Lun Xin M.Sc.

Lun Xin is a scientist with the Formulation and Drug Product Development Group at Catalent Biologics in Bloomington, IN. He received a Masters of Science in Biotechnology from Northwestern University, Chicago, IL and is currently working on his distance doctorate in Pharmaceutical Chemistry from the School of Pharmacy at the University of Kansas.

Mr. Xin is a specialist in high-throughput formulation (HT formulation) development. Through the application of his computer programming skills and deep knowledge in pharmaceutical chemistry, he has led multiple successful HT formulation programs for protein and oligonucleotide therapeutics. He recently led the design, building and operation of Catalent Biologics Protein Formulation Development Center of Excellence. This newly established facility in Bloomington features fully automated pipetting, buffer exchange, concentration and a host of analytical assays with high levels of automation and throughput.

Currently, Mr. Xin’s main focus is on establishing formulation development and manufacturing capabilities for mRNA-LNP delivery platform at Catalent. He is also collaborating with Catalent’s global data science team to couple the high-throughput formulation development lab with automated data flow and reporting workflow. 

Finally, Mr. Xin has extensive knowledge in pharmacokinetics/pharmacodynamics (PK/PD), and non-invasive drug delivery as applied to biologics.

Key Expertise: High-throughput formulation development, analytical method development, statistical programming, DMPK, non-invasive drug delivery.

Connect with Lun Xin on LinkedIn

A CONVERSATION WITH LUN XIN

What made you pursue a career in biologics drug development?

I started my career working as a clinical scientist in a hospital. My work there focused on developing assays for infectious diseases and investigating disease biomarkers. Patients that I had contact with showed me what pharmaceuticals can do to change their lives. A year later, I had my first contact with biologics, when my own grandfather was put on one for his lung cancer treatment. That exposure piqued my interest in pharmaceutical development and directed me to transition from biology to biotechnology. Having studied and worked in the drug development industry, I now have a better appreciation of the difficulty in producing a quality product consistently over time. 

What is important in developing analytical assays for biologics?

Although there are some very difficult assays to perform, such as mass spectrometry for post-translational modification, the difficulty of assay development in the industry is often not from the technologies themselves, but rather how to optimize these assays to reduce variance. Biologics are inherently complex molecules, and there are often over a dozen methods developed to characterize each molecule. The key is how to get the most information from the least number of experiments. At Catalent Bloomington, we believe the answer is Design-of-Experiment (DoE). With a wealth of experience within our team, we apply different types of DoE designs for methods at different stages of their lifecycle. We also believe it is important to finish each assay development with our version of Ruggedness Study, where we cross the important noise factors, such as instrument, columns, days, reagent lots and analysts to systematically examine sources of variances. We believe this information not only allows us to understand the total variance from analytical methods and help determine fitness-for-use but also provide critical insights during out-of-specification investigations and method transfer.

What is important in developing formulation for biologics?

I think the combination of high-throughput (HT) screening and knowledge in pharmaceutical chemistry is the key to successful formulation development. When approaching the problem of formulation development, one has dozens of options for excipients, and a wide range of buffers to choose from. Here again, the key is how to get the most amount of information from the least number of experiments. A well-designed HT screening experiment can significantly shorten the timeline required for formulation development. Our unique platform combining thermal stress, mechanical stress, solubility challenge, and diffusivity measurement allows us to comprehensively study the API in 96 formulations at a time. A successful HT screening design relies on knowledge in pharmaceutical chemistry. A formulator should be able to predict potential degradations pathways and specifically target those pathways with the HT screening design. With the large amount of data generated from the HT screening experiments, we apply statistics, such as multivariate analysis, to help us find the answer with confidence.

Tell me about the computer programming side of your work.

Computer programming is about problem-solving. An observant eye can often find inefficiencies and risks in any process, even as monotonous as writing a data report. Once we identify the problem, we can start to think about how to solve it with programming. One of the problems that I saw was that we are often blinded to future workloads when we discuss potential projects, so I created a Shiny web application that helps us analyze, visualize and predict workload and allocate resources. The goal is to have more visibility on our workloads and create more synergy within the Catalent network. For example, this app will tell us our remaining capacity for the entire fiscal year so that we can plan resources and prioritize the most critical projects. It also allows people from different Catalent sites to find the expertise they need within the network and connect with each other. There are simply so many cool things someone with even the basic working knowledge in computer programming can build that will totally change your day. 

What are your main responsibilities at Catalent?

Currently, I am most involved in managing analytical and formulation development projects. With analytical development projects, my focus is to understand customers’ need, design the most appropriate experiments for each project, and report them to our customers. A fair amount of my time is spent researching literature to stay current in my scientific knowledge. The time spent studying is never wasted because it allows me to be a more effective scientist. For formulations, my focus is on analyzing drug molecules, leveraging my skills in pharmaceutical chemistry and determining the developability of each molecule. I would then help design a panel of conditions and perform the HT screening experiments. When I get some free time, I would jump into statistical programming to keep myself sharp on those skills. 

What do you think are your biggest achievements at Catalent?

I was involved in developing our unique HT formulation screening platform. I have seen it successfully applied to many molecules now and witnessed the power of these tools. The molecules that we help formulate are now able to move further in the development pipeline and some of them will be saving and improving people’s life soon. I also take pride in my assay development work, particularly when I can take a crude assay, refine it with DoE, and witness it mature into an assay that is suitable for GMP use. When I take a pill, I trust that the drug I take has been tested with reliable methods. I now appreciate how much effort is behind the design and optimization of these tests. Lastly, seeing the web applications that I developed improving my colleagues’ work efficiency each day really gives me a sense of satisfaction knowing that something so simple that I created had made a difference in their day.

ACCESS LUN XIN’S WORKS

• Poster: Developing a High-Throughput Formulation Development Platform for High-Concentration, Therapeutic Monoclonal Antibodies
• Dou, Y.L., Qi. X.L., Xin, L., Chen, D., Zhang, H.Q., Cui, Q.C. (2013). Taqman ARMS vs Direct Sequencing in the Detection of EGFR Mutations in MSCLC Patients. National Medical Journal of China, 93(10): 768.
• Refaat, T., West, D., El Achy, S., Parimi, V., May, J., Xin, L., et al. . (2016). Distribution of Iron Oxide Core-Titanium Dioxide Shell Nanoparticles in VX2 Tumor Bearing Rabbits introduced by Two Different Delivery Modalities. Nanomaterials, 6(8): 143.
• Chen Y, Doud E, Stone T, Xin L, Hong W, Li Y. (2019). Rapid Global Characterization of Immunoglobulin G1 Following Oxidative Stress. MAbs. 11(6): 1089. doi: 10.1080/19420862.2019.1625676. Epub 2019 Jul 4. PMID: 31156028; PMCID: PMC6748588.