Identifying Regulatory Concerns: A Case of Highly Variable Drugs
Introduction
Bioequivalence studies involving highly variable molecules, such as mesalamine, ranolazine, albendazole, and mebendazole, present significant challenges. There are multiple factors to take in consideration while conduct of the study which may contribute high Subject-to-subject variability and finally failures in achieving study objectives. Zenovel, with extensive experience in handling highly variable drugs, offers valuable insights to minimise the variation and achieve optimum compliance during clinical study conduct.
With a deep understanding of drug Pharmacokinetics, Technical, Administrative & Operational Challenges, Zenovel adds significant value to the conduct of highly variable drug studies. Our focused approach, with skilled monitors and auditors, addresses the areas where data alteration and manipulation are possible.
This case study explores how Zenovel’s investigated a successful bioequivalence study of highly variable drug Ranolazine.
Background
In this case study, we delve into a situation where a sponsor conducted a BE study involving a highly variable molecule, (i.e., Ranolazine). After facing repeated failures in previous studies, the sponsor made many modifications in the formulation and decided to repeat the entire study to demonstrate Bioequivalence and got surprisingly favorable results. The sponsor became suspicious when they received seemingly unbelievable bioanalytical data for the molecule which were too good to believe.
To investigate the case comprehensively, the sponsor approached Zenovel. The Expert Auditors of Zenovel played a crucial role in identifying significant concerns in the study data that had been overlooked by QMS of the CRO and the initial monitoring agency who monitored the study in-process. This case underscores the importance of experience and thoroughness exhibited by Zenovel in conducting critical studies and averting potential regulatory issues.
Discovery of Abnormal Trends
During the retrospective audit of bioanalytical data, Zenovel’s auditors paid close attention to subject profiles. They noticed that some of the subjects out of 60, exhibited very near or superimposable plasma drug profiles for both the test and reference treatments. This finding is considered unusual for highly variable drugs, where individual variability is expected to be higher.
Further Investigation
Recognizing the significance of these abnormal trends, Zenovel’s auditor delved deeper into the data. They discovered that not only were some subjects’ profiles similar, but they also closely resembled profiles of other subjects in the study. This raised serious concerns about the authenticity of the data.
Lack of Justification from CRO
Upon identifying these concerning trends, Zenovel promptly communicated their findings to the CRO responsible for conducting the study. However, the CRO was unable to provide a satisfactory explanation for the observed anomalies. The inability to justify the abnormal trends raised doubts about the credibility of the study results.
Sponsor’s Decision and Regulatory Concerns
As a consequence of the identified concerns, the sponsor chose to drop the regulatory submission, despite the study results showing bioequivalence (i.e., a “Pass”). The sponsor’s decision resulted in significant loss of resources, including time, energy, and money. Regulatory agencies are highly concerned about cases like these, where abnormal trends are observed without any reasonable explanations. Such concerns have prompted regulatory bodies to issue warning letters to CROs.
The Role of Zenovel in Strengthening Ethical Conduct
Zenovel’s expertise in handling highly variable drug studies and their rigorous monitoring and auditing practices enable them to detect and prevent such practices. Our monitors and auditors are highly experienced and trained to identify and address potential issues, especially in the areas where data alteration and manipulation are more likely to occur. By ensuring transparent and trustworthy conduct during the study, Zenovel contributes to maintaining the highest standards of research ethics in the CRO industry.
Conclusion
This case study underscores the importance of choosing the right CRO with rich experience in handling highly variable drugs for critical studies.
Regulatory Agencies have not only given red flags but have also taken steps against certain CROs involve in such practices in recent times.
Choosing Zenovel for monitoring your clinical studies can safeguard against losses of time, energy, and money due to improper oversight and deliver reliable and compliant study results.
Zenovel also provides services like:
- Risk-Based Monitoring
- Root Cause Investigations
- Pre-Submission Audit
- Pre-Inspection Readiness Audit
These services not only help our clients in meeting their expectation but also ensures compliance with regulatory standards, ensuring data integrity to avoid potential regulatory concerns and significant losses for the sponsor.
