHC Principal