For the last decade or so, the outsourcing of crucial research functions by pharmaceutical and biotechnology companies has become increasingly common and has resulted in the rapid growth of the Contract Research Organization (CRO) industry. But the selection of the best CRO partner to work on your critical research programs is not an easy determination and, in this blog, we dive into some of the key drivers behind this decision.
But let us start with a step back and review the reasons why outsourcing has become more commonplace. At their core, CROs are designed to reduce the costs for developing new drugs and maximize the value of intellectual property around these drugs by closing the time-to-market gap. As drug development has become a more precise and targeted undertaking, the tools used by pharma and biotech companies to stratify patients in clinical trials and evaluate safety and efficacy have also changed and specialty drugs often need highly specialized and tailored clinical trial approaches. As a result, highly technical, multiparameter analyses such as flow cytometry are now more commonplace in reports filed with regulatory agencies. However, these niche technical platforms can be expensive to use and challenging to optimize for clinical applications, and for many companies, outsourcing provides the easiest means to accomplish program needs. This is especially important as clinical trials now are a global initiative, and CROs with footholds across different continents can help expedite approvals in different markets. The stakes for clinical trials are very high, so working with a CRO who can fulfill all of your program requirements and who truly understands the value of the clinical samples can be a key driver behind the success of your study.
So, what features does a high-quality CRO offering flow cytometry services need to offer?
Quality Driven Workflow
One of the first considerations for quality-driven workflow is the regulatory requirement for your study. In the US, GLP and GcLP guidelines are the gold standards for clinical trial support services. At FlowMetric we hold to these standards through our robust Quality Management System and SOPs that cover all aspects of the organization, the workflow, documentation and data handling, and security. We employ driving documents including Controlled Methods and Analytic Plans to ensure the quality of the work performed, and that all study requirements are met. Our Quality Team supports internal and external audits to ensure our Quality Program is continually improved and in-line with regulatory requirements for the sponsor initiatives we support.
Highest Quality Scientific and Technical Support
Particularly for pre-clinical and translational studies, technical support and the highest quality of scientifically driven decision-making is a key differentiator between CROs. Selecting a CRO team with a proven track record and advanced technical know-how is a key consideration in order to make sure that failures and experimental limitations are identified early, and research programs course-corrected to minimize costs. For complex analyses such as flow cytometry, technical expertise is critical in the design of high complexity, multiparameter panels, and the experimental controls which are all paramount for robust and accurate sample analysis. The FlowMetric team can support even the most complex panel designs for detailed cellular characterization.
Customized Approach to Studies
For many scientists, the idea of outsourcing their flow cytometry study requirements may be difficult to come to terms with since most require a customized approach for optimal flow cytometry panel design and analysis. At FlowMetric many of the management team have been in your shoes and understand the challenges of outsourcing critical work to an external scientific team. There are several factors that FlowMetric offers that can help mitigate risk and manage expectations. Firstly, each program is customized to fit the specific needs of your study, which is determined through in-depth discussions of the scientific goals, objectives, and timelines. There is certainly an aspect of trust between the sponsor and the CRO and this requires strong communication; at FlowMetric this is mediated through a concierge approach with dedicated project managers. However, we understand that ultimately the sponsor retains responsibility for the study, and so audits are encouraged, and frequent scientific discussions along with built-in go-no-go decision points are valuable to establish and maintain trust between parties.
Strong Communication, Planning, and Execution
At the core of every successful CRO-sponsor relationship is strong communication around the planning and execution of the program. The FlowMetric team understands the importance of communication for every program we support. This communication runs through all aspects of the workflow, from the initial conversations with our Business Development Team to highlight the goals of the study and craft a Statement of Work, to the development of an experimental plan with our Lab Ops Team. Our involvement in the experimental design varies from project to project, from a complete blank slate to an assay transfer from another laboratory. All workflow and related documentation are reviewed by our Quality Team to ensure compliance and the highest level of accountability. Never is this accountability higher than with our clinical validations. Our validation specialists provide expert guidance on the design of test scripts and statistical analysis of endpoints to ensure validated parameters are clearly defined, and our sponsors receive the concise validation reports needed for their filing with the FDA. All of this is managed over weekly or biweekly update calls, and our team is happy to provide ad hoc calls during critical phases to review data and discuss amendments to the original Statement of Work as well as make go/no-go decisions. Real-time responsiveness is the cornerstone of FlowMetric’s success as a CRO and the growth of the organization over the past 11 years.
Resource and Capacity Planning
Most clinical trials scale-up overtime and it is therefore essential that the CRO you are partnering with provides the resource capacity planning to support all phases of the clinical trial, and the varying number of samples coming in. Harmonized instrumentation and the cross-training of scientists are important considerations for project continuity. FlowMetric also provides expedited data turnaround for time-sensitive clinical applications such as dosing studies.
The highest efficiency of sample processing can be achieved using frozen samples, such as frozen PBMCs, however for some clinical sample collection sites this service isn’t available, and in these instances, the FlowMetric team can work with sponsors to evaluate alternative solutions such as the selection of optimal anticoagulant for the collection fresh whole blood samples for processing to PBMCs at FlowMetric, or alternatively assess sample preservation solutions including CytoChex™ and Smart tubes™ and TransFix™ reagent. Our fit-for-purpose validation approach ensures that the limitations of sample stability are defined to ensure the quality of the clinical data acquired in the most efficient way possible through all phases of clinical research.
One major advantage of outsourcing flow cytometry to a CRO is the access to state-of-the-art instrumentation. Flow cytometers are both expensive to purchase and labor-intensive to maintain. Most CROs including FlowMetric have service contracts on all instrumentation to ensure any issues are quickly resolved and there is minimal disruption to sample acquisition. In addition, FlowMetric has a series of processes employed to ensure the performance of the instruments is monitored continuously, and all acquisition is Tech QC-reviewed in real-time. Application settings can be used across studies for consistency in instrument settings and calibration / MFI targeting processes implemented when needed. Furthermore, our flow cytometers are all harmonized to ensure the optimal performance of all validated panels across our laboratories in the US and Italy.
Stability and Growth of the CRO
For many sponsors, understanding the stability and growth of the partnering CRO is a real consideration. Over the growth of FlowMetric in the CRO space, we have managed to develop and maintain a diverse and well-rounded profile of sponsors that not only includes many of the largest pharmaceutical and biotechnology companies but also a significant number of mid and small-sized sponsors who have grown with us. This has required FlowMetric to support programs across a wide range of therapeutic areas of focus, and study types -for example translational-, toxicity-, clinical and preclinical studies in various model systems and analyzing a variety of matrices. We have accomplished this through the strategic recruitment of scientific expertise and the development of a robust in-house training program that is designed to cultivate and develop our scientists. This has enabled us to establish a world-class team of flow cytometrists to support the most challenging flow cytometry programs.
Making the Most of Your Data
Every sample counts, and by using multiparameter flow cytometry, each sample can be the source of rich data set; so how do you make the most of this data? FlowMetric has a dedicated team of analysts to ensure the quality and turnaround time for clinical data. But beyond this, we work with our clients to ensure the format of that data fulfills your needs and requirements for its utility. Whether simple or cumulative files CSV files, raw FSC files, t-SNE plots, or PTA/PCA analyses, we have a dedicated Data Transfer Manager who will work with you to transfer data on a pre-determined schedule through your secure portal or account. We offer statistical analysis of data endpoints (ANOVA or t-testing for example) and even a plug-in solution for powerful, non-intuitive data mining known as AstroLabe™, that couples cellular biology with flow cytometry profiles to tease out cell populations that are driving responses.
FlowMetric has focused on building an IT infrastructure that provides the foundation of robust data security. We understand the importance of security measures that protect data throughout processing, transfer to the client, and longer storage. FlowMetric works with a 3rd party IT security firm to incorporate top-rated tools to protect and backup your data regularly and securely. All of this is governed by a series of SOPs outlining our IT infrastructure requirements, validation-, data security-, backup processes, and penetration and recovery testing protocols.
Collaborations and Partnerships
Another positive characteristic of a CRO is the involvement of the company’s team within the scientific community through collaborations and partnerships. A track record of publications and collaborative presentations with CROs and sponsors, coupled with representation at scientific conferences demonstrates that science is a priority for the organization. FlowMetric is involved in several scientific collaborations and is a member of the NIST Flow Cytometry Consortium with a goal of advancing flow cytometry through standardization of approaches and tools for clinical applications. In addition, FlowMetric actively engages sponsors for feedback through client surveys and has received grant funding with several academic partners. All of this reflects our commitment to scientific excellence and contribution to the scientific community.
When evaluating which CRO to partner with for your study it is important to take several factors into consideration.
Does the CRO provide the technical and regulatory expertise needed to complete the work?
Are they collaborative and responsive to your pre-study questions?
Do they provide services across the geographical areas included in your study?
And although cost is always a factor in any decision, it is important to acknowledge that quality of work is the key driver for selecting a CRO partner, and that requires time, coordinated effort, and expertise.
FlowMetric has a proven track record in flow cytometry expertise across a wide array of pre-clinical and clinical fields of research, providing flow cytometry solutions for even the most complex studies. All of this is coupled with world-class data analysis/reporting, and data security to provide enhanced confidence across all aspects of your study.