nature :inside view

By: Richard D. Connell, Vice President and Worldwide Head of External Research Solutions, Pfizer Global Research and Development

Life science research is often hindered by a lack of access to compounds discovered by big pharma or biotech organizations. Mechanisms like compound transfer agreements can make these compounds available. However, the research community may be unaware of such avenues to sample access, and those in the know may become frustrated by the time and effort it takes to apply.

In 2009, Pfizer expanded access to its compound collection by partnering with Sigma-Aldrich. The company allowed clients from credentialed research organizations access to research grade (non-GMP) samples of Pfizer compounds in order to further research in drug discovery. Access to these compounds allows researchers to examine them, with the hope of combatting serious diseases.

In 2012, research carried out at Stanford University, US, led to the revelation that a substance being sold to researchers as bosutinib by at least 18 separate, unlicensed suppliers was in fact a different compound with the same chemical formula (C&En News 21, 34-35; 2012). Through the licensing agreement with Pfizer,
Sigma-Aldrich was able to offer samples of known purity and identity to researchers.

Here Rick Connell argues that a more open approach can not only avoid costly research inconsistencies but also speed up innovation and help a large numbers of patients.

Q: What was the spark of the Pfizer-Sigma-Aldrich partnership?

A Sigma-Aldrich customer asked if they could provide a sample of celecoxib, an antiinflammatory compound marketed by Pfizer. Sigma-Aldrich approached us for a license at a time when we were keen to foster more open innovation. We discussed the cost and effort needed to license a single compound and decided it might be advantageous to establish a broader relationship across the Pfizer portfolio of compounds. The alliance provided a new avenue for researchers to access our authentic, quality-controlled samples. There was still some anxiety within Pfizer about things going wrong, so we proceeded in stages, starting with off-patent and non-patented compounds and expanding from there. It was important for us to partner with a company with a strong reputation like Sigma-Aldrich. They do their own quality control on every batch and insist on greater than 98% purity for each sample.

"Science should be
 reproducible around
 the world."


Q: How big a problem is sample purity and identity?

The reality is we don’t know. We only find out about it anecdotally or when there is a high profile problem as in the case of bosutinib. There have also been reports of batches of crizotinib, a lung cancer drug, having different potencies in experiments. Crizotinib has an enantiomer, or “mirror image” analog with the same formula but different biological properties. Batches of crizotinib could have different potencies if they are not enantiomerically pure since the active component is effectively “diluted” with the chemically similar, but inactive enantiomer. I worry there are other cases that aren’t reported because they involve lower profile compounds, or researchers don’t have access to the right analytical tools to assess the true purity and identity of their reagents.

Q: What are the consequences?

If everybody is using the same set of conditions and protocols, and the same proteins and chemical probes, science should be reproducible around the world. But if people use impure or incorrect compounds it’s a different story. In the bosutinib case, we were told many suppliers provided replacement samples to customers who were sold the wrong compound. However doing all of the experiments again takes time and money for what is essentially an avoidable event.

Q: How does the partnership work in practice?

When we disclose a new small molecule inhibitor in a scientific journal, we make an effort to ensure the key compound in the article is made available through Sigma-Aldrich. In cases where a molecule is chiral and there is an active and an inactive enantiomer (like crizotinib), we try to make both enantiomers available. It’s not always possible to coordinate the material availability with a publication under review but so far we’ve managed it 24 times in 2015. All in all the agreement now encompasses close to 200 reference compounds.

Q: Where does the partnership go from here?

We will certainly continue to add new compounds as we discover them while also looking to provide older compounds from Pfizer on a case-by-case basis where there appears to be interest from the research community. Where we have material, we are keen to provide analogs related to the more popular compounds like the aforementioned regioisomers of bosutinib, enantiomers of chiral compounds as well as intermediates, metabolites, and stable-label derivatives that might be of use to researchers. The biggest step change will take place when other pharma companies and biotech organizations adopt a similar relationship with credible distributors like Sigma-Aldrich. Such an industry-wide change would further enhance access to a broader range of tool compounds of known identity and purity to the research community.

Q: What difference will this make in the industry?

Those doing basic research in the life sciences are seeing the benefits of this enhanced access to research tools. What excites me is the idea that access to a Pfizer compound will allow invention down the road by people outside of Pfizer. The quicker we can get these materials out to other researchers, the quicker they can do new and exciting things with them.

It would be great for the research community if more pharma companies were to take a more open approach with their in-house compounds. Such openness has the potential to speed up and reduce the cost of drug discovery, benefiting patients around the world.