Upstream processes are those in which biological materials are either obtained from an outside source or inoculated and grown in culture, under controlled conditions, to manufacture certain types of products.
Downstream processes are those in which the products are harvested, tested, purified and packaged.
Many forms of biomanufacturing require technicians to carefully control the environment in which cells are grown or biological processes take place. If the final product will be used as a drug, biomanufacturing technicians will need to work together in environments where current Good Manufacturing Practices (cGMP) are strictly followed.
Technicians who carry out the complex steps in both upstream and downstream processes must communicate with each other and work together. They have to monitor equipment and pay attention to details.Full scale biomanufacturing requires technicians to work with other departments in a company, these departments may include - Process Development, Manufacturing, Regulatory, Quality, and Engineering Services - to define, design, develop and execute critical biomanufacturing processes , control parameters, and adhere to performance standards.
In pharmaceutical biomanufacturing, tasks are carried out in sterile or clean-room environments. In these environments, cells are grown in large stainless-steel bioreactors. The equipment for monitoring cell growth and purifying products is linked together by pipes and connected to electronic computerized controls.
Upstream Biomanufacturing Technicians work with living cells or other forms of biological materials They grow cells in specialized environments and ensure that cells with transfected genes have the factors they need to grow and produce the desired proteins. Many types of cells are grown in a liquid media inside tanks or bags called bioreactors (mammalian) or fermenters (microbial). Upstream Manufacturing Technicians follow recipes to cook and prepare sterile media. The ingredients in the media are specific for each stage of the growth and production processes- from starting the culture to the harvest. They weigh materials, measure characteristics of the environment such as temperature, pH, and dissolved oxygen, and check the raw materials that are used to prepare media and buffers.
When the bioreactor is filled with media, it must be calibrated to fit within specific ranges for temperature, dissolved oxygen, and pH. Then cells are added to the media. Technicians count the cells during growth and measure the health of the culture by comparing the number of cells that are living and dead. Viable (live) cell concentration and viability are used as Forward Processing Criteria (FPC) as well as Critical Process Parameters (CPP) in the culture. Accurate and consistent cell counts are essential in creating a robust production process.
Common activities for upstream biomanufacturing technicians include starting and monitoring the growth of cultures, monitoring different processes, and sampling. Aseptic technique is critical to prevent contamination. Special procedures are are used in upstream biomanufacturing to maintain sterility, prevent contamination, and minimize the chance of exposing the product to the environment. Biosafety cabinets must be used to protect cells. Special procedures and equipment are used to ensure that connections between the bioreactor, harvest tank, hold tanks, and additional containers remain sterile.
Upstream processing concludes with harvesting the products, typically by using centrifuges to separate liquid materials from larger cells. The next step is filtration, including depth filtration and sterile grade membrane filtration.
Other responsibilities for upstream technicians include:
- Keep work areas ready for inspection.
- Follow cGMPs and Standard Operating Procedures (SOPs) to maintain a clean room environment that complies with regulatory requirements
- Maintain records
Demanding manufacturing schedules may include four-day, ten-hour shifts, weekend days, evenings or night hours. Expect to be on your feet eight to ten hours a day. Technicians working in this environment must wear special clothing such as protective gowns and steel toe boots.