Pharmaceutical manufacturers need to understand the compatibility and performance of the primary packaging system with both the drug and its delivery system.
Jennifer Riter, West Pharmaceutical Services
As more pharmaceutical manufacturers develop combination products, they identify new and complex interactions among packaging components and delivery systems. Understanding this interplay is critical to developing a successful drug-device combination.
Different types and classes of drugs warrant varying approaches; for example, there are specific expectations around particulate in biologics due to aggregates, sub-visible and visible particles, potentially posing a risk to patient safety and product efficacy. For any drug, creating a risk-based testing strategy early in development is a key to ensuring success of a combination product.
This includes developing and applying a strategy for component and system qualification, which is critical to ensuring drug product quality, safety and efficacy. Not only do manufacturers need to understand the chemical compatibility of any given drug with its packaging components, but also how physical and functional aspects of packaging components and the device all come together and function as a system.
Key areas of consideration for analytical testing
- Compendia assessment is typical testing required of materials to be used in the system, such as glass, plastic and elastomers. Because a material may meet compendia compliance doesn’t mean it’s qualified for its intended use.
- Biocompatibility is required testing of combination products and their components, including cytotoxicity, sensitization, irritation and acute systemic toxicity.
- Extractables and leachables analysis is an essential part of qualifying packaging and delivery systems during drug development, as it’s well-established that packaging materials can contribute leachables to drug products. Along with primary and secondary packaging materials, interim storage containers and processing equipment must be evaluated for compounds that may leach into drug products to maintain the drug’s quality, sterility and efficacy.
- Particle analysis is critical as particles can have a dangerous impact on drugs. They may be visible or subvisible and categorized as intrinsic, extrinsic or inherent. Intrinsic particles may come from processing or primary packaging materials, including stainless steel components, gaskets, packaging glass, rubber components or fluid transport tubing. Extrinsic particles are foreign to the manufacturing process, such as hair or non-process-related fibers. Inherent particles are associated with specific drug product formulations such as suspensions, emulsions or aggregates. Specific expectations around particulate in biologics due to aggregates, sub-visible and visible particles pose a risk to patient safety and product efficacy.
- Container closure integrity (CCI) is the ability of a packaging system to prevent product loss. It blocks the ingress of microorganisms and limits entry of detrimental gases or other substances over the shelf life and lifecycle of the drug product — thus ensuring that the drug product meets safety and quality standards. CCI failures can include leakage, loss of product, increased concentration, contamination and pressurization issues.
- Performance analysis and essential performance requirements (EPRs) are required in devices and combination products. The FDA defines EPRs as a subset of design input requirements necessary for a device constituent to safely and effectively achieve the combination product’s intended use. EPRs should consider the desired level of reliability of the product and the level of risk associated with failure and should be evaluated during stability testing. Drug-filled containers like syringes, vials and cartridges typically have interfaces resulting from components such as pistons and glass barrels. For any container, these interfaces must be understood thoroughly, with fundamental performance aspects substantiated and demonstrated, often through what may appear very rudimentary tests.
Opportunity for device manufacturers
Device manufacturers who offer analytical lab testing and other contract services are in a unique position to better serve customers throughout a product’s development. This includes an ability to help customers scale up combination product device and assembly, contract manufacture parts of the device, and walk customers through development, including what needs to be tested and performing the testing for the drug manufacturer.
Operating as a one-stop-shop can help customers bring combination products to market more efficiently. This isn’t to say contract manufacturers shouldn’t have partners for certain elements of the process — in fact, it’s common and strategic to do so as a means of closing any gaps (for example, West partners with other companies for filling capabilities) and can be an integral part of a cohesive and integrated solutions approach.
An integrated solutions approach can provide seamless customer engagement and collaboration early in the development process. Device manufacturers can help guide partners and establish a roadmap for each phase of development and lifecycle management that continues through post-commercialization. This can even include human factor studies — formative followed by summative, prior to clinical trials — helping to manage processes for customers and the devices under development.
It also involves working with engineers to ensure they’re looking at materials appropriately, being involved in characterization and scaling, and deciding on the right primary packaging. With medical devices in the past, the drug product wasn’t always taken into consideration because it’s developed separately from the device. With combination products today, it’s essential to ensure all materials, such as primary packaging and fluid path materials such as tubing, are analyzed and tested, as any or all may play a role in the extractable and leachable profile of what may ultimately go into the patient.
Device manufacturers can also test and store products for stability studies and assist drug manufacturers to assess the delivery system for commercialization.
Combination products are still relatively new, and rapidly evolving in terms of developmental requirements, patient needs and regulatory guidelines. Manufacturers must be aware of the changing landscape, technologies and guidelines to steer partners and customers in the right direction, inform what they need to be thinking of during all critical development phases, and ensure appropriate and thorough analytical testing is executed throughout a product’s lifecycle.
Jennifer L. Riter is senior director of global business operations and analytical services in services and solutions for West Pharmaceutical Services, Exton, Pa. Her experience blends knowledge of West’s components, containment, and delivery systems with hands-on technical support and analytical solutions for packaging, delivery systems and combination products to multi-national customers.
The opinions expressed in this blog post are the author’s only and do not necessarily reflect those of Medical Design and Outsourcing or its employees.