This members only document serve as a reference document on the impact of Annex 1 on CCI for existing and new workstream members and is a collation of responses surveyed, narrative and notes made during discussions between SMEs and where applicable guest speakers.
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The importance of viral vector-based gene therapies continues to grow as they have demonstrated promising clinical results and gained regulatory approval for treating genetic diseases, and different types of cancers.
The scope of this paper focuses on CCIT of viral vector gene therapy drug product (DP). Cell therapies are out of scope. The strategy proposed here for CCIT is applicable to all advanced therapy medicinal product (ATMP) drug products that are manufactured in small lot sizes, typically <500 vials.
This paper provides some considerations and guidance on defining a justifiable sample size for CCIT when required for parenteral biopharmaceutical finished products. This is a particularly important consideration when using destructive test method. It also summarizes a practical and risk-based strategy, both representing scientifically justified approaches. These approaches prevent unnecessary sampling and testing while retaining high product quality. Where the integrity of each individual container is assured by a suitably qualified process, additional CCI sampling and testing would not normally be required.
Container Closure Integrity: User requirements specification (URS) for optimized container closure integrity testing equipment
The paper highlights a long-term desired view of CCIT to help develop equipment that can better meet end-user requirements. It will also provide confidence that CCIT methods can effectively demonstrate container integrity, such as microbial, headspace (gas, vacuum and moisture) and product integrity. It provides a long-term goal for companies that often use multiple CCIT technologies, with varied capabilities, to support the requirements of an expanding product portfolio. The URS will help overcome the significant inefficiencies that companies face. It will also help resolve the problem that the range of deterministic CCIT methods currently available do not represent a panacea for CCIT.
Jun 2020 | Fill Finish
Finish Biopharmaceutical Drug Products for a Modern Age is a formulation/fill-finish eBook containing two articles. One of these articles, written by Scott Ewan BioPhorum Fill Finish facilitator, brings together details on activity in the Container Closure Integrity workstream.
Container closure (CCI): Dye ingress methods for container-closure integrity testing: An industry position paper
The release of the expanded USP<1207> in 2016 cast doubt over the validity of so-called probabilistic analytical methods, including one the biopharmaceutical industry’s most universal tests – the dye ingress method for container closure integrity
With the dye ingress method ubiquitously used without issue for decades, this paper highlights the continued value and applicability of this and other probabilistic analytical tests. In addition, this paper also describes how any method, whether probabilistic or deterministic, stands or falls on the quality of its development and validation, and not necessarily on the properties of the test itself.
The most important factor is to apply a test method is not how it is labelled, but lies in its development, qualification and whether it meets the need for which it is designed.
Jan 2017 | Fill Finish
USP published its revised and expanded guidance, USP<1207>, in 2016 ostensibly asking as many questions as it answered.
Specifically, USP<1207> implies ’probabilistic’ tests such as the ubiquitous dye ingress method are inferior and proposes a preference for so-called deterministic tests. The added assertions that deterministic methods can achieve high levels of sensitivity and accuracy do not reflect the ‘real world’ experience of the industry’s CCI experts whose work with the newer methods highlight a range of improvements that must be addressed before such claims can feature in guidance.
This paper makes the distinction that any method – probabilistic or deterministic – when properly validated may be regarded as acceptable, with no one method type worthy of a preferred status
Container closure integrity (CCI): Container closure integrity control versus integrity testing during routine manufacturing
In 2014 uncertainty around regulation for container closure and integrity testing (CCIT) fed a perceptible shift in mindset across the industry, causing some concern amongst many subject matter experts in biological manufacturers. Their concern was that gaps in guidance was enabling skewed expectations such that they would promote 100% CCIT for the release of drug product batches. This paper addresses this concern by re-stating the principles of CCI, qualification, process control and in-process testing to establish the framework within all effective container closure integrity programs. It concludes that performing 100% CCIT does not provide certainty that a process is well controlled and introduces an additional step that is not always necessary or suitable for the high processing speeds in the industry.