Non-Compartmental Analysis of Pharmacokinetic Data: Considerations to Gain Efficiencies and Meet SEND Requirements

Pharmacokinetic (PK) data gathered in the early phases of drug discovery program can provide insights on a compound’s mechanism of action, identify specific attributes of interest and guide decision points to optimize downstream development. Selecting the most appropriate analysis technique is essential to computing PK parameters.

This article discusses how non-compartmental analysis (NCA) of pharmacokinetic data can help support regulatory filings, create predictive simulations and help researchers select lead molecules or formulations. We also explore the topic of data handling as differing approaches and anomalous results can cause delays through investigations and inconsistencies across a program. Finally, we’ll cover unique considerations when working with biologics and the challenges involved with submitting regulatory filings formatted to the Standard for Exchange of Nonclinical Data (SEND) specifications. Continue reading

The Promise of Vaccines for Fighting C. difficile

Over the last decade, Clostridium difficile (C. difficile) infection has rapidly become more prevalent. C. difficile, often abbreviated as C. diff, usually spreads through hospitals and other healthcare facilities, and the elderly are particularly vulnerable. Our society’s overuse of antibiotics has been eliminating normal microbes, allowing C. difficile to take over. Infected patients then release bacterial spores and spread the pathogen to others.

Vaccines are a promising strategy to address this critical public health issue. They are a well-established form of medicine that could be utilized to prevent illness rather than treating an existing infection. While fecal transplants also are being explored, these treatments are very new, and clinicians do not yet know the long-term effects of such procedures. Continue reading

Exploring New Opportunities for Biomarkers in Immuno-Oncology

Pharmaceutical companies are increasingly relying on biomarkers to deliver precisionOpportunities for Biomarkers in Immuno-Oncology medicine in immuno-oncology. Biomarkers can accelerate drug development and reduce the overall cost; they also allow sponsors to identify failed treatments sooner so that resources are not wasted on expensive, late-stage trials with unsafe or inactive compounds. Finally, these tests lead to better outcomes for patients, which help companies make a stronger case for reimbursement.

However, biomarker discovery requires substantial time and resources. While expenses will likely be outweighed by increased development efficiency, companies must ensure that drug and diagnostic timelines are closely aligned so that the treatment and test can launch simultaneously. Technical, workflow and commercial factors are critical to the successful use of immuno-oncology biomarkers. Continue reading

Dr. Barbara Gillespie to participate in a scientific workshop collaboration with the National Kidney Foundation, EMA and FDA

Kidney disease is often called a “silent killer” as it often develops unrecognized and DrGillespie_Headshot
gradually progresses into chronic kidney disease. Earlier detection to identify kidney disease and slow its progression has relied on measuring changes in two key biomarkers – glomerular filtration rate (GFR) and albuminuria.

Dr. Barbara Gillespie, vice president and therapeutic head of nephrology at Covance, was recently asked to attend an invite-only workshop on March 15-16, 2018 sponsored by the National Kidney Foundation (NFK), U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA).

As the only representative from a CRO invited to this unique meeting, Dr. Gillespie will offer valuable insights from the perspective of clinical research. She also serves on the NFK regional medical advisory board and is the only CRO member of the NFK scientific advisory board for chronic kidney disease (CKD) registry.

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Moving the Needle for Rare Diseases

Each year, we designate the last day in February as Rare Disease Day to raise awareness about the potential impact we can make for this important segment of the world’s population. From policy makers to researchers to health authorities, we all play a part in making a difference for more than an estimated 300 million people in the world suffering from a rare disease.

To mark the event, I would like to reflect on my role to move the needle and make a difference to patients that are awaiting life-changing treatment. My journey started as a clinician where I had the privilege in caring for patients with a variety of rare diseases. At a personal level, I am also the aunt of a very special boy who suffered for 8 years with a rare cardiopulmonary disease. To me, rare diseases are not so rare.  Continue reading

Establishing Control Over the Manufacturing Process and the Quality of your Biologic

101679_Large-Molecule_1575263331When a patient reads the label on their medicine bottle, he or she naturally relies on the medicine to contain the correct drug, be safe, work as intended and list the correct dosage. The pharmaceutical companies that produce these medicines similarly must rely on their internal manufacturing processes and quality control testing to generate the medicine responsible for this patient trust.

For the development of biologic medicines, the process of generating a quality product is less straightforward than that of a small-molecule medicine, like pain relievers such as aspirin. Selecting the right partner, such as Covance and its ‘Central GMP Testing Laboratory’ model, can smooth the path to validation and consistent manufacturing quality for your biologic.    Continue reading

Achieving Compliance with E6: Exploring the Workflow Challenges

Most sponsors are well aware of the recent revision (R2) of ICH GCP E6, which outlines recommendations to unify standards across the EU, Japan and the U.S. with defined requirements for sponsors regarding the role of monitoring and risk management, there are many factors to consider for a successful implementation.

This article discusses a variety of challenges sponsors may face when preparing to address these recommendations and also examines opportunities to drive greater efficiencies in today’s complex trial ecosystem.

Addressing varying levels of adoption

According to the latest revision, sponsors are tasked with a requirement to employ an adaptable quality management system and are expected to maintain oversight of CROs. But with various tracking systems, vendor logs, CTMS and monitoring platforms, seeing the complete picture can be an overwhelming, error-prone effort. Continue reading

Target-Mediated Drug Disposition

“Affinity” is defined as, “a spontaneous or natural liking or sympathy for someone or or datasomething.” This concept applies also to the biologics (large molecules) we help to develop. Drugs like monoclonal antibodies (mAb) or bispecific antibodies are ideal drug candidates since they have very high affinity to bind to their target substance or site. Given the variability of the targets, safety profiles, and therapeutic windows, it is important to understand the characteristics of the affinity of the target and how to translate phenomena such as target mediated drug disposition (TMDD). Continue reading

Challenges in the Diagnosis of NAFLD, NASH and Comorbidities in the Pediatric Population

Nonalcoholic fatty liver disease (NAFLD) is the accumulation of fat or lipids in the liver in NASH NAFLD Blogthe absence of significant alcohol uptake or viral infection. Within NAFLD there is a spectrum of disease ranging from excess storage of fat in the liver (NAFL) to fat plus inflammation (called nonalcoholic steatohepatitis or NASH), to liver fibrosis and cirrhosis, or end stage liver disease with loss of liver function. NASH is the most common cause of liver disease in developed countries, largely due to the increased prevalence of obesity and type 2 diabetes. A percentage of patients with NASH and liver fibrosis will progress to liver failure or hepatocellular carcinoma or liver cancer. In fact, NASH is expected to be the number one cause for liver transplantation in a few years, making it critical to identify high-risk patients early. Continue reading

5 Tips for Proactively Managing Risks in Your Clinical Studies

Facing ever-increasing costs of running a clinical trial, sponsors must ensure they are properly directing their budget and resolving the areas of highest risk while maintaining patient safety and data integrity.

How can sponsors implement a robust process to allow earlier identification of emerging risks during the course of a trial? This article covers five tips for defining risk levels, categorizing risk and maintaining oversight to ensure that risks and responses are appropriately identified, documented, tracked and managed throughout the life cycle of a study. Continue reading