Preservando proteínas humanas por liofilização

The small volume parenterals (SVP) department is mainly responsible for our lyophilised (freeze-dried) products.

Freeze-drying is a preservation process in which heat-sensitive substances are rapidly frozen before being dried in a vacuum.

The products we work with are finished, formulated products. During filling and freeze-drying, the product is always open and this, of course, presents a certain risk of contamination, which must be avoided. A human being is the greatest risk factor when making sterile products. We receive the product from the purification department.

Clean rooms

Our work is very complex. Everyone has to work extremely precisely and be constantly alert. The fewer direct human interventions, the lower the risk of contamination. We work with a lot of machines and different processes in 15 rooms with different levels of clean room classification. A clean room is a controlled environment with a specified maximum number of particles per cubic metre at a specified particle size, which is measured by a particle counter. We operate in class D, C, AB and A . When moving between the different levels of clean room, you must have a complete change of clothes, including overalls, mouth protection, glasses, gloves and protective overshoes. Such rules are set by the regulatory authorities, and our staff members are thoroughly trained in the necessary procedures. We use personnel monitoring which means that every operator has to make a copy of his or her gloveprints and also from different places on their sterile overalls. This monitoring allows us to confirm that an operator has not contaminated his or her work.

Filling

Our monitoring framework conditions (MFC) system is used to monitor the whole of the filling process. There are four main parameters: air velocity, differential pressure or room pressure, temperature and humidity. If any of these parameters are exceeded, an alarm is sounded. When this occurs, our work is halted, filling is stopped and we have to investigate and report on what has happened. It could be that there has been a drop in pressure or that the room temperature is too high.

Our patients count on us. Everything has to be absolutely right, from start to finish.

Freeze-drying/lyophilisation

One of my main tasks is preparing the freeze-drying machines, or lyophilisers (“lyos”, for short), for production. We use automated processes (“chains”) to clean the lyophilisers, including “sterilisation in place” and we perform various filter tests, leakage tests and endurance tests before using the lyos in production.

We have six lyos at our Vienna manufacturing site, four of which are completely automated. The automated machines are able to load and unload the freeze dryer in what we call an isolator, a closed system. The isolator is a sealed clean-room system, independent of the environment and free of any human influence.

Loading temperature is important. We load at 20°C , but there are products that we load at lower temperatures. In this latter case, the equipment’s loading shelf is pre-cooled to match the specified loading temperature.

Freeze-drying stabilises and preserves the product’s proteins. The product begins in liquid form, and is then frozen, causing crystals to form. Next, the product is dried in a vacuum before the temperature is increased. The product of the freeze-drying process is a white powder we informally refer to as “lyo cakes”.

At the end of the freeze-drying process, the product bottles are sealed, but the risk of contamination remains for as long as the bottle doesn’t have a bottle cap. That’s why we carry out vacuum checks to ensure all vials are vacuum sealed.

Once the product has been freeze-dried, it is unloaded with robots, i.e. fully automatically, without any human intervention. The injection number and the lead number are printed which means that each product and batch can be easily identified. With one of our human coagulation factor VIII concentrate, for example, we have to test every bottle for residual moisture and vacuum. After a period of up to 14 days, we carry out the 100°C terminal dry heat step, which inactivates enveloped and non-enveloped viruses.

We work a four-shift model – four days working from 6am to 6pm, followed by four days off. Then we work the night shift from 6pm to 6am, again followed by four days off. When you are working with machines and computers, technical problems can and do happen, which can be frustrating. On the other hand, everyone is pleased when we have freeze-dried our products, taking them one step closer to patients.

I’m happy to be a member of this big family that is Octapharma. I’ve been here for 21 years and I’ve watched how we have grown. I’m proud of our company and of the fact that we produce more products every day and bring new products to market to help more patients. My colleagues and I are life savers. We make absolutely certain that we work in accordance with all standards, in a clean environment, and that we follow all regulations. Our patients count on us for these vital medicines. Everything has to be absolutely right, from start to finish.