Author: Richard Juskowiak, Donaldson process filtration division
Filtration systems are used at many stages of pharmaceutical production. Contaminants contained in the gas, compressed air, steam and liquids used can enter liquid or solid dosage medicines. Such contaminants include solid particles, moisture, oil and microbes.
To save time and money, try to retain these contaminants at the early stages of the process. Use the redundancy principle to facilitate the isolation of contamination sources. For example, if the growth of bacteria is detected on the surfaces of process equipment used at later stages of the process, searching for their source and cleaning the entire production line will require a significant amount of time and money.
Taking these principles into account, the following main filtration locations can be identified.
The utility room
Install the first filtration systems in the area of utility equipment and storage, where tap or well water is supplied, steam is generated, and compressed air and nitrogen are produced or stored. Before these liquids and gases enter the technological process, they must be pre-cleaned. The pre-filters installed here increase the efficiency and extend the service life of the fine filters located downstream.
A 5-micron element removes contaminants larger than 5 microns in diameter from the water. This is a sufficient level of filtration for cleaning-in-place (CIP) and steaming-in-place (SIP) systems. (To purify water used as part of the product, a reverse-osmosis or microfiltration system will need to be installed at later stages of the process.)
If nitrogen cylinders are used, airborne contaminants can enter open pipelines when the cylinders are replaced. It is recommended to install a pre-filter in the nitrogen supply line.
Process tanks
The next stage where filtration is required is the preparation and storage of active pharmaceutical ingredients (API). Steel tanks can become a site of mass growth of microorganisms entering them from the surrounding air or from personnel.
Creating a protective environment in tanks with active pharmaceutical ingredients using clean dry air or nitrogen is a recommended way to combat contamination. It also makes it possible to equalize the air pressure when emptying or filling tanks. To remove moisture and contaminants from the air or nitrogen for the protective environment, it must be passed through a 0.2-micron filter installed on the nitrogen- or air-pressurizing equipment. Microorganisms do not survive in nitrogen, but it can carry microscopic contaminant particles from pipelines.
The ingredient-introduction area
The introduction of each substance into the process involves a risk of contamination. This also applies to the area of intermediate introduction, where active pharmaceutical ingredients are mixed with other ingredients, for example shells or binders, to obtain the finished product.
Fine filters must be installed on all steam, water and compressed-air supply lines that have direct contact with ingredients or with surfaces in contact with ingredients. For water and liquid chemicals, 1–0.2 micron filters can be used; for sterile air — down to 0.03 microns.
Immediately before encapsulation or filling, formulations can be in intermediate-storage tanks. For these tanks, an additional set of equipment for supplying nitrogen or dry compressed air must be used, as well as filters at the points of use.
Packaging
During the storage or transport of packaging materials, contaminants can get on them. To ensure the aseptic packaging of pharmaceuticals, it is recommended to clean the liquid tanks with culinary steam before bottling. The foil and plastic used for packaging must be scalded with hot steam and dried with filtered compressed air to prevent the growth of microbes in the finished product. To produce culinary steam, the removal of 95 % of particles 2 microns in size and larger must be ensured.
The advantages of redundancy
Multi-stage filtration of air, water and steam may seem excessive, but it provides several advantages.
- Pre-cleaning makes it possible to save money by preventing an excessive load on the expensive filter elements downstream.
- Intermediate filtration reduces the amount of contaminants, for example metal particles, that can form in process equipment.
- Fine filters at the final processing and packaging stage guarantee compliance with the requirements for the aseptic process.
In a word, filtration with redundancy helps to minimize risks and produce quality products at lower cost.
Conclusion
Each production is unique, and in each specific case different questions may arise regarding filtration. How to choose the rating and efficiency of a filter at a certain point in the process? How many CIP and SIP sterilization cycles can an element withstand? How do different filter materials differ?
Donaldson, an experienced supplier of filtration solutions, including for the pharmaceutical industry, has the answers to all these questions. We will help you create a filtration plan to protect the product and the process at minimal cost.
