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Making highly potent active pharmaceutical ingredients (HPAPIs) can be costly because the process often requires equipment specialized to achieve containment and extra attention to safety concerns. Pharmaceutical professionals may wonder whether disposable components, which have reduced the cost of some operations, might be appropriate in the manufacture of HPAPIs.
A widespread focus on cancer therapies is increasing drugmakers’ interest in highly potent active pharmaceutical ingredients (HPAPIs). To satisfy rising demand, contract manufacturers such as SAFC (St. Louis, MO) have expanded their ability to produce these ingredients. Making these drugs can be costly because the process often requires equipment specialized to achieve containment and extra attention to safety concerns. Pharmaceutical professionals may wonder whether disposable components, which have reduced the cost of some operations, might be appropriate in the manufacture of HPAPIs.
Until recently, disposable components have been uncommon in nonaqueous API manufacturing processes, which often require aggressive solvents that can degrade disposable components. But new polymer materials such as polyvinylidene fluoride (PVDF) are more robust. Meissner Filtration Products uses PVDF as the as the product-contact layer for its FluoroFlex biocontainer portfolio, which is more compatible with solvents such as dimethylacetamide and dichloromethane better than common polyethylene-based biocontainers, according to the company. The FluoroFlex film also is twice as strong as comparable polyethylene films and incorporates a gas-barrier layer to limit oxygen transfer, says Christian Julien, Meissner’s business-development manager.
Disposable components now represent a small share of the equipment that handles HPAPIs, including sterilizing filter capsules, transfer systems, valves, and liquid-handling systems. But in 5 to 10 years, disposable components will account for more than 90% of such equipment, according to Richard Denk, director of the pharmaceutical department at Hecht Technologie. One reason for this rapid growth is that disposable components eliminate the need for the extensive cleaning that HPAPI manufacture requires, especially in multipurpose facilities.
Disposable components’ increasing safety also could prompt more pharmaceutical companies to adopt them. In the near future, single-use equipment will be able to provide an occupational exposure limit (OEL) of less than 1 ng/m3, says Denk.
Currently available disposable components can be just as safe as stainless-steel equipment, provided that risk is assessed before installation. A secondary system usually can mitigate risk, says Hari Floura, president of consulting firm Floura. For example, a flexible-film disposable bag system can be appropriate as an in-process container, but it cannot withstand excessive temperature or pressure. An insulated interface and safety interlocks and controls can protect the bag from exposure to potentially damaging conditions.
In some ways, disposable components can be considered safer to use for HPAPI production than stainless steel. Operators often handle stainless-steel containment equipment roughly because it appears stable, but this treatment sometimes damages the equipment. Personnel tend to handle disposables with greater care because they seem more delicate, Denk says. Unlike disposable containment valves, stainless-steel mechanical closing systems are subject to wear that may cause unnoticed leaks and expose operators to hazardous substances. And because disposable components do not require disassembly or cleaning, they significantly reduce the risk of operator exposure to process fluid.
The economics of using disposable versus stainless components has to take into account several factors. At first glance, disposables may seem to offer a clear cost advantage over stainless-steel equipment, which can be 30–50% more expensive, depending on the necessary OEL level. But even though the initial cost of disposables is low, it can quickly escalate, depending on the rate at which a company uses them. In six months, a facility could easily spend on disposables what it might have paid for a piece of stainless-steel equipment, says Floura. Personnel should undertake a cost–benefit study before implementing disposable components, he adds.
But other factors have to enter the calculation before one can estimate the true cost of one type of equipment over the other. For instance, stainless-steel equipment must be maintained regularly and cleaned through validated procedures that require additional supplies, labor, and associated expenses. In addition, multipurpose facilities must establish the traceability of the materials in their stainless-steel containment equipment. And, compared with disposable components, stainless-steel containment equipment necessitates a large number of documents, inspections, and instructions. These considerations reveal the sometimes-hidden expenses of stainless-steel equipment.
The benefits generally are worth the cost of disposable components, particularly for contract manufacturers, says Floura. Disposable components help enable these companies to change over between products quickly. Contract manufacturers also can demonstrate that they have reduced the potential for cross-contamination more easily when they use dedicated disposable components. And the added operator safety that closed disposable systems provide often outweighs cost considerations.
Pharmaceutical manufacturers are incorporating disposable components into their operations more and more, and newly developed materials are broadening the variety of applications for which these items are appropriate. Disposable components can protect properly trained operators from toxic ingredients as well as stainless-steel equipment can, provided appropriate precautions are taken. These factors, combined with a favorable cost–benefit analysis, make it likely that disposable components will become more widespread in HPAPI-manufacturing operations in the future.