The importance of individual patients has long been recognized by the medical industry. There is an old saying that helps highlight the concept of personalized medicine, which is: “physicians must understand what person the disease has, rather than what disease the person has.” However, until fairly recently a “one size fits all” approach aimed at treating the “average” patient (with subtle variations), versus treating the individual, was often the only available option for physicians. Personalized or “precision” medicine is about providing a more tailored treatment for patients, one that pre ..read more

Developing drugs for pediatrics has been historically challenging due to the vulnerable nature of this special population. When it comes to developing pediatric drugs, it is vitally important to understand the nuances inherent in the field. Gaining informed consent from families, encountering possible dissent from the children involved, and achieving acceptability from study personnel are all hurdles that drug developers may face that can contribute to the success or failure of a clinical study in children. In addition, ensuring the appropriate study designs, understanding the many ways in wh ..read more

Oligonucleotides are short strands of DNA or RNA molecules that contain a small number of nucleotides. Each nucleotide consists of a nitrogenous heterocyclic base (or nucleobase), a five-carbon pentose sugar (deoxyribose in DNA or ribose in RNA), and a phosphate group. The development of nucleotide and oligonucleotide therapeutics has been growing in importance over the past few decades. Cellular genomic blueprints are being targeted for treating diseases, as evidenced by the expanding number of FDA-approved nucleic acid medicines. These types of treatments can achieve long-lasting or even cu ..read more

Pharmacokinetics (PK) is the study of how a drug moves throughout the body and provides important information on the systemic exposure to the drug over time. Conversely, pharmacodynamics (PD) describes what a drug does to the body, meaning, the pharmacologic response that occurs when a drug has reached the site of action. In order to collect relevant PK and PD data for a drug, clinical studies must be conducted which help determine the onset, magnitude, and duration of a drug’s effect. Together, PK and PD data can be used to describe the safety and efficacy of a drug by establishing dose-expo ..read more

The “Clinical Data Interchange Standards Consortium” (CDISC) is a not-for-profit organization that develops data standards for drug development. CDISC works with global regulatory agencies to develop guidelines and requirements that influence the standards for both clinical and nonclinical study data. Standard CDISC formatting guidelines help enable a more efficient submission and review process by providing regulatory agencies with clean, consistent, and standardized data. Within CDISC, an important subset of clinical trial data is pharmacokinetic data. Pharmacokinetics (PK) is the study of ..read more

Drug development is a complex process where clinical pharmacology data must be generated to support regulatory approval and marketing authorization. Each drug program has unique challenges and special circumstances, but programs often make the same types of mistakes. These mistakes can range from simple errors to large missteps that can threaten a drug’s chance for approval. This is particularly evident regarding clinical pharmacology, pharmacokinetic (PK), and pharmacodynamic (PD) data. One of the most common mistakes in clinical pharmacology drug development is simply not taking full advant ..read more

Pharmacokinetic (PK) modeling is a tool used to help drug developers understand a drug’s effects on the body by analyzing its absorption, distribution, metabolism, and excretion (ADME) properties. These effects are typically summarized using PK parameters such as clearance and volume of distribution which are necessary for understanding the effects of a drug on the body. PK models can range in complexity from models with a single compartment to models containing hundreds of compartments. Each type of model from the simplest, one-compartment model to more complex models have their own applicat ..read more

First-in-Human (FIH) studies are designed and conducted based on nonclinical data submitted to and reviewed by regulatory authorities. For the very first trial in humans, nonclinical toxicology, pharmacology, pharmacokinetics, in vitro assays, etc. are conducted with the investigational compound and are used (among other purposes) to establish a “maximum recommended starting dose” (MRSD). There are two categories of approaches that can be used to help choose this dose: model-independent approaches and model-based approaches. Model-Independent Approaches Model-independent approaches use noncli ..read more

A 505(b)(2) application is a hybrid of a full new drug application and an abbreviated new drug application. The terms 505(b)(2), 505(b)(1), and 505(j) all refer to sections of the federal 505 code that governs the applications for new and generic drugs. Modeling and simulation is a broad field that uses mathematical models to describe and predict the actions of drugs and can be utilized across almost all types of regulatory applications. Modeling and simulation can be particularly useful for efficiently filling in some of the requirement gaps to support and optimize a 505(b)(2) application wh ..read more

Modeling and simulation utilize existing and prospectively collected data from Phase 1 and 2 clinical studies, nonclinical studies, and from the literature to provide important insights on a drug’s effectiveness and safety. This can be accomplished by examining the variability in drug concentrations and the relationship between drug concentrations and clinical outcomes (e.g., measurements of disease activity) or safety and tolerability (e.g., rates of adverse events, changes in vital signs). The insights gained from modeling and simulation can be used to select dose regimens to optimize benef ..read more