More and more newer drugs contain high potency active pharmaceutical ingredients (APIs), which require careful handling and specialised equipment. Here, Precision Polymer Engineering (PPE) highlights why split butterfly valves offer a cost-effective solution and offer insight into the best sealing material for containment processes.
Butterfly
High containment valves: High potency sealing in pharmaceuticals
A significant proportion of new drugs under development contain high-potency active pharmaceutical ingredients (APIs), leading to explosive growth in demand for their production.
However, the cytotoxicity of APIs presents a number of challenges, including handling of said ingredients, and the required investment in specialised containment to ensure that employees and their working environment are protected from exposure.
What is driving force for better containment processes, and what are the challenges facing manufacturers?
An increase in the number of highly active substances, and much more restrictive regulations in terms of operations and environmental safety, has brought a significant growth in the demand for containment installations across the globe.
Increasingly potent drugs have required the industry to implement dramatic changes in plant design and operating procedures to ensure adequate containment. However, current expectations of levels of containment often far exceed the capabilities of equipment designed and manufactured only a few years ago.
When selecting sealing components for high containment applications, it is essential to consider the potential problems which may arise in the event of a leak or valve seal failure:
- Operator exposure: Employees and the general public must be protected from the product. Exposure to just a small quantity of a highly potent compound can pose significant health risks.
- Cross-contamination: There is a particular risk for patient safety in relation to the quality of the product in production. In order to satisfy the requirements on contamination protection in production, efficient technologies are vital.
Highly potent active ingredients such as hormones, retinoids, certain antibiotics and some narcotic substances require special containment during processing. This is defined by the occupational exposure limit (OEL) or occupational exposure band (OEB) assigned for the active drug substance.
Current technologies available to minimise high potency risk
Historically, personal protection equipment has been used for risk protection. However, whilst being undeniably important in providing protection to employees, there is a present risk of cross contamination in the working area through product transfer from containment suits, as well as uncomfortable working conditions.
In order to protect equipment operators and decrease the levels of product contamination from microgram to nanogram levels, it has been necessary for the pharmaceutical industry to advance its containment strategies.
There are three containment approaches which are typically utilised:
- Downflow booths and extracted tables
- Isolators and gloveboxes
- Split butterfly valves (SBVs)
However, challenges can arise when trying to find containment solutions for existing equipment and facilities. It is with this consideration that PPE believes the addition of a SBV can prove to be a cost-effective solution, particularly where space and existing equipment constraints limit the options available. These valves have demonstrated the ability to meet the containment targets required for handling APIs.
SBVs minimise the amount of airborne particle exposure during the transfer of potent powders from one process step to the next. A fundamental feature of all SBVs is that they consist of two halves which dock together, namely the active ‘Alpha’ unit and the passive ‘Beta’ unit.
Each half consists of half of the ‘butterfly’ disc, which is sealed against the main body with an elastomeric seal to create a high containment facility. Elastomer seals are used within each half as a ‘seat’, providing an effective containment seal between the active and passive halves once docked together.
Split butterfly valve cross section
PPE image
Sealing challenges in containment processes
Valves and the elastomer components within them are routinely exposed to a variety of chemicals and solvents, such as aggressive cleaning agents. Therefore, the chemical compatibility of the elastomer material within any containment process is a critically important design consideration.
Valve manufacturers have long relied on materials such as EPDM (ethylene propylene terpolymer) as a material of choice for pharmaceutical SBV seats. However, with API potency on the rise, there is a requirement for more resilient elastomer materials.
PPE recommends the use of perfluoroelastomer (FFKM) seats, in such chemically aggressive applications. The outstanding mechanical properties of FFKM, combined with almost universal chemical resistance (similar to that of PTFE) and excellent thermal capabilities (from -30 °C to +325 °C), make it ideal for SBVs used in high-potency API processing environments.
Through simple equipment and material considerations, such as using FFKM seats instead of EPDM ones in SBVs, it may be possible to extend the operational capabilities of a high containment valve without expensive redesigns.