Delivering Process Improvements Through Single-Use Operations And Lean Strategies
Intense pressure to demonstrate increased productivity and a robust return on R&D investment is leading the pharmaceutical industry to focus aggressively on cost control and process improvement. To address these challenges, drug developers are increasingly leveraging lean manufacturing initiatives. Based on principles largely developed by Toyota, lean manufacturing seeks to identify and eliminate waste in order to reduce the cost of bringing a product to market. Centered on creating more value with less work, lean manufacturing generally focuses on reducing eight specified wastes to improve overall customer value (Table 1).
In parallel with this focus on lean process improvement, the industry is actively evaluating and leveraging single-use products and systems to reduce costs, increase productivity, and speed time to market. The move to single-use solutions, either alone or in conjunction with stainless steel, is likely to continue growing in an effort to address these imperatives.
When managed properly, implementation of single-use systems can deliver key benefits as defined in the principles of lean manufacturing:
• Improved quality
• Reduced waste
• Increased productivity
• Optimized resource utilization
This article will highlight industry trends that are driving adoption of single-use systems and describe the implementation of single-use filtration to deliver lean process improvement efficiencies and drive waste out from the manufacturing workflow.
A Market in Transition
The biopharmaceutical industry is undergoing a number of changes that are having a significant impact on manufacturing (Table 2).
Where once a few major drug companies were the industry leaders and had little competition, contract manufacturing organizations (CMOs) and generic manufacturers are now playing an increasing role in bringing drugs to the market. Adding to this new reality is the need to evolve from a focus on large batches manufactured at a single facility to production of numerous, low volume, high variability batch runs at multiple facilities around the world.
One of the most challenging trends is the shift of drug development phases (research and development, pilot scale, commercial scale manufacturing) from single, vertically integrated facilities to separate locations around the world. While use of multiple sites across multiple countries can bring great value into the system, the practice puts increased demands on technology transfer processes.
Different manufacturing equipment, materials, and design may be used in each phase, presenting significant process optimization and validation challenges due to inconsistencies among bioprocess equipment across scales. Rapid and seamless technology transfer processes are thus essential to maintain consistency across all scales.
In an effort to address these challenges, many manufacturers are turning to single-use manufacturing solutions. The benefits of single-use products in manufacturing are widely known and well-documented. When implemented properly, single-use systems can accelerate production, improve flexibility, reduce costs and waste – benefits that are well-aligned with lean process initiatives.
What can prevent a company from fully realizing these
benefits, however, is the manner in which single-use systems are sometimes
employed – on an ad hoc basis without a cohesive plan for applying the
technology across all process scales. Lack of an overarching single-use
strategy can actually increase process inefficiencies (Table 3).
When single-use assemblies are sourced from different vendors, inefficiencies can be amplified as operators must become familiar with multiple systems, and components are likely to have different expiration dates and lack compatibility. Further, a smooth and seamless technology transfer process may be much more challenging when different materials are used at various manufacturing scales.
Consideration of the principles of lean process improvement during implementation of single-use systems can help ensure that maximum value is achieved.
Delivering Value with Single-use Filtration
In order to deliver lean process benefits, single-use systems must be able to speed production processes, reduce the risk of deviations, maintain consistency, and have an immediate and favorable impact on the bottom line through improved efficiency. Assemblies must effectively keep pace with changing product, scale and site requirements via a modular structure that is replicable and scalable across geographies.
To fully support lean initiatives, the single-use filtration system should offer fully optimized, customized and integrated assemblies, and reduce waste.
Single-use storage and filtration systems based on Mobius® Flexible Filtration approach (EMD Millipore) are designed to target the wastes identified by lean process initiatives: overproduction, defects, excess inventory, overprocessing, unnecessary transportation and motion, waiting, and underutilized talent (Table 4).
Most critical to the successful implementation of single-use systems and delivery of the full array of benefits, however, is the applications support process. This practice brings together users, applications engineers and lean process improvement experts. Through observation of existing process and direct interface with operators, performance gaps and opportunities for improvement are identified.
The team then works in a collaborative fashion to develop the new process designed on Flexible Filtration principles.
Reducing Process Production Time
We have found that single-use filration assemblies can reduce processing time by as much as 50% through decreased preparation and set-up time. A number of innovative elements are the drivers of this reduction. A modular manifold design allows a manifold to be built on site, to scale as needed. The easy filling bag design eliminates the need for operator handling during bag filling. A universal bag design and scalable sterile filtration assemblies facilitate technology transfer between early development, late development and commercial manufacturing. Unique disconnection technology reduces the time required for sterile disconnection to less than a minute as compared to five to ten minutes required by a tube sealer.
Improving Process Consistency
As with any lean process initiative, the ability of single-use technologies to consistently deliver the full range of expected benefits depends on a thorough assessment of the current processes, opportunities for improvement, and a clear definition of objectives.
To this end, EMD Millipore mimics the customer’s pilot
manufacturing setup in our Biomanufacturing Sciences and Training Center
(BSTC, Figure 1). The center enables prototyping of solutions and performance
testing in a laboratory setting before the definitive solution is finalized and
delivered. Consultants review process parameters such as flow rate and pressure
drop requirements, and recommend appropriate filter membrane and size when
designing filtration sub-assemblies.
As many as ten to fifteen operators can gather at the training center to see, touch, and use the prototypes in the training center. Hands-on testing gives operators a greater degree of confidence than a typical new processing setup might foster. In addition, operators can provide real-time feedback, allowing the solution to be better adapted to their actual process.
Facilitating Tech Transfer
The effectiveness of the technology transfer process is critical to maintaining product quality and speeding time-to-market. Use of different systems from different vendors can impede an efficient and accurate transfer and force processes developed at one scale to be recreated and re-optimized at other scales.
Use of replicable, modular single-use systems help facilitate cost-effective and timely technology transfer across multiple sites and different scales.
Impacting the Bottom Line
Table 4 summarizes the reduction in waste that can be achieved through proper incorporation of single-use systems. Properly established single-use systems can deliver as much as a 20% reduction in materials usage.
In addition to significant reductions in processing time and waste, Flexible Filtration based single-use systems can significantly reduce the number of part numbers needed to be maintained. One customer has reported to us a 70% reduction in material master maintenance when the number of single-use vendors was consolidated; with each new catalog number requiring an investment of up to $1200 to maintain it annually in an ERP system, this reduction represents an impressive cost savings.
Drug developers are actively exploring and leveraging single-use operations to deliver lean process improvements. When incorporated as part of an overall strategy to reduce waste and process time, improve process consistency, and facilitate technology transfer, single-use systems designed with lean process improvement principles can deliver measureable benefits to the bottom line.
Critical success factors include consolidation of single-use
vendors and equipment to minimize variability and create consistency across
processes, and a collaborative approach with applications support engineers and
lean process improvement experts to assess current process and identify
opportunities for improvement.