Archive by Author

Big Data Pentetrates the Pharma Industry

big-dataEveryone is talking about big data. Many IT companies put their focus on analyzing tons of information. Also the pharmaceutical industry collects very large data volume during their drug research, discovery and above all during the clinical phases.

This article from addresses the big data analysis demands of the pharma industry in a very interesting way. Therefore, I encourage everyone to read the article.

Visit “Leveraging big data to solve Pharma’s hard to cure problems”

Different QM/QA Levels for Genomics Analyses

quality1High quality standards are essential for non-clinical QC testing. When we obtained GLP certification, people ask me about relevant QM/QA levels for genomics analyses. This is what I tell them:

ISO 9001 – the basis

The ISO 9001 standard is a global quality management standard that favours process orientation, customer orientation, satisfaction and continuous improvement. ISO 9001 provides the basis for a quality management system ensuring that all processes are documented and defined in SOPs. In an ISO 9001 compliant laboratory responsibilities are clearly defined, all work environment and infrastructure is suited for its intended purpose. Equipment and facilities are qualified and maintained and measuring and testing equipment requires regular calibration. Also the staff is qualified and well trained and the training is recorded. Supplier management and purchase are controlled processes. Non-conforming work and failures are corrected and documented. Processes for corrective and preventive actions are implemented, as well as a proper complaint management. In an ISO 9001 QM system all business processes are monitored (e.g. by internal and external audits). Customer feedback and all data obtained are analysed on a regular basis. These data and information are the basis for continuous improvement of the ISO 9001 QM system.

ISO 17025 – assures technical valid results

The ISO 17025 is derived from ISO 9001. With an ISO 17025 accreditation a laboratory demonstrates its technical competence and the ability to generate technical valid and correct results. In addition to the ISO 9001 standard the participation in external proficiency testings is mandatory. Furthermore, the documentation of the lab procedures is a lot more detailed and involves dedicated protocolling procedures.

GLP – the gold standard to conduct non-clinical safety studies

The GLP (Good Laboratory Practice) standard adds on top of that a framework in which laboratories non-clinical safety studies are planned, performed, monitored, recorded, reported and archived. GLP helps to assure regulatory authorities that submitted data are a true reflection of the results, obtained during the study and can therefore be relied upon when making risk/safety assessments. In addition to the requirements of ISO 9001 and ISO 17025, GLP involves the nomination of a study director and dedicated trained personnel for GLP compliant processes. A study will involve always the creation of a study plan which will be signed by the study director. All processes applied in the study need to be described within the study plan. Any deviations to the study plan will lead to an amendment of the study plan. After completion of the analyses the study director generates a final report signed by Study Director and QA/QM. It also includes a signed QA-and GLP compliance statement. Each study is audited by quality assurance staff. Furthermore, there needs to be restricted laboratory access and restricted access to relevant data as well as dedicated archiving procedures (GLP archive) for all GLP documents and raw data..

GCP – similar to GLP with focus on clinical studies and patient safety

The GCP (Good Clinical Practice) standard is very similar to the GLP standard; however it is relevant only for clinical studies and has thus a focus on patient safety and reporting of adverse drug events. In a study that involves GCP compliance it has to be assured that only such things are analyzed that a study patient has consented to.

Feel free to write a comment for further clarification. I am looking forward to get in contact with you.

Cheers, Katrin

Note: NGS in Diagnostic Testing

Yes, this amazing technology is not just a tool for basic researcher anymore, but has made its way in to the clinical routine testing. It currently all about exome sequencing and targeted gene panel analysis, but whole genome sequencing is expected to come into clinical routine soon. Have a read through this comprehensive article which describes very nicely which applications are suitable for the diagnostic testing and which may come in the future.

Read the article about NGS in diagnostic testing

Update on NGS and Clinical Validation

Clinical validationThere is an increasing demand for the development of regulated next-generation sequencing based diagnostic tests. The review that I would like to draw your attention to is thoroughly discussing all challenges and issues that arise when developing NGS-based diagnostic tests or even CDx. The experts form the Merck Research Laboratories take very thing into account starting from the choice of the platform, bioinformatics through to the regulatory approval process.

Have a read, it’s really worth it!

Exome Sequencing At A Glance

Selective characterisation of the genome’s complete coding region

In humans, only 1-2 % of the genome is protein coding, the so-called exome. Exome sequencing is favoured over whole genome sequencing due to costs, efficiency and the easier interpretability of a much lower data volume compared to whole genome sequencing. It gains more and more clinical relevance in the determination of rare diseases as well as for cancer research and diagnostics. Furthermore, it’s a very important screening tool for genetic variations e. g. involved in mental disorders such as schizophrenia and is therefore increasingly used as one genomic application in drug discovery. Exome analyses are frequently conducted as trio analyses with one patient plus healthy parents, who serve as controls to filter out benign variants. They are not only performed on behalf of companies or academic research organisations, but also gain more importance in diagnostic applications for individuals.

The most common technologies for exome analysis are based on in-solution hybridisation. They use a protocol that first generates a whole genome library, and then enriches the exome portion of the genome. The well-established kits for this kind of analysis are from NimbleGen, Agilent and Illumina. The exome enriched DNA is then primarily sequenced with Next Generation Sequencing systems from Ilumina, like Illumina HiSeq. This approach is typically selected for projects with large sample numbers. One limitation is the incomplete coverage for some genetic loci. More consistent sequence coverage can be achieved by using a PCR based exome capture approach offered by Ion Torrent. This approach allows a very fast and a more uniform exome analysis ideal for small to mid-size sample numbers.


Tumor Heterogeneity And The Underlying Genetics

Although this recorded seminar is promoted by Illumina, I still can recommend it as a very good talk about basic concepts on tumor heterogeneity and the underlying genetics. Kenneth Bloom, Chief Medical Officer at Clarient (GE Healthcare) and a pathologist, explains the needs for the application of NGS in clinical lab in a simple and very vivid manner. While watching this video I gained a better idea of the needs of a diagnostics lab and the challenges in developing a diagnostic NGS panel.

Adventitious Virus Testing Via Next Generation Sequencing

Adventitious viruses are a major safety concern in biological products. For a substance to be considered “free” of an adventitious agent, assays must demonstrate that a defined quantity of the biological product is negative for an agent at a defined level of sensitivity. In vivo animal testing, in vitro cell culture testing, transmission electron microscopy and molecular assays like quantitative PCR (qPCR) are the current gold standards for viral safety testing. However, if for example the cell substrate contains potential contaminating agents coming from a tumor derived cell line, then current standard methods need to be supplemented by using novel technologies.

Deep sequencing approaches via the next generation sequencing (NGS) techniques may be the method of choice. They allow the detection not only of known viruses but also of unknown viruses or viral subspecies at the detection limit of qPCR-based methods. On the Pathogen Safety Summit (Munich (Germany), November 27-28, 2012) the application of NGS testing approaches were introduced and intensely discussed. The application of NGS into routine testing of production cell banks is presently evaluated by several biological and vaccine producing companies.

Currently, NGS is used for initial characterisation of cell banks, but it iss expected that this new technology will become a standard method for adventitious agent testing soon. There are still challenges that need to be overcome with regard to bioinformatic analyses as well as to the speed of the technological development. Furthermore, also the biological relevance of the NGS data needs to be confirmed. In this regard the expectation is that with the ability to purify active viral particles and subject them to NGS analysis this problem can be overcome.

Btw: Eurofins Medigenomix offers the detection of adventitious viruses in biologicals and biotechnological products by next generation sequencing on platforms from Illumina and Roche 454.

NGS Moving Towards Forensics

To me the article “Early Adopters Say NGS-based Forensic Testing Could Lead to More Precise Identification” by GenomeWeb ( is a very good sign of the “maturation” of the rather young next generation technology. It may find its way into criminal police offices soon.

Currently, forensic profiling is based on STR analysis with capillary electrophoresis, or analysis of mitochondrial DNA with PCR and Sanger sequencing. But next gen sequencing opens up new possibilities. Researchers are now looking at moving both STR profiling and mitochondrial DNA analysis to next gen sequencing, but are also looking to develop SNP-based targeted sequencing panels for forensics, which would enable researchers to identify a person’s ancestry, hair color, or other defining characteristics based on their DNA.

So, what do you think: Will there still be classical DNA profiling or will NGS have taken over in the next decade?

Genetics of Cancer

While I was browsing the internet for news on NGS and cancer sequencing, I came across the YouTube link below.  The famous oncologist Bert Vogelstein gave this amazing talk about genetics of cancer over a year ago. To my opinion he outlines very nicely the concepts of oncological marker discovery and how we could/should make use of the next generation sequencing technology. Although it’s a long talk, it is worth while watching at least the first part of the talk.