WHAT CDMOs SHOULD KNOW ABOUT CONTAINER CLOSURE INTEGRITY?

Pharmaceutical companies pursuing new and increasingly complex molecules are doing so against a backdrop of supply chain disruptions, changing regulatory expectations, and a growing strain on industry talent. As a result, the CDMO market is seeing higher demand than ever, as manufacturers look to outsourcing to facilitate their path to market through expanded expertise, experience, and capacity. A top priority for potential customers during CDMO selection is quality assurance, as rigorous quality control measures are the difference makers when it comes to protecting a product in its journey to the patient.

A critical component essential to maintaining the quality of a drug is its packaging, which safeguards the product as well as the company’s promise to patient safety throughout the life cycle until delivery. According to USP <1207>, container closure integrity testing (CCIT) offers assurance of a package’s ability to prevent loss and maintain product sterility.¹ However, a lack of understanding about CCIT could put a CDMO at a disadvantage among those competitors adopting advanced CCIT solutions that accommodate the individual needs of their customers’ products. So, as a CDMO, what do you need to know about CCIT, and what solutions are available to not only protect your customers’ products but also help instill the culture of quality that is driving accountability and resiliency across today’s industry?

NEW ERA OF PHARMA CALLS ON ADVANCED CCIT SOLUTIONS

Innovation in pharmaceutical packaging has paved the way for a wide range of advanced technologies and materials that allow drug manufacturers to design container and closure systems that are based on the unique characteristics of their product. This is particularly important as novel yet complex biologics aimed at dramatically improving patient care as well as addressing some unmet medical needs are changing the future of medicine.

Given the diversity of these products and their container closures, there is no one test method that can be applied to all product packaging systems. Traditional methods, such as the dye ingress leak test and vacuum decay, have historically been the most common for leak testing, but their effectiveness ? like that of any CCIT method ? is based on physics and the interaction of the product and package combination. And with a variety of package and product combinations in use in the industry, factors such as the head space within a container and product viscosity and chemistry can impact how successful one method is over another. The dye ingress leak test can also be destructive to the product itself, and with limited quantities of some products, such as with cell and gene therapies, this is a risk manufacturers cannot take.

Several regulatory documents are available to provide recommendations about CCIT, with USP <1207> providing a thorough overview of available CCIT technologies and approaches while also identifying critical differences between those solutions categorized as probabilistic vs. deterministic. Probabilistic methods rely on a series of sequential and/or simultaneous events, each associated with uncertainties, yielding random outcomes described by probability distributions.² Conversely, deterministic methods follow a predictable chain of events, and leakage is measured using physiochemical technologies that are readily controlled and monitored, yielding objective quantitative data.² Although there is no requirement for one over the other, manufacturers that use probabilistic methods are more likely to have their filing highly scrutinized by regulators, who may require significant justification as to why that method was used over one that is deterministic and, ultimately, based on more definitive results. This aligns with a statement from former CDER Director Janet Woodcock on FDA’s quality revolution, when she said that, “Measurement is a fundamental concept to managing quality.”³

Therefore, as manufacturers look to CDMOs for development and manufacturing support, understanding the options for CCIT and how to effectively execute it for a specific product is critical, especially as the FDA stresses the importance of establishing a culture of quality over one of just compliance. Providing the best service to your customer and fulfilling the needs of patients worldwide means no longer seeing CCIT as a checkbox on the path to market but rather an integral component of ensuring patient safety through accurate and reliable measures of container closure quality.

DELIVERING ON THE PROMISE OF SCIENCE

The nature of the CDMO business is one of flexibility and adaptability; specifically, as the needs of the industry and your customers change, operations within your facility must be able to change with them. While this can be challenging, it also means every site is ripe with opportunity to implement a specific CCIT method that fits the needs of the product at hand. Oftentimes, the customer will mandate that a CDMO deploys a certain test method. Yet, the next customer may request a different one, leading to multiple technologies and methods that must be validated, maintained, and calibrated ? resulting in added costs and delays ? and an overall disjointed quality platform. To avoid this scenario, consider a holistic view of what container formats you are utilizing and pursue a deterministic CCIT technology that is balanced for your application.

Doing so requires thorough vetting of potential inspection technology providers. However, with an increasing number of CCIT technologies available today, it is important to look for suppliers that offer a gamut of options rather than only one or two. Consider even pursuing opportunities with GMP laboratories that offer CCIT and discuss what their approach may be. Find out the limitations of each technology and which would be the most appropriate for the specificities of your customers’ products. You may decide to develop a method within that laboratory or, instead, work with a CCIT technology provider that operates under GLP standards. Should you choose the latter, make sure the supplier is able to provide a feasibility study for the product’s application and that they have a comprehensive understanding of the pharmaceutical regulatory environment and expectations. The solutions they offer should also be scalable, so they have the ability to grow with the needs of your company, from process development to the production line.

At PTI, our goal is to support our clients by delivering on the promise of science through exceptional CCIT solutions. The incredible advancements in science and technology that are yielding life-changing products rely on reliable, high-quality delivery systems that can withstand the rigors of the journey from the lab to the patient. CDMOs play a key role in this journey, as they often serve as a vital link between an innovative idea and a successful commercial product. That is why our experts are passionate about providing robust CCIT through outstanding engineering and an organizational drive to fulfill our own purpose and mission. We understand the criticality of our role in delivering safe and efficacious products and are excited about the opportunity to work with you in advancing the future of medicine.