There are many options out there for choosing assay development services, and finding what you need can be a challenging endeavor. Here we outline five items to look for when searching for the CRO that is right for your project. To narrow things down a bit, this article will focus on biochemical assay development services for enzyme drug targets.
Does the CRO Understand Your Target?
If you’ve gotten this far, you probably have a good understanding of the biology of your target. You probably have an idea of how to screen. A well-schooled CRO can provide quality insight into the right screening approaches. One thing that can be difficult is having a reliable source of highly purified, yet active enzyme. Sometimes scaling up and getting the right amount for HTS can also create a roadblock. If you are unsure about the protein source, ask the CRO what experience they might have with the target. It’s possible they’ve worked similar proteins in the past, know a good source, or can make it for you.
What Are the Goals for the Assay and the Project?
Each assay certainly has its pros and cons. But, knowing your screening goals upfront can help determine what direction to go with the assay. For example, if you are looking to perform a large biochemical screen, does the CRO have that capability? Can they transfer the assay to you or a robotics lab for a screen? Are you interested in hit-to-lead? In which case does the CRO have the enzymology experience to understand hit confirmation, MOA, residence time, and other triaging strategies. It’s important to understand what throughput you are looking for early because it will help you find a CRO that will match your project goals.
CRO Assay Expertise – Selecting the Right Assay Technology
Assays are critical to getting accurate results. Many large drug discovery CROs have a set of go-to assays to use if they fit into a universal bucket. A kinase is a great example. There are many assays available off-the-shelf that can detect enzymatic activity in a variety of ways. It sounds simple enough, but many different factors go into assay selection. Here are three brief examples:
- Readout. Do you prefer TR-FRET, fluorescence polarization, fluorescence intensity, luminescent, colorimetric, or potentially another readout? Some readouts are a better fit for different goals. If proximity is required, a TR-FRET assay might be the best choice. Still, others lend themselves to only measuring FP. Some have natural endpoints, while others can provide continuous detection of activity.
- Sensitivity. The assay needs to be sensitive enough to detect under initial velocity conditions. Understanding the target Km will help provide the CRO an understanding of a trade-off that might need to be made between throughput and sensitivity while also pointing to potential assay technologies.
- Throughput and Cost. It is essential to consider if the assay technology can provide results under the right conditions. If you are looking to perform a 100K+ high throughput compound screen, the cost will undoubtedly be a factor. To keep cost low, a homogenous, mix-and-read assay provides the ability to get fast, accurate results while considering the price. A radioassay might be more sensitive, but also more expensive, making a large screen impractical.
Do You Require an Entirely Novel Assay Design?
If you require an assay that is unique and doesn’t fit under that universal assay umbrella, custom assay development services are necessary. Some CROs specialize in an assay technology where it may or may not be amiable to your target. I’ll use an internal example. BellBrook Labs developed Transcreener Assays; obviously, we have an affinity to that design. The assays are universal for various enzyme targets; however, if you require an assay for something much more novel, we’d have to develop something entirely new. Sometimes we can use a coupling enzyme to transform your enzyme’s product into something we can detect with a Transcreener Assay. Alternatively, you might be looking for a target engagement assay and your not interested measurement of the enzyme’s product. For that reason, you probably should look for a CRO that has better expertise in that area.
Company Size, Speed, and Support of the Assay Development Services CRO
Finding the right fit is very important to the long term success of the project. Do you want to work with a large CRO that has services from discovery to clinical trials? Are you more interested in working with a company with expertise in a specific area such as assay development? Large CROs often reserve their best scientists for their large clients. If you are a small company, will they provide the same level of support? Maybe you are just interested in the raw data and have a team ready to crunch the numbers for you. If you need more help, you may want to look to a CRO with proven expertise with the target or target family. Please consider the backlog as well. How long will it take before the CRO starts the development process? How long will it take for them to complete ongoing work? What happens if things don’t go as planned? These are all questions to consider as you look for a custom services provider.
Assay development services entail much more than what is in this short article. If you have a target and are considering future assay design, please contact us, and we’ll see if we can help or point you in the right direction.