Authors
Dr. Volker Kraft
JMP
Muralidhara A
JMP
Claire Baril
Lonza Group AG
Andreas Trautmann
Lonza Group AG
Objective
Use Design of Experiments (DOE) to optimize the microbial cultivation process.
Background
Lonza is a Swiss multinational biotech and pharmaceutical company, headquartered in Basel, with major facilities in Europe, North America, and South Asia. Lonza was founded in 1987 and it’s known for technological innovation with world class manufacturing and process excellence. The company provides product development services, early phase discovery and custom manufacturing of active pharmaceutical ingredients for the pharma, consumer health and nutrition sector. This also includes scientific innovation and manufacturing technology optimization.
Lonza has established a purpose to Enable a healthier world and the company believes that this is the reason for its existence. The vision of the company is Bring any therapy to life. Lonza is involved in the manufacturing of biologics with several pharmaceutical companies and is recognized by Ethisphere as one of the world's most ethical companies. As of 2021, Lonza has more than 5,278 trademark fillings, 792 brands and 1,065 small and large molecules.
Lonza Group comprises two segments, namely Lonza Pharma, Biotech & Nutrition (LBPN) and Lonza Specialty Ingredients (LSI). LBPN focuses on delivering innovative solutions that prevent, treat or even cure disease. LSI focuses on microbial control for personal care, as well as for the protection of homes, schools, workplaces and the environment from mold and other potential pathogens. Lonza has divided its business into four divisions: Small Molecules, Biologics, Cell & Gene, and Capsules & Health Ingredients.
A microbial cultivation process is a method of multiplying microorganisms by letting them reproduce in predetermined culture media under controlled laboratory conditions. Microbial cultures are used to determine the type of organism, its abundance in the sample being tested, or both. A bioreactor is a manufactured device or system that supports a biologically active environment. It refers to a device or system designed to grow cells or tissues in the context of cell culture. These devices are used for 3 biochemical/bioprocess engineering. The sizes of the bioreactor can vary over several orders of magnitudes. One of the microbial cultivation processes uses three different sizes: small scale (0.25 L), lab scale (2-30 L) and pre-pilot scale (1500 L).
The Task
The Manufacturing team was tasked to speed development of this novel biomanufacturing processes to help products reach the market in a short time. The team focused on increasing the yield of the process, because a poor yield translates to higher manufacturing costs. An economically unprofitable product will not reach the market even if it were to be beneficial to customers.
The process involves four continuous process variables: feed rate, complex compounds, temperature, and pH. Instead of actual values, the standard convention of -1 and +1 are used to represent the low and high levels of factor settings.
The initial factor settings and corresponding yield are:
| Feed rate | Complex Compounds | Temperature | pH | Yield |
| 0 | -0.6 | 0 | 0 | 41% |
The goal is to find out the key process variables and their optimal process settings that would maximize the yield. The team also wants to understand the relationship between input and output variables.