Principles, Assumptions, and Processes Established to Designate Biologics Assets as a Fast to FIH (First-in-Human) Program and the Associated Core Concepts for the Utilization of low and High-Risk Activities, Timelines and Functional Level Expectations

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DOI: 10.21522/TIJCR.2014.05.01.Art002

Authors : Olga Karagiozova


Biologics development represents a substantial advancement in the pharmaceutical industry because of their promise and huge success in the oncology, immunoscience, and cardiovascular disease areas. Prior to entering the marketed product development phase, each biopharmaceutical needs to go through series of stages that will allow or disallow the biologics asset to become a commercialized product. Each of those phases includes development planning and designing of studies to test relevant hypotheses to support the drug label if approved.

The current thesis will focus on the principles, assumptions, and processes that are established to designate an asset (biologics) as a targeted first-in-human program. First-in-human studies are included under phase 1 trials, where initial human exposure is initiated to the investigational new drug (IND). Phase 1 is critical since it affirms if a compound’s mechanisms of action in humans and its development can result in a potentially new drug entity.

Subsequently, step by step initiatives and processes from the perspective of different functional groups within the pharma will be revised to outline the staged procedures, methods, critical, and non-critical paths taken when a molecule is nominated as a clinical candidate. Overall alignment of deliverables will be presented between the different functional areas that partake in the first-in-human development.

Strategic changes to the biologics development process, cell line development with multiple candidate sequences, initial platform fit assessment for a process, analytical and formulation will be acknowledged. Platform strategy for drug substance production, as well as, drug product composition will be outlined along with boilerplates for analytical method development to fit or not fit the platform approach. The functional groups that will be reviewed will be; Discovery, Cell line development, Drug Substance process development, Formulation development, Toxicology, Quality, Drug Substance manufacturing, Drug Product manufacturing, Stability and regulatory.

Keywords: Fast to First in Human, Biologics, Development, Clinical.


[1]. Adler, E. S., & Clark, R. (2014). An invitation to social research. Belmont, CA: Cengage Learning.

[2]. Andrew X. Zhu, P. J.-k., & Philip, P. A. (2013). First-in-Man Phase I Study of GC33, A Novel Recombinant Humanized Antibody against Glypican-3, in Patients with Advanced Hepatocellular Carcinoma. Clinical Cancer Research.

[3]. Atanasov, A. G., et al. (2015). Discovery and resupply of pharmacologically active plant-derived natural products: A review. Biotechnology Advances, 33(8), 1582–1614.

[4]. Bartlett, D. L. (2011). Surgical Oncology: Fundamentals, evidence-based approaches and new technology. New Delhi: Jaypee Brothers Pvt. Ltd.

[5]. Berger, A. A. (2011). Media and communication research methods: An introduction to qualitative and quantitative approaches. Thousand Oaks: SAGE Publications.

[6]. Bumbaca, D., et al. (2011). Highly specific off-target binding identified and eliminated during the humanization of an antibody against FGF receptor 4. MAbs Journal, 3(4), 376–386.

[7]. Conner, J., et al. (2014). Biotechnology entrepreneurship. New York: Elsevier Inc.

[8]. Creswell, J. W. (2014). Research design: Qualitative, quantitative, and mixed methods approaches. Thousand Oaks, CA: SAGE Publications.

[9]. Dostalek, M., Prueksaritanont, T., & Kelley, R. (2017). Pharmacokinetic de-risking tools for selection of monoclonal antibody lead candidates. MAbs Journal, 9(5), 756-766.

[10]. Ehnert, I. (2009). Sustainable human resource management: A conceptual and exploratory analysis from a paradox perspective. Heidelberg: Physica-Verlag Press.

[11]. Eisenhauer, E. A., Twelves, C., & Buyse, M. E. (2015). Phase I Cancer Clinical Trials : A Practical Guide. New York: Oxford University Press.

[12]. European Medicines Agency. (1988). Pharmacokinetic Studies in Man. Retrieved 09 15, 2017, from European Medicines Agency: Retrieved from

[13]. FDA. (2017a). Step 2: Preclinical research. Retrieved from

[14]. FDA. (2017b). Step 3: Clinical research. Retrieved from

[15]. FDA. (2017c). Inside clinical trials: Testing medical products in people. Retrieved from

[16].  Feldman, E. J., Lancet, J. E., Kolitz, J. E., Ritchie, E. K., Roboz, G. J., & List, A. F. (2011). First-In-Man Study of CPX-351. Journaal of Clinical Oncology , 979-985.

[17].  Food and Drug Agency. (2005). Guidance for Industry:Clinical Studies. New York: Rockville,.

[18].  Forum on Neuroscience and Nervous System Disorders,Board on Health Sciences Policy, & Institute of Medicine. (2014). Improving and accelerating therapeutic development for nervous system disorders: Workshop summary. Washington DC: National Academies Press.

[19]. Gad, S. C. (2011). Safety evaluation of Pharmaceuticals and Medical Devices : International Rregulatory Guidelines. New York: Springer.

[20]. Giese, G. (2017). Clinical pharmacology 1: Phase 1 studies and early drug. Retrieved from

[21]. Hanauer, S. B. (2008). The ethics of phase I trials of biologic agents. Nature Clinical Practice Gastroenterology & Hepatology, 5(10), 533.

[22]. History of Vaccines. (2017). Vaccine development, testing, and regulation. Retrieved from

[23].  Hojjat-Farsangi, M. (2014). Small-Molecule Inhibitors of the Receptor Tyrosine Kinases: Promising tools for targeted cancer therapies. International Journal of Molecular Sciences, 15(8), 13768–13801.

[24]. Institute of Medicine (US) Committee. (2010). Accelerating Rare Diseases Research and Orphan Product Development. In M. J. Field, & T. Boat, Rare Diseases and Orphan Products: Accelerating Research and Development (p. Chapter 5: Development of New Therapeutic Drugs and Biologics for Rare Diseases). Washington DC: National Academies Press. Available from:

[25]. Klein, J., & Blaser, G. (2016, Novemeber). Expression of next generation biologics requires next generation expression systems. Retrieved from

[26]. Kudrin, A. (2012). Overview of cancer vaccines. Human Vaccines Immunother, 8(9), 1335–1353. doi:10.4161/hv.20518.

[27]. Li, F., et al. (2010). Cell culture processes for monoclonal antibody production. MAbs Journals, 2(5), 466–477.

[28]. Li, Y., et al. (2016). Quantitation and pharmacokinetic modeling of therapeutic antibody quality attributes in human studies. MAbs Journal, 8(6), 1079–1087.

[29]. Lybecker, K. M. (2016, January). The biologics revolution in the production of drugs. Retrieved from

[30].  Macnee, C. L., & McCabe, S. (2008). Understanding nursing research: Using research in evidence-based practice. Philadelphia, PA: Wolters Kluwer Health/Lippincott Williams & Wilkins.

[31].  Marion, D. (2013). An Introduction to Biological NMR Spectroscopy. Mol Cell Proteomics , 12(11), 3006–3025.

[32]. Medina, C. (2003). Compliance handbook for pharmaceuticals, medical devices, and biologics. London: CRC Press.

[33]. Mócsai, A., Kovács, L., & Gergely, P. (2014). What is the future of targeted therapy in rheumatology: biologics or small molecules? BMC Medicine, 12(43), 1-9.

[34]. Phrma. (2017). Biopharmaceutical research & development: The process behind new medicines. Retrieved from

[35]. Prueksaritanont, T., & Tang, C. (2012). ADME of biologics—What have we learned from small molecules? The AAPS Journal , 14(3), 410-419.

[36].  Rahman, M. S. (2016). The advantages and disadvantages of using qualitative and quantitative Approaches and methods in language “testing and assessment” research: A literature review. Journal of Education and Learning, 6(1), 102-112.

[37].  Roberts, A. (2015). Maintaining the stability of biologics. BioPharm International Journal, 28(3), 38-41.

[38].  Rosenberg, A., & Demeule, B. (2015). Biobetters: Protein engineering to approach the curative. New York: Springer Publications.

[39].  Rubin, A., & Babbie, E. R. (2010). Essential research methods for social work. Belmont, CA: Brooks/Cole, Cengage Learning Press.

[40].  Suh, H. Y., Peck, C. C., Yu, K.-S., & Lee, H. (2016). Determination of the starting dose in the first-in-human clinical trials with monoclonal antibodies: a systematic review of papers published between 1990 and 2013. Drug Design, Development and Therapy.

[41]. The Conversation. (2015, August 5). Explainer: what are biologics and biosimilars? Retrieved from

[42].  Tibbitts, J., et al. (2016). Key factors influencing ADME properties of therapeutic proteins: A need for ADME characterization in drug discovery and development. MAbs Journal, 8(2), 229–245.

[43].  Tolley, E. E., Ulin, P. R., & Robinson, E. T. (2013). Qualitative methods in public health: A field guide for applied research. San Francisco, CA: Jossey-Bass Press.

[44]. U.S. Department of Health and Human Services, et al. (2015, July). Analytical procedures and methods validation for drugs and biologics: Guidance for industry. Retrieved from

[45].  Vugmeyster, Y., et al. (2011). Complex pharmacokinetics of a humanized antibody against human amyloid beta peptide, anti-abeta Ab2, in nonclinical species. Pharmaceutical Research, 28(17), 1696–1706.

[46].  Waltz, E. (2014). It's official: Biologics are pharma's darlings. Nature Biotechnology, 32(2), 117.

[47].  Wang, W., & Prueksaritanont, T. (2010). Prediction of human clearance of therapeutic proteins: Simple allometric scaling method revisited. Biopharmaceutics & Drug Disposition Journal , 31, 253–263.

[48].  Wang, W., & Singh, M. (2014). Biological drug products: Development and strategies. New York: John Wiley & Sons, Inc.

[49].  Wang, W., et al. (2011). Monoclonal antibodies with identical Fc sequences can bind to FcRn differentially with pharmacokinetic consequences. Drug Metabolism and Disposition Journal, 39, 1469–1477.

[50].  Wiley, F. (2016, July). What are biologics? Retrieved from

[51]. Wong, G. (2009). Biotech scientists bank on big pharma's biologics push. Retrieved from

[52].  Zhao, L., Ren, T.-h., & Wang, D. D. (2012). Clinical Pharmacology Considerations in Biologics Development. Acta Pharmacologica Sinica, 1339–1347.

[53]. Zimney, E. (2008). Understanding biologics: How they differ from Drugs and why they cost more. Retrieved 09 15, 2017, from Every Day health: