The Particle Articles

On May 14th, Rebekah Byrne, Scientist I and David Exline, Senior Vice President at Gateway Analytical hosted a webinar designed for developers of parenteral drug products.  During this webinar, our presenters identified commonly found contaminants in parenteral drug products, how these contaminants are introduced into the manufacturing process, how they can be detected both visibly and non-visibly and laboratory techniques used to identify contaminates. They provided insight into terminology used when discussing parenteral contamination including the difference between particle-free vs. sterile and the standards for visual inspection. They also discussed the importance of taking a pro-active approach to quickly source and manage contaminant issues in the manufacturing process to reduce the risk of future contamination and potentially save your company money by preventing potential recalls.

For more details on the webinar, you can use the links below.

• View the webinar
• Download the presentation slides

We received a number of questions from attendees during the Q&A segment, and you can find those questions and answers below. If you have any questions about this or any other topic, please contact us.

1. What would you say is the leading cause of contamination in drug products?
   Historically we have found that raw materials and wear and tear of equipment have been leading causes of contamination issues in drug products.
2. What are some causes of delamination?
   Various studies have indicated that both temperature changes and chemical interactions between glass surface and the liquid in a vial can cause delamination issues.
3. How do you determine what analytical methods you want to use for a particular sample?
   When deciding what methods you want to use, you need to determine the type of material during initial observations. That is, if something appears to be metallic, you would treat it very differently than if something is fibrous. A lot of these decisions are made easier as an analyst gains experience.
4. Can you ever say if something absolutely came from a particular source?
   Generally not, unless we have the potential for a physical match.
5. Could you share a few cases of out of box sample preparation?
   I had a project were swirls of fine particulate were present in a liquid, and we could not manually extract them with a pipette due to size. We ended up preparing the sample onto a gold filter, and performed analysis directly from the filter.
6. Say you find particle contamination in one sample, how do you make a conclusion about the quality of the whole batch? Most of the analytical methods mentioned in this presentation require sample prep and removing the sample from the original package. Therefore, examining every sample in the same way is obviously not practical. How do you address this issue?
   Typically, we are talking about 100% inspection in parenterals, so we gauge the number of types of particles in a batch. We can take representative particles based on optical observations. Quality by Design (QbD) allows a process of counting particles, and when counts fall outside of the acceptable range, we will move to testing.
7. What are some of the common causes of fiber particles?
   There are a wide range of possibilities, ranging from PPE to laboratory wipes to personnel. This is why identification of the material is so critical.
8. Do you think that Micro-Flow Imaging (MFI) analysis could be useful for characterization of a particle in a solution?
   While we have limited knowledge of micro-flow imaging, both particle sizing and detailed analytical analysis of particles during investigations are important.
9. How far can an investigation go in a case of human hair contamination in a drug product vial?
   When we are specifically talking about human hair, many times a hair can give indications of the racial and body origin of the person who shed the hair, through optical microscopy. Additionally, DNA testing is a possibility to consider. That being said, many times the hairs found in vials are not in pristine conditions (hair fragments, thermal degradation, etc.). How far an investigation of a human hair can go is going to be dependent on the condition of the hair.
10. Do you have examples of oil "particles" - e.g. haziness, tyndal cone effect, Silicone oil? How would you ID it?
    A customer was observing “round clear particles” on the surface of the liquid of a vial. When trying to manually extract the particles, they were slipping away from the pipette. They were oil-like. The customer was contacted and they indicated that silicone oils were commonly used in their processes. We performed a liquid-liquid extraction, followed by Raman and SEM analysis. This confirmed the presence of silicone oils.