Therapeutics


Avastin® (bevacizumab), are ending their patent lifespan by 2020, which is spurring the develop- ment of several biosimilar and biobetter therapies5. However, unlike generics, biologicals are large and complex proteins that cannot be precisely replicat- ed, which are in stark contrast to small-molecule drugs. Additionally, high expectations are being placed on the safety and efficacy of biosimilars and biobetters6. Therefore, the notion of a generic equivalent cannot be applied to biologicals. Another technology that has revolutionised the biological drug pipeline is automation. Recent state-of-the-art systems allows for increased throughput, streamlined workflows, enhanced reproducibility and decreased variability compared to manual methods. Additionally, reagent and material costs can be reduced when miniaturising and automating 3D methods, while minimal hands-on time frees users to focus on other labora- tory tasks. Finally, automation also monitors and tracks the entire process from R&D, through scale- up and on to manufacturing. The concept on an integrated automation facility has been adapted and applied to each of those areas of R&D, screen- ing, scale-up, manufacturing and even in the clini- cal setting. Robust automated systems are already known in compound screening, characterisation and development to increase throughput and reduce time and variability. What may not be readily apparent is how these automated systems can facilitate standardisation and control across the global project and through- out the project lifetimes. First, document and data control via laboratory information management systems (LIMS) is a way for automatic information transfer between all of the integrated systems in the automated process. Additionally, systems can be set up for parallel development (ie companion diagnostics) for precision medicine. Similarly, sys- tems can be standardised as a single platform across all global sites, with pre-set workflows to reduce variability and errors, to enable easy data comparison and consolidation. Automation also allows facilities to do more with less for high throughput parallel processing of multiple dis- parate samples or assays at once for drug screen- ing,


development, testing and monitoring.


Ultimately, by incorporating automated workflows across global projects, CROs can help their clients to bring effective products to market efficiently. Looking ahead, production of biotherapies in human cell lines is growing. While some are still under development in multiple therapeutic areas, several of the products are currently approved for clinical use. Human expression systems are well


Drug Discovery World Summer 2017


Dr Michael Mouradian received a doctorate in biochemistry at the University of Nevada Reno, followed by a postdoctoral fellowship at the Medical College of Wisconsin. With a career-span- ning focus on cancer research, he currently serves as Scientific Leader for drug discovery applications at Hamilton Robotics in Reno, NV.


49


developed and accomplish equal efficiency to other cell lines for the production of proteins. The future holds such promise with new technological advancements and continued research investments to better optimise human cell lines for a more sophisticated product collection strategy in order to become one of the standard platforms for the production of biological therapies. Additionally, pharmacists will play a critical role in the biosimi- lar adoption into healthcare. While the framework has already been set, practical considerations still remain for pharmacists regarding biosimilars. These include manufacturer attributes, product labelling, interchangeability, substitution, thera- peutic drug monitoring, logistics of product use and payer reimbursement7. Thus, by understand- ing the evolving regulatory guidelines, the princi- ples of biosimilar and biobetter development will bridge the gap between the pharmacists making informed decisions regarding chemical formulary inclusion, and healthcare providers and patients understanding the practical benefits. Additionally, the data from the


clinical trials will provide


increased confidence in biologic originator com- pared to the biosimilar. Taken together, this will be good news for pharma companies which develop successful, patent obtained, biologics to reap the high revenue benefits for longer.


Biologics are the wave of the therapeutic future. From a clinical perspective, these biopharmaceuti- cals can offer reduced therapeutic toxicity, better tolerance to increase patient safety and enhance efficacy for improved patient outcomes. They can be targeted for personalised medicine initiatives. From a business perspective, biologics offer increased opportunities with reduced risks com- pared to chemically-derived small molecules. And they can lock out generic threats to improve or extend revenue over the product lifecycle. Thus, the future for drug discovery and development will continue to be a diverse industry, which is less con- strained by the limitations of large pharma, but that good science is the only essential requirement. The time is right; the technologies are ready, and the rewards are sweet, and the healthcare industry is finally catching up.


DDW


References 1 Ho, RJ and Chien, J. Trends in Translational Medicine and Drug Targeting and Delivery: New Insights on an Old Concept –Targeted Drug Delivery with Antibody-Drug Conjugates for Cancers. J. Pharm. Sci., vol. 103, no. 1, p. 71, 2014. 2 Zelenetz, AD et al. NCCN Biosimilars White Paper: Regulatory, Scientific, and Patient Safety Perspectives. J. Natl. Compr. Cancer Netw., vol. 9, no. Suppl 4, p. S-1, 2011. 3 Jacquemart, R, Vandersluis, M, Zhao, M, Sukhija, K, Sidhu, N and Stout, J. A Single-use Strategy to Enable Manufacturing of Affordable Biologics. Comput. Struct. Biotechnol. J., vol. 14, pp. 309- 18, 2016. 4 Will ‘Biosimilar’ Medications Reduce the Cost of Biologic Drugs? – Scientific American Blog Network. [Online]. Available:


https://blogs.scientificamerican. com/guest-blog/will-ldquo- biosimilar-rdquo-medications- reduce-the-cost-of-biologic- drugs/. [Accessed: 07-Jun- 2017]. 5 Looking Ahead: Pharma Projections for 2016 – And Beyond. [Online]. Available: https://www.drugs.com/slidesh ow/looking-ahead-pharma- projections-for-2016-and- beyond-1230. [Accessed: 08- Jun-2017]. 6 Camacho, LH. Current Status of Biosimilars in Oncology. Drugs, vol. 77, no. 9, pp. 985-997, Jun. 2017. 7 Stevenson, JG, Popovian, R, Jacobs, I, Hurst, S and Shane, LG. Biosimilars. Ann. Pharmacother., p. 106002801769074, Feb. 2017.


Page 1  |  Page 2  |  Page 3  |  Page 4  |  Page 5  |  Page 6  |  Page 7  |  Page 8  |  Page 9  |  Page 10  |  Page 11  |  Page 12  |  Page 13  |  Page 14  |  Page 15  |  Page 16  |  Page 17  |  Page 18  |  Page 19  |  Page 20  |  Page 21  |  Page 22  |  Page 23  |  Page 24  |  Page 25  |  Page 26  |  Page 27  |  Page 28  |  Page 29  |  Page 30  |  Page 31  |  Page 32  |  Page 33  |  Page 34  |  Page 35  |  Page 36  |  Page 37  |  Page 38  |  Page 39  |  Page 40  |  Page 41  |  Page 42  |  Page 43  |  Page 44  |  Page 45  |  Page 46  |  Page 47  |  Page 48  |  Page 49  |  Page 50  |  Page 51  |  Page 52  |  Page 53  |  Page 54  |  Page 55  |  Page 56  |  Page 57  |  Page 58  |  Page 59  |  Page 60  |  Page 61  |  Page 62  |  Page 63  |  Page 64  |  Page 65  |  Page 66  |  Page 67  |  Page 68  |  Page 69  |  Page 70  |  Page 71  |  Page 72