Basic Science and Regulatory considerations, with ‘quality’ as the focal point are two vital comp... more Basic Science and Regulatory considerations, with ‘quality’ as the focal point are two vital components of Regulated bioanalysis (RegBio). With the advancement in scientific practices through continuous learning, RegBio has progressed significantly in the past two decades. At the same time, technological advancements and new regulatory requirements have propelled local and international regulatory agencies to bring about constructive improvements to their regulatory guidance and other relevant documents. Thus, the dynamism of RegBio demands not only sound scientific knowledge but also correct understanding of regulatory aspects. The conceptualization, creation and implementation of an appropriate ‘Quality Management System (QMS)’ for a bioanalytical lab necessitate focussed and sustained efforts from the doers (analysts, laboratory professionals), quality control (QC)/quality assurance (QA) personnel as well as the management (leadership). With inference to decades of globalized pra...
Bioana lysis is an integral part of various drug-development processes, whether it is a new chemi... more Bioana lysis is an integral part of various drug-development processes, whether it is a new chemical entity for investigational new drug application or a generic version of an existing drug approved for abbreviated new drug application. The importance of HPLC/UPLC–MS/MS method can be envisaged from its role in PK and metabolism studies at various drug-development stages since its introduction to the pharmaceutical industry. Bioanalytical science has progressed significantly in the past two decades and the advancement and learning out of progressive and purposeful innovations are invaluable. Such levels of transformations signify the highly dynamic nature of regulated bioana lysis. To cope with its ever-increasing demand, it is imperative to follow correct scientific practices, have adequate knowledge of principal and allied sciences, and technological innovations backed up by incessant efforts of bioscientists. The dynamic nature of biological fluids has always perplexed researchers especially in the context of bioanalytical measurements. Controlling bioanalytical variability is a challenging pursuit due to several compelling reasons:
The AAPS Workshop 2008 on Current Topics in GLP Bioanalysis: Assay Reproducibility for Incurred S... more The AAPS Workshop 2008 on Current Topics in GLP Bioanalysis: Assay Reproducibility for Incurred Samples was the defining moment in establishing incurred sample reanalysis (ISR) as a mandatory exercise in demonstrating assay reproducibility using incurred (study) samples. The importance of ISR can be envisaged from its role in clinical as well as non-clinical studies. Incurred samples can differ significantly in their composition when compared with the calibration standards and quality control samples that are used to validate the developed method. The present article attempts to summarize five troubleshooting cases encountered in the analyses of incurred samples for bioanalytical methods developed in our laboratory for mesalamine, hydrochlorothiazide, clopidogrel, sildenafil and rabeprazole. The issues identified were related to: sample inhomogeneity, sample processing error, impact of buffer pH during sample preparation, instability of metabolite and change in laboratory environmen...
“In the year 2011, during a vendor (CRO) qualification audit, I asked the analyst what is the rea... more “In the year 2011, during a vendor (CRO) qualification audit, I asked the analyst what is the reason for the failure of an analytical run? He responded “the root cause of analytical run failure is the non-compliance of QC samples to pre-defined acceptance criteria” ... Can this be a root cause? I thought. Although I was not convinced with the analyst’s response, but at the same time realized the significance of correct bioanalytical practices especially with regard to post bioanalysis phase.” Rationale interpretation of regulated bioanalysis implies intrinsic use of bioanalytical science, ‘quality’ aspects, regulatory requirements and good practices (GxP). With an increasing demand for reconstruction of bioanalysis using available documents on-site, laboratory data on accuracy and reproducibility, time-bound performance and continuous efforts to improve method efficiency, signify the importance of controlling quality and thoughtful human intervene using a robust quality management system (QMS). In addition to bioanalysis, this system also applies to drug substance and drug product analysis. As per current understanding, regulated bioanalysis can be categorized into four key phases: method development, method validation, bioanalysis (study sample analysis) and post bioanalysis, which includes reviews, hypothesis creation, reinvestigations and corrective actions and preventive actions (CAPA). Although these phases have evolved significantly in the last two decades, post bioanalysis phase has been a subject of intense scientific discussions at different forums. The issues related to the failure of analytical batches, pharmacokinetic repeats, conduct, failure and reporting of incurred sample reanalysis (ISR) have indeed highlighted the importance of this crucial phase. The expertise of rationale interpretation of regulated bioanalysis not only emphasizes the adequate use of an error-proof QMS but also implies prudent use of good quality practices (GxP; good laboratory practice [GLP]; good clinical practice [GCP]; good documentation practice [GDP] and good manufacturing practice [GMP]) for various bioanalytical phases by taking into account the scientific, quality or regulatory calls rationally based on the type and intensity of the analytical problems. The bioanalytical method validation and application phase of a validated method are well established, and are accepted as process-driven phases (standard operating procedures [SOPs], protocols, instructions and training, among others). On the contrary, similar method development phase, post bioanalysis phase demands a high degree of thinking and innovative approaches to hypothesize, investigate and resolve problems encountered by bioscientists in their day to day regimen. At the same time, it poses different level of challenges as most of the problems encountered in this phase are required to be resolved through detailed investigation, conclusion, CAPA and documentation within a stipulated time frame. From the historical front, the preregulations era in mid to late 1990s, bioanalysis was characterized by basically two phases, Significance of ‘post bioanalysis phase’ in bioanalysis: is GMP creeping into GLP?
Background. Many factors are responsible for this impaired healing, especially in long bones, but... more Background. Many factors are responsible for this impaired healing, especially in long bones, but a possible genetic predisposition for the development of this complication remains unknown till now. In the present study, we aim to examine the CYR61 gene polymorphism in fracture nonunion patients and the correlation with clinical findings. Materials and Methods. We performed SNP analysis of the CYR61 gene in 250 fracture nonunion patients and 250 healthy subjects were genotyped in this hospital-based case control study, and 56 cases were further evaluated for mRNA expression of CYR61 by real-time quantitative reverse-transcription PCR. Results. CYR61 gene TT, TG, and GG genotype frequencies of total fracture nonunion cases were 41.6%, 49.2%, and 9.20% and 54.4%, 39.2%, and 6.40% in healthy controls. Heterozygous TG genotype was found statistically significant in fracture nonunion cases compared with that in controls, whereas homozygous mutant GG genotype was not found significant. Moreover, we found that TG + GG genotypes were significantly different in serum expression of CYR61 mRNA when compared with cases (TT genotypes). Conclusions. Our result signifies that genotype of CYR61 affects the mRNA expression and acts as a risk factor that could synergistically increase the susceptibility of a patient to develop fracture nonunion.
The present study was conducted to see whether preoperative ultrasonography can be used as a pred... more The present study was conducted to see whether preoperative ultrasonography can be used as a predictor of difficult lapariscopic cholecystectomy or not. 50 patients of cholelithiasis, selected from surgical OPD of Rajindra Hospital Patiala, who fulfilled all inclusion and exclusion criteria for the study underwent elective cholecystectomy. Ultrasonography was done pre-operatively on all cases in the same setup and with same probe and patients underwent laparoscopic cholecystectomy in same setup. A significant prediction was found between ultrasonographic parameters and conversion of the procedure to open cholecystectomy which proved that pre-operative ultrasonography is a good predictor of difficulty in laparoscopic cholecystectomy in majority of the cases and should be used as a screening procedure. Preoperative ultrasonography should be used as a screening procedure as it is a good predictor of difficulty in laparoscopic cholecystectomy in majority of the cases. It can help surgeon to get an idea of potential difficulty that he can face in the particular patient.
2012 International Conference on Enabling Science and Nanotechnology, 2012
Increasing short channel effects like drain induced barrier lowering (DIBL) and VT roll-off are s... more Increasing short channel effects like drain induced barrier lowering (DIBL) and VT roll-off are serious impediments to further scaling of conventional MOSFET. These limitations instigated all researchers to look for innovative devices. Non-scalable sub-threshold swing in MOSFET limits its application in high speed and low power application. Tunnel FET is a strong candidate in high speed and low power application
The manipulation and characterization of residual stress and wafer curvature in anodically bonded... more The manipulation and characterization of residual stress and wafer curvature in anodically bonded structures is useful in improving the reliability of devices built on silicon on glass substrates. Conventional anodic bonding procedures lead to uncontrolled curvature of the bonded substrates as a ...
Applied Pharmaceutical Analysis (APA) India 23-26 February 2014, Ahmedabad, India The fifth Appli... more Applied Pharmaceutical Analysis (APA) India 23-26 February 2014, Ahmedabad, India The fifth Applied Pharmaceutical Analysis (APA) India meeting was held in February 2014 at Hyatt Ahmedabad, India. With the theme of 'The Science of Measurement: Current status and Future trends in Bioanalysis, Biotransformation and Drug Discovery Platforms', the conference was attended by over 160 delegates. The agenda comprised advanced and relevant research topics in the key areas of bioanalysis and drug metabolism. APA India 2014 provided a unique platform for networking and professional linking to participants, innovators and policy-makers. As part of the global research community, APA India continues to grow and receive considerable attention from the drug discovery and development community of India.
2008 International Conference on Condition Monitoring and Diagnosis, 2008
... STUDY A family of two winding Power transformer rated 150MVA, 220/66/11kV, and voltage regula... more ... STUDY A family of two winding Power transformer rated 150MVA, 220/66/11kV, and voltage regulation on HV winding neutral. ... Denny Chelladurai E1*, Santosh Kumar A2, Manish Yadav1 and AVenkatasami2 1 Crompton Greaves Ltd, Transformer Division (T-3), Bhopal 462 ...
Basic Science and Regulatory considerations, with ‘quality’ as the focal point are two vital comp... more Basic Science and Regulatory considerations, with ‘quality’ as the focal point are two vital components of Regulated bioanalysis (RegBio). With the advancement in scientific practices through continuous learning, RegBio has progressed significantly in the past two decades. At the same time, technological advancements and new regulatory requirements have propelled local and international regulatory agencies to bring about constructive improvements to their regulatory guidance and other relevant documents. Thus, the dynamism of RegBio demands not only sound scientific knowledge but also correct understanding of regulatory aspects. The conceptualization, creation and implementation of an appropriate ‘Quality Management System (QMS)’ for a bioanalytical lab necessitate focussed and sustained efforts from the doers (analysts, laboratory professionals), quality control (QC)/quality assurance (QA) personnel as well as the management (leadership). With inference to decades of globalized pra...
Bioana lysis is an integral part of various drug-development processes, whether it is a new chemi... more Bioana lysis is an integral part of various drug-development processes, whether it is a new chemical entity for investigational new drug application or a generic version of an existing drug approved for abbreviated new drug application. The importance of HPLC/UPLC–MS/MS method can be envisaged from its role in PK and metabolism studies at various drug-development stages since its introduction to the pharmaceutical industry. Bioanalytical science has progressed significantly in the past two decades and the advancement and learning out of progressive and purposeful innovations are invaluable. Such levels of transformations signify the highly dynamic nature of regulated bioana lysis. To cope with its ever-increasing demand, it is imperative to follow correct scientific practices, have adequate knowledge of principal and allied sciences, and technological innovations backed up by incessant efforts of bioscientists. The dynamic nature of biological fluids has always perplexed researchers especially in the context of bioanalytical measurements. Controlling bioanalytical variability is a challenging pursuit due to several compelling reasons:
The AAPS Workshop 2008 on Current Topics in GLP Bioanalysis: Assay Reproducibility for Incurred S... more The AAPS Workshop 2008 on Current Topics in GLP Bioanalysis: Assay Reproducibility for Incurred Samples was the defining moment in establishing incurred sample reanalysis (ISR) as a mandatory exercise in demonstrating assay reproducibility using incurred (study) samples. The importance of ISR can be envisaged from its role in clinical as well as non-clinical studies. Incurred samples can differ significantly in their composition when compared with the calibration standards and quality control samples that are used to validate the developed method. The present article attempts to summarize five troubleshooting cases encountered in the analyses of incurred samples for bioanalytical methods developed in our laboratory for mesalamine, hydrochlorothiazide, clopidogrel, sildenafil and rabeprazole. The issues identified were related to: sample inhomogeneity, sample processing error, impact of buffer pH during sample preparation, instability of metabolite and change in laboratory environmen...
“In the year 2011, during a vendor (CRO) qualification audit, I asked the analyst what is the rea... more “In the year 2011, during a vendor (CRO) qualification audit, I asked the analyst what is the reason for the failure of an analytical run? He responded “the root cause of analytical run failure is the non-compliance of QC samples to pre-defined acceptance criteria” ... Can this be a root cause? I thought. Although I was not convinced with the analyst’s response, but at the same time realized the significance of correct bioanalytical practices especially with regard to post bioanalysis phase.” Rationale interpretation of regulated bioanalysis implies intrinsic use of bioanalytical science, ‘quality’ aspects, regulatory requirements and good practices (GxP). With an increasing demand for reconstruction of bioanalysis using available documents on-site, laboratory data on accuracy and reproducibility, time-bound performance and continuous efforts to improve method efficiency, signify the importance of controlling quality and thoughtful human intervene using a robust quality management system (QMS). In addition to bioanalysis, this system also applies to drug substance and drug product analysis. As per current understanding, regulated bioanalysis can be categorized into four key phases: method development, method validation, bioanalysis (study sample analysis) and post bioanalysis, which includes reviews, hypothesis creation, reinvestigations and corrective actions and preventive actions (CAPA). Although these phases have evolved significantly in the last two decades, post bioanalysis phase has been a subject of intense scientific discussions at different forums. The issues related to the failure of analytical batches, pharmacokinetic repeats, conduct, failure and reporting of incurred sample reanalysis (ISR) have indeed highlighted the importance of this crucial phase. The expertise of rationale interpretation of regulated bioanalysis not only emphasizes the adequate use of an error-proof QMS but also implies prudent use of good quality practices (GxP; good laboratory practice [GLP]; good clinical practice [GCP]; good documentation practice [GDP] and good manufacturing practice [GMP]) for various bioanalytical phases by taking into account the scientific, quality or regulatory calls rationally based on the type and intensity of the analytical problems. The bioanalytical method validation and application phase of a validated method are well established, and are accepted as process-driven phases (standard operating procedures [SOPs], protocols, instructions and training, among others). On the contrary, similar method development phase, post bioanalysis phase demands a high degree of thinking and innovative approaches to hypothesize, investigate and resolve problems encountered by bioscientists in their day to day regimen. At the same time, it poses different level of challenges as most of the problems encountered in this phase are required to be resolved through detailed investigation, conclusion, CAPA and documentation within a stipulated time frame. From the historical front, the preregulations era in mid to late 1990s, bioanalysis was characterized by basically two phases, Significance of ‘post bioanalysis phase’ in bioanalysis: is GMP creeping into GLP?
Background. Many factors are responsible for this impaired healing, especially in long bones, but... more Background. Many factors are responsible for this impaired healing, especially in long bones, but a possible genetic predisposition for the development of this complication remains unknown till now. In the present study, we aim to examine the CYR61 gene polymorphism in fracture nonunion patients and the correlation with clinical findings. Materials and Methods. We performed SNP analysis of the CYR61 gene in 250 fracture nonunion patients and 250 healthy subjects were genotyped in this hospital-based case control study, and 56 cases were further evaluated for mRNA expression of CYR61 by real-time quantitative reverse-transcription PCR. Results. CYR61 gene TT, TG, and GG genotype frequencies of total fracture nonunion cases were 41.6%, 49.2%, and 9.20% and 54.4%, 39.2%, and 6.40% in healthy controls. Heterozygous TG genotype was found statistically significant in fracture nonunion cases compared with that in controls, whereas homozygous mutant GG genotype was not found significant. Moreover, we found that TG + GG genotypes were significantly different in serum expression of CYR61 mRNA when compared with cases (TT genotypes). Conclusions. Our result signifies that genotype of CYR61 affects the mRNA expression and acts as a risk factor that could synergistically increase the susceptibility of a patient to develop fracture nonunion.
The present study was conducted to see whether preoperative ultrasonography can be used as a pred... more The present study was conducted to see whether preoperative ultrasonography can be used as a predictor of difficult lapariscopic cholecystectomy or not. 50 patients of cholelithiasis, selected from surgical OPD of Rajindra Hospital Patiala, who fulfilled all inclusion and exclusion criteria for the study underwent elective cholecystectomy. Ultrasonography was done pre-operatively on all cases in the same setup and with same probe and patients underwent laparoscopic cholecystectomy in same setup. A significant prediction was found between ultrasonographic parameters and conversion of the procedure to open cholecystectomy which proved that pre-operative ultrasonography is a good predictor of difficulty in laparoscopic cholecystectomy in majority of the cases and should be used as a screening procedure. Preoperative ultrasonography should be used as a screening procedure as it is a good predictor of difficulty in laparoscopic cholecystectomy in majority of the cases. It can help surgeon to get an idea of potential difficulty that he can face in the particular patient.
2012 International Conference on Enabling Science and Nanotechnology, 2012
Increasing short channel effects like drain induced barrier lowering (DIBL) and VT roll-off are s... more Increasing short channel effects like drain induced barrier lowering (DIBL) and VT roll-off are serious impediments to further scaling of conventional MOSFET. These limitations instigated all researchers to look for innovative devices. Non-scalable sub-threshold swing in MOSFET limits its application in high speed and low power application. Tunnel FET is a strong candidate in high speed and low power application
The manipulation and characterization of residual stress and wafer curvature in anodically bonded... more The manipulation and characterization of residual stress and wafer curvature in anodically bonded structures is useful in improving the reliability of devices built on silicon on glass substrates. Conventional anodic bonding procedures lead to uncontrolled curvature of the bonded substrates as a ...
Applied Pharmaceutical Analysis (APA) India 23-26 February 2014, Ahmedabad, India The fifth Appli... more Applied Pharmaceutical Analysis (APA) India 23-26 February 2014, Ahmedabad, India The fifth Applied Pharmaceutical Analysis (APA) India meeting was held in February 2014 at Hyatt Ahmedabad, India. With the theme of 'The Science of Measurement: Current status and Future trends in Bioanalysis, Biotransformation and Drug Discovery Platforms', the conference was attended by over 160 delegates. The agenda comprised advanced and relevant research topics in the key areas of bioanalysis and drug metabolism. APA India 2014 provided a unique platform for networking and professional linking to participants, innovators and policy-makers. As part of the global research community, APA India continues to grow and receive considerable attention from the drug discovery and development community of India.
2008 International Conference on Condition Monitoring and Diagnosis, 2008
... STUDY A family of two winding Power transformer rated 150MVA, 220/66/11kV, and voltage regula... more ... STUDY A family of two winding Power transformer rated 150MVA, 220/66/11kV, and voltage regulation on HV winding neutral. ... Denny Chelladurai E1*, Santosh Kumar A2, Manish Yadav1 and AVenkatasami2 1 Crompton Greaves Ltd, Transformer Division (T-3), Bhopal 462 ...
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