Dieter Zimmer

Recommendations on the interpretation of the new European Medicines Agency Guideline on Bioanalytical Method Validation by Global CRO Council for Bioanalysis (GCC)

) Guideline on Bioanalytical Method Validation (BMV), during the 4th GCC (23 October 2011, Washington DC, USA) and 5th GCC (14 November 2011, Barcelona, Spain) Closed Forums. These North American and European events provided a unique opportunity for CRO leaders to openly share opinions and perspectives and to agree on unified bioanalytical recommendations specifically in relation with the new EMA guideline.The Global CRO Council for Bioanalysis (GCC)

Internal standard application to dried blood spots by spraying: investigation of the internal standard distribution.

BACKGROUND The scientifically and logistically best way of application of the internal standard (IS) in the analysis of dried blood spots (DBS) analysis is still a matter of debate and investigation. Most commonly the IS is added in the solvent used for extraction of the discs punched from DBS. In this case, the recovery of the non-extracted IS is complete while the recovery of the analyte extracted from DBS is different from the IS. RESULTS An alternative way for addition of the IS was investigated. A homogeneous distribution and absorption of the test compound across the spots was demonstrated by spraying a solution of a radiolabeled test compound (mimicking an IS solution) onto DBS. CONCLUSION This spray-on technique is convenient and easily automatable. Spraying of the solution was rapid, precise and reproducible, and therefore seems to be suitable for routine analysis of DBS by offline and online extraction.

The changing world of bioanalysis: summary of panel discussions

2017 The world of bioanalysis is changing rapidly. The move toward the measurement of endogenous molecules to understand drug pharmacodynamics (PD), efficacy and toxicity and the expanding numbers of novel molecular constructs for pharmaceuticals (peptides, proteins, oligonucleotides, antibody–drug conjugates, gene therapy, etc.) bring exciting analytical challenges. Further, novel analytical instrumentation and workflows are continually being developed, offering benefits, new ways of working and bringing associated challenges (e.g., microsampling, high resolution mass spectrometry [HRMS], capillary separations, etc.). In addition to this, pharmaceutical companies (Pharma) are increasingly turning to outsourcing as a routine approach, requiring different ways of working. On top of this, the regulatory landscape is continually changing. All of these changes inevitably bring stimulating challenges and opportunities for current and future practitioners of bioanalysis, requiring them to continually develop themselves in order to stay current. In November 2016 at a venue in Barcelona, Bioanalysis Zone brought together eleven bioanalytical experts from Pharma, Contract Research Organizations (CROs) and consultancy companies to discuss these issues that are facing the quantitative bioanalytical community. The panel discussion was filmed and can be viewed full on the Bioanalysis Zone website [1]. The following is a summary of this insightful and honest dialogue, which was built on a similar event e arlier in 2016 in Orlando [2,3]. How do we access the required skill sets? The initial discussion centered around whether staff in quantitative bioanalytical laboratories in Pharma and CRO companies have the skills to equip them for the challenges arising from these novel analytical constructs, workflows and instrumentation, and consequently whether we are adequately training the next generation of bioanalytical scientists. It was agreed that to meet these analytical challenges, new skill sets are required including learning how to use and apply novel instrumentation, and to combine technologies and develop novel analytical approaches from what have traditionally been separate areas. It was noted that even for small molecule pharmaceuticals, the nature of the molecules is changing, with them becoming harder to analyze using standard LC–MS/MS approaches and that alternative methods such as derivatization and supercritical fluid chromatography are now often being required. Further, project teams are increasingly requiring bioanalytical scientists to have broader based scientific understanding of drug development for both small and large molecules in addition to their analytical contributions. This includes understanding the pharmacology and toxicology of the test molecule and close involvement in clinical trials. It was considered that while the bioanalytical scientists have the tools and instrumentation they require to solve these emerging exciting analytical challenges, it is apparent that in general they are still acquiring the additional The changing world of bioanalysis: summary of panel discussions

Outsourcing strategy: local versus international contract research organizations

General aspects of bioanalytical (BA) outsourcing, such as: history and current outsourcing strategies; advantages, disadvantages and challenges; factors influencing contract research organization (CRO) selection; different models of contractor and CRO relationships; cost management in a CRO; and the future and perspectives of outsourcing have been discussed before [1,2]. At the 20th International Reid Bioanalytical Forum, a full session was dedicated to “collaborative partnerships between CROs and pharmaceutical companies” [3], demonstrating the increased importance of outsourcing to the pharmaceutical industry, which is experiencing probably the most turbulent time in its history due to continuous increase of drug-development costs, while blockbusters are running out of patents and fewer novel drug candidates gain regulatory approval. Neil Spooner (GlaxoSmithKline, Hertfordshire, UK) reported in his talk at the Reid Forum, that at GlaxoSmithKline, BA outsourcing had grown from approximately 30% in September 2010 to nearly 75% in March 2012, while toxicokinetics outsourcing rose from approximately 11 to 28% in the same period [3]. When talking about outsourcing in bioanalysis, one usually means regulatory bioanalysis; however, outsourcing even of discovery bioanalysis in the drug discovery stage has started. Graeme Clark (Cyprotex, Macclesfield, UK) illustrated at the Reid forum, by using real examples, the risk of wrong analytical results, since at this early stage usually no structural information on the analyte is provided to the CRO [3]. For the time being, it remains open if outsourcing of exploratory bioanalysis becomes a success story. This article presents a personal perspective on BA outsourcing strategies with a focus on differences, benefits and challenges of BA outsourcing to local (national) versus international CROs.