Welcome to Biotechnology by Amgen

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Process Development

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The first phase of Amgen's manufacturing process is the cell culture, which begins with process development. In this step, cells from the cell bank grow in flasks to start the production process. First, a vial of cells is selected from Amgen's cell bank. Amgen scientists identify the DNA sequence of a therapeutic protein to insert into living cells to create a new cell line. Once inside, the DNA uses the cells' machinery to transcribe and translate the DNA's message into a biological medicine. Access to the cell bank is limited to very few people and carefully controlled to ensure the identity, safety and purity of the finished product. Before we get started, let me explain the many ways you can explore our beautiful space. -You can jump to the next stop by clicking on the "Next" button. -Now, if you already know where you want to go, you can select any location by using the list. -Lastly, remember that you can explore any particular location in more detail by clicking the 360, Photos, or Video icons.

Seeding

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Seeding is where cell growth continues. It takes several weeks to manufacture a single batch of biologic medicines. Cells continue to divide as long as their environment remains favorable. Here, growing cells are transferred to successively larger vessels as their number and concentration increase. Sterile plastic biobags are filled with cell culture and growth media and loaded into the 50 liter bioreactor, where they remain for a few days before moving to a 150 liter bioreactor. Cell count increases in a controlled manner and contents are then moved to a 750 liter bioreactor where growth continues. Temperature, pH, agitation speed, and dissolved oxygen concentrations in the cultures are continuously monitored.

Production

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The final step in cell culture is production, which means growing cells have reached the large production bioreactors. Here, we shift to the complex process of producing a specific protein that will become a biological medicine. Bioreactors are filled with production medium that is equilibrated to the proper temperature, pH, and oxygen levels to stimulate protein production. We carefully control the product environment. Staff wear special uniforms and a HEPA filtration system replaces all of the air in the room every two minutes to ensure a clean environment. Nine bioreactors work at a volume of 15,000 Liters each – providing capacity to make enough protein for millions of doses of medicine.

Purification Buffer

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The first step in the recovery and purification phase is called the purification buffer. In this step, once the protein is produced, the protein solution is mixed with buffer – a pH stable liquid – to begin the purification process. This step involves eleven 20,000 liter buffer tanks. Buffers can be made for one-time use or in quantities large enough to cover an entire month. Our special cooling system ensures that buffer tanks are steam-sanitized at 121-126 degrees Celsius. Chilled water flows through a cooling jacket around each buffer tank to maintain them at room temperature.

Harvest

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The next step in the recovery and purification phase is called the harvest. During protein harvesting, the therapeutic protein is separated from the cells in which it has grown. There are generally at least six separate purification steps for Amgen medicines. In this area, dozens of filters remove impurities and cell debris and aid in separating media from cells. Amgen achieves very high levels of product purity, which are required by product standards. Additionally, samples are taken to monitor cell growth and cell density, while levels of pH and oxygen are maintained and monitored continuously with probes.

Purification

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Next, the protein solution is purified. At this point in the process, the cells have produced all of the protein that they’re going to make, so we separate them from the solution containing the protein. Next, we take that solution and purify it down to the protein that’s specific to our medicine. Chromatography columns are responsible for 95 percent of purification in the manufacturing process. This equipment is used to preform liquid chromatography, just one of many steps we take to purify the solutions containing our medicines. After that, we collect our protein again to preform our next unit operation.

Quality Testing

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Quality testing is the final step in the recovery and purification phase. During this step, Amgen ensures product quality through more than 250 tests of facility, utilities, raw materials, and product throughout the manufacturing process. We are actively and continuously pursuing new approaches and testing strategies through the deployment of innovative technologies. Onsite labs provide continual research and development for improving the manufacturing process. Workstations equipped with robotic arms provide significant ergonomic and performance benefits for lab analysts. In some cases, tests that would usually take two weeks can now be done in just two days, without sacrificing accuracy or quality.

Filling & Accumulation

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Next, our product is formulated and filled into the vials or syringes that will be packaged and distributed to patients. During formulation, the therapeutic protein is put into a mixture of inert components to help ensure that it remains stable during distribution and storage. This step takes place in aseptic suites to ensure sterility. Individual trays of 100 syringes each move into an accumulation room via conveyor belt. Syringes are inspected manually for quality, temporarily boxed, and moved for further inspection. Technicians continuously check for particles, cracks, discoloration or staining, stray fibers or substances in the liquid, seal integrity, and correct stopper usage. Various controls and quality inspections are conducted.

Inspection

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During the inspection process, every batch of product is thoroughly tested and inspected. Amgen was an early user of automated inspection equipment, which checks vials for color, clarity, and foreign particles. Automation allows Amgen to inspect more units of product faster but does not fully replace manual inspection. Units that provide test results at the boundaries of tight specifications are re-inspected twice by highly trained staff. Manual inspection of products is aided by state of the art safeguards designed to help prevent human error. A warning prompt will sound if vials aren’t being held in the correct viewing position for proper inspection.

Assembly & Labeling

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Next, we receive the bulk material. The bulk material gets formulated in place inside tanks. The tanks are then transferred to the filling area where the product is filled inside vials or syringes. As with all stages in the manufacturing process, during labeling and assembly, quality is paramount and any product that does not meet Amgen’s exacting standards is removed from the manufacturing line. Amgen produces hundreds of thousands of product every day, and we ensure quality by utilizing automated and manual inspection. Once our product passes final inspection, it’s ready for distribution around the world.

Packaging

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Now that we’ve reached the packaging step of the formulation to distribution phase, vials, syringes, or devices are placed in packaging along with all required inserts. Sophisticated automated systems are employed to increase efficiency and ensure consistent product delivery. It can take around 32 hours – or 4-5 shifts – to package 100,000 syringes. Temperature changes can affect product quality. Therefore, Amgen has implemented sophisticated packaging and shipping container features for select products that allow a health care provider or patient to tell if the product has become too cold or warm during shipping.

Distribution

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The final step in our process is distribution. During this step, packaged product is shipped to wholesalers and ultimately distributed to patients. Before any product can move to distribution, each batch must pass all inspections and be approved for release within ten days. Manufacturing a high-quality, reliable supply of complex biologic medicines requires significant skill and experience. Over 80% of Amgen manufacturing staff members have a college degree and about 25% have advanced degrees. Amgen products are shipped to physicians and patients in 72 countries around the world. The Amgen distribution process is a model of efficiency, managing stringent shipping requirements and tight schedules.

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