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B Managing immunogenicity in clinical practice and during drug development was a recent topic at the ASCPT 2019 annual meeting. The intent is to provide a rationale for ongoing research into the current gaps in assessing and interpreting immunogenicity in drug development and managing clinical immunogenicity for an approved drug. A Quantitative Systems Pharmacology (QSP) approach can open an avenue toward prediction of ADA impact on PK in patient populations; thus, enabling model-informed management of immunogenicity. [Extracted from the article]

The article offers information on the panel discussion on "Regulatory and ethical issues in clinical research in children" held in collaboration with Indian Academy of Pediatrics and the Federation of Obstetrics and Gynecological Societies of India in April 2017 in Mumbai, India. Topics discussed include clinical pharmacology for maternal and child health; new drug development and clinical trials in children; and pediatric clinical research and drug development by pharmaceutical industry.

Monoclonal antibodies (MAbs) have become a substantial part of many pharmaceutical company portfolios. However, the development process of MAbs for clinical use is quite different than for small-molecule drugs. MAb development programs require careful interdisciplinary evaluations to ensure the pharmacology of both the MAb and the target antigen are well-understood. Selection of appropriate preclinical species must be carefully considered and the potential development of anti-drug antibodies (ADA) during these early studies can limit the value and complicate the performance and possible duration of preclinical studies. In human studies, many of the typical pharmacology studies such as renal or hepatic impairment evaluations may not be needed but the pharmacokinetics and pharmacodynamics of these agents is complex, often necessitating more comprehensive evaluation of clinical data and more complex bioanalytical assays than might be used for small molecules. This paper outlines concerns and strategies for development of MAbs from the early in vitro assessments needed through preclinical and clinical development. This review focuses on how to develop, submit, and comply with regulatory requirements for MAb therapeutics. [ABSTRACT FROM AUTHOR]

The article focuses findings of a study on use of aminomethyl spectinomycins as therapeutics for drug-resistant respiratory tract and sexually transmitted bacterial infections. It states that the compounds had ribosomal inhibition values comparable to spectinomycin but showed increased potency against the common respiratory tract pathogens, like Streptococcus, and demonstrated no mammalian cytotoxicity. It infers that N-benzyl aminomethyl spectinomycins are suitable for drug development.

Target specificity and generally good tolerability of therapeutic proteins (TPs) present desirable treatment opportunities for pediatric patients. However, little is known on the ontogeny of processes related to the pharmacokinetics (PK) and disposition of TPs. The science, regulatory requirements and strategy of developing TPs for children are evolving. Our current review of TPs, (with focus on monoclonal antibodies and fusion proteins) that were approved for pediatric use indicates that dose-selection for pediatric pivotal studies is often based on adult PK information alone. This approach might not be sufficient if more complex PK properties than simple linear PK are present. Body weight-based dosing for pediatric patients directly scaled down from adult dosing can lead to under-exposure in young pediatric patients who are usually in the lowest body-weight range. Tiered-fixed dosing can be reasonably effective for TPs in achieving comparable exposure in children over a wide age range. The uniqueness of the pediatric population, the practical challenges in conducting clinical studies in this population, as well as regulations from health authorities warrant including pharmacometrics as an integral component of pediatric drug development. We propose a framework distinct from previous proposals, to guide clinical pharmacology strategy for pediatric drug development specifically for TPs. [ABSTRACT FROM AUTHOR]

With the increased emergence of anti-infective resistance in recent years, much focus has recently been drawn to the development of new anti-infectives and the optimization of treatment regimens and combination therapies for established antimicrobials. In this context, the field of pharmacometrics using quantitative numerical modeling and simulation techniques has in recent years emerged as an invaluable tool in the pharmaceutical industry, academia and regulatory agencies to facilitate the integration of preclinical and clinical development data and to provide a scientifically based framework for rational dosage regimen design and treatment optimization. This review highlights the usefulness of pharmacometric analyses in anti-infective drug development and applied pharmacotherapy with select examples. [ABSTRACT FROM AUTHOR]

Significant gains have been made in the appreciation of pediatrics as an important population in which rationale pharmacotherapy guidance is warranted but often currently lacking. Although the regulatory framework for major improvements in pediatric drug development was implemented in Europe a decade later than the United States, recent efforts, including the 2007 "Better Medicines for Children" initiative, indicate that the awareness of this problem is indeed a global phenomenon. Nevertheless, there still remains a gap between the awareness and the implementation of rationale and scientifically based drug development and applied pharmacotherapy in children. Specifically, a vision of how best to move from empiricism toward a plan that incorporates biologic knowledge about the maturation of physiologic processes as well as the drug- and disease-specific knowledge generated from drug development and applied pharmacotherapy in adults must evolve from the present intentions. Modeling and simulation approaches can facilitate such a vision that ultimately should provide benefit to pediatric patients. Although recent examples of pediatric in silico approaches are compelling, their ultimate value may be in the identification of data and studies that better guide drug therapy and in the education of pediatric caregivers to the principles of clinical pharmacology that underlie optimal pharmacotherapeutic decisions in children. [ABSTRACT FROM AUTHOR]

The article discusses pharmacometrics as a discipline, knowledge sharing in precompetitive research, and the development of standards at the U.S. Food and Drug Administration (FDA). The discussion focuses on three data-sharing projects based on the use of modeling and computer simulation in drug development. Training for pharmacometricians is also discussed.