In order to ensure smooth operation during bioanalytical studies, structured business processes that facilitate rapid performance and internal and external communication are essential. A novel model, where a principal investigator (PI) with direct control over the entire study is the core of the bioanalytical project, has been developed.
This model positions the PI as the main point of contact for the client and extends the traditional project management (PM) role, as the PI has direct control over all aspects of the study including, scientific, technical, and regulatory decision-making. Expanded authority allows the PI to act not only as a client liaison and coordinator but also to respond quickly to client needs and queries, regulate internal resources and deliver results on schedule. This article will discuss how the harnessing of the PI model in a contract research organization (CRO) can improve bioanalytical study management and facilitate meeting stringent quality standards and project timelines.
The PI model consists of a team of laboratory analysts and information management specialists. The PI serves as the leader of the team, acts as a mentor to team members, and has direct control over the project. The central members of the team work together to establish a reliable and effective working relationship.
The PI is a senior scientist with expert knowledge in the development and assessment of analytical chemistry or biology methods. These skills are usually developed over at least five to seven years, during which the prospective PI takes on an expanding role in first performing and later managing laboratory work. As the team’s senior scientist, the PI is able to both perform and supervise significant scientific and technical operations.
The lead laboratory analyst carrying out the method development works under the supervision of the PI to execute an efficient method. Once pre-validation testing is complete, the analyst will continue to perform the validation. In some cases, additional analysts join the team as part of the method validation or perform individual qualifications following method validation.
In many CRO laboratories, once validation is complete, the method will be transferred to a new set of analysts or technicians to perform sample analysis. Direct experience with the method is lost in this transfer. The PI system avoids this setback as the same PI and analyst(s) work continually from method development to validation and through to sample analysis. The PI continues to supervise and analyze all data while the same analysts perform sample extraction, instrument operation, and initial data processing.
Staff continuity means laboratory technique is consistent throughout method operation and avoids “method creep,” where a written method is handed from analyst to analyst resulting in minor changes in unwritten techniques. The PI team with experience from the validation recognizes acceptable method performance and has the expertise to troubleshoot the method if problems occur. For example, asymmetry in chromatographic peak shape from dosed subject samples can be indicative of problems with method performance. These problems will not appear in the calibration standard or quality control sample statistics and can easily be missed by technicians lacking substantial method experience.
The report coordinator (RC) works closely with the PI and analysts to complete and organize all of the documentation of the study. The RC is responsible for all information for the study, from the receipt of the first samples through to completion of the final report. The RC is also responsible for resolving sample identification discrepancies..
Managing change effectively
Throughout the working relationship, the total workload may rise and fall significantly. In order to meet both the client and CRO operational objectives the PI teams must be flexible.
The team usually consists of a core group of analysts that remain together for extended periods of time. When the workload increases, for example, to accommodate large-scale clinical studies, additional analysts will join the team. The core group with the critical method and compound experience remain engaged and the team’s capacity is simply increased. The same applies if data management capacity needs to be increased, additional report coordinators will then join the core RC team.
Case study: Fast turnaround GLP bioanalysis
A recent case study demonstrates the effective operation of a PI team. A client scheduled multiple clinical programs to have simultaneous studies, all of which required rapid data delivery turnaround (results issued within three to five days of sample receipt, depending on the study). The swift scale-up required by the PI team is reflected in Figure 1, in which the weekly sample receipt volume is represented. The weekly sample flow varied between 300 to 3500 samples, many of which required analysis by multiple analytical methods. Timelines were met due to the flexibility of the PI team and the ability to appropriately adjust its capacity.
The PI system creates a simple approach to bioanalytical study management for the client. By combining the CRO roles of communication, scientific and regulatory decision-making, and resource management and scheduling, the PI can respond rapidly to changing client needs and deliver efficient and effective service to the client. A single point of contact for the client can facilitate initial communication, when the CRO-client work practices and first analytical methods are established. As the relationship grows and the PI begins to manage additional programs for the client, the frequency of timeline change will increase.
Filed Under: Drug Discovery