URS for small flexible filler technology

The biopharmaceutical industry is transitioning from an era of blockbuster drugs that treat large segments of the population with a common ailment, to one of more personalized/specialized medicines for much smaller patient populations. Consequently, manufacturing operations are evolving from large batches and high-speed filling lines aimed at driving down unit costs, to agile lines that can rapidly switch between various lower volume products line to maximize utilization.

One of the more promising recent advancements in pharmaceutical manufacturing is the development of single-use systems. These systems require far less capital to build and great promise for easy technology transfer, enabling companies to manufacture at sites around the world at a lower cost. However, the success of this approach has been limited by a lack of available single-use technologies such as sensors and mixers.

To meet increasing sterility requirements, the industry has embarked in an ongoing quest to move the operator further away from the filling process, literally. Historically, operators used to hover above the filling operation, wearing minimal gowning or personal protective equipment. Through the years, however, filling operations have become much more sensitive to environmental conditions, leading to the introduction of stringent gowning requirements and placing operators behind isolators in sophisticated garments. Before long, most filling will be performed robotically, removing operators even further from the proximity of the filling operation. Eventually, operators will likely control filling from a central control room that may not be located in the same state as operations, let alone the same building.

Modularity will also play a major role in filling operations. Soon, massive, highly customized single-product systems will replaced with simple, modular systems that can be turned on or off in response to demand for a plant’s numerous products. With longer-lasting treatments and the move toward boutique lots and personalized medicine, ease of changeover from one product to another will be critical to a manufacturer’s success and competitiveness.

Principal requirements of BioPhorum’s small flexible filler URS

Modular plug-and-play capability is a key concept. Likewise the capability to handle multiple platforms — vials, syringes, or cartridges — is also important. Modularity enables flexibility in terms of capacity expansion or contraction for a particular product, enabling a manufacturer to respond rapidly to patient needs, large or small. Modularity also enables continuous improvement, unlike the one-of-a-kind systems in use today; one modular unit could be used temporarily for testing without halting production entirely.

Other key requirements include:

A gloveless isolator, which improves sterility assurance level
A low reject rate of <0.05 percent
30 minute changeover time between last good filled unit to first good filled unit
- 30 minute changeover time between last good filled unit to first good filled unit
- Standardized, ready-to-use components
- No human intervention needed inside sterile area after decontamination

How the URS will benefit the industry

This URS establishes an industry benchmark for flexible filling needs and serve to streamline the acquisition and approval of new equipment by both pharma company leadership and regulatory bodies. This will help the industry to move forward in terms of sterility assurance levels, turnaround times, reject rates, and disposable technology.

It will “enable the industry to bring products to patients faster and reduced costs through use of standard components and processes. Standard components and processes mean less customization, reducing the cost of the equipment and the associated cost of qualification. Ultimately, this enables organizations to develop small-batch capabilities in preparation for the future of personalized medicines. In so doing, cost and time-to-market for new treatments will be reduced, ultimately leading to more available and more affordable treatments for patients

The URS lays the foundations of the industries expectations to the equipment supplier. It allows the suppliers to develop the appropriate technology and to focus on the areas that are important to the industry. The URS should also help the vendors understand where future technology innovations needs the industry is having as part of a vision of the future manufacturing state.”

Next steps

The BioPhorum team plans to continue collaborating on establishing alignment and innovation across the industry and with vendors on other unit operations. The biopharmaceutical industry is a highly immature one compared to the automotive, semiconductor, and other sectors. We owe it to patients to continue to improve operations, reduce costs, and increase output of safe and effective treatments for unmet medical needs.