Expect Nothing Less: Expectations of a Contract Research Organization

By Jon Rhodes, M.S.
Senior Scientific Advisor
ABC Laboratories
www.abclabs.com

The pharmaceutical, agrichemical, chemical, and biotechnology industries depend heavily on Contract Research Organizations (CRO’s) to provide high quality, scientifically sound laboratory and field-based services.  And to do so with minimal input from the Sponsoring organization on the routine aspects of study design, conduct, and reporting.  After all, many CRO’s have decades of cumulative experience relative to experimental design and execution as well as what regulators are likely to accept.  In addition CRO’s have deep knowledge of standard practices and individual registrant nuances that can be leveraged to ensure high quality and regulatory acceptability. The overriding goal is to ensure quality science while meeting challenging development timelines.

The basic expectations of a Contract Research Organization have not changed:

• The CRO will conduct studies that satisfy scientific regulatory requirements and customer reporting standards

• The CRO will ensure communication is proactive and timely

• The CRO will offer proactive technical advice and feedback based on practical experience

• The CRO will ensure consistency of approach across all projects within the organization

Likewise the basic expectations of a Registrant have not changed:

• The registrant will provide all study specific information relative to desired project design and will provide deadlines for deliverables

• The registrant will supply specific information about the test material (if available) including analytes and analytical methods, expected behavior of test material, expected toxicity, and any specific requirements required to ensure consistency of testing strategy

• The registrant will provide technical advice and feedback based on practical experience with the test material and experience of approaches received from regulators

• The registrant will ensure timely communication to the CRO relative to study plan and report reviews, responses to study updates and suggestions/questions, and timeline changes

A lot of what makes a successful partnership isn’t strictly science – communication and transparency are everything.

Upcoming ABC Webinar: "The Use of High Resolution Accurate Mass Spectrometry in Environmental Fate and Metabolism Studies"

The use of liquid chromatography coupled with high resolution mass spectrometry (LC-HRMS) can be a powerful tool in the characterization and identification of metabolites and degradation products of environmental pollutants in environmental fate and metabolism studies, whether conducted in the laboratory or the field. Advantages of HRMS include:

• Improved accuracy – important in distinguishing analytes from isobaric interferences in complicated matrices

• Improved post-acquisition data processing – important in reducing the number of analyses and experiments required to get results

• Scientific and regulatory necessity – important owing to the required non-targeted analysis of novel compounds dosed at ever lower levels

This webinar will review the merits of employing LC-HRMS by addressing these basic concepts:

• Scientific and regulatory importance of metabolite identification

• Instrument Platforms

• Mass resolution and accurate mass measurements

• Molecular Formula Information (Most Probable Elemental Composition)

• Data-Processing Techniques (mass defect filtering, isotope pattern, etc.)

• The Importance of Separations Chemistry

• Future Developments of HRMS in Environmental Fate and Metabolism

The presentation will also review case studies in the scientific literature and examples from our laboratory to illustrate how HRMS can be employed in environmental fate and metabolism studies to answer both scientific and regulatory questions.

Gene Editing - A New Frontier

By Glenn Petrie, Ph.D.
Senior Scientific Advisor
ABC Laboratories
www.abclabs.com

A new technology for “editing” genes has scientists excited about an entirely new method for treating disease. The CRISPR technique, along with other gene-editing technologies (TALENS, zinc finger nucleases) allow for the precise deletion of specific DNA sequences. CRISPR involve a Cas9 protein linked to an RNA strand. The RNA sequence serves to target the specific DNA sequence of interest and once bound the Cas9 enzyme cleaves both strands of the DNA.

Above graphic credit (link) to Scitechweb.com 

Since RNA synthesis is relatively cheap and easy this technology has exploded in the last 2 years. Feng Zhang and Eric Lander at MIT have created CRISPR libraries that target essentially the entire human genome. The promise of the technology is to delete genetic mutations and replace them with the correct genes.  Initial targets involve only a single mutation, e.g. sickle-cell anemia, progressing to diseases involving multiple mutations.

As with any new technology there are calls for caution. Chinese scientists reported attempts to repair defective genes in human embryos. This held up the specter of future “designer babies” enhanced in their embryonic stages. Others warn that this technology could be used to “weaponize” bacteria or viruses. Several prominent scientists have proposed a complete moratorium on gene editing until proper safeguards are in place.

Despite these concerns several biotech start-ups have been founded in the last 2 years including Intellia Therapeutics, Editas Medicine and Crispr Therapeutics. Successful in vitro results have been reported for the repair/modification of clinically important genes in hematopoietic stem cells, fibroblasts and T-cells. A quick internet search yields a number of companies offering their services to utilize CRISPR to perform gene editing in both cell lines and whole animals. Based on the extremely rapid advances in this area, gene-editing using CRISPR and other technologies promises to revolutionize our ability to manipulate the genome and attack genetic diseases.

Don't get caught in a regulatory hot seat: Using Radiolabeled CTMs in Early Phase Development

Studies conducted using 14C-radiolabeled clinical trial materials (CTMs) result in detailed DMPK, ADME and mass balance information, providing great insight into a drug’s behavior in vivo. While CMC requirements for traditional “cold” clinical trial materials (CTMs) are well understood, successfully incorporating “hot” or “blended” versions of drugs into your development plan requires specialized expertise.

Hot Challenges

Attaching the radioactive isotope to your CTM sometimes involves developing a new synthetic pathway—a process that requires radiochemistry expertise and rigorous CGMP-compliant facilities, processes and systems.

Click here for more.

The Land of Lakes - Madison Wisconsin

By Harley Everett Wilcox, MBA

Senior Scientific Advisor

ABC Laboratories
www.abclabs.com

I have attended the Land o Lakes analytical conference sponsored by the University of Wisconsin about 7 times with the prior 6 occasions being held at the resort and some 15 years in the past.  The conference has moved to Madison and I attended the analytical session last month. How does the new venue compare to the historic Devil’s Head Resort conferences?

First, I was pleasantly surprised that Madison Wisconsin in early August is one of the most beautiful and socially involved cities I have visited.  Lunch at the Memorial Union on the shores of Lake Mendota was outstanding but the trip during one evening was spectacular with over 1000 locals, students and tourist gathering for an evening of socializing.  The capital building, street artist and many restaurants added to wonder of this conference.  I remember an unforgettable seasonal BLT, with local toasted bread, heirloom tomatoes, thick sliced bacon, with a pile of greens that appeared to have just been picked.

Second, the analytical conference speakers presented topics covering USP, elemental impurities, GTX impurities, stability, dissolution, forced degradation and a special session for Q&A for methods transfer. As the number of attendees is less than 100, I found the technical discussions to be intimate and educational.  The conference format allows one to have meaningful interactions with other attendees representing the pharmaceutical analytical disciplines.  I am looking forward to next year’s event in wonderful Madison Wisconsin.

Of Science Fairs and the Republic of Letters

By Jim Schmidt
Sr. Scientific Advisor
ABC Laboratories
www.abclabs.com
 

A couple of weeks ago I had the privilege and pleasure of attending the 250th national meeting of the American Chemical Society in Boston.  I've attended ACS national meetings before, but for the uninitiated it can be a bit overwhelming: nearly 14,000 attendees; more than 9,000 individual oral papers presented to about thirty of the society's specialized divisions; and more than 300 companies exhibiting their services, instruments, publications, etc.; all spread out over more than a dozen meeting locations across Beantown.

I heard many terrific and relevant presentations sponsored or co-sponsored by the AGRO (Agrochemicals), ENVR (Environmental Chemistry), and ANYL (Analytical Chemistry) divisions, and even managed to catch a very interesting one on patents in the CHAL (Chemistry and the Law) division.  My colleagues and I also met with customers - both established and prospective, colleagues at our sister-companies of EAG, and some old friends as well.

One of the best parts of any scientific conference is the “poster session” – the poster presentations are almost always more focused and practical than the oral papers.  For me, they also evoke great memories of participating in “science fairs” from my younger days: the middle school tri-fold boards may be replaced by bigger, glossier, and more elegant professional posters; the lemon batteries and baking soda/vinegar volcanoes are replaced by more sophisticated investigations; still, the essence of the Scientific Method and the need to condense experiments to a short form of communication are all there.

AGRO poster session - ACS Fall 2015 Meeting - photo by Jim Schmidt

Most of all, for me, these meeting always evoke the spirit of the “Republic of Letters” – the intellectual exchange, over long-distances, among scholars in Europe and the Americas in the 1600s and 1700s.  I highly recommend a book I read a couple of years ago - Deborah Harkness’s The Jewel House: Elizabethan London and the Scientific Revolution (Yale University Press (2007) – for a sense of how it operated back then.  Centuries later, the ACS meeting in Boston remained witness to a thriving community of people who happily share their discoveries, interests, questions, and collections.

(As a modern bookend to the subject matter of The Jewel House, I also recommend the short and interesting article, “Cultivating Collaborations Online,” in the August 17, 2015 issue of Chemical & Engineering News, in which Bethany Halford explains how the Internet has “made chemistry partnerships blossom around the world”).

Look for my ABC colleagues at other upcoming conferences.

What meetings do you plan on attending in the near future? What excites you about attending them?