Modelling & Simulation in Drug DevelopmentPharma companies look to improve experimental drug success rate and accelerate clinical development while striving to improve efficiency cost-effectively. It is imperative for companies to be cautious in decision making to increase the probability of commercial success for developing the drug. Major pharmaceutical companies have been exploring use of computer-based simulation and modelling techniques for making informed decisions. Some of the strategies these companies focus on are Clinical Trial Simulation (CTS), Modelling and Simulation (M&S), Computer-Assisted Trial Design (CATD), Model-based Drug Development (MBDD), and model-informed drug discovery and development (MID3). Regulators have also taken note of such strategies to enable increased efficiencies in drug development.
From the business perspective, M&S is being leveraged to showcase virtual bio-equivalence and receive bio waivers. M&S follows an in-vitro in-vivo correlation (IVIVC), which the US Food &Drug Association (FDA) defines as “a predictive mathematical model describing the relationship between an in-vitro property of a dosage form and an in-vivo response”. While developing and optimising a new drug formulation, there may be changes in composition of drug, manufacturing process, equipment used or the batch size. These changes can occur frequently prompting the need to conduct bioavailability studies for determining equivalence and IVIVC is a tool used to demonstrate this equivalence during the drug development and optimising formulation.
Be it clinical trials or Research & Development (R&D), M&S in particular has significantly impacted both development and formulation of drugs. With clinical trials, M&S has shown to add value in optimising study design, while pursuing the objective of improving efficiency by choosing an accurate trial size and collecting relevant data at optimal times. A 2012 research paper highlights the positive impact of M&S in clinical trials on FDA approval and labelling decisions. From 2000 to 2008, Pharmacometric analysis have contributed to 64 per cent of drug approval decisions and 67 per cent of labelling decisions. FDA is believed to have necessitated use of M&S in identifying and approving an experimental drug Peramivir to curb an influenza epidemic in 2009. Today, it is not surprising that around 90 per cent of FDA approvals are deemed to be around M&S. Such is the importance M&S has achieved over the years.
A recent paper titled “Regulatory Experience with In Vivo In Vitro Correlations in New Drug Applications” published by the FDA, offered guidance in using IVIVC for pre-approval and post-approval changes, and thus minimise the need for in vivo bioequivalence studies. The paper also emphasised on how IVIVC has been aiding in drug development decisions in the wake of Quality by Design paradigm. Regulators including FDA, European Medical Agency, Japanese Pharmaceuticals and Medical Devices Agency and other regulatory agencies have been advocating the use of IVIVC as they believe it to be a key tool enhancing product and process understanding and ensuring steady performance through the product life cycle. IVIVC plays a strategic role enabling pharma manufacturers to replace expensive, time consuming bioavailability and bioequivalence studies with cost-effective and time efficient IVIVC analyses. For scientists, IVIVC offers better product insights enabling them to change a drug’s formulation to increase its in vivo performance as well as probability of regulatory success.
In the cover story of this issue, Mikku Nagata of Certara GK emphasizes on how Modelling & Simulation can be a game changer in drug development saving time and money for companies, and also aiding in improved patient care. I am hopeful you will find the cover story and other articles equally interesting.