Media Fill Inspection using Headspace Analysis
The widely used method by visually inspecting the media filled samples for turbidity is very time consuming. Some package configurations may not even allow visible control due to the package properties. A new approach using non-destructive Headspace Analysis (HSA) for the determination of gas concentration changes is an alternative method.
As a verification of the sterility of aseptic processes media fills need to be implemented regularly. During media fills the aseptic process is simulated by using a broth instead of the sterile liquid drug product. Potential contaminations in the process would lead to turbidity of the broth which can be inspected visually. Often this visual inspection process is done manually. As media fills need to represent a normal batch size, which can sometimes be thousands of test samples, this procedure can be very time consuming.
For some container types, such as brown glass or non-transparent plastic containers, the visual inspection is not applicable and requires additional steps by transferring the broth into clear containers in an aseptic environment. This step requires even more time and adds the risk of contamination that may even lead to false results.
Our customer approached us for a joint development of an automated Media Fill inspection platform using Headspace Analysis. With years of experience in both Headspace Analysis Wilco qualified as the development partner. In the first place, the gas concentration changes caused by the contamination of various microbial organisms were identified using laboratory systems. Oxygen and carbon dioxide concentrations inside the vial headspace were measured over several days. Based on this information the required detection limits could be derived, as well as the required incubation time, allowing the detection with a high reliability. In the next step, the method was transferred from lab scale to an automated system in order to understand the applicability of the method for larger batch sizes.
The engineering and method development studies resulted in an automated HSA inspection platform that can test multiple product sizes. The concentration of both oxygen and carbon dioxide can be measured non-destructively and at a high throughput.
- Significant time reduction for media fill inspection
- Application for difficult to inspect containers
- Quantitative data for media fills
- Operator independent results
- Automated inspection with batch records