In the complex landscape of pharmaceutical and biopharmaceutical product development, the initiation stage of technology transfer (TT) is critical for ensuring successful scale-up and manufacturing. This stage involves a multidisciplinary approach, where business, technical, and regulatory considerations must be meticulously assessed to determine the feasibility and strategy for TT. Effective coordination is essential to navigate the challenges and set the foundation for subsequent stages of product transfer.
An Overview of the Initiation Stage
The Initiation stage is crucial in determining whether the transfer of Chemistry, Manufacturing, and Controls (CMC) activities for a pharmaceutical or biopharmaceutical product should proceed. This stage involves evaluating the need for Technology Transfer (TT) with limited information on product characteristics, process requirements, and analytical testing, especially if the product is still under development. The primary driver of this stage is the Business function of the Marketing Authorization Holder (MAH), supported by technical experts conducting high-level risk assessments. Here, we look at the key roles and associated activities across the functional groups.
Key Roles and Activities
Developing the Business Case
In the Initiation stage, the Business function at the Marketing Authorization Holder (MAH) takes the lead role. It develops the business case for initiating TT activities, facilitating the acquisition of key information from the Sending Unit (SU), such as the Quality Target Product Profile (QTPP) and/or specifications. This information helps identify product characteristics and high-level process requirements. Through a high-level risk assessment, the Business function develops the product strategy to guide the TT decision. Legal counsel is engaged for intellectual property reviews to ensure operational freedom if needed.
The Receiving Unite (RU) site selection process begins at this point. If the product will be sourced externally, the Business function secures nondisclosure agreements or confidentiality agreements with potential RUs. The criteria for site selection include capability, facility age, location, capacity, resourcing, costs, tax implications, compliance history, and other logistical considerations. Once an RU site is selected, the initial TT charter is approved, and a steering committee is formed. This stage gate results in a decision to proceed with the TT, the selection of the RU (often with a signed contract), and approval of the initial charter.
Providing Leadership and Accountability
The Project Manager (PM) plays a critical role during the Initiation stage, providing overall leadership and accountability for the project. The PM needs to be knowledgeable across all relevant functional areas and communicate effectively across organizational levels. This role also requires soft skills such as facilitation, negotiation, decision-making, and motivation to lead a cross-functional team effectively.
The PM coordinates an initial high-level risk assessment using cross-functional expertise and drives site selection by ensuring the proper due diligence of the RUs under consideration. One key deliverable for the PM is the establishment of a charter with the steering committee, documenting the boundaries, major risks, and assumptions for determining whether the TT will proceed. Additionally, the PM creates an initial, high-level project plan estimating timing, resource needs, and budget.
Assessing Process Fit and Scale-Up Requirements
The Process function determines the subject matter expertise required for the product under evaluation. This involves developing a preliminary process flow and working with the SU to develop or obtain the QTPP and/or specifications. Using assumptions provided by the Business function, Process develops batch size options and assesses scale-up or scale-down requirements. Process also works with Engineering, Manufacturing, and Analytical functions to assess the process fit and evaluate the facilities, equipment, and operations group of the potential RU site.
Evaluating Testing Requirements and Laboratory Capabilities
The Analytical function uses the SU’s QTPP and/or specifications to determine product testing requirements and evaluate potential testing needs for raw materials, single-use components, and packaging. Analytical assesses the potential RU’s laboratory capabilities and capacity, providing a high-level estimate of what would be required for the TT. This includes evaluating instrumentation needs, glassware, reference standards, personnel, and external laboratory services. The Analytical function documents laboratory and method evaluations as part of due diligence.
Conducting Facility Fit Assessments
The Engineering function evaluates site manufacturing capabilities through a facility fit assessment, covering site utilities, infrastructure, processing equipment, and automation capabilities. Working closely with Process, Analytical, and Manufacturing functions, Engineering performs this assessment to form an initial rough estimate of the required capital.
Assessing Capability and Resource Flexibility
The Manufacturing function assesses the potential RU’s ability to implement the process, focusing on resource flexibility, operational training programs, previous and current manufacturing activities, organizational structure, current operating shifts, and process data management systems. Environmental, health, and safety (EHS) issues at the potential RU are also evaluated, along with the necessary environmental and occupational permits or certifications.
Developing the Regulatory Strategy
The MAH Regulatory function’s involvement is critical from the beginning of a TT project. A regulatory strategy is developed to align with the product strategy, addressing filing categories, regulatory assumptions, data requirements, potential health authority meetings, submission timing, and applicable regulations. This strategy is a living document that evolves throughout the project and is reviewed and updated at each stage based on new information.
Conducting Quality Assessments
The Quality function at the MAH performs due diligence on potential RUs, including compliance history and the maturity of the RU’s quality system. Quality assesses the RU’s adherence to GMPs and provides a compliance risk evaluation. This involves requesting the RU to complete a questionnaire and searching for compliance history records.
Developing Capacity Planning Models
The Sourcing/Supply Chain function develops initial capacity-planning models using estimated yield and cycle times to evaluate potential RUs for batch size, manufacturing cycle time, and on-site storage needs. The capacity model incorporates product volumes for development, validation activities, and commercial scale. The Sourcing/Supply Chain function also prepares a preliminary supply chain strategy, assessing the impact of each potential RU on the product value chain and identifying any long-lead items and specially regulated materials.
In summary, the Initiation stage of pharmaceutical technology transfer is a comprehensive phase involving multiple functions working collaboratively to determine the feasibility of the TT. Each function plays a vital role in evaluating risks, assessing capabilities, and developing strategies to ensure a smooth and successful transfer process.
The Road to Successful Technology Transfer
In summary, the Initiation stage of pharmaceutical technology transfer is a comprehensive phase involving multiple functions working collaboratively to determine the feasibility of the TT. Each function plays a vital role in evaluating risks, assessing capabilities, and developing strategies to ensure a smooth and successful transfer process.
Follow CAI’s Tech Transfer blog series as we step through each of the stages of an effective technology transfer shown below.
