American Association Of Pharmaceutical Scientists Research Articles

Perspectives on gender parity in bioanalysis: an interview with Binodh DeSilva.

Biography Binodh DeSilva, PhD Vice President Analytical Strategy & Operations at Bristol-Myer Squibb (BMS) Company in New Brunswick, NJ, USA. She is responsible for leading the regulated analytical (small and large molecule), microbiology and industrial hygiene laboratories as well as the Chemistry, Manufacturing & Controls (CMC) regulatory document management functions in Product Development. She received her Bachelor's in Analytical Chemistry from the University of Colombo, Sri Lanka in 1987, and a PhD in Chemistry (Bioanalytical) in 1994 from the University of Kansas. She was a Post-Doctoral Research Associate in the Pharmaceutical Chemistry Department at the University of Kansas from 1994 to 1995. She was at Procter & Gamble Pharmaceuticals, Norwich, NY, USA, from 1995 to 2001 and at Amgen, Thousand Oaks, CA, USA leading the bioanalytical team from 2001 to 2010. She joined BMS in November of 2010. Dr DeSilva is the Past President of the American Association of Pharmaceutical Scientists. In addition, she is a member of the American Chemical Society, Association for Women in Science, and the Health Care Business Women's Association NY/NJ metro chapter.

First-Principles and Empirical Approaches to Predicting In Vitro Dissolution for Pharmaceutical Formulation and Process Development and for Product Release Testing

This manuscript represents the perspective of the Dissolution Working Group of the International Consortium for Innovation and Quality in Pharmaceutical Development (IQ) and of two focus groups of the American Association of Pharmaceutical Scientists (AAPS): Process Analytical Technology (PAT) and In Vitro Release and Dissolution Testing (IVRDT). The intent of this manuscript is to show recent progress in the field of in vitro predictive dissolution modeling and to provide recommended general approaches to developing in vitro predictive dissolution models for both early- and late-stage formulation/process development and batch release. Different modeling approaches should be used at different stages of drug development based on product and process understanding available at those stages. Two industry case studies of current approaches used for modeling tablet dissolution are presented. These include examples of predictive model use for product development within the space explored during formulation and process optimization, as well as of dissolution models as surrogate tests in a regulatory filing. A review of an industry example of developing a dissolution model for real-time release testing (RTRt) and of academic case studies of enabling dissolution RTRt by near-infrared spectroscopy (NIRS) is also provided. These demonstrate multiple approaches for developing data-rich empirical models in the context of science- and risk-based process development to predict in vitro dissolution. Recommendations of modeling best practices are made, focused primarily on immediate-release (IR) oral delivery products for new drug applications. A general roadmap is presented for implementation of dissolution modeling for enhanced product understanding, robust control strategy, batch release testing, and flexibility toward post-approval changes.

Flow Cytometry Method Validation Protocols.

Analytical method validation provides a means to ensure that data are credible and reproducible. This unit will provide a brief introduction to analytical method validation as applied to cellular analysis by flow cytometry. In addition, the unit will provide practical procedures for three different types of validation. The first is a limited validation protocol that is applicable for research settings and non-regulated laboratories. The second is validation protocol that presents the minimum validation requirements in regulated laboratories. The third is a transfer validation protocol to be used when methods are transferred between laboratories. The recommendations presented in this unit are consistent with the white papers published by the American Association of Pharmaceutical Scientists and the International Clinical Cytometry Society, as well as with Clinical Laboratory Standards Institute Guideline H62: Validation of Assays Performed by Flow Cytometry (currently in preparation). © 2018 by John Wiley & Sons, Inc.

Recommendations for the Development and Validation of Neutralizing Antibody Assays in Support of Biosimilar Assessment

The American Association of Pharmaceutical Scientists (AAPS) biosimilar focus group on nonclinical and clinical assays has developed this manuscript to guide the industry on best practices and testing strategies when developing neutralizing antibody (NAb) assays for biosimilar programs. The immunogenicity assessment to biosimilar and originator drug products is one of the key aspects of clinical programs for biosimilars to demonstrate biosimilarity. Establishing that there are no clinically meaningful differences in immune response between a proposed product and the originator product is a key element in the demonstration of biosimilarity. It is critical to collect, evaluate, and compare the safety and immunogenicity data from the clinical pharmacology, safety, and/or efficacy studies especially when the originator drug product is known to have potential for immune-mediated toxicity. This manuscript aims to provide a comprehensive review and recommendations on assay formats, critical reagents, approaches to method development, and validation of the neutralizing antibody assays in extrapolation within the scope of biosimilar drug development programs. Even if there are multiple options on the development and validation of NAb assays for biosimilar programs, the type of drug and its MoA will help determine the assay format and technical platform for NAb assessment (e.g., cell-based or non-cell-based assay). We recommend to always perform a one-assay approach as it is better to confirm the biosimilarity using one-assay for NAb. If a one-assay approach is not feasible, then a two-assay format may be used. This manuscript will provide all the details necessary to develop NAb assays for biosimilars.

Network on veterinary medicines initiated by the European Federation For Pharmaceutical Sciences.

The European Federation for Pharmaceutical Sciences (EUFEPS) was founded 25years ago by more than 20 national pharmaceutical societies and faculty members. As a pan-European organization, it brings together pharmaceutical societies as well as academic, industrial and regulatory scientists engaged in drug research and development, drug regulation and education of professionals working in these fields. EUFEPS represents pharmaceutical sciences in Europe and is recognized as such by both the European Commission and the European Medicines Agency. EUFEPS cooperates with the European Federation of Pharmaceutical Industries and other European organizations and maintains global connections with agencies such as the US Food and Drug Administration and the American Association of Pharmaceutical Scientists. EUFEPS has established specified networks forming the basis of its activities. The creation of a Network on Veterinary Medicines is prompted by the manifold problems resulting from the use of veterinary drugs and its inherent interconnections with human medicine, environmental and public health. A long-term goal of this initiative was to expand the spectrum of available therapeutics for use in animals, including the development of innovative delivery systems.

Food Effect on Oral Bioavailability: Old and New Questions.

Food Effect on Oral Bioavailability: Old and New Questions.

Highlights From the American Association of Pharmaceutical Scientists/ International Transporter Consortium Joint Workshop on Drug Transporters in Absorption, Distribution, Metabolism, and Excretion: From the Bench to the Bedside - Clinical Pharmacology Considerations.

The American Association of Pharmaceutical Scientists/International Transporter Consortium Joint Workshop on Drug Transporters in absorption, distribution, metabolism, and excretion was held with the objective of discussing innovative advances in transporter pharmacology. Specific topics included (i) transporters at the blood-brain barrier (BBB); (ii) emerging transport proteins; (iii) recent advances in achieving hepatoselectivity and optimizing clearance for organic anion-transporting polypeptide (OATP) substrates; (iv) utility of animal models for transporter studies; and (v) clinical correlation of transporter polymorphisms. Here, we present state-of-the-art highlights from this workshop in these key areas of focus.

Wide Spread use of LC-MS in Bioequivalence Studies

Submit Manuscript | http://medcraveonline.com FDA guidance on analytical method validation, in one form or another, has been adopted universally as a standard procedure for validating bioanalytical assays used for pharmcokinetic, bioavailability, and bioequivalence studies intended for regulatory submission [2]. Before the first bioanalytical method validation workshop, there was lack of uniformity in conducting validation of bioanalytical methods and submission of data to regulatory agencies. The bioanalytical validation workshop in 1990 was the first major workshop dedicated to investigating and harmonizing procedures in method validation. The workshop was cosponsored by the American Association of Pharmaceutical Scientists (AAPS), the US FDA, the International Pharmaceutical Federation (FIP), the Health Protection Branch (HPB), and the Association of Analytical Chemists (AOAC). The conference focused on the requirements for bioanalytical method validation procedures to establish reliability of the analytical method, parameters to ensure acceptability of analytical method performance, method development (prestudy validation), and method application (instudy validation). The workshop defined important parameters for method validation e.g. accuracy, precision, selectivity, sensitivity, reproducibility, limit of quantification as well as addressing “how to” evaluate and determine these parameters. It was also clarified that it is not essential to have 100% recovery, but it is important that the recovery be reproducible. One of the most important outcomes of the first workshop was that it defined “the acceptance criteria for a run”. The recommendations of the first workshop were well received within the scientific community. These recommendations did not become did not become official until the draft guidance on bioanalytical method validation was published in January 1999 by the US FDA with the intention of seeking public opinion prior to finalizing the guidance. The second bioanalytical method validation workshop was cosponsored by the AAPS and the US FDA in January 2000 a year after the draft guidance went into effect and ten years after the first workshop took place. The main advances occurred in the field of mass spectrometry. Two issues were addressed in relation to LC-MS;

Introduction to Editorial Board Members: Prof Nicholas A. Peppas

Introduction to Editorial Board Members: Prof Nicholas A. Peppas

2015 American Association of Pharmaceutical Scientists

2015 American Association of Pharmaceutical Scientists

AAPS and US FDA Crystal City VI workshop on bioanalytical method validation for biomarkers.

Crystal City VI Workshop on Bioanalytical Method Validation of Biomarkers, Renaissance Baltimore Harborplace Hotel, Baltimore, MD, USA, 28-29 September 2015 The Crystal City VI workshop was organized by the American Association of Pharmaceutical Scientists in association with the US FDA to continue discussion on the bioanalysis of biomarkers. An outcome of the Crystal City V workshop, convened following release of the draft FDA Guidance for Industry on Bioanalytical Methods Validation in 2013 was the need to have further discussion on biomarker methods. Biomarkers ultimately became the sole focal point for Crystal City VI, a meeting attended by approximately 200 people and composed of industry scientists and regulators from around the world. The meeting format included several panel discussions to maximize the opportunity for dialogue among participants. Following an initial session on the general topic of biomarker assays and intended use, more focused sessions were held on chromatographic (LC-MS) and ligand-binding assays. In addition to participation by the drug development community, significant representation was present from clinical testing laboratories. The experience of this latter group, collectively identified as practitioners of CLIA (Clinical Laboratory Improvement Amendments), helped shape the discussion and takeaways from the meeting. While the need to operate within the framework of the current BMV guidance was clearly acknowledged, a general understanding that biomarker methods validation cannot be adequately depicted by current PK-centric guidelines emerged as a consensus from the meeting. This report is not intended to constitute the official proceedings from Crystal City VI, which is expected to be published in early 2016.

Editorial for an official journal of the American association of pharmaceutical scientists

I am delighted and honored to have been selected as the first Editor-in-Chief of AAPS Open, an open-access journal devoted to the rapid publication of quality articles in the pharmaceutical sciences. The journal will be a global forum for the barrier-free publication of reports of original research, as well as other significant work that demonstrates applications of scientific concepts and techniques across the entire breadth of the field. Thus AAPS Open will provide an important outlet for members of AAPS sections and focus groups to publish papers of interest to their communities, as well as for scientists throughout the field. All AAPS Open articles will be fully peer reviewed by scientists with extensive knowledge in the subject matter. The editorial team, consisting of the associate editors and myself, has been aligned with the sections of AAPS to ensure that all aspects of the pharmaceutical sciences are covered, including but not limited to pharmaceutical and biomedical analysis, quality control, quality assurance, pharmaceutical biotechnology, biopharmaceutics, clinical pharmacology, translational research, drug discovery and its interface with drug development, formulation design, manufacturing science and engineering, physical pharmacy, pharmacokinetics, pharmacodynamics, drug metabolism, and regulatory affairs. I want to thank the following eight well-known pharmaceutical scientists for agreeing to join the AAPS Open editorial team as associate editors: Nagesh Bandi (Pfizer), Varsha Bhatt-Mehta (University of Michigan), Panos Constantinides (BioPharmaceutical & Drug Delivery Consulting), Nikoletta Fotaki (University of Bath), Jayne Hastedt (JPD Pharma), Tim Hickling (Pfizer), Jaime Marach (CUSTOpharm) and Jean Lee (BioQualQuan). We are in the process of assembling a noteworthy editorial board comprised of internationally recognized pharmaceutical scientists who will help guide the journal.

A dynamic career in MS: applications to biomedical research.

Ian A Blair speaks to Francesca Lake, Managing Editor: Blair received his PhD in Organic Chemistry in 1971 from Imperial College of Science and Technology, London, under the mentorship of the 1969 Nobel Laureate, Sir Derek HR Barton. He was appointed as the AN Richards Professor of Pharmacology at University of Pennsylvania in 1997 and Director of a new Center for Cancer Pharmacology. In 2002, Blair was appointed as Vice-Chair of the Department of Systems Pharmacology and Translational Therapeutics. In 2014, he became Director of the NIEHS-funded Penn Superfund Research and Training Program Center. Blair is an expert in the use of mass spectrometric methods for the structural elucidation and quantification of endogenous biomolecules. His current research is involved with the development of biomarkers in order to establish genetic/phenotype correlations and to assess the interaction between genes and exposure to environmental chemicals. He is particularly interested in the regulation of cellular oxidative stress and how this underpins mechanisms involved in carcinogenesis, cardiovascular disease and neurodegeneration. Blair discovered electron capture atmospheric pressure chemical ionization, a technique that makes it possible to conduct high sensitivity quantitative analyses of chiral biomolecules. He is a Fellow of the American Association for the Advancement of Science and the American Association of Pharmaceutical Scientists. He received the 2011 Eastern Analytical Award for Outstanding Achievements in Mass Spectrometry. Blair is Senior Editor of Future Science OA, and a member of the Editorial Board of several journals.

Workshop Report: In Quest of More Affordable and More Accessible Medicines

The 3rd Biennial International Bioequivalence, Biowaivers, and Dissolution Testing Conference took place on December 2–3, 2013 and was cosponsored by the American Association of Pharmaceutical Scientists (AAPS), the Canadian Society of Pharmaceutical Sciences (CSPS), and Rhodes University. The conference was a follow-up of two previous workshops and conferences held at Rhodes University in 2009 and 2011. Members of the organizing committee were Professor Isadore Kanfer–Chair, Professor Rod Walker, Dr. Mike Skinner, Dr. Murray Ducharme, and Mr. Michael Aeroboe.

Immunogenicity of antibody drug conjugates: bioanalytical methods and monitoring strategy for a novel therapeutic modality.

Immunogenicity (the development of an adaptive immune response reactive with a therapeutic) is a well-described but unwanted facet of biotherapeutic development. There are commonly applied procedures for immunogenicity risk assessment, testing strategies, and bioanalysis. With some modifications, these can be applied to new biotherapeutic modalities. For novel therapies such as antibody-drug conjugates (ADCs), the unique structural components may contribute additional complexities to both immunologic responses and bioanalytical methods. US product inserts (USPIs) for two commercially available ADCs detail the incidence of immunogenicity; however, the body of literature on immunogenicity of ADCs is limited. We recently participated in a conference session on this topic (Annual meeting of the American Association of Pharmaceutical Scientists, held November 2013 in San Antonio, TX, USA. The meeting featured the Symposium: Immunogenicity Assessment for Novel Antibody Drug Conjugates, Nonclinical to Clinical) which prompted an effort to share our perspectives on how immunogenicity risk assessment, testing strategies, and bioanalytical methods can be adapted to reflect the complexity of ADC therapeutics.

Systematic verification of bioanalytical similarity between a biosimilar and a reference biotherapeutic: committee recommendations for the development and validation of a single ligand-binding assay to support pharmacokinetic assessments.

For biosimilar drug development, it is critical to demonstrate similar physiochemical characteristics, efficacy, and safety of the biosimilar product compared to the reference product. Therefore, pharmacokinetic (PK) and immunogenicity (antidrug antibody, ADA) assays that allow for the demonstration of biosimilarity are critical. Under the auspices of the American Association of Pharmaceutical Scientists (AAPS) Ligand-Binding Assay Bioanalytical Focus Group (LBABFG), a Biosimilars Action Program Committee (APC) was formed in 2011. The goals of this Biosimilars APC were to provide a forum for in-depth discussions on issues surrounding the development and validation of PK and immunogenicity assays in support of biosimilar drug development and to make recommendations thereof. The Biosimilars APC's recommendations for the development and validation of ligand-binding assays (LBAs) to support the PK assessments for biosimilar drug development are presented here. Analytical recommendations for the development and validation of LBAs to support immunogenicity assessments will be the subject of a separate white paper.

Bioanalytical Method Validation: Concepts, Expectations and Challenges in Small Molecule and Macromolecule—A Report of PITTCON 2013 Symposium

The concepts, importance, and implications of bioanalytical method validation has been discussed and debated for a long time. The recent high profile issues related to bioanalytical method validation at both Cetero Houston and former MDS Canada has brought this topic back in the limelight. Hence, a symposium on bioanalytical method validation with the aim of revisiting the building blocks as well as discussing the challenges and implications on the bioanalysis of both small molecules and macromolecules was featured at the PITTCON 2013 Conference and Expo. This symposium was cosponsored by the American Chemical Society (ACS)-Division of Analytical Chemistry and Analysis and Pharmaceutical Quality (APQ) Section of the American Association of Pharmaceutical Scientists (AAPS) and featured leading speakers from the Food & Drug Administration (FDA), academia, and industry. In this symposium, the speakers shared several unique examples, and this session also provided a platform to discuss the need for continuous vigilance of the bioanalytical methods during drug discovery and development. The purpose of this article is to provide a concise report on the materials that were presented.

Biorelevant In Vitro Performance Testing of Orally Administered Dosage Forms—Workshop Report

Biorelevant in vitro performance testing of orally administered dosage forms has become an important tool for the assessment of drug product in vivo behavior. An in vitro performance test which mimics the intraluminal performance of an oral dosage form is termed biorelevant. Biorelevant tests have been utilized to decrease the number of in vivo studies required during the drug development process and to mitigate the risk related to in vivo bioequivalence studies. This report reviews the ability of current in vitro performance tests to predict in vivo performance and generate successful in vitro and in vivo correlations for oral dosage forms. It also summarizes efforts to improve the predictability of biorelevant tests. The report is based on the presentations at the 2013 workshop, Biorelevant In Vitro Performance Testing of Orally Administered Dosage Forms, in Washington, DC, sponsored by the FIP Dissolution/Drug Release Focus Group in partnership with the American Association of Pharmaceutical Scientists (AAPS) and a symposium at the AAPS 2012 Annual meeting on the same topic.

Perspectives on a pharmacokinetics legend: C versus T (contributions over time)

Leslie Z. Benet is Professor and Former Chair at the University of California San Francisco (UCSF), Department of Bioengineering and Therapeutic Sciences, and Department of Pharmaceutical Chemistry. Professor Benet has had a profound impact on the development of fundamental concepts in pharmacokinetics, and the application of these principles in patient care and drug development. This theme issue is dedicated to Professor Benet in tribute to his significant contributions to the pharmaceutical sciences. An outstanding commentary that details Professor Benet’s career path and scientific achievements over the past 50 years was published recently in Pharm Res.1 We chose to provide a different perspective for the reader by focusing this commentary on those intangible factors that make Professor Benet truly a legend in the pharmaceutical sciences. In gathering information for this “C versus T” commentary, we interviewed Professor Benet and contacted scientific colleagues, professional mentees, and family. We asked each to share a brief perspective from their vantage point on this giant in the field. Many great “Les Benet” attributes emerged including energy, pas-

2012 AAPS National Biotech Conference Open Forum: A Perspective on the Current State of Immunogenicity Prediction and Risk Management

The immunogenicity profile of a biotherapeutic is determined by multiple product-, process- or manufacturing-, patient- and treatment-related factors and the bioanalytical methodology used to monitor for immunogenicity. This creates a complex situation that limits direct correlation of individual factors to observed immunogenicity rates. Therefore, mechanistic understanding of how these factors individually or in concert could influence the overall incidence and clinical risk of immunogenicity is crucial to provide the best benefit/risk profile for a given biotherapeutic in a given indication and to inform risk mitigation strategies. Advances in the field of immunogenicity have included development of best practices for monitoring anti-drug antibody development, categorization of risk factors contributing to immunogenicity, development of predictive tools, and development of effective strategies for risk management and mitigation. Thus, the opportunity to ask "where we are now and where we would like to go from here?" was the main driver for organizing an Open Forum on Improving Immunogenicity Risk Prediction and Management, conducted at the 2012 American Association of Pharmaceutical Scientists' (AAPS) National Biotechnology Conference in San Diego. The main objectives of the Forum include the following: to understand the nature of immunogenicity risk factors, to identify analytical tools used and animal models and management strategies needed to improve their predictive value, and finally to identify collaboration opportunities to improve the reliability of risk prediction, mitigation, and management. This meeting report provides the Forum participant's and author's perspectives on the barriers to advancing this field and recommendations for overcoming these barriers through collaborative efforts.