scholarly journals Quantitative CPP Evaluation from Risk Assessment Using Integrated Process Modeling

2019 ◽  
Vol 6 (4) ◽  
pp. 114 ◽  
Author(s):  
Daniel Borchert ◽  
Thomas Zahel ◽  
Yvonne E. Thomassen ◽  
Christoph Herwig ◽  
Diego A. Suarez-Zuluaga
Keyword(s):  
Process Modeling ◽  
Potential Effect ◽  
Risk Assessments ◽  
Effect Sizes ◽  
Quality Attribute ◽  
Integrated Process ◽  
Risk Priority Number ◽  
Mathematical Operation ◽  
Critical Quality Attribute ◽  
Mathematical Algorithm

Risk assessments (RAs) are frequently conducted to assess the potential effect of process parameters (PPs) on product quality attributes (e.g., a critical quality attribute (CQA)). To evaluate the PPs criticality the risk priority number (RPN) for each PP is often calculated. This number is generated by the multiplication of three factors: severity, occurrence, and detectability. This mathematical operation may result in some potential errors due to the multiplication of ordinal scaled values and the assumption that the factors contribute equally to the PPs criticality. To avoid these misinterpretations and to assess the out of specification (OOS) probability of the drug substance, we present a novel and straightforward mathematical algorithm. This algorithm quantitatively describes the PPs effect on each CQA assessed within the RA. The transcription of severity and occurrence to model effect sizes and parameters distribution are the key elements of the herein developed approach. This approach can be applied to any conventional RA within the biopharmaceutical industry. We demonstrate that severity and occurrence contribute differently to the PP criticality and compare these results with the RPN number. Detectability is used in a final step to precisely sort the contribution of each factor. To illustrate, we show the misinterpretation risk of the PP critically by using the conventional RPN approach.

A Scale-up Approach for Film Coating Process Based on Surface Roughness as the Critical Quality Attribute

2018 ◽  
Vol 19 (3) ◽  
pp. 1243-1253 ◽  
Author(s):  
Hiroyuki Yoshino ◽  
Yuko Hara ◽  
Masafumi Dohi ◽  
Kazunari Yamashita ◽  
Tadashi Hakomori ◽  
...  
Keyword(s):  
Surface Roughness ◽  
Scale Up ◽  
Film Coating ◽  
Coating Process ◽  
Quality Attribute ◽  
Critical Quality Attribute

Integrated process modeling: An ontological evaluation

2000 ◽  
Vol 25 (2) ◽  
pp. 73-87 ◽  
Author(s):  
Peter Green ◽  
Michael Rosemann
Keyword(s):  
Process Modeling ◽  
Integrated Process

scholarly journals NONDESTRUCTIVE FIRMNESS MEASUREMENT OF KIWIFRUIT

HortScience ◽  
1992 ◽  
Vol 27 (6) ◽  
pp. 599b-599
Author(s):  
Judith A. Abbott ◽  
D. R. Massie
Keyword(s):  
Data Processing ◽  
Resonance Frequency ◽  
Vibrational Spectra ◽  
Storage Time ◽  
Maximum Force ◽  
Dynamic Force ◽  
Quality Attribute ◽  
Critical Quality Attribute ◽  
Resonance Frequencies ◽  
Highly Correlated

Firmness is a critical quality attribute for kiwifruit, as it is for most commodities. Firmness is related to flesh elasticity and rigidity which, along with geometry and density, determine vibrational behavior. Firmness changes in kiwifruit were followed during storage at 0C by three methods: sonic vibrational spectra from 0 to 2000 Hz, dynamic force/deformation (F/D) in the range 40 to 440 Hz, and Magness-Taylor puncture (MT) on an Instron. Frequencies of sonic resonances and dynamic F/D peaks, as well as MT maximum force, decreased as storage time increased. Sonic resonance frequencies were highly correlated with MT maximum force and apparent elasticity (r=0.79 and 0.88). Frequencies of peaks in the dynamic F/D traces were correlated with MT maximum force and apparent elasticity (r=0.68 and 0.72) and with resonance frequency (r=0.81). Further data processing improves the ability of the nondestructive vibrational measurements to estimate the destructive MT test values.

Effects of sialic acid linkage on antibody-fragment crystallizable receptor binding and antibody dependent cytotoxicity depend on levels of fucosylation/bisecting

Bioanalysis ◽  
2019 ◽  
Vol 11 (15) ◽  
pp. 1437-1449 ◽  
Author(s):  
Marco Thomann ◽  
Sebastian Malik ◽  
Felix Kuhne ◽  
Cecile Avenal ◽  
Friederike Plath ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Receptor Binding ◽  
Antibody Fragment ◽  
Quality Attribute ◽  
Fcγ Receptor ◽  
Critical Quality Attribute ◽  
Cytotoxicity Activity ◽  
Terminal Galactose ◽  
The Impact ◽  
Different Levels

Aim: Fragment crystallizable (Fc) glycosylation of immunoglobulin G-type monoclonal antibodies applied to therapeutic applications is regarded a critical quality attribute and can influence bioactivity, pharmacokinetics and/or immunogenicity/safety. Investigating the impact of certain Fc N-glycans is therefore of importance to assess its criticality for a therapeutic product. This has been done for N-glycan types like fucosylation, galactosylation or sialylation. There were contradictory results reported for functionality especially with regard to sialylation. Material & methods: We elucidated the effect of terminal sialic acid residues on Fcγ receptor binding and antibody dependent cytotoxicity activity of two immunoglobulin G1 antibodies with different levels of fucosylation/bi-secting. Conclusion: We found the impact to be specific to the sialylation linkage type, in other words, α2,3- versus α2,6-linked sialic acid attached to the terminal galactose residues

scholarly journals Best practices in bioassay development to support registration of biopharmaceuticals

BioTechniques ◽  
2019 ◽  
Vol 67 (3) ◽  
pp. 126-137 ◽  
Author(s):  
John R White ◽  
Marla Abodeely ◽  
Sammina Ahmed ◽  
Gaël Debauve ◽  
Evan Johnson ◽  
...  
Keyword(s):  
Biological Activity ◽  
Best Practices ◽  
Mechanisms Of Action ◽  
Point Of View ◽  
Relative Potency ◽  
Quality Attribute ◽  
Critical Quality Attribute ◽  
Statistical Approaches ◽  
And Control

Biological activity is a critical quality attribute for biopharmaceuticals, which is accurately measured using an appropriate relative potency bioassay. Developing a bioassay is a complex, rigorous undertaking that needs to address several challenges including modelling all of the mechanisms of action associated with the biotherapeutic. Bioassay development is also an exciting and fast evolving field, not only from a scientific, medical and technological point of view, but also in terms of statistical approaches and regulatory expectations. This has led to an industry-wide discussion on the most appropriate ways to develop, validate and control the bioassays throughout the drug lifecycle.

scholarly journals Biomimicry: Do Frames of Inquiry Support Search and Identification of Biological Models?

Designs ◽  
2018 ◽  
Vol 2 (3) ◽  
pp. 27 ◽  
Author(s):  
Emily Kennedy ◽  
Peter Niewiarowski
Keyword(s):  
Research And Development ◽  
Case Studies ◽  
Model Identification ◽  
Potential Effect ◽  
Effect Sizes ◽  
Biological Model ◽  
Biological Models ◽  
Crucial Step ◽  
Four Frames ◽  
Design Challenge

A crucial step in the biomimicry process is the search and identification of biological models relevant to the design challenge. Anecdotal observations from case studies in authentic business contexts, as well as emerging literature on biomimicry methods, suggest that tools, which focus the search for biological models, could help research and development (R&D) professionals execute this step more effectively. We prototyped one such tool, a set of four frames of inquiry, to test whether it helped R&D professionals identify a greater quantity and variety of biological models. The tool we prototyped did not significantly improve biological model identification; however, its use was associated with a trend of higher quantity and variety of biological models. Our study, as well as previous work, both empirical and theoretical, suggests that tools, like ours, could improve the search and identification of biological models. We encourage further tests using larger samples sizes and/or conditions that maximize potential effect sizes.

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