CSA: Much Ado About Nothing?

FDA guidance helps facilitate drug co-development

Patients would suffer under draft FDA guidances, pharmacists say

Crystal City V meeting on Quantitative Bioanalytical Method Validation and Implementation: 2013 Revised US FDA Guidance 3-5 December 2013, Hilton Baltimore, MD, USA The meeting provided an opportunity for Industry and regulators from the US FDA to discuss the recently published revised draft FDA Guidance for Industry on Bioanalytical Methods Validation during the 90 day review period. Key perspective and philosophical positions were shared leading to a healthy exchange of views and ideas on topics in the revised document. Discussions covered all aspects of bioanalytical method validation and method utilization. However, the main dialogue was focused on chromatographic methods, ligand-binding assay methods and biomarker analysis. The resulting open debate led to greater understanding of the document, but also provided clear feedback, including the request on harmonization with approved Bioanalytical Methods Validation guidance's release from other health authorities, as well as the consensus view between industry and the FDA. Members of the European Bioanalysis Forum summarized prospective discussions during the meeting in Baltimore; however, this Report is not intended to constitute the official proceedings from the meeting, which are expected to be published later this year.

BackgroundClinical trials are underway to treat familial frontotemporal lobar degeneration (f‐FTLD). This is a rare disease, and a limited number of mutation carriers have been identified; thus, efficient trial design is critical. Multimodal, latent disease progression models (DPM) can estimate time to symptom onset and define the temporal ordering of biomarker changes. DPMs can also be leveraged to select endpoints and potentially supplement analyses by integrating historical data. Recent draft FDA guidance for gene therapy trials in neurological disease supports these novel approaches to clinical trials.MethodParticipants included 1,049 members of families affected by f‐FTLD, due to mutations in GRN, MAPT, or C9orf72 genes, who were enrolled in ALLFTD or GENFI. A Bayesian repeated measures model incorporated multimodal data to estimate disease progression, conditional on latent disease age (proximity to symptom onset), in 677 mutations carriers (GRN (n=233), MAPT (n=151) and C9orf72 (n=293)). Family members without pathogenic mutations were used as the reference group. Mean follow‐up was 1.1 (SD=1.1) years. Jointly modeled longitudinal variables included neuropsychological scores, CDR®+NACC‐FTLD Box Score, MRI volumes of brain regions affected by f‐FTLD, and plasma levels of neurofilament light chain (NfL).ResultDisease progression curves were similar across ALLFTD and GENFI cohorts. Plasma NfL elevations occurred earliest, up to 10 years before symptom onset, and NfL was the most powerful endpoint in the asymptomatic stage. MRI abnormalities occurred next, closer to symptom onset. The earliest MRI changes relative to symptom onset were observed in C9orf72+. GRN mutation carriers showed the most rapid acceleration in all biomarkers, and this acceleration occurred in close proximity to symptom onset. Neuropsychological measures and CDR®+NACC‐FTLD Box Score were among the most promising endpoints in the symptomatic stage. Trial simulations indicated that using latent disease age as an enrollment criterion would allow some asymptomatic mutation carriers to be enrolled without sacrificing power.ConclusionSimilarity in disease progression across ALLFTD and GENFI participants suggests these models will apply to international trials. Model‐derived estimates of disease progression curves indicate that endpoint selection should be specific to disease stage and mutation, and DPMs would facilitate greater participant enrollment.

FDA CDER analysis of non-human primate (NHP) data in monoclonal antibody (mAb) development to support the streamlining of nonclinical safety studies.

Open Source Software (OSS) is software products available to the public, with its source code to study, change, and improves its design. Open Source Software Development (OSSD) is the process by which open source software is developed within the confines of software engineering life-cycle methods. However when open source used for commercial purpose, then an open source license is required. Open source software is very often developed in a public and collaborative manner. The quality assurance principle under open source software development is an approach to improve software product quality against traditional methods and techniques. Despite the fact that the open source developments have seen remarkable successful in recent years, there are a number of product quality issues and challenges facing the open source development model. Many industries and business sectors are following or using OSSD, since they realize the benefits, but they do have some reservations concerning quality assurance in the form of program code quality, maintenance of the code and its quality, over the life-cycle of the product and third party usage. This paper reviews the literature of the process of the latest quality assurance, under open source software development methods and techniques. The result from this review is to show the process of quality assurance of open source software and that how it can affect the overall quality assurance principal.

Besides the conceptual phase IT-Security focuses on the two main parts in the life cycle of the software product, the operational and the constructional phase. The constructional phase as a foundation of the correctness of the software product is currently the scope of a project called DA (Developmental Assurance) running at the BSI (Bundesamt fur Sicherheit in der Informationstechnik) in Bonn, Germany, with coordination of these activities in the international scope. One of the key technologies to manage the software engineering process is the use of a tool driven Software Configuration Management.