Publications by authors named "Lauren Mihalcik"

4 Publications

  • Page 1 of 1

Use of nonclinical toxicity studies to support biosimilar antibody development.

Regul Toxicol Pharmacol 2021 Mar 1;122:104912. Epub 2021 Mar 1.

Amgen Inc., One Amgen Drive, Thousand Oaks, CA, USA. Electronic address:

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http://dx.doi.org/10.1016/j.yrtph.2021.104912DOI Listing
March 2021

Outcomes of the European Federation of Pharmaceutical Industries and Associations Oligonucleotide Working Group Survey on Nonclinical Practices and Regulatory Expectations for Therapeutic Oligonucleotide Safety Assessment.

Nucleic Acid Ther 2021 02 15;31(1):7-20. Epub 2020 Oct 15.

Pfizer Drug Safety Research and Development, Cambridge, Massachusetts, USA.

The Oligonucleotide Working Group of the European Federation of Pharmaceutical Industries and Associations (EFPIA) conducted a survey of companies to understand the trends in nonclinical practices and regulatory expectations for oligonucleotide drug safety assessment. Twenty-two companies of different types, with varying oligonucleotide experience levels in the field, participated. The survey identified key regulatory challenges and areas of perceived health authority (HA) concern regarding nonclinical safety strategies for oligonucleotides, such as the choice of toxicology species, approaches to dose setting in toxicity studies, dose scaling from animals to humans, the implementation (and regulatory acceptability) of lean packages, and methods for dealing with impurities and human-specific off-targets. The perceived oligonucleotide experience of HAs and the relevance of guidance to oligonucleotide development were also assessed. The results showed a general lack of consensus on nonclinical safety assessment approaches being used for this growing class of medicines and highlight the need for continuing collaboration between sponsors and HAs to better define best practices.
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http://dx.doi.org/10.1089/nat.2020.0892DOI Listing
February 2021

Community Opinions on the Collection and Use of Historical Control Data in Nonclinical Toxicity Studies.

Ther Innov Regul Sci 2016 Mar;50(2):174-187

9 Integrated Nonclinical Development Solutions, Ann Arbor, MI, USA.

Background: Access and use of historical control data was identified as a top stakeholder concern across organizations according to results of a survey of needs and challenges related to nonclinical data conducted by the FDA/PhUSE Nonclinical Working Group in 2011. There is a perception there may be additional ways to capitalize on historical control data to enhance studies or submissions across industry, academia, and government. During the working sessions of the FDA/PhUSE Computational Sciences Symposium in March 2012, a Historical Control subgroup of the FDA/PhUSE Nonclinical Working Group was formed to investigate how the industry might more effectively harness the vast amount of data from untreated/vehicle control animals. The subgroup includes broad representation of stakeholders with interest in nonclinical data.

Methods: This paper describes progress to date and includes results of a second survey to determine how organizations use and would like to use historical control data.

Results: Respondents to the survey strongly support that historical control data are useful and should be in an accessible format. Four potential project options were posed in the survey, with an overall positive response; also, several write-in options were suggested by respondents.

Conclusions: Community-supported projects to increase the availability of well-annotated and scientifically curated collections of historical control data appear to be of most interest.
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http://dx.doi.org/10.1177/2168479015600203DOI Listing
March 2016

Adenosine A2A receptor signaling and golf assembly show a specific requirement for the gamma7 subtype in the striatum.

J Biol Chem 2010 Sep 16;285(39):29787-96. Epub 2010 Jul 16.

Weis Center for Research, Geisinger Clinic, Danville, Pennsylvania 17822, USA.

The adenosine A(2A) receptor (A(2A)R) is increasingly recognized as a novel therapeutic target in Parkinson disease. In striatopallidal neurons, the G-protein α(olf) subtype is required to couple this receptor to adenylyl cyclase activation. It is now well established that the βγ dimer also performs an active role in this signal transduction process. In principal, sixty distinct βγ dimers could arise from combinatorial association of the five known β and 12 γ subunit genes. However, key questions regarding which βγ subunit combinations exist and whether they perform specific signaling roles in the context of the organism remain to be answered. To explore these questions, we used a gene targeting approach to specifically ablate the G-protein γ(7) subtype. Revealing a potentially new signaling paradigm, we show that the level of the γ(7) protein controls the hierarchial assembly of a specific G-protein α(olf)β(2)γ(7) heterotrimer in the striatum. Providing a probable basis for the selectivity of receptor signaling, we further demonstrate that loss of this specific G-protein heterotrimer leads to reduced A(2A)R activation of adenylyl cyclase. Finally, substantiating an important role for this signaling pathway in pyschostimulant responsiveness, we show that mice lacking the G-protein γ(7) subtype exhibit an attenuated behavioral response to caffeine. Collectively, these results further support the A(2A)R G-protein α(olf)β(2)γ(7) interface as a possible therapeutic target for Parkinson disease.
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http://dx.doi.org/10.1074/jbc.M110.142620DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2943273PMC
September 2010