MFI BioPharma Application Note - Quantitization of Silicone Oil Droplets in Biopharmaceutical Formulations
Silicone oil is widely used in the pharmaceutical industry as a lubricant or coating in devices such as syringes, needles and pharmaceutical containers and has been implicated in aggregation and particulation of proteins and antibodies. Aggregation of therapeutic protein products induced by silicone oil can pose a challenge to their development and commercialization(1). Although these aggregated species may constitute only a minute fraction of the total protein population, their presence can render a product clinically unacceptable due to potential for immune response in the patient(2). As a result, quantification of silicone oil droplet populations in pharmaceutical products is important.
An inherent challenge for characterization and quantification of silicone oil droplets in biopharmaceutical formulations is the difficulties in detecting and differentiating them from other particulates in the formulation.
United States Pharmacopeia (USP) General Chapter <788> and the harmonized versions in the European and Japanese Pharmacopoeias set limits and cite enumeration methods for sub-visible, foreign particulate matter in parenteral products. USP <788> does not consider intrinsic sources of particulate matter such as protein aggregates, silicone oil droplets, air bubbles, micelles, or precipitates. However, the test methods cited in the section, which include automatic light obscuration and filter membrane microscopic analysis, might also in principle be applied to mixed silicone droplet and aggregate populations. However, both particle types are highly transparent and not easily measured by either of these techniques. In addition, automated light obscuration provides no capability, and membrane microscopy limited capability, to differentiate between these two highly transparent particle types.
MFI with automated particle classification is an emerging technology that can play a useful role in understanding and controlling silicone-oil-droplet-induced aggregation of proteins in parenteral pharmaceuticals. More generally, the ability of the technology to resolve and independently characterize mixed particle populations, including a wide range of sub-visible and visible particle types, offers a rapid and powerful means of evaluating sub-visible and visible particle populations in parenteral products.
The Brightwell Application Note (Document# D-0000021-00) can be found at Brightwell's website: CLICK HERE
Scientific Publication - Silicone Micro-Droplets in Protein Formulations - Detection and Enumeration
The authors describe a novel analytical approach that uses the shape-analysis capabilities of MFI to detect and enumerate silicone oil microdroplets in protein formulations that also contain aggregates of similar size and in a similar concentration.
Apr 2, 2009
By: Deepak K. Sharma, Peter Oma, Sampath Krishnan
Pharmaceutical Technology
Volume 33, Issue 4, pp. 74-79
The complete article can be found at:
http://pharmtech.findpharma.com/pharmtech/article/articleDetail.jsp?id=591864
Upcoming Oral Presentation - Pre-Filled Syringes Americas
Pre-Filled Syringes Americas - April 12-14, 2010
The Colonnade Hotel, 120 Huntington Ave., Boston MA USA
Day 1, 16:00 - Silicone Oil Droplet Enumeration using Microflow Imaging (MFI)
Speaker: Dr. Clark Merchant
Please visit the following site for more conference details:
http://www.visiongain.com/Conference.aspx?cid=262
- Silicone oil droplets from pre-filled syringes can introduce a significantly large and varying population of sub-visible particles into an exposed protein formulation.
- Quantifying the degree of silicone oil droplet introduction, in order to understand their affect (if any) upon formulation stability in terms of protein aggregation formation.
- Classifying and reporting on protein aggregates alone in a formulation containing both oil droplets and aggregates, in order to track the stability of a formulation.
- Micro-Flow Imaging (MFI) is a relatively new highly sensitive imaging-based particle analysis technique designed to image, count, and size sub-visible particles in protein formulations.
- Demonstrating how MFI can be used to quantify very low quantities of silicone oil droplets introduced by a pre-filled syringe.
- How the morphological parameters may be used to classify and isolate the protein aggregate population from the silicone oil droplet population.
