There are thousands of Contract Research Organizations (CROs) globally and that number is expected to increase by approximately 12% in 2022 and reach $71.7 billion by 20241. As the number of CROs continues to expand, it becomes increasingly important to identify a CRO best suited to meet your company needs.
The Sponsor must ensure proper alignment with the CRO’s level of expertise, and although most CROs have extensive experience across numerous disease processes, it is important to keep this consideration in mind.
With that said, there are many advantages to working with a reputable CRO.
With the high and growing volume of unmet medical needs in today’s pharmaceutical landscape, Sponsors are tasked not only with the complexity of navigating the hurdles of FDA applications and correspondence, but also striving towards successful and expeditious clinical trial execution. As a result, the engagement of a CRO has become even more vital to the research process than before. Not only does a CRO streamline the clinical process, but also encourages greater adherence to strategic timelines, thus reducing costly delays that often plague innovative drugs from reaching the market.
In addition to supporting trial execution, CROs can support complex pre-clinical needs such as toxicology programs followed by IND applications.
Toxicology Programs and IND Applications
Before focusing on the IND application, a toxicology program should be well underway. To execute these essential tasks, the program should include the following (but not limited to):
- Test article availability and manufacturing strategy
- Formulation development
- Sound laboratory methods
- Biomarker identification
- Animal species selection and studies
- Therapeutic indications of interest
- Patient populations of interest
The success of your IND program relies as much upon the planning as the execution. By utilizing the expertise of scientists who understand the compound and program management professionals who hold extensive experience in drug discovery and development, the Sponsor is set up for the greatest possibility of success and FDA buy-in2.
As data from the toxicology program becomes available, the Sponsor’s overall drug development strategy will continue to move forward through the IND process.
Although labor-intensive, an IND application is required to perform clinical trials. Working with a CRO who has a thorough understanding of this process can prepare for unanticipated issues to ensure timelines remain intact. The IND application includes the following key modules:
- Investigator Brochure (IB)
- Chemical, Manufacturing, and Control (CMC)
- Pharmacology and Toxicology
- Clinical Trial Protocol
The Sponsor typically maintains the Investigator Brochure as this includes data from initial discovery, nonclinical and clinical development. As new data becomes available, the IB is updated to ensure the most up-to-date information is readily available should the FDA require additional information, new indications are identified, and/or new safety information is provided.
The CMC module focuses on ensuring proper identification, quality, purity, stability, and strength of the drug and to provide a thorough explanation as to the manufacturing process of the compound.
The Pharmacology and Toxicology module focuses on nonclinical data and additional summaries that include pharmacology, safety pharmacology, bioanalytical method development and validation, and toxicology.
The clinical trial protocol clearly articulates all planned study-related activity for the investigational drug and its intended population. This document includes all relevant safety information and details supporting the primary, secondary, and exploratory objectives as applicable.
Study Operations and Execution – Managing a Phase I/II Study
Due to the complexity of Phase I/II clinical trials, Sponsors prefer to outsource daily study operations and oversight to the CRO. Because the CRO is facilitating communication at the site level, the Sponsor can remain fully engaged in projects and initiatives in support of its long-term goals and overall vision.
As a result, the CRO will oversee the following actives:
- Protocol Design and Review (as noted above)
- Clinical Trial Monitoring/Management
- Regulatory Submissions/Approvals
- Data Management and Analysis
- Electronic case report form (eCRF) Creation and Source Documentation Development
- Compliance
- Budget/Timeline Management
Clinical trial monitoring and management includes site visits to ensure adherence to the protocol and data collection procedures, accurate record keeping, and proper reporting standards. This ensures that all standardized operation procedures are being followed as previously agreed upon between the Sponsor, CRO, and site.
Regulatory submissions and approvals are also managed by the CRO. This eases the regulatory burden as amendments and/or protocol changes or informed consent form changes are necessary. The CRO is able to submit initial applications, continuing renewals, and/or study amendments to the central IRB.
Data management and analysis includes not only database development, but also all tasks required up until database lock. The data captured supports all study objectives outlined in the protocol, allows the medical monitor, sponsor and CRO to evaluate subject safety and medication dosing levels over the course of the study.
An eCRF increases the availability of data and ability to transfer it more efficiently than the traditional paper form. The eCRF also allows security and quality checks to take place, and streamlines reporting for regulatory purposes.
Because CROs have already established SOPs, Sponsors find it beneficial to rely on their procedures in addition to their own (as applicable) to ensure FDA guidelines are upheld, all training (investigator and study personnel) are up to date, and only qualified individuals are executing study related tasks.
In addition to managing these tasks, CROs manage budgets as outlined by the Sponsor and adherence to timelines. In any drug development program, the timeline for study execution relies heavily on clinical trial execution and completion of the tasks mentioned above.
A successful collaboration and partnership between the Sponsor and CRO enables trials to move forward with fewer barriers, thus saving the Sponsor time and money. As each study serves as a building block supporting the drug development program, maximum value must be obtained to stay true to the overall drug development strategy and vision.
About the author
Jenna Brager, PhD, RN, MS, is the director of regulatory affairs at MyMD Pharmaceuticals®. Prior to joining MyMD, Dr. Brager served as the Director of Clinical Research for LifeBridge Health and was a clinical investigator at Johns Hopkins Hospital. Dr. Brager received her B.S. in Nursing from the University of North Florida, graduating cum laude and received her Ph.D. from the Johns Hopkins University School of Nursing.
Dr. Brager welcomes comments, questions, and requests for future blog topics. Please email jbrager@mymd.com.
References
1.https://www.forbes.com/sites/forbestechcouncil/2021/04/09/contract-research-organizations-key-partners-in-the-drug-development-journey/?sh=4d9372f77a58
2.https://www.criver.com/resources/investigational-new-drug-development-programs-eguide