QbD and Drug Packaging and Delivery: A Guide to Creating Safer Components

The increase in injectable biologic and biosimilar treatments is requiring a stronger focus on quality requirements with respect to how the drugs are packaged and delivered.

By Fran DeGrazio, Vice President of Scientific Affairs and Technical Services, West Pharmaceutical Services, Inc.

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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. 

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Heightened focus on quality by regulatory agencies means manufacturers need to select components that have high levels of reliability, consistency and compatibility. By building QbD principles into design and development from the very beginning, manufacturers can decrease variability in the manufacturing process and the end product – helping to product patients.

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.

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