The AAPS Journal

Journal Information
EISSN : 1550-7416
Published by: Springer Nature (10.1208)
Total articles ≅ 1,871
Current Coverage
SCOPUS
SCIE
LOCKSS
MEDICUS
MEDLINE
PUBMED
PMC
Archived in
SHERPA/ROMEO
Filter:

Latest articles in this journal

Jane Weitzel, , Gregory M. Banik, Amy R. Barker, Elizabeth Bladen, Narendra Chirmule, Joseph DeFeo, Jennifer Devine, Steven Emrick, Taha Kass Hout, et al.
Published: 15 October 2021
The AAPS Journal, Volume 23, pp 1-8; https://doi.org/10.1208/s12248-021-00634-5

Abstract:
Recent changes in the pharmaceutical industry have led to significant paradigm shifts in the pharmaceutical quality environment. Globalization of the pharmaceutical industry, increasingly rapid development of novel therapies, and adoption of new manufacturing techniques have presented numerous challenges for the established regulatory framework and quality environment and are impacting the approaches utilized to ensure the quality of pharmaceutical products. Regulators, industry, and standards-setting organizations have begun to recognize the need to rely more on integrated risk-based approaches and to create more nimble and flexible standards to complement these efforts. They also increasingly have recognized that quality needs to be built into systems and processes throughout the lifecycle of the product. Moreover, the recent COVID-19 crisis has emphasized the need to adopt practices that better promote global supply chain resilience. In this paper, the USP Quality Advisory Group explores the various paradigm shifts currently impacting pharmaceutical quality and the approaches that are being taken to adapt to this new environment. Broad adoption of the Analytical Procedure Lifecycle approach, improved data management, and utilization of digital technologies are identified as potential solutions that can help meet the challenges of these quality paradigm shifts. Further discussion and collaboration among stakeholders are needed to pursue these and other solutions that can ensure a continued focus on quality while facilitating pharmaceutical innovation and development.
Elizabeth S. Levy, Jesse Yu, Alberto Estevez, Jialin Mao, Liling Liu, Elizabeth Torres, ,
Published: 14 October 2021
The AAPS Journal, Volume 23, pp 1-12; https://doi.org/10.1208/s12248-021-00651-4

The publisher has not yet granted permission to display this abstract.
Jin Niu, Van Anh Nguyen, Mohammad Ghasemi, Ting Chen,
Published: 7 October 2021
The AAPS Journal, Volume 23, pp 1-15; https://doi.org/10.1208/s12248-021-00640-7

The publisher has not yet granted permission to display this abstract.
Andrew F. Dengler, Rachel Weiss, Tiffany Truong, Susan C. Irvin, Nidhi Gadhia, Mohamed Hassanein, Camille Georgaros, Jessica-Ann Taylor, Anne Paccaly, Giane Sumner, et al.
Published: 4 October 2021
The AAPS Journal, Volume 23, pp 1-10; https://doi.org/10.1208/s12248-021-00643-4

Abstract:
Monoclonal antibodies (mAbs) are a leading class of biotherapeutics. In oncology, patients often fail on early lines of biologic therapy to a specific target. Some patients may then enroll in a new clinical trial with a mAb specific for the same target. Therefore, immunoassays designed to quantify the current mAb therapy or assess immunogenicity to the drug may be susceptible to cross-reactivity or interference with residual prior biologics. The impact of two approved anti-PD-1 mAbs, pembrolizumab and nivolumab, was tested in several immunoassays for cemiplimab, another approved anti-PD-1 mAb. The methods included a target-capture drug concentration assay, a bridging anti-drug antibody (ADA) assay and a competitive ligand-binding neutralizing antibody (NAb) assay. We also tested bioanalytical strategies to mitigate cross-reactivity or interference in these assays from other anti-PD-1 biologics. Both pembrolizumab and nivolumab cross-reacted in the cemiplimab drug concentration assay. This was mitigated by addition of antibodies specific to pembrolizumab or nivolumab. ADA specific for pembrolizumab and nivolumab did not interfere in the cemiplimab ADA assay. However, pembrolizumab and nivolumab generated a false-positive response in a target-capture NAb assay. Our results demonstrate that similar exogenous pre-existing anti-PD-1 mAbs (biotherapeutics) such as pembrolizumab and nivolumab are detected and accurately quantified in the cemiplimab drug concentration assay. However, once steady state is achieved for the new therapy, prior biologics would likely not be detected. Cross-reactivity and interference in immunoassays from previous treatment with class-specific biotherapeutic(s) pose significant bioanalytical challenges, especially in immuno-oncology. Graphical abstract
, Mitra Azadeh, George Buchlis, Travis Harrison, Mike Havert, Vibha Jawa, Brian Long, Jim McNally, Mark Milton, Robert Nelson, et al.
Published: 16 September 2021
The AAPS Journal, Volume 23, pp 1-17; https://doi.org/10.1208/s12248-021-00628-3

The publisher has not yet granted permission to display this abstract.
, Alexander Abbott, Yelizaveta Babayan, Jenny Carhart, Chi-Wan Chen, Elke Debie, Mingkun Fu, Cherokee Hoaglund-Hyzer, Andrew Lennard, Hanlin Li, et al.
Published: 16 September 2021
The AAPS Journal, Volume 23, pp 1-9; https://doi.org/10.1208/s12248-021-00641-6

The publisher has not yet granted permission to display this abstract.
Ruchika Bajaj, Lisa B Chong, Ling Zou, Eleftheria Tsakalozou, Zhanglin Ni, Kathleen M Giacomini,
Published: 15 September 2021
The AAPS Journal, Volume 23, pp 1-12; https://doi.org/10.1208/s12248-021-00631-8

The publisher has not yet granted permission to display this abstract.
Zhicheng Wang,
Published: 10 September 2021
The AAPS Journal, Volume 23, pp 1-8; https://doi.org/10.1208/s12248-021-00630-9

The publisher has not yet granted permission to display this abstract.
Asha J Kapetas, , Michael J Sorich, Ross A McKinnon, A David Rodrigues, Andrew Rowland, Ashley M Hopkins
Published: 31 August 2021
The AAPS Journal, Volume 23, pp 1-8; https://doi.org/10.1208/s12248-021-00632-7

The publisher has not yet granted permission to display this abstract.
, Michael Pourdehnad, Soraya Carrancio, Daniel W. Pierce, Shailaja Kasibhatla, Mark McConnell, Matthew W. B. Trotter, Remco Loos, ,
Published: 27 August 2021
The AAPS Journal, Volume 23, pp 1-13; https://doi.org/10.1208/s12248-021-00623-8

Abstract:
Avadomide is a cereblon E3 ligase modulator and a potent antitumor and immunomodulatory agent. Avadomide trials are challenged by neutropenia as a major adverse event and a dose-limiting toxicity. Intermittent dosing schedules supported by preclinical data provide a strategy to reduce frequency and severity of neutropenia; however, the identification of optimal dosing schedules remains a clinical challenge. Quantitative systems pharmacology (QSP) modeling offers opportunities for virtual screening of efficacy and toxicity levels produced by alternative dose and schedule regimens, thereby supporting decision-making in translational drug development. We formulated a QSP model to capture the mechanism of avadomide-induced neutropenia, which involves cereblon-mediated degradation of transcription factor Ikaros, resulting in a maturation block of the neutrophil lineage. The neutropenia model was integrated with avadomide-specific pharmacokinetic and pharmacodynamic models to capture dose-dependent effects. Additionally, we generated a disease-specific virtual patient population to represent the variability in patient characteristics and response to treatment observed for a diffuse large B-cell lymphoma trial cohort. Model utility was demonstrated by simulating the avadomide effect in the virtual population for various dosing schedules and determining the incidence of high-grade neutropenia, its duration, and the probability of recovery to low-grade neutropenia.
Back to Top Top