The pharmaceutical industry continues to prioritize a focus on the patient, from both an experience and safety standpoint. This shift is sending waves across the industry, from trial design, regulatory guidelines and drug delivery, as well as impacting the types of drugs that are coming to market, such as biologics.
Biologics are used to treat chronic conditions such as multiple sclerosis, and help acute conditions, such as certain types of cancer, become manageable chronic conditions by targeting specific components of a disease in a completely new way.
But the increase in injectable biologic and biosimilar treatments is also requiring a stronger focus on quality requirements with respect to how the drugs are packaged and delivered. For example, efforts addressing container closer integrity (CCI), preventing extractables and leachables from primary packaging and the use of novel materials such as cyclic olefin polymers (COPs) to overcome incompatibility concerns with traditional materials like glass.
To navigate these areas, and ensure that novel drug treatments are delivered safely to patients, drug development and delivery manufacturers should adopt quality-by-design (QbD) principles supported by regulatory guidance (e.g., International Council for Harmonization [ICH] 8, 9, and 10).
New Challenges to Patient Safety
Biologics offer promising potential for patients through targeted treatments; however, biopharmaceutical companies and their manufacturing partners must address new considerations around drug packaging and delivery and risk mitigation. Particularly in the Western markets, there are three main areas of concern when addressing patient safety: particles, extractables and leachables, and CCI.
Particles in a drug product, whether visible or sub-visible, are a concern. This is magnified for products that are injectable because there is the risk that small particles in the drug product could be drawn into a syringe and subsequently injected into the patient. When particles are found in a vial of injectable drug, it will be a race against time to determine the source of the particles, the extent of the issue, and the impact of the defect. The defective product may also need to be removed from the market. Specific to biologic drugs, sub-visible particulate has been connected to immunogenicity issues, which has direct patient safety implications.
Regulators also are looking to understand any potential for leachables to impact drug quality or patient safety. And regulators are paying more attention to CCI, especially since the release of USP Chapter 1207 in August 2016. CCI deals with making sure that, through the lifetime of the drug product, the container closure system is appropriately sealed, protecting both the drug and patients. Ensuring CCI becomes more complicated when dealing with sophisticated drug therapies such as biologics, which are temperature-sensitive and therefore may be handled, stored, transported and dispensed in cold environments throughout their labeled shelf life. Any deviation from the ideal environment — or break in the “cold chain” — can affect CCI and jeopardize the drug’s safety and quality, or cause a loss of potency or efficacy, or even create the need to discard the product entirely. The goal is to keep the container closure system integral to assure sterility and that no harmful substances are migrating into the drug vial and that no drug product is escaping from the vial. Companies can solve for this by understanding the fit of components and build a design space for sealing the package.
Given that most biologics are injectable, drugmakers are increasingly exploring the use of prefillable syringe and self-injection systems to provide patients with the option of self-managing diseases outside of traditional healthcare settings. While injectable drug delivery systems offer the potential for newfound freedom for patients, advanced biologics possess specialized needs around containment and delivery. For example, they are often highly viscous with sensitive chemical compositions that pose the potential for interaction with materials traditionally used for packaging and delivery systems.
The convergence of these trends is putting increased focus on how to best contain and administer new biologic therapies, while also spurring drugmakers to consider alternate materials and technologies. In particular, many biopharmaceutical companies are exploring the use of high-quality COPs for primary container closure systems.
COPs are designed to add value to sensitive biologics through enhanced cleanliness and decreased interaction with the drug product. Additionally, COPs can be molded into a variety of shapes and designs, offering the ability to create innovative delivery systems around customized primary containers. This is ideal for biologics, as systems designed with COP materials can be molded to accommodate larger fill volumes and tighter dimensional tolerance, while remaining compatible with established filling technologies. When combined with barrier films and other high-quality components, such options can enable pharmaceutical companies to offer products in a unique combination or primary container and delivery device or system that may differentiate the product.
QbD and Drug Packaging Components
Drug packaging components play a vital, but often overlooked, role in drug safety and efficacy. The heightened focus on quality by regulatory agencies, combined with the growing use of biologics and the trend toward self-administration means manufacturers need to select components that have high levels of reliability, consistency and compatibility with sophisticated drug products and delivery systems over the course of their lifecycle. Components are a critical part of combination products and other integrated drug delivery systems and are essential to ensuring delivery systems are safe, intuitive, and easy to use. However, it can be difficult to know which component is the best quality fit for a particular drug product.
One class of products in particular that is essential to understand and assess during the drug development process is prefillable syringe plungers. Plungers (also called pistons and stoppers) are important elements in injectable drug delivery because they serve as the primary seal for container/closure integrity — helping to maintain the purity of drugs during shelf life. Plungers are typically made from butyl rubber and can be coated with a fluoropolymer film to increase lubricity and serve as a barrier between the drug and the elastomer, reducing the potential for leachables.
Problems with primary containment materials such as plungers can result in product variability, which can lead to delayed regulatory approvals and potential shortages of needed drug products on the market. These issues can significantly damage a company’s bottom line as well as its reputation. But higher quality can come with higher investment, so the challenge for drug packaging manufacturers becomes achieving the balance between managing the costs of providing higher-quality products while staying mindful of the pharmaceutical company’s total cost and profitability.
To address these challenges, the adoption of QbD concepts in the design and manufacturing of packaging components is gathering momentum within the industry. QbD delivers an improved, data-driven output, providing manufacturers with superior product and process understanding that minimizes risk, emphasizes patient-critical quality requirements, and enhances drug product effectiveness. In today’s market, there are new component offerings on the market designed to address the need for high-quality packaging solutions, including components designed using QbD principles to provide high reliability for breakloose and glide force, dimensional accuracy and consistency, subvisible and visible particulate control, and low parts per million (ppm) defect attributes.
By building QbD principles into design and development from the very beginning, manufacturers can decrease variability in the manufacturing process and the end product. High-quality packaging components designed using QbD processes can enhance the performance of drug delivery systems and protect sensitive drug products with exceptional cleanliness and barrier properties, while helping to ensure patient safety and drug product efficacy.
Conclusion: Early Collaboration is the key to Success
Now, more than ever, employing a QbD approach to component design and manufacturing keeps the needs of both patients and drug manufacturers at the forefront. This is especially important as many sensitive biologics are coming on the market as combination products and the compatibility of packaging components with injectable drugs and their delivery systems is being closely scrutinized by regulatory agencies.
To have the greatest chance at success, start early. Pharmaceutical companies and their packaging and delivery partners should build this level of quality monitoring and risk mitigation into the development and manufacturing process from the very beginning. Early collaboration leads to the best-possible quality and ensures that you’re prioritizing what matters most — the safety of patients.