At Interphex earlier this year, Jennifer Riter, Senior Director, Global Analytical Services and Andy Polywacz, Vice President Quality Assurance at West Pharmaceutical Services, Inc. discussed the challenges dealing with particles in drug packages in the presentation, “Particles Causing End of Line Rejects and Drug Product Recalls: Overcoming Packaging Challenges and Need for Adequate Controls." PMP News asked Riter and Polywacz to share more details and what steps pharmaceutical companies should take.
PMP: Analytical testing typically relies on older methods—what are those?
JR: ISO 8871 has been the standard for analytical testing for more than twenty years. It provides a strong basis, however, there have been several developments in packaging materials since that time. At West, we’re taking a different approach by going beyond ISO 8871 to take into consideration the specific chemical properties of materials that are used commonly today, including new elastomer formulations.
PMP: The challenge would be to develop specific methods for each particle type—can you offer examples of particle types? Why would each need its own method?
JR: Particles can come from elastomers themselves or from the environment. After the different types of elastomers are washed and prepared, they go into various types of packaging before reaching the customer. Therefore, it’s important to take into consideration whether or not there is any particle burden within that packaging that the elastomer could take on before it is shipped it to the end-user.
Each particle type requires its own method of analysis because the methodology for properly identifying the level of particulates can vary. For example, a clear fiber may require different lighting when you’re looking at it under a microscope versus a gray type of particle that may have abraded from the elastomer. You may not be able to see everything under one focus or under one light source. It’s important to incorporate multiple methodologies of identification and analysis to ensure the accuracy of your data.
PMP: It is also hard to answer this question: how do you remove particles? So does this challenge mean that suppliers/users should work upfront to ensure that packaging, people, and environments have minimal amounts of particles in the first place? Should maximum thresholds be set and expected? How would this be monitored?
JR: There are a variety of different ways to remove particles – it all depends on the surface chemistry of the material you’re using, and the proper way to remove that particle from the surface area. For example, one might utilize a surfactant, or water, or both combined. Other approaches include vacuuming the particles off of the material’s surface. Whatever methodology is chosen, one must be careful not to pull out additional particle from within.
AP: In order to ensure the best quality drug product and optimal patient outcomes, it’s important for drug manufacturers to foster a collaborative effort with their packaging suppliers from the beginning. By working closely with our customers early in the drug development process, we are able to clearly understand what the specific containment and delivery requirements are for their drug product and select the appropriate packaging and delivery systems and materials. Additionally, we encourage our pharmaceutical partners to examine the potential for particulates across the entire supply chain, right down to the end-user. These early conversations allow us to set appropriate thresholds and ensure we’re meeting those thresholds throughout the entire process.
For example, we need to consider the particle load throughout the supply chain – including other facilities, materials and processing involved in the production and delivery of the drug product – to ensure that we’re mitigating any additional burden that may exist later in the process that could impact the final quality. West takes an active role in supporting our pharmaceutical partners in this process, working collaboratively to develop a solution for the total supply chain.
PMP: When are particles ok?
AP: There will always be some level of particle burden. Particles can either be intrinsic, i.e., an expected output of the material or process being used, or extrinsic, meaning that they’re originating unexpectedly as part of the manufacturing process. If particles are found to be intrinsic, we work proactively to put processes in place to ensure that the risk of particles is mitigated before it gets to the patient. For example, filter needles and other types of delivery devices can help mitigate any intrinsic particulates from getting to a patient. If an extrinsic particle is found, additional time and analysis is required to identify the source and update manufacturing processes accordingly.
PMP: Jennifer also said that pharma companies do not always understand the magnitude of particle analysis. Can this point be expanded?
JR: A thorough analysis of particulate matter is a complex, customized process and we work closely with our pharmaceutical partners to ensure that we design a testing and analysis process that best meets their expectations from the very beginning. We have to look closely at all the different factors that could affect the particle testing. For example, if you are utilizing a flask to extract the particles into a solution, you will need to consider how the shape of the flask can affect the data around particle burden. A wider flask might have a different affect than a narrow flask.
Going beyond running ISO 8871 and understanding every part of the analytical test and what impact it has on the result is important. Every product and its intended purpose is different, so it’s important to recognize that the analytical process cannot be one size fits all.
PMP: Andy stated that there is a need for new standards—what are those?
AP: How a drug is manufactured and delivered to the patient is incredibly important, and quality standards need to be relevant to emerging drug molecules and delivery devices. Previous standards didn’t necessarily take into account the unique containment needs of biologics or other large molecule drugs. Additionally, old standards didn’t address the total drug containment and delivery system, but instead focused on individual components, such as stoppers and vials. It’s a completely different supply chain now, and the standards need to be updated to address the needs around current drug molecules and delivery systems as well as future therapeutic offerings.
PMP: The presentation explores manual versus automated counting. How does a company decide?
JR: Deciding on the most appropriate technology depends on what the company has established as its desired outcome and the accuracy of the software. Not all software is created equal. When you are looking at particles of different sizes, colors and types, you have to ensure you have the right software to appropriately account for different types of particles and materials.
PMP: Should pharma companies ask their suppliers for guaranteed maximum particulate counts and then verify those counts upon receipt? Inline? During sampling?
AP: For products that are going to be directly introduced into their fill suite, the answer is yes – it is the responsibility of the supplier to prepare those products beforehand. That’s why it’s crucial to work collaboratively throughout the process so that all parties understand the total particle burden across the supply chain and where the responsibility lies to ensure the end product is what is needed and expected.
PMP: Andy also stated that pharma companies need to be aware of how their own processes contribute to particles. What evaluations should they perform?
JR: We encourage pharmaceutical companies to be aware of the inherent variability within their processes, as well as their range of capabilities. Additionally, it’s important to have confidence in their data and the repeatability of acceptable outcomes, especially when it comes to particulates. And the data should encompass the entire supply chain.
PMP: What control should they institute? Should there be ongoing sampling and monitoring? What other steps should they take?
AP: Given the different areas of manufacturing within pharmaceutical companies, it’s important to have ongoing monitoring, as well as a sound understanding of the factors affecting the particle levels within their specific operations. Some of these factors may be seasonal, while others are related to inherent change. Monitoring and understanding where and when those shifts occur and how to mitigate them is critically important.
PMP: Are particles and particulates the same?
AP: Yes. The two terms are used interchangeably.
PMP: Any other advice for overcoming packaging challenges as they contribute to particles?
AP: When we work with our pharmaceutical partners, it always starts with the patient and their needs, and then we work back through the whole process from there. Whether it be the secondary packaging manufacturer or our suppliers, we all need to understand the potential for particulates each step of the way before the drug product reaches a patient. At West, we serve as an advocate for our pharmaceutical partners among suppliers—ensuring that the end product is of the highest quality possible and meets the needs of the patients relying on these therapies.
PMP: What special steps is West taking to help customers?
AP: West is able to offer a broad view of trends in the marketplace and we pride ourselves with staying on the cutting edge of new materials and methodologies for manufacturing and quality analysis. We educate our customers on these trends and new developments, based on their individual needs, and serve as a trusted partner to ensure that what they’re ultimately delivering to the patient is of the highest quality.