Preclinical Assessment of Genotoxic Impurities : An Overview of Current Regulatory Guidance, Available Assays, and Data Interpretation

2014 ◽  
pp. 228-253
Keyword(s):  
Data Interpretation ◽  
Regulatory Guidance ◽  
Genotoxic Impurities

scholarly journals Principles for Assessing Adversity in Toxicologic Clinical Pathology

2017 ◽  
Vol 45 (2) ◽  
pp. 260-266 ◽  
Author(s):  
Lila Ramaiah ◽  
Lindsay Tomlinson ◽  
Niraj K. Tripathi ◽  
Laura C. Cregar ◽  
Allison Vitsky ◽  
...  
Keyword(s):  
Clinical Pathology ◽  
Integrated Approach ◽  
Data Interpretation ◽  
Weight Of Evidence ◽  
Regulatory Guidance ◽  
Regulatory Affairs ◽  
Safety Studies ◽  
American Society ◽  
The Impact

There is limited direction in the literature or regulatory guidance on determination of adversity for clinical pathology (CP) biomarkers in preclinical safety studies. Toxicologic clinical pathologists representing the American Society for Veterinary Clinical Pathology—Regulatory Affairs Committee and Society of Toxicologic Pathology—Clinical Pathology Interest Group identified principles, overall approach, and unique considerations for assessing adversity in CP data interpretation to provide a consensus opinion. Emphasized is the need for pathophysiologic context and a weight-of-evidence approach. Most CP biomarkers do not have the potential to be adverse in isolation, regardless of magnitude of change. Rather, they quantify or describe the impact of effects, provide adjunct or supportive information regarding a process or pathogenesis, and provide translational biomarkers of effect. Most often, CP changes are part of a constellation of findings that collectively are adverse. Thus, most CP changes must be interpreted in conjunction with other study findings and require contextual and integrative interpretation. Exceptions include critical CP changes without correlates that indicate a health risk in the tested species. Overall, CP changes should not be interpreted in isolation and their adversity is best addressed with an integrated approach.

scholarly journals GENOTOXIC IMPURITIES: AN IMPORTANT REGULATORY ASPECT

2020 ◽  
pp. 10-25 ◽  
Author(s):  
ANITA R POUNIKAR ◽  
MILIND J UMEKAR ◽  
KRISHNA R GUPTA
Keyword(s):  
In Silico ◽  
High Performance ◽  
Drug Application ◽  
Data Interpretation ◽  
Regulatory Agencies ◽  
Chromosomal Structure ◽  
New Drug ◽  
Regulatory Guidelines ◽  
Genotoxic Impurities ◽  
New Drug Application

Genotoxins are agents/carriers such as chemical or radiation that can cause the damage to DNA or chromosomal structure, thereby causing mutations and the process are called as genotoxicity. Identification and understanding of genotoxins at a primary stage of drug development would enable us to prevent the potential damage that can be caused by these genotoxic agents. Various regulatory agencies such as International Council for Harmonization and EMEA, USFDA, European Pharmacopeia guidance, guidance for oncology products provide guidelines to limits the level of impurities in drug substances and drug products. Nowadays, conventional protocol of isolation, various spectral analysis high-performance liquid chromatography (LC), Fourier transform infrared to on-line analysis using modern, sophisticated hyphenated tools, like gas chromatography-mass spectroscopy, LC-MS so on, as well as modern software based in silico drug designs are extensively used by industry, research, and development areas and also there is tremendous increase in publications in the literature involving their use. Our review article focused on the various regulatory guidelines, application of hyphenated tools, and in silico techniques in genotoxic impurity and degradation product profiling of small molecules. A brief explanation is made on possible pitfalls in the experimentation and data interpretation. From this review, it concluded that there are various countries having their own regulatory agencies and regulatory guidelines for drug approvals, which may be followed by applying new chemical entities the new drug application title (NDA) in new drug application as well as there are various conventional to modern software based techniques to quantification of genotoxic impurities.

High Resolution Microscopy of Multi-Layered Biological Crystals

1982 ◽  
Vol 40 ◽  
pp. 80-83
Author(s):  
H.A. Cohen ◽  
T.W. Jeng ◽  
W. Chiu
Keyword(s):  
High Resolution ◽  
Low Dose ◽  
Three Dimensional ◽  
Data Interpretation ◽  
Two Dimensional ◽  
Biological Objects ◽  
Density Maps ◽  
Density Map ◽  
Complex Crystal ◽  
High Resolution Microscopy

This tutorial will discuss the methodology of low dose electron diffraction and imaging of crystalline biological objects, the problems of data interpretation for two-dimensional projected density maps of glucose embedded protein crystals, the factors to be considered in combining tilt data from three-dimensional crystals, and finally, the prospects of achieving a high resolution three-dimensional density map of a biological crystal. This methodology will be illustrated using two proteins under investigation in our laboratory, the T4 DNA helix destabilizing protein gp32*I and the crotoxin complex crystal.

GPR data interpretation by the deep learning with coloring data

2019 ◽  
Vol 72 (0) ◽  
pp. 68-77
Author(s):  
Shinichiro Iso ◽  
Kazuya Ishitsuka ◽  
Kyosuke Onishi ◽  
Toshifumi Matsuoka
Keyword(s):  
Deep Learning ◽  
Data Interpretation

Development of Backside Scanning Capacitance Microscopy Technique for Advanced SOI Microprocessors

2006 ◽  
Author(s):  
Vinod Narang ◽  
P. Muthu ◽  
J.M. Chin ◽  
Vanissa Lim
Keyword(s):  
Plasma Etching ◽  
Data Interpretation ◽  
Parameters Optimization ◽  
Scanning Capacitance Microscopy ◽  
Microscopy Technique ◽  
Thermal Oxide ◽  
Specific Analysis ◽  
Thin Oxide ◽  
P Type ◽  
Uv Ozone

Abstract Implant related issues are hard to detect with conventional techniques for advanced devices manufactured with deep sub-micron technology. This has led to introduction of site-specific analysis techniques. This paper presents the scanning capacitance microscopy (SCM) technique developed from backside of SOI devices for packaged products. The challenge from backside method includes sample preparation methodology to obtain a thin oxide layer of high quality, SCM parameters optimization and data interpretation. Optimization of plasma etching of buried oxide followed by a new method of growing thin oxide using UV/ozone is also presented. This oxidation method overcomes the limitations imposed due to packaged unit not being able to heat to high temperature for growing thermal oxide. Backside SCM successfully profiled both the n and p type dopants in both cache and core transistors.

Auto-Metrology on TEM Images of FinFET

2014 ◽  
Author(s):  
Sajal Biring
Keyword(s):  
Data Analysis ◽  
Data Interpretation ◽  
Visual Judgment ◽  
Manual Measurement ◽  
Size And Shape ◽  
Highly Sensitive ◽  
Edge Detecting ◽  
Geometrical Data ◽  
Precision And Accuracy ◽  
Device Size

Abstract The FinFET has been introduced in the last decade to provide better transistor performance as the device size shrinks. The performance of FinFET is highly sensitive to the size and shape of the fin, which needs to be optimized with tighter control. Manual measurement of nano-scale features on TEM images of FinFET is not only a time consuming and tedious task, but also prone to error owing to visual judgment. Here, an auto-metrology approach is presented to extract the measured values with higher precision and accuracy so that the uncertainty in the manual measurement can be minimized. Firstly, a FinFET TEM image is processed through an edge detecting algorithm to reveal the fin profile precisely. Finally, an algorithm is utilized to calculate out the required geometrical data relevant to the FinFET parameters and summarizes them to a table or plots a graph based on the purpose of data interpretation. This auto-metrology approach is expected to be adopted by academia and/or industry for proper data analysis and interpretation with higher precision and efficiency.

Sign in / Sign up

Export Citation Format

Share Document