Q: What do you think triggered the setup of your training facility, and how does it help people learn more about biopharma analysis?
A: The idea for setting up a biopharmaceutical analysis training lab was talked about as early as 2008. In practicality, the lab came into operation in 2014 as a collaboration between Northeastern University and Waters Corporation. I have been involved with setting up the lab and deciding what equipment we need.
I have also helped develop the curriculum, courses, and classes, and have been intricately involved in every aspect, from our humble beginnings to the global recognition [that] we have now received. I think the tipping point that led to its creation was the increase in demand for analysis of biologics, particularly biosimilars. This lab was created keeping in mind that analytical characterization of those products would be crucial in the immediate and long-term future.
Q: Can you talk about the curriculum and what is it that people come to learn?
A: The training involves three core sets of courses. The first one is the more general, hands-on training for students at Northeastern University on how to use mass spectrometry for protein analysis. The second grouping of the curriculum is capacity building designed for local and international industry people. The capacity building is based off of three main courses—two days of hands-on activities and half a day of lecture to put things into context, including data analysis, which is a big part of the training. The three main courses are intact protein analysis, which is crucial in biopharma but hasn’t been talked about in terms of MS; the analysis of antibodies and biosimilars, which are the most predominant biologics in the field currently; and glycoproteins and glycans, which analytical scientists have always been interested in but [have] hesitated to study because they are so complicated. However, recent advances in the field have made them easier to deal with, so we spend a whole short course on it. All these courses developed for students and people in industry have further led to training courses to enable regulatory convergence. Regulatory convergence obviously hopes to get regulators from around the world to apply the same guidelines for drug approval.
In collaboration with the Asia-Pacific Economic Corporation Life Science Innovation Forum Regulatory Harmonization Steering Committee, we have developed a curriculum in biotherapeutics and we have been executing training based on that curriculum since September 2017. We have also worked with the International Council for Harmonization to develop a curriculum related to quality, which includes topics related to drug stability, quality by design, and others. We are now expanding those collaborations to develop curriculum for advanced cell therapy, [for] medical devices, and for looking at continuous analysis throughout the manufacturing process. The curriculum is rapidly expanding to cover topics related to regulatory convergence and will be taught both in my lab here and around the world. The curriculum is mobile, and we always try to include online homework, lectures, case studies, and learning based on hands-on experience.
Q: Do you focus only on protein-based drugs?
A: Not at all. A large part of what we teach, especially in terms of quality, focuses on proteins as well as small molecules. As part of the advanced therapy curriculum that we are developing, which will be executed in 2019, we will also cover cell and gene therapy, CAR-T, CRISPR/ Cas, and gene editing. In July 2019, we [will be] moving into a space that is much bigger than what we currently have, and it will include analytical labs and cell culture facilities. We are also hoping to expand it to include manufacturing for GMP [good manufacturing practices] and more.
Q: What are some of the recent advances in tools and technologies for biopharmaceutical analysis?
A: We are constantly talking to regulators and people in industry, and we find that HPLC [high-performance liquid chromatography] alone or coupled with MS seems to be the most commonly used technique for biopharma analysis. MS has been around for a long time, and we are trying to be on the leading edge of that technology. We have the quadrupole time-of-flight MS instruments for intact protein analysis and peptide mapping for sequencing, and also for lipid and small molecule analysis. We are training people in the analysis of glycoproteins using MS, which is still new. We are trying to push the envelope of MS to include sequencing, where we don’t have to do a protein digest first. Top-down sequencing is efficient for molecules less than 10–12 kDa [kilodaltons], but we are trying to expand that molecular weight to include antibodies that are around 50 kDa. We also use SDS-PAGE [sodium dodecyl sulfate-polyacrylamide gel electrophoresis] gels and other instrumentation for protein analytics and purification that we often still see in industry. A couple of areas where we are seeing huge interest are technologies that analyze higher-order structures, especially for biopharmaceuticals. There is crystallography, NMR [nuclear magnetic resonance] and MS, but right now we have to use a whole bunch of orthogonal technologies for this type of analysis. Hopefully in the future there will be just one technology that will work well for looking at structures as well as for detecting impurities in the protein or small molecule.
Another area that is gaining importance is finding ways to detect protein-protein or protein-small molecule interactions. Surface plasmon resonance is a technique that is used for such studies and we are looking to get that for our center, as the regulators are also getting interested in it.
Q: How is biopharmaceutical analysis changing as new drug modalities continue to be introduced in the market?
A: We are developing an online course to include stem cells [and] cell and gene therapy. A lot of training in that space involves teaching people how those products are made and used. There will be some hands-on training for gene and cell therapy, but our larger focus will be on quality. Clearly, products like CAR-T that are taken from patients, edited, and then put back into the patients require a focus on quality. Training for GMP and GLP [good laboratory practices] along with using sterile techniques can be boring, and hence, most people don’t pay much attention to it. However, it’s probably the most important thing to do, and it’s important to know how to do it right. There is also a need to ensure that the supply chain management for such products is intact. We also take advantage of all the resources we have around campus in terms of lab instrumentation.
Q: What are scientists, clinicians, and regulators struggling with when it comes to biopharmaceutical analysis?
A: Today, we are on the cutting edge of science, and things are evolving rapidly. Staying abreast of the new technologies and the vast amounts of data being released is not easy. Using the same terminology and producing results that can be trusted [are] very important. We can get stuck in the minutiae, but keeping in mind why we are doing this—whether as a scientist at the bench or as a clinician working with patients or as a regulator—which is ultimately to benefit the patient, is key. One of the reasons I am so passionate about regulatory convergence is that once a drug gets approved in a country, it may still be a few months or even years before it gets approved in another country due to different laws and regulations in place. So there is an entire population of patients who are not getting the drugs that they need. Making sure that the patient remains in the forefront is something that we all need to pay attention to. With our training and teaching, we are trying to help people who can then help the patients. Clearly, we are not the only center offering this kind of knowledge and expertise in biopharmaceutical analysis. However, what makes us unique is our emphasis on hands-on learning. We try to complement each other and work together whenever we can.
Jared R. Auclair, PhD, is currently an associate teaching professor in the department of chemistry and chemical biology at Northeastern University. In addition, Dr. Auclair is the director of Biotechnology and Bioinformatics, as well as the director of the Biopharmaceutical Analysis Training Laboratory (BATL) and the Asia-Pacific Economic Cooperation Center of Regulatory Excellence in Biotherapeutics, and oversees the International Council for Harmonisation training. These latter appointments allow Dr. Auclair to collaborate with both academic researchers and industry in the area of biopharmaceutical development and analysis. He has expertise in molecular biology, protein biochemistry, analytical chemistry, protein crystallography, and biological mass spectrometry, and is interested in understanding the molecular mechanisms of neurodegenerative diseases as well as advancing diagnostics for women’s health