Drug Substance Freezing and Why It Doesn’t Have To Be a Bottleneck

Drug substance freezing has moved on.

Traditionally it was inefficient in a multitude of ways. Issues such as product loss, reduction of product potency, or a lack of flow with the surrounding processes such bulk filling, storage and shipping were common. Now it can be a tight operation, bridging the gap between downstream processes and fill and finish operations.

Modern plate freezing options that allow full control and are intelligent in design, have not only sped up the freezing process but have reduced naturally occurring phenomenon such as cryoconcentration, and has moved drug substance freezing from being a process bottleneck to an efficient end-to-end solution. In a biopharmaceutical world whose eyes are continually focussed on speed, quality and yield, traditional ‘slow freezing’ methods utilizing static freezers are increasingly seen as inefficient. The nature of ‘slow freezing’ is such that cold temperatures penetrate the substance from the outside-in which can lead to expansion of the core and potential damage to the surrounding material. Research has highlighted that static freezers can be responsible for up to 56%1 of viral potency product loss in drug substance manufacturing. A figure that has beckoned change.

Controlled plate freezing is that change. Characterized by rapid freezing technology that simultaneously freezes single-use biocontainer bags from both sides, it quickly removes heat from a liquid through direct transfer of the cold. The result is far more than a welcome reduction in freezing time, plate freezing also instigates a chain of linked advantages that include more homogenous freezing kinetics, a reduction in the degree of cryoconcentration observed (and the damage it causes), and assures consistent quality for critical products such as vaccines, mAbs and viral vectors.

The benefits of rapid plate freezing technology have a pathway that is clearly interlinked with the necessity for frozen drug substance stability and effective shelf-life, but when fill and finish processes are undertaken in another location, or even another country, robustness in how drug substances are stored and shipped also becomes paramount. This is where freezing, storage, shipping and thawing has the benefit of being viewed as an end-to-end solution and not as individual isolated processes.

When processes that connect bulk filling, freezing, storage, shipping and thawing become seamless, controlled and fully traceable, you have entered a world where the freeze-thaw process has become an end-to-end solution that can address the three basic needs in today’s biopharmaceutical industry:

• Preserving the quality of a frozen drug substance
• Facilitating organized and easy storage and transportation of drug substances
• Scalability of product in both volume and quantity

Rapid plate freezing is the first step in preserving the quality of frozen drug substances. As part of a forward thinking end-to-end solution, ultra cold storage of frozen single-use biocontainer bags can be integrated in protective shells that are not only robust enough to withstand the rigors of complex supply chains, but can preserve the cold chain at temperatures which can typically reach down to minus 80°C. It is this robustness and integration of freezing and storage as a wholistic solution that reduces the potential for human error and the inevitable possibility of product loss through handling damage during shipping. Shipping that forms part of a fully traceable cold chain ensuring single-use biocontainer bags full of highly valuable product reach their destination safely intact.

Unquestionably the intrinsic value of frozen drug substances in terms of patient need and financial return lends ample room for consideration of modern freeze-thaw platforms to reduce bottlenecks as part of an integrated end-to-end solution.

Author Details:

David Rigterink
Biotech Specialist
Pall Corporation
https://www.pall.com/

About Pall Corporation:

Pall Corporation is a filtration, separation and purification leader providing solutions to meet the critical fluid management needs of customers across the broad spectrum of life sciences and industry. Pall works with customers to advance health, safety and environmentally responsible technologies. The Company’s engineered products enable process and product innovation and minimize emissions and waste.