In our previous post, we outlined the dangers of Cytokine Release Syndrome (CRS) and the importance of preclinical Cytokine Release Assays (CRAs) when developing monoclonal antibodies (mAbs) that interact with the patient’s immune system. In this second post, we describe the different kinds of assays in use and how these may fit into your drug development program. An alternative type of CRA, peripheral blood mononuclear cell (PBMC) blood outgrowth endothelial cell (BOEC) co-culture, will be discussed in more detail in our next blog post.Continue reading
What is a cytokine storm?
Cytokine Release Syndrome (CRS), otherwise known as cytokine storm, is a systemic inflammatory response caused by complications due to disease, infection or an adverse effect of biologic therapy. The clinical symptoms of a cytokine storm are massive release of a potent cocktail of pro-inflammatory cytokines into the general circulatory system, leading to severe multi-organ damage, failure or potentially death. This is an extremely unwanted immunotoxicological side effect in drug development.Continue reading
Although a range of regulatory definitions exist, a biosimilar drug is generally defined as a biological compound that is highly similar to the reference drug, with no clinically meaningful differences in safety, purity and potency.1,2 In addition, biosimilars can be characterized as reducing healthcare costs while maintaining clinical efficacy and safety outcomes similar to the originator biologic.1Continue reading
Covance Shanghai is pleased to announce an expansion of its general toxicology capabilities to include safety pharmacology studies, allowing our Asia-Pacific clients to more easily complete their IND requirements for CFDA regulations.
What are the new safety pharmacology offerings?
The general tox team in Shanghai is now capable of running cardiovascular safety studies with dogs, using DSI PhysioTel Digital L11 telemeters to monitor drug elicited effects on electrocardiograms and hemodynamic parameters, heart rate and blood pressure. They are also able to run neurological and respiratory studies in rat models.
Team members from Shanghai were trained in these experimental procedures by experienced safety pharm specialists from the Covance Madison site. After several months of personnel training, beginning in June 2018, validation studies at the Shanghai site were completed in early 2019.Continue reading
Patient recruitment represents the biggest challenge in clinical trials. From general patient identification and participation to reducing screen failure rate or limiting patient drop out after enrollment, drug developers face many massive pain points to initiate their clinical trials.
Patient recruitment and retention continue to be the biggest challenge in clinical studies. Designing protocols with patient needs in mind will lead to higher levels of better clinical research recruitment, drive up participation rates and save both time and money.Continue reading
Real-world evidence (RWE) can be used to meet different objectives, and RWE studies can be designed using different study types and methodologies, as well as multiple sources of real-world data (RWD). Teams often work separately and could benefit from a shared learning experience in the planning and execution process. A publicly-available RWE framework tool was recently released to help enhance collaborative efforts in RWE studies.
Earlier blogs in this series discussed closing the knowledge gap with RWE studies and how Covance and industry professionals worked to develop an RWE framework tool. This third and final blog further explores how the tool was applied in actual case studies to better support RWE efforts in treatments for diabetes and pain management.Continue reading
While assisting clients with their clinical development plans, and post-marketing studies, our team is witnessing a trend in designing RWE studies with both traditional and virtual elements. With growing interest in hybrid designs, Covance is exploring how we can help our clients incorporate their study objectives while evaluating a range of alternative options for evidence generation that enable faster, less resource intensive and more patient-centric, study execution.
In this second article in our series of three, learn how we collaborated with RWE professionals to create a unique RWE framework tool that can help your teams with study planning in today’s rapidly evolving environment.Continue reading
SEND [Standard for Exchange of Nonclinical Data] is more than just a tool to facilitate nonclinical data submissions to the FDA. SEND datasets are rich in information, albeit in a form that’s time-consuming for non-experts to parse. With the right visualization tools, SEND data sets can inform nonclinical programs and yield important insights.
The SEND [Standard for Exchange of Nonclinical Data] Implementation Guide v3.1, “SEND 3.1,” changes the model for the reporting of cardiovascular and respiratory endpoints.
SEND 3.1 became effective 15 March 2019 for NDA/BLA submissions; and it will become effective 15 March 2020 for IND submissions, overlapping with the effective period of the previous version, SEND 3.0. (See chart below.)
Chart 1. SEND 3.0 and 3.1 roll-outs.
Some additional regulatory considerations during this transition period include:
- The SEND version required for your submission is determined by the study start date (aka protocol finalization date).
- If you are including non-GLP studies in a regulatory submission, a SEND dataset is also required.
- If you have legacy studies in your submission, an abbreviated TS file (Trial Summary file) is required for each one.
The third edition of the ISO 14155 standard for medical device clinical investigations is expected to be published in 2019. It could be published as early as this spring and probably arrive no later than mid-year.
According to the International Organization for Standards (ISO), the updated edition will focus on a more stringent risk management approach across all stages of clinical investigations from pivotal to Post-Market Clinical Follow-up (PMCF). Continue reading