American Association Of Pharmaceutical Scientists Research Articles

Anti-cancer Potential of Phytoflavonoidal Drugs against Gynecological Cancer

Background: Flavonoids, one of the major bioactive constituents of herbal drugs, have been scientifically reported to possess diverse therapeutic potentials such as anticancer, immunomodulatory, neuroprotective, cardioprotective, antioxidant, etc. This manuscript enlightens the anticancer potential of traditional herbal flavonoids in gynecological cancer i.e., is one of the major life-threats in women. Objective: This manuscript is aimed at an insightful compilation of scientific substantiations of herbal flavonoids in gynecological cancer along with targeted drug delivery systems for the same. Materials and Methods: The contents and data represented in the article have been reviewed using institutional libraries and online database resources (available in the public domain) such as PubMed, Science-Direct, Web of Science, American Association of Pharmaceutical Scientists, Google Scholar, Hinari, SciFinder, Research Gate, etc. Results: Flavonoids are natural compounds and have potential against cervical, ovarian, and endometrial cancer. In-vitro and in-vivo experiments have demonstrated the significant potential of flavonoids in gynecological cancer, especially cervical, ovarian, and endometrial cancer. It was reported from in-vitro experimentations that targeted drug delivery system improves the anticancer effect of flavonoids. Conclusion: Phytoflavonoids have the potential to prevent gynecological cancer by induction of apoptosis cell cycle arrest and reactive oxygen species generation. Further studies on the drug delivery system of flavonoids are warranted.

Recommendations for Method Development and Validation of qPCR and dPCR Assays in Support of Cell and Gene Therapy Drug Development

 The emerging use of qPCR and dPCR in regulated bioanalysis and absence of regulatory guidance on assay validations for these platforms has resulted in discussions on lack of harmonization on assay design and appropriate acceptance criteria for these assays. Both qPCR and dPCR are extensively used to answer bioanalytical questions for novel modalities such as cell and gene therapies. Following cross-industry conversations on the lack of information and guidelines for these assays, an American Association of Pharmaceutical Scientists working group was formed to address these gaps by bringing together 37 industry experts from 24 organizations to discuss best practices to gain a better understanding in the industry and facilitate filings to health authorities. Herein, this team provides considerations on assay design, development, and validation testing for PCR assays that are used in cell and gene therapies including (1) biodistribution; (2) transgene expression; (3) viral shedding; (4) and persistence or cellular kinetics of cell therapies.Graphical

Applications of Modeling and Simulation Approaches in Support of Drug Product Development of Oral Dosage Forms and Locally Acting Drug Products: a Symposium Summary.

The number of modeling and simulation applications, including physiologically based pharmacokinetic (PBPK) models, physiologically based biopharmaceutics modeling (PBBM), and empirical models, has been constantly increasing along with the regulatory acceptance of these methodologies. While aiming at minimizing unnecessary human testing, these methodologies are used today to support the development and approval of novel drug products and generics. Modeling approaches are leveraged today for assessing drug-drug interaction, informing dose adjustments in renally or hepatically impaired patients, perform dose selection in pediatrics and pregnant women and diseased populations, and conduct biopharmaceutics-related assessments such as establish clinically relevant specifications for drug products and achieve quality assurance throughout the product life cycle. In the generics space, PBPK analyses are utilized toward virtual bioequivalence assessments within the scope of alternative bioequivalence approaches, product-specific guidance development, and food effect assessments among others. Case studies highlighting the evolving and expanding role of modeling and simulation approaches within the biopharmaceutics space were presented at the symposium titled "Model Informed Drug Development (MIDD): Role in Dose Selection, Vulnerable Populations, and Biowaivers - Chemical Entities" and Prologue "PBPK/PBBM to inform the Bioequivalence Safe Space, Food Effects, and pH-mediated DDIs" at the American Association of Pharmaceutical Scientists (AAPS) PharmSci 360 Annual Meeting in Boston, MA, on October 16-19, 2022, and are summarized here.

Flow Cytometry Method Validation Protocols.

Analytical method validation provides a means to ensure that data are credible and reproducible. This article will provide a brief introduction to analytical method validation as applied to cellular analysis by flow cytometry, along with practical procedures for four different types of validation. The first, Basic Protocol 1 (the limited validation protocol), is recommended for research and non-regulated laboratories. Next, Basic Protocol 2) presents a reasonable, fit-for-purpose validation approach appropriate for biopharma and research settings. Basic Protocol 3 addresses the type of validation performed in clinical laboratories for moderate-risk tests developed in house. Finally, Basic Protocol 4 describes the process that should be applied whenever a method is being transferred from one facility to another. All four validation plans follow the fit-for-purpose validation approach, in which the validation parameters are selected based on the intended use of the assay. These validation protocols represent the minimal requirement and may not be applicable for every intended use such as high-risk clinical assays or data to be used as a primary endpoint in a clinical trial. The recommendations presented here 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 (CLSI, 2021). © 2023 Wiley Periodicals LLC. Basic Protocol 1: Limited validation Basic Protocol 2: Fit-for-purpose validation for biopharma and research settings Basic Protocol 3: Validation for moderate clinical risk laboratory developed tests Basic Protocol 4: Transfer validation.

Neutralizing Antibody Validation Testing and Reporting Harmonization

Evolving immunogenicity assay performance expectations and a lack of harmonized neutralizing antibody validation testing and reporting tools have resulted in significant time spent by health authorities and sponsors on resolving filing queries. A team of experts within the American Association of Pharmaceutical Scientists’ Therapeutic Product Immunogenicity Community across industry and the Food and Drug Administration addressed challenges unique to cell-based and non-cell-based neutralizing antibody assays. Harmonization of validation expectations and data reporting will facilitate filings to health authorities and are described in this manuscript. This team provides validation testing and reporting strategies and tools for the following assessments: (1) format selection; (2) cut point; (3) assay acceptance criteria; (4) control precision; (5) sensitivity including positive control selection and performance tracking; (6) negative control selection; (7) selectivity/specificity including matrix interference, hemolysis, lipemia, bilirubin, concomitant medications, and structurally similar analytes; (8) drug tolerance; (9) target tolerance; (10) sample stability; and (11) assay robustness.Graphical

Survey Outcome on Immunogenicity Risk Assessment Tools for Biotherapeutics: an Insight into Consensus on Methods, Application, and Utility in Drug Development.

A survey conducted by the Therapeutic Product Immunogenicity (TPI) community within the American Association of Pharmaceutical Scientists (AAPS) posed questions to the participants on their immunogenicity risk assessment strategies prior to clinical development. The survey was conducted in 2 phases spanning 5years, and queried information about in silico algorithms and in vitro assay formats for immunogenicity risk assessments and how the data were used to inform early developability effort in discovery, chemistry, manufacturing and control (CMC), and non-clinical stages of development. The key findings representing the trends from a majority of the participants included the use of high throughput in silico algorithms, human immune cell-based assays, and proteomics based outputs, as well as specialized assays when therapeutic mechanism of action could impact risk assessment. Additional insights into the CMC-related risks could also be gathered with the same tools to inform future process development and de-risk critical quality attributes with uncertain and unknown risks. The use of the outputs beyond supporting early development activities was also noted with participants utilizing the risk assessments to drive their clinical strategy and streamline bioanalysis.

To blind or not to blind first in human and exploratory clinical trials: Acceleration of development vs. risk of bias

An IQ consortium working group (WG) conducted a survey across multiple biopharmaceutical companies to gain information about the level of blinding commonly utilized for early clinical development trials. The main objectives were: (1) to understand blinding practices between healthy volunteer (HV) and early explorative patient trials in all therapeutic areas except oncology where early clinical trials are commonly open‐label; (2) to understand the rationale for blinding/unblinding practices; (3) to understand the groups and personnel involved in unblinding; and (4) strategic considerations around blinding/unblinding options in early clinical development trials—risk of bias vs. potential for acceleration. A survey containing 31 main questions with additional sub‐clarifying questions was conducted. Sixteen large and mid‐size pharmaceutical companies responded. Responses were aligned across functions within each participating company. Additional information was gathered at an American Association of Pharmaceutical Scientists (AAPS) webinar with polling options to roughly 550 registered attendees to evaluate the reason for the unblinding decisions. The results revealed divergence across companies in the blinding approaches most commonly applied but with some study types, there were clearly favored options. Based on these results, the WG developed strategic considerations for first‐in‐human HV trials and nonpivotal explorative trials in patients. This paper should facilitate discussions among various clinical development functions, such as Clinical Pharmacology, Statistics, Clinical, Bioanalytics, and Regulatory Functions. Such discussions on study design and operations are warranted to allow implementation of more flexible blinding approaches to accelerate data driven decisions in drug development and allow earlier access of patients to needful medicines.

New pediatric analysis establishes novel dosing framework for the future

Pharmacists have all heard the phrase “children are not little adults.” It’s popular for a reason: it represents the dangers of simply scaling adult drug dosages to children. Adult physiology, however, has historically been used to scale pediatric dose recommendations. Currently, the most accurate way to determine the initial dosage of a drug is to use a physiologically based pharmacokinetic model (PBPK) to mathematically extrapolate drug dosing from an adult to a child population. Unfortunately, the development of a PBPK remains a challenge, as it requires a deep level of raw, quantitative, physiological data related to developmental stage, disease processes, and any other variable that can affect the pharmacokinetics of a drug. This task may have become significantly less herculean, however, thanks to an open-source, comprehensive, quantitative database, published in March 2021 in the Journal of the American Association of Pharmaceutical Scientists, on the mathematical age relationships among weight, height, organ weight, and organ blood flow—all critical parameters needed when designing a pediatric PBPK. Until recently, this kind of data have been difficult to consolidate or have been locked tightly behind proprietary software. The authors hope that by making it open-source, their database will encourage the creation of widespread pediatric PBPK models that can help predict optimal dosing for pediatric patients with both old and new drugs. One of the first steps in the clinical development for most drugs seeking a pediatric indication is to demonstrate similar exposure levels at various dosages. The first dose is informed by adult pharmacokinetic data leveraged in mathematical models that rely on assumptions regarding the drug’s pharmacokinetics. These data are then scaled down to different child age groups using allometric functions of basal metabolic rates and body weight. Although this is usually sufficient, it may be inaccurate for non-small drug molecules that do not exhibit linear kinetics with time-dependent clearance or target-mediated drug disposition. Biologics pose a particular problem. Using a PBPK model to achieve more accurate results presents a solution. The general process involves creating a simulation of a population of adults whose pharmacokinetics of a particular drug is expressed as rate-based equations. The adults are then swapped with virtual children with all other pharmacokinetic parameters being held constant and their drug exposure metrics compared. If the virtual pediatric exposures are similar to that of the virtual adult population, the presumed first-in-pediatric dose can progress to a more practical application. Chang and colleagues created a comprehensive database of physiological parameters in children from newborns to 20 years. They found a singular function that described the relationships between body weight and age, height and age, organ weight and age, and organ blood flow and age. The formula can be used to estimate any of these parameters—as they relate to age—by referencing the appropriate tables and variable values in the author’s library. The analysis also includes functions predicting pediatric organ weight and blood flow for a library of organs—including heart, lung, muscle, skin, fat, bone, bone marrow, brain, kidney, liver, intestine, pancreas, thymus, and spleen—as well as blood volume and extracellular water. In fact, Chang and colleagues published a follow-up study in June 2021 in the British Journal of Clinical Pharmacology, in which they put the database to the test using it to develop their own PBPK model to characterize monoclonal antibody (mAb) pharmacokinetics in pediatric patients. The results of the investigation were in concordance with the rest of the literature: that mAb pharmacokinetics often require higher doses or more frequent dosing in order to achieve therapeutic levels. The confirmatory results appear to demonstrate a practical application of their database for use in PKPB modeling and will hopefully serve as an accessible framework for pediatric pharmacologists—particularly for biologics—in the years to come.

Social Networks and Problem-solving in the Context of Biopharmaceutical Research and Development

Problem-solving is a vital aspect of scientific innovation. It is especially important in the biopharmaceutical field which, despite its innovative reputation, faces high project failure rates. To cope with research obstacles, these organizations utilize an evolving matrix structure with structured turnover of cross-functional (interdisciplinary) research teams. Problem-solving becomes social and relies on scientists’ ability to activate network contacts. What kind of social network contact facilitates problem-solving? Two different theoretical perspectives set different expectations. The needs perspective suggests specific types of resources are useful at different problem-solving phases. Different types of resources are locked into different types of social network ties. As problem-solving progresses and the required resources change, profiles of network contacts change. Turnover should be greatest between problem-identification, which calls for interpersonal support and familiarity, and problem-understanding, which calls for new knowledge and formal authority. In contrast, what I call the strong core perspective posits a stable core of multi-purpose network contacts. In terms of the types of network contacts, the needs perspective expects problem-solving phases to be independent; the strong core perspective expects path dependence. To explore network contact characteristics associated problem-solving phases and test for path dependence, I surveyed members of the American Association of Pharmaceutical Scientists, the largest pharmaceutical professional organization, about the contacts they utilized while dealing with the most serious research obstacle they encountered in the past year and which contacts were useful for identification and understanding. A multi-level path model copes with the nested data structure and tests for path-dependence. Results support the strong core perspective; strong path dependence indicates that scientists utilize contacts associated with strong tie strength and competence-based trust for both problem-identification and problem-understanding. Scientists form stable sets of social contacts during nascent problem-solving phases.

A bright future for lipid nanoparticles in gene therapy

<div class="authors authors-lg"><div class="author"><div class="author-img"><img src="https://cdn.insights.bio/uploads/Hongwei Zhang PhD copy.jpg" data-image="1"></div><div class="author-det"> <b>Hongwei Zhang</b> is Associate Professor and Director of Pharmaceutical Sciences Program at Massachusetts College of Pharmacy and Health Sciences University (MCPHS University) in Boston. The research in Zhang lab is focused on nanomedicine and drug/gene delivery. Dr Zhang received his BS in Pharmacy and PhD in Pharmaceutics from the West China School of Pharmacy at Sichuan University and completed postdoctoral training in the Gene Therapy Center at the University of Massachusetts Medical School. Dr Zhang has published ~70 peer-reviewed journal articles and conference papers in the field of gene delivery and gene therapy. He is the recipient of the Biotechnology Innovation Award from the American Association of Pharmaceutical Scientists. He is the co-inventor of an AAV gene therapy patent. </div></div></div>

Meeting Report: N-Nitrosamine Impurity Control Strategies in the Pharmaceutical and Biotechnology Industries

The American Association of Pharmaceutical Scientists (AAPS) Chemistry, Manufacturing, and Control (CMC) Community hosted a virtual panel discussion on December 9, 2020, to provide a forum to discuss N-nitrosamine control strategies in the pharmaceutical and biotechnology industries. The panel included staff from the US Food and Drug Administration (FDA) and industry subject matter experts. Meeting topics included acceptable intake levels for nitrosamine impurities, definitions of "acceptable level of risk," water as a contributor in nitrosamine risk assessments, nitrosamine impurity control strategies based upon fate/purge data, early vs. late development assessment expectations, application to oncology programs developed under ICH S9, and Drug Master File (DMF) regulatory expectations. During the meeting, divergence in global health authority expectations was additionally discussed. One of the most important outputs from this AAPS panel discussion was the criticality of continued dialog between industry and health authorities to help understand actual versus perceived risks and provide pragmatic, scientifically justified solutions to ensure patients are provided with an uninterrupted supply of safe medicines based on globally harmonized requirements.

The Journal of Clinical Pharmacology Adds 2 Associate Editors

Drs. Bertino (Editor-in-Chief) and Reed (Associate Editor), Ms. Marshall (Managing Editor), and The Journal of Clinical Pharmacology (JCP) are pleased to announce the addition of 2 associate editors: Joan Korth-Bradley, PharmD, PhD, received her BSc at the University of Toronto and completed a residency in hospital pharmacy at Ottawa General Hospital. She then received her PharmD from the University of Minnesota, completed a clinical pharmacy fellowship at the University of Texas at Austin, and then completed a PhD under Dr. Tom Ludden in the Division of Pharmaceutics at the University of Texas at Austin. After a brief career in academia and hospital pharmacy, Dr. Korth-Bradley joined Wyeth-Ayerst in 1991 and then Pfizer Inc. (which acquired Wyeth-Ayerst) in 2009. She is currently a Senior Director in Clinical Pharmacology at Pfizer Inc. Dr. Korth-Bradley is a Fellow of the American College of Clinical Pharmacology, the American College of Clinical Pharmacy, and the American Association of Pharmaceutical Scientists. She has served on numerous ACCP committees and is currently an ACCP Regent. She has also been a member of the Editorial Board of JCP. She has an extensive track record of publications and presentations in clinical pharmacology. Janice E. Sullivan, MD, started her career in nursing (as a nurse practitioner) and then received her MD from the University of Minnesota. She completed a pediatric residency at the University of Arkansas and a Fellowship in Pediatric Pharmacology and Critical Care from Case Western Reserve University. Dr. Sullivan is currently a Professor at the University of Louisville, the Vice Chair of Research in the Department of Pediatrics at the University of Louisville, and a consultant at the Kentucky Regional Poison Center of Norton Children's Hospital. She has recently stopped her many years of pediatric critical care work to focus on her research activities. Dr. Sullivan is board-certified in Pediatrics, Pediatric Critical Care, and Clinical Pharmacology. She holds fellowships in the American Academy of Pediatrics and the Society of Critical Care Medicine. She has an extensive record of extramural research funding as well as a long record of publications and presentations. We welcome Drs. Korth-Bradley and Sullivan as Associate Editors for The Journal of Clinical Pharmacology.

AAPS Perspective on the EURL Recommendation on the use of Non-Animal-Derived Antibodies.

In May 2020, the EU Reference Laboratory for alternatives to animal testing (EURL ECVAM) published a recommendation report entitled "Recommendation on nonanimal-derived antibodies". In this report, the EURL ECVAM specifically states: "Therefore, taking into consideration the ESAC Opinion on the scientific validity of replacements for animal-derived antibodies, EURL ECVAM recommends that animals should no longer be used for the development and production of antibodies for research, regulatory, diagnostic and therapeutic applications. The provisions of Directive 2010/63/EU should be respected, and EU countries should no longer authorise the development and production of antibodies through animal immunisation, where robust, legitimate scientific justification is lacking." (1). Here, we are providing the American Association of Pharmaceutical Scientists (AAPS) opinion on the EURL ECVAM recommendation report. In brief, there has been a clear and strong progress in reduction of animal use in the drug discovery and development process, including significant reduction of animal use in production of antibody reagents. Yet, it is proposed that more data need to be generated, shared and discussed within the scientific community before a decision to implement the change to non-animal derived antibodies is made.

MSc. Development of the In-house Specifications and Study of the Stability of Self-nanoemulsifying Drug Delivery System Containing Rosuvastatin

This study develops the in-house specifications of self-nanoemulsifying drug delivery system (SNEDDS) containing rosuvastatin based on the following criteria: description, identification, droplet size (≤200 nm) and polydiversity index (not more than 0.3), drug proportion in the oil phase (≥ 90.0%), assay (≥ 95.0% and ≤105.0% of the labeled amount of rosuvastatin (C22H28FN3O6S). The criteria were validated and the results were suitable for identification and determination of rosuvastatin in SNEDDS. Additionally, the results of the stability study show that the rosuvastatin SNEDDS met the criteria of description, droplet size, PDI, assay and drug rate in the oil phase for 12-month storage under the long-term condition (12 months) and 6 months on accelerated condition.&#x0D; Keywords&#x0D; Rosuvastatin, SNEDDS, specification, droplet size, entrapment efficiency.&#x0D; References&#x0D; [1] A. Luvai, W. Mbagaya, A.S. Hall, I.H. Barth, Rosuvastatin: A Review of the Pharmacology and Clinical Effectiveness in Cardiovascular Disease, Clinical Medicine Insights: Cardiology 6 (2012) 17–33. https://doi.org/10.4137/CMC.S4324. [2] K. Balakumar, C.V. Raghavan, N.T. Selvan, R.H. Prasad, S. Abdu, Self nanoemulsifying drug delivery system (SNEDDS) of Rosuvastatin calcium: Design, formulation, bioavailability and pharmacokinetic evaluation, Colloids and Surfaces B: Biointerfaces. 112 (2013) 337–343. http://dx.doi.org/10.1016/j.colsurfb.2013.08.025. [3] S. Elkadi, S. Elsamaligy, S. Al-Suwayeh, H. Mahmoud, The Development of Self-nanoemulsifying Liquisolid Tablets to Improve the Dissolution of Simvastatin, American Association of Pharmaceutical Scientists 18(7) (2017) 2586–2597. https://doi.org/10.1208/s12249-017-0743-z. [4] D. Patel, K.K. Sawant, Self Micro-Emulsifying Drug Delivery System: Formulation Development and Biopharmaceutical Evaluation of Lipophilic Drugs, Current Drug Delivery 6 (2009) 419–424. https://doi.org/10.2174/156720109789000519. [5] S.D. Maurya, R.K.K. Arya, G Rajpal, R.C. Dhakar, Self-micro emulsifying drug delivery systems (SMEDDS): A review on physico-chemical and biopharmaceutical aspects, Journal of Drug Delivery and Therapeutics 7(3) (2017) 55–65. https://doi.org/10.22270/jddt.v7i3.1453.[6] P. Borman, D. Elder, Q2(R1) Validation of analytical procedures: text and methodology, in: A. Teasdale, D. Elder, R.W. Nims (Eds), ICH quality guidelines: an implementation guide, John Wiley &amp; Sons Inc., Hoboken, 2018, pp. 127-166. [7] United States Pharmacopoeia 41, rosuvastatin tablets monograph. &#x0D;  &#x0D;  &#x0D;  &#x0D;  &#x0D;  

Prospects of Establishing a Saudi Version of the United States Food and Drug Administration Orange Book

BackgroundThe recent incidents of generic drug recalls have shaken the public confidence in the quality of generic drugs in Saudi Arabia. Therefore, many clinicians and health policymakers are calling for the establishment of a national reference or formulary that rates different generic drugs based on their therapeutic equivalence to the listed reference drugs, such as the Orange Book of the United States Food and Drug Administration (USFDA). MethodTo explore the prospects of establishing a Saudi version of the USFDA Orange Book, the Saudi discussion group of the American Association of Pharmaceutical Scientists (AAPS) called for a group meeting to discuss the issue with stakeholders representing different sectors (regulatory, industry, purchasing and supply chain, and patient safety). The meeting was audio-recorded and transcribed verbatim. Thereafter, the text was reviewed and analyzed. ResultsThe participants agreed that there is no national guide or reference that can be used in generic substitution. Moreover, it was indicated that the Saudi Food and Drug Authority (SFDA) is working on establishing a Saudi version of the USFDA Orange Book, which will help in choosing the right generic drugs whenever medication substitution is performed to ensure patient safety. ConclusionThe establishment of a Saudi version of the USFDA Orange Book would help healthcare providers in choosing the right generic drug for their patients, which will hopefully improve health outcomes.

Translational Modeling Strategies for Orally Administered Drug Products: Academic, Industrial and Regulatory Perspectives.

During non-clinical and clinical development of a new molecular entity (NME), modeling and simulation (M&S) are routinely used to predict the exposure and pharmacokinetics (PK) of the drug compound in humans. The basic methodology and output are generally understood across all functional disciplines. However, this understanding is mostly restricted to traditional methods such as those in simplified kinetic models and void of adequate mechanistic foundation to address questions beyond the observed clinical data. In the past two decades, alternative and more mechanistic methods, particularly for describing absorption, distribution, excretion and metabolism (ADME) of drugs have been developed and applied under the general umbrella of physiologically-based pharmacokinetic (PBPK) methods. Their mechanistic nature gives the ability to ask many other questions which were not traditionally asked and provide some logically and evidenced-based potential answers. Whilst traditional PK methods are mainstream and understood by most scientists, mechanistic absorption models alongside other PBPK approaches are still deemed eclectic, despite making significant strides in the fundamental science as well as regulatory acceptance. On November 3rd, a short course was held at the annual American Association of Pharmaceutical Scientists (AAPS) meeting in San Antonio, Texas. The different talks were tailored to provide a basis or rationale for the subject, introduction to fundamental principles with historical perspective, a critique of the state-of-the-art, examples of successful application of the methods across different phases of the drug development process and the specific standards these mechanistic models should meet to be fully reliable from a regulatory perspective.

Recent innovations in 3D-printed personalized medicines: an interview with Abdul Basit

Abdul Basit holds the position of Professor of Pharmaceutics at the UCL School of Pharmacy, University College London (UK). Basit is an internationally leading authority on oral drug delivery, digital health and innovative pharmaceutical technologies including 3D printing. Basit is a world authority on translational research; he has founded two spin-out companies (FabRx Ltd and Intract Pharma, both in London, UK) and has invented several drug products that have entered the clinic. More than a million patients to date have benefited from the treatments originating from his laboratory. Across his career, Basit has received prestigious awards from the American Association of Pharmaceutical Scientists, Academy of Pharmaceutical Sciences, GlaxoSmithKline and AstraZeneca and was listed among the world’s most highly influential researchers in 2019.

American Association of Pharmaceutical Scientists (AAPS) and Chinese National Institutes for Food and Drug Control (NIFDC) Joint Workshop on Dissolution, Bioequivalence, Product Performance, and Quality

American Association of Pharmaceutical Scientists (AAPS) and Chinese National Institutes for Food and Drug Control (NIFDC) Joint Workshop on Dissolution, Bioequivalence, Product Performance, and Quality

Challenges of Using Closed System Transfer Devices With Biological Drug Products: An Industry Perspective.

Hazardous drug is a common term used by the National Institute of Occupational Health and Safety (NIOSH) to classify medications that may induce adverse mutagenic and reproductive responses in health care personnel. NIOSH publishes a list of drugs it defines as hazardous where it may be appropriate for health care workers to take protective measures to reduce the potential for occupational exposure. Recent updates and proposed updates to this list have included large molecule biological products with oncology indications. Both NIOSH and USP <800> recommend the use of closed system transfer devices (CSTDs) during compounding. CSTDs are required for administration of prepared solution in NIOSH. However, USP has suggested that the principles of <800> are broadly applicable to hazardous drug handling activities across all facility types. USP encourages the widespread adoption and use of <800> across all health care settings, which many health care workers have interpreted beyond compounding to include administration and preparation of conventionally manufactured sterile products per approved labeling. Although the use of CSTDs may reduce exposure of health care personnel to chemotherapy agents in health care setting, the impact of CSTDs on quality of biologic drug products, including monoclonal antibodies and other proteins, is not fully understood. To complicate this issue further, there are several commercially available CSTDs in the market which have different fluid paths and material of construction that comes in contact with the drug. Testing every combination of CSTD and drug product for potential incompatibilities can be a labor intensive and impractical approach and cause delay in getting essential drugs to patients. A panel discussion was held at a recent American Association of Pharmaceutical Scientists 2018 PharmSci 360 conference to discuss the impact of CSTDs on biologics. Impact on subvisible and visible particulates and impact to other product quality attributes such as high molecular weight species formation upon contact with CSTDs were reported in American Association of Pharmaceutical Scientists meeting. Impact to deliverable dose, holdup volumes of various CSTDs, and stopper coring were also reported that has significant impact to patient safety. Given the fact that USP chapter <800> will be implemented in December 2019, feedback from health authorities regarding the use of CSTDs for biological drug products is needed to provide an appropriate risk/benefit balance to ensure patient safety and quality of the biologic drug product while also protecting the health care worker and the environment. The purpose of this commentary is to provide an industry perspective on the challenges during the use of CSTDs for biologic drug products and is intended to raise caution and awareness on the benefits and shortcomings of these devices.

Perspectives on the draft ICH-M10 guidance: an interview with Mark Arnold.

Biography Mark E Arnold, PhD, is Director of Science for Covance Laboratories. In that role, he develops the bioanalytical strategy for immune-, cell-based, quantitative polymerase chain reaction(qPCR) and LC-MS/MS assays to quantify drugs and metabolites, antidrug antibodies and biomarkers in animal and clinical samples for pharmacokinetic and pharmacodynamic assessments. Mark was previously Executive Director of Bioanalytical Sciences at Bristol-Myers Squibb. He received a BS (biology) from Indiana University of Pennsylvania and PhD (pharmacology) from the University of Pittsburgh. For more than 30years, Mark has been involved in the evolving field of bioanalysis, including the science and the review and interpretation of regulations and guidance. He co-chaired the AAPS Crystal City V and VI Workshops on the US 'FDA Draft Revised Guidance on Bioanalytical Method Validation' and 'Biomarkers'. He is actively involved in the Land O'Lakes Bioanalytical Conference and American Association of Pharmaceutical Scientists (AAPS, named Fellow in 2014).Mark has over 100 peer-reviewed publications, and numerous invited podium presentations. This interview was conducted by Sankeetha Nadarajah, Managing Commissioning Editor of Bioanalysis.