Vincent Guido, director of sales at Terracon, a ChargePoint Technology company, explores the challenges of fluid management in pharmaceutical manufacturing and argues that the right equipment is key to optimum efficiency, worker safety and quality.
Key insights:
- Selecting the right components for the fluid being handled can remove the need for costly and time-consuming additions to the process.
- Harsh chemicals present a key obstacle to pharma companies and their CDMO partners as compatibility with the vessels and other key infrastructure they can come into direct contact with is vital.
- Customised vessels can integrate seamlessly with existing equipment to minimise the risk of containment breaches at the connectors. Secondary vessels can be designed to fit beneath primary containers to act as an emergency safeguard against overspill.
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Liquid – or fluid – processing and management is an essential feature of many modern pharmaceutical manufacturing lines. Many finished drug formulations are necessarily liquid, in the case of injectable and ophthalmic treatments, or semi-liquid, in the case of topical products. Biopharmaceutical treatments require purified water and other liquid processing due to the media used to culture the active molecules. Harsh liquids, including acids and alkalis, frequent the manufacturing process for many small-molecule active pharmaceutical ingredients, as well as for excipients, either as vital raw materials or as solvents.
The presence of fluids in any production process, especially when they are harsh or reactive, can pose efficiency, safety, and product quality challenges for pharmaceutical manufacturers that need to be overcome. How can pharmaceutical companies address these fluid management issues, and ensure that their liquid processing lines are as efficient and productive as possible? The choice of the right transfer tote, storing or freezing cart, mixing vessels, and other components is not an easy task. Ensuring the right connections between equipment can hold the key to effective liquid processing.
Understanding the challenges
Fluid management refers to a number of key procedures within a pharmaceutical manufacturing environment. These include the processing of liquids and other ingredients in mixers, their storage in containers for later use, or even the transfer of liquid material from one process to another in dedicated bottles or other vessels. The fluids involved can come in a variety of forms, from purified water, to a high salt content buffer solution to reactive hydrochloric and sulphuric acid, and high-pH alkalis.
These harsh chemicals in particular present a key obstacle to pharmaceutical companies and their contract development and manufacturing organisation (CDMO) partners as compatibility with the vessels and other key infrastructure they can come into direct contact with is vital.
Careful consideration must be given to how the fluid will interact with any production system or component. Standard stainless steel vessels – and the accompanying seals connecting them with surrounding equipment – may react with the acid or alkali, pitting, corroding or dissolving over time. This has a number of implications:
- Containment for worker safety: Any production line handling harsh fluids requires robust containment protocols to safeguard the health and wellbeing of line operatives working in the vicinity. Failure to maintain optimum containment can result in serious injury for team members, as well as legal and financial ramifications from regulatory non-compliance. If the components are incompatible with the fluids they are handling, they may weaken or embrittle over time, increasing the risk of containment breaches.
- Frequent component replacement schedules impacting on manufacturing efficiency: If the vessels and components are not compatible with the fluids they are holding, they may need to be replaced more frequently to maintain containment. The processing downtime required to remove old parts and install new equipment can reduce the productivity of the site, impacting on profitability.
- Product purity and quality challenges: Incompatibility issues between the fluids being processed and the surrounding equipment can result in compounds leaching out from the containers to contaminate material downstream. These leachable impurities could have ramifications for the efficacy of the finished product, or even for patient safety. Chemical contaminants can be filtered out from drug formulations prior to finishing, but this is an additional step with cost and time implications.
Overcoming liquid processing challenges
With all of this in mind, pharmaceutical companies and their contract partners need to explore solutions to ensure effective liquid processing. Increasing the maintenance frequency for mixing, storage, and transport of vessels on a line, or adding in filtration steps downstream reduces manufacturing efficiency – an undesirable outcome in a fast-growing and competitive market. Selecting the right components for the fluid being handled can remove the need for costly and time-consuming additions to the process.
A number of equipment options are available to help companies achieve this goal, particularly when it comes to the mixing, transfer, and storage vessels for liquids. Vessels made of super-alloys, for instance, are chemically inert in the presence of many harsh acidic or basic liquids. However, these can be very expensive to source, with long lead times for delivery.
Specialist plastic mixing, transfer, and storage vessels for liquids offer the same performance as those made of super-alloys, but are also more cost effective, with shorter delivery lead times. Vessels made of USP Class VI polypropylene are particularly useful – they are chemically inert, so they do not react with the fluids they are intended to handle. As a result, they can offer a long useable life, lowering maintenance downtime, reducing costs, and optimising productivity while also ensuring effective containment. Their USP classification, meanwhile, means that they pose no leachable risk, so no contaminants affect product purity, eliminating any quality fears or the need for additional filtration steps.
It is possible to source turn-key USP-certified plastic solutions. However, working with suppliers that are experienced in custom-designing mixing, transfer, and storage vessels can ensure that any new equipment is perfectly suited to the needs of the line.
From a containment perspective, a customised vessel can integrate seamlessly with existing equipment to minimise the risk of containment breaches at the connectors. Secondary vessels can be designed to fit beneath primary containers to act as an emergency safeguard against overspill, protecting workers on the line.
Components can also be created to fit the scalability needs of a line, from low-volume 10-20-litre mixers, containers and transfer bottles, to process tanks and storage vessels able to hold tens of thousands of litres. Whatever the requirements of the project, expert suppliers can provide tailor-made vessels quickly, within the timeframes needed to ensure a smooth and efficient line upgrade.
Looking ahead
Effective fluid management can be a complex process, even for experienced pharmaceutical manufacturers, especially when handling harsh chemicals. The right infrastructure is essential for growing their output and their business.
By working closely with specialist equipment experts, pharmaceutical companies and CDMOs can be confident they have the guidance they need to overcome the challenges of processing harsh fluids. In doing so, they can maximise efficiency and productivity, while ensuring optimum safety for workers and product quality for patients.