Research Model Trends: How will CRISPR technology affect the pharmaceutical industry?

May 27, 2015 in Blog by ws-lssg

By Dr. Wade Sunada, Managing Consultant

With the recent introduction of CRISPR/Cas9 gene editing technology by companies who develop research models for the pharmaceutical industry, the possibilities for custom generating research models for pharmaceutical research and development have increased.   Interest in CRISPR/Cas9 from pharma is high, but what do pharma researchers need to know about CRISPR?  What is possible?  What is changing?  How will this affect research programs going forward?  The OutsourcePharma Advisory Board spoke with representatives from some of the leading companies using CRISPR technology to custom generate research models about their views on how CRISPR technology will affect the pharmaceutical industry.

For Alexandre Fraîchard, CEO of genOway, conversations with clients often start with CRISPR.  “What I can tell you is, clearly people hear about the Cas9 story and we have more people coming to us about okay, then how long would it take and how much would it cost to create a new model using the Cas9 technology.  So clearly there is an interest.  For me it clearly means that there’s a lot of scientists in the industry that are still believing that creating an animal model and using it is a two year program, risky and with maybe an average outcome.  So, this Cas9 story clearly opens up a new window to these guys that can say, maybe it is different now.

While nuclease-based gene editing technologies have been around for several years (TALEN, zinc finger, etc.), it is really the advent of CRISPR/Cas9 technology that is starting to change how pharma looks at research models.  Personalized medicine is a catch phrase that entered the lexicon since the turn of the century, but is really now becoming a process instead of a far-off goal.  From genetically modified research models to biomarkers to companion diagnostics to adaptive trial designs, it is difficult to bring a therapeutic to market without at least considering a targeted approach.

The ability to quickly modify genes with CRISPR gives unprecedented power and flexibility in the creation of genetically modified research models.  This translates into 3 tangible benefits to pharma researchers: 1) Reduced timelines for custom generation of research models; 2) Lower cost of custom generating research models; and 3) feasibility of more complex custom generated research models.  Clearly the ability to custom generate models cheaper and faster has obvious benefits, but there are a few hidden benefits as well.  For example, pharma companies can now custom generate a simple knockout model fast enough that it may be a better choice to custom generate a model that is available from repositories strictly for IP reasons, as the time and cost tradeoffs get smaller and smaller.

What is the impact of reduced timelines for CRISPR custom generated research models?  According to James Vitale, Director, Product Management at Taconic Biosciences, “CRISPR will allow investigators at pharmaceutical companies to generate GEMS very quickly.  This speed will provide quick answers to critical questions.  The CRISPR models may be simple, for proof of concept in model development, or may serve as the model used in drug development discovery research.

How much faster is CRISPR?  Lara Reid, Product Manager at Sage Labs, project times for custom generating models have decreased by months.  “I would say at least a couple months.  We used to quote our knockout rat models using the ZFNs around six to eight months and now we can do them in as little as five, and we see the same trend with all of our knockin projects.  Those could take almost a year sometimes and now we can get conditional knockins between six and eight months.”  Having access to custom generated models faster can allow for the use of custom models in situations where previously researchers may have not had the time to wait for custom model development, or did not have the ability to plan far enough ahead to develop a custom model.  Fraîchard believes that the strength of CRISPR technology is the speed that simpler models can be created.  “With CRISPR/Cas9, you benefit if you are really in a hurry and if you want low sophistication model.  Then you will benefit from this technology and you will save a few weeks or few months in your development time.

While the lower cost of CRISPR models is certainly a benefit, Fraîchard cautions that the design of the model is more important than the cost. “If you do it quick and dirty, you will save a little bit of time, a few months and maybe a few tens of thousands of U.S. dollars but then when you’re going to use it, you’re going to spend much more time and much more resources to use it.  One very simple example is if it’s not properly designed, after a year you will see the limit of the model.  You will say okay, I got the first result but if I go more in detail, I can see that it’s not working so you need a new model.”

Creating more complex models furthers the possibilities of developing personalized medicines.  By more closely mimicking the human response, animal models can go beyond target validation and better predict results in humans.  Vitale notes that custom generated rat models are a key benefit of CRISPR technology.  “Developing GEM rats has been difficult; CRISPR technology offers a way to generate GEM rats in a targeted manner which is not possible through traditional transgenic technology.  Reid notes that Sage thinks the future of animal models is in more complex species than mice.  “I know that’s always been the hope of Sage is that the rat models would really pick up and become as popular model as the mouse.  I think that that trend is increasing and I know we just hope to see it continue to increase, especially over the next five years.”

Humanized models offer a stern test for CRISPR technology.  While clearly a fantastic technology, CRISPR is still a young technology with potential pitfalls.  The possibility of off-target effects is greater with CRISPR than with ES cell technology, but that can be mitigated by screening for off-target effects and with the quality of design of the model.  CRISPR may be less suited for humanized models until there is more experience creating those models using CRISPR because of the potential difficulties inserting the large fragments required for humanization.   Fraîchard notes: “If you do need a full humunization of the target or if you need something sophisticated like chimeric proteins – partly human, partly mouse – so that you get signal transduction, if you should need that today, we don’t use Cas9 for that because it’s not robust enough.  So, that’s exactly the issue with the Cas9 today is simply the efficacy level for insertion of large fragments plus the off target risk.”  Reid notes that Sage only uses CRISPR technology, and believes the technology is validated based on their successful completion of complex models such as humanized models, conditional knockins and conditional knockouts.  “We’ve proven that the technology is useful across the board.”


So is CRISPR the right technology for your next research model?  Vitale notes that “We are finding that scientists come to Taconic with a CRISPR model in mind, but after discussions with our Scientific Project Managers realize that a different technology will be better suited to deliver the model they had in mind.  I would offer this piece of advice; seek out a vendor who has capabilities beyond just CRISPR, otherwise the model may be developed using CRISPR, but it may not be the best possible model to meet the goals of your study.  Seek out a vendor who has a variety of model generation tools and who can also provide the downstream breeding and analysis.  This will maximize the chances of success.”

As exciting as CRISPR technology is today, in the end the models that can be created using the technology are going to have the greatest effect on the pharma industry.  Fraîchard states: “Will it change anything in the way we do business in the industry?  No, because it’s just one more tool in the toolbox.  It’s a nice tool, a great tool but that’s not what is important.  What is important for pharma or for the scientist or the PI is the intrinsic value that will be growth to the project by the animal model.  The way the animal model was created does not matter.

Blog Article on Future of Biopharmaceutical Outsourcing

January 16, 2015 in Blog by jmeyer

As posted on BioStorage Technologies’ Blog:

The biopharmaceutical industry faces a unique challenge in its quest to develop new and innovative therapies. Unlike any other industry, Biopharma research is dependent upon the human body and its genome. In a sense, it is working to drive continual innovation within a highly complex, but closed environment. Not surprisingly, Biopharma is finding it more and more difficult and costly to discover, develop and commercialize new therapies. Just this November, the Tufts Center for the Study of Drug Development reported the cost to develop and win marketing approval for a new therapy has reached nearly $2.6 Billion – a far cry from the $802 Million estimate Tufts published just 11 years ago. To offset this increasing challenge Biopharma has and continues to actively pursue strategies to do things better, faster and cheaper. One of the key strategies used by Biopharma is outsourcing R&D activities to contract research organizations (CROs).

Recently, Life Science Strategy Group (LSSG) conducted research with 100 biopharmaceutical R&D professionals globally that have responsibility and visibility into R&D strategies, budgets and outsourcing practices to better understand trends driving change in R&D innovation, efficiency and outsourcing strategies. Top outsourcing trends uncovered by LSSG are below.

Top Factors Driving Biopharma R&D Outsourcing Strategies

Pic 1Source: The Future of Pharma Outsourcing, Life Science Strategy Group, LLC, 2014

The key takeaway from our trend analysis is that over the past year and in the future, Biopharma companies will place an even greater emphasis on outsourcing.   Specifically, the majority of R&D effort will stay focused on late stage (Phase 2-4) opportunities, which are closer to market dollars – Biopharma needs to ensure revenue streams to drive its programs. However, Biopharma companies depending on their size have different ideas on who they will turn to for support. Respondents from large Biopharma companies indicate they will increasingly turn to large full-service CROs, while small/mid-size Biopharma will turn to mid-size CROs.

Trends in CRO Utilization

Pic 2Source: The Future of Pharma Outsourcing, Life Science Strategy Group, LLC, 2014

Large Biopharma will look to bigger CROs because of their global footprint, breadth of capabilities and ability to reach, access and monitor trials in an increasing array of countries in Eastern Europe, Asia (China, India) and Latin America (BRIC countries). As large Biopharma expands its R&D efforts into more, specialized therapeutic areas, access to patients will become more difficult. Large CROs are well suited to address this challenge both with their internal capabilities and geographic reach. In order to expand their breadth of core service offerings even further, large CROs will seek collaborations with other niche CROs and specialty service organizations, which are critical to their success as “soup-to-nuts” providers.

Just as biopharmaceutical companies are outsourcing to CROs so that they can focus on their core expertise, CROs are finding the need to build collaborations with niche specialty service organizations who provide best-in-class solutions in areas that are not the core expertise of the CRO. The types of niche specialty service providers who are indirectly benefiting from this trend include global sample storage and management companies, clinical trial technology companies, as well as esoteric, diagnostic and genomic testing laboratories. In addition, the growing number of academic-based strategic research institutions will provide large CROs with a collaborative avenue for research capability expansion.

Small and Mid-size Biopharma are shifting their outsourcing efforts towards mid-size CRO companies due to their ability to provide them with more personalized attention to their larger trials, while maintaining a high level of customer service – something small to mid-size Biopharma may perceive is missing when working with a larger CRO. Again, niche CROs and specialty service providers will play a critical role in supporting mid-size CROs’ in their ability to deliver a deeper breadth of service capabilities with their Biopharma customers often indirectly through partnerships and alliances.

A second outsourcing strategy to be used by Biopharma over the next few years will be to shift from transactional to more strategic relationship models with CROs. In its research, LSSG found that both large and small/mid-size Biopharma will decrease its use of fee-for-service (transactional) types of CRO relationships while increasing its use of preferred-provider and strategic partnerships. Specifically, large Biopharma respondents expect use of fee-for-service relationships to decrease from 24% to 19% of trials while use of strategic partnerships will increase from 23% to 28% of trials. Small/mid-size Biopharma respondents indicate a similar trend with fee-for-service relationships decreasing from 40% to 32% of trials while strategic partnerships should increase from 15% to 21% of trials.

A third outsourcing strategy Biopharma will utilize to drive further efficiency with CROs is service bundling. In particular, large Biopharma expects to increase bundling of routine study conduct activities with upstream study feasibility support, among other areas. Small/mid-size Biopharma respondents anticipate further service bundling across trial planning, conduct, technology and reporting services.

Clinical Trial Services Bundling

Pic 3 Source: The Future of Pharma Outsourcing, Life Science Strategy Group, LLC, 2014

Considering the current pressures facing the Biopharma industry and the need to drive innovation under increasing complexity, it is clear CROs will play an increasing role as an enabler of success in the future. As such, Biopharma will continue to evaluate its relationships with CROs and how it can maximize its return on its investment. Over the next 2-3 years and (likely) beyond, it is clear that Biopharma companies will look to further streamline and improve relationships with CROs. Strategies including greater use of preferred and strategic partnerships, more careful CRO selection and further service bundling are but a few of the strategies Biopharma will utilize with the goal of reducing administrative time, FTEs and spend. The goal of these strategies will be to ensure resources are more efficiently allocated to Biopharma’s core competencies such as the science and execution of R&D with the goal of doing more with less and improving drug development success.

OutsourcePharma Advisory Board Featured in New Report – Biopharma RFP Flow

October 27, 2014 in Publications and Posters, Resources by jmeyer

The OutsourcePharma Advisory Board members’ contributions are featured in a new report published by Life Science Strategy Group.  The story can be found on’s website. Website Features

June 9, 2014 in Blog by lucymcn

By Lucy McNamara

Hello, everyone!

Now that Outsource Pharma is up and running I thought I’d take a moment to walk you through some of the features of the site to set you off on the right foot to have the best experience possible. There is much to share! As you may well know, Life Science Strategy Group is constantly out in the field trying to better understand the current and future climate of outsourcing, CRO performance and satisfaction, alongside many other relevant topics. To participate in our market research, you can share your own experiences and contribute to the mix on the ‘Surveys’ tab. There you can view the studies du jour, which we constantly update, and find one that fits your interests and experiences. As a bonus, you even get paid for surveys you complete!

If you are looking to keep up with the times, or just looking to learn something new, we have the ‘Resources’ tab exactly for this purpose. Under ‘Resources’ is where you will find relevant articles, white papers, external links and other informative material to help you stay current with goings-on in outsourcing. In our ‘Blog’ we will touch on the most important of these topics as well as feature guest writers (this could be you!). If you are interested send us an email and we’ll give you the details. And that’s just the beginning…

Outsource Pharma’s goal is to bridge new connections between biopharmaceutical outsourcing professionals. One way we hope to do this is through the ‘Groups’ tab. Here, you can join a group specific to each phase of development, based on your professional experience or personal interests. Once a member in a group you can view user profiles, connect with individuals, contribute to threads and send private messages. Don’t forget to favorite the most attention-grabbing topics and conversations that so you can revisit them next time you sign on. As you establish your network on you can also tag colleagues and friends in posts they may find interesting or pertinent to their work. To facilitate these new connections and conversations, we also have a page of ‘Forums.’ ‘Forums’ is a space where industry professionals can post topics for discussion in a more formal, organized fashion than in ‘Groups.’ Topics can be posted under stages of development or into the general discussion based on subject matter. And you can rest assured, your comments and posts are limited to members of The OutsourcePharma Advisory Board, not the general public.

If you are looking for a CRO for your next project, ‘Reviews’ offers a groundbreaking interface combining CRO ratings and reviews from professionals with direct experience, like you! With its Yelp-like design, you can research, read reviews, and post about your own experiences with popular CROs. CROs are rated numerically on fifteen different performance metrics, which can easily be compared between vendors. Now you know who to choose for best turnaround time and lowest prices! You can also read testimonials and verbatim evaluations before selecting that partner for your next project. Who is the best CRO to work with for Phase II trials? Who doesn’t come through on timelines and budgets? What will be the trends in outsourcing over the next 3 to 5 years? All of the answers can be found at Outsource Pharma.


– Lucy