What is the Optimal Timing for POCT Scale-Up Production?

When developing the cartridge for your Point of Care Testing (POCT) instrument, critical activities and timelines required to develop and qualify high-volume production can be overlooked. These important considerations must be addressed early in the project timeline to ensure there are no gaps in product availability for clinical trials and beyond.

This is particularly true in startup companies where the primary allocation of resources is directed to proving technology feasibility. Alternatively, in larger or established organizations, the strategy to use existing production automation may need modification to meet requirements for the new product manufacturing process.

This critical commercial step is referred to as “scale-up.” The scale-up timeline typically requires a minimum of 18 months and a significant investment in resources, such as high precision consumable tooling, complex production automation and specialized packaging equipment.

Production scale-up: plan early with later needs in mind

Planning for the eventual production scale-up of an automated cartridge assembly process is an essential activity to initiate early in Point of Care diagnostic product development. The primary consideration is to provide a flexible strategy that accommodates the demand and forecast uncertainty associated with a new product launch, as well as options for quickly reacting to changes in the volume and timing forecast.

Specific areas to address include:

  • Plan for the transfer to production early in the design phase.
  • Align capacity needs with project timing and requirements for capital investment.
  • Anticipate that initial yield may be lower than desired and factor the yield ramp into planning for capacity.
  • Understand that total production workflow may include non-functioning time such as production set-up and line clearance—activities that can adversely impact expected yield per shift.

For example, multiple factors need to be considered when calculating manufacturing capacity:

  • A standard process for calculating manufacturing capacity assumes seven hours per shift, accounting for lunch and breaks non-productive time.
  • Kit manufacturing model assumes a three second cycle time, seven-hour shift with typical yield at 85 percent.

What some companies may neglect to include in the capacity calculation is workflow set-up before production, time for line clearance to reduce risk of cross contamination, cleaning the system, and independent verification after each production batch.

As an example, the workflow setup will include off-line front-end and back-end activities including reagent preparation, reagent QC and then complete release acceptance testing. For low-volume filling in the early development phase, manual dispensing of reagents into cartridges and a small volume reagent batch made daily can meet the production demand; however, as the batch size must ramp to meet the forecast for validation testing and later clinical trials, the transition to a high-volume process must be pre-validated for seamless cartridge manufacture ramp up. Keeping these important factors in mind, companies need to develop a plan for the following:

  • Automation and scale-up of low volume lines
  • Replicate production line for down-time redundancy or higher volume needs
  • Ongoing development and engineering support requirements
  • Modular production line sections to enable rapid scale around bottlenecks

Why implement a representative production process?

One of the key considerations for seamless scale-up of cartridge manufacturing is developing a representative production process in the early stages of system design to demonstrate the production of consistent, high-quality microfluidic cartridges at the volumes required.

This approach promotes an interactive development model involving designers, engineers and production personnel, where the hands-on experience with the manufacturing process development informs the cartridge design throughout the development cycle. Using this cross-functional process enables confirmation of the manufacturing process capability to produce assemblies that meet design requirements at an acceptable manufacturing yield.

Implementing a representative production process

When developing a representative production process, the key steps are to:

  • Identify the critical to quality processes—those processes which have the biggest impact on the quality and performance of the microfluidic cartridge, such as ultrasonic welding, reagent deposition, drying and sealing.
  • Ensure that early work to develop the production workflow and process, such as technology selection and prototyping of anticipated automated methods, includes a plan for volume automation components such as appropriate welding horns and reagent deposition pumps, valves and dispense heads.
  • Develop methods for assuring quality and monitoring consistency of the process. It is ideal to use non-destructive verification methods such as visual confirmation, pressure monitoring, positive displacement feedback, etc.
  • Determine process capability versus requirements to understand how much margin your process has under normal conditions. This provides the potential for simplifying the ultimate validation of the automated process.
  • Understand sensitivities of the assay and design. For example, your process may include depositing five reagents, but only one reagent is volume sensitive; if your cartridge welding process creates one area that is not perfect, the imperfection may impact the entire cartridge performance.

Production scale-up planning is a key driver for long term profitability

When developing your Point of Care diagnostic instrument and cartridge, integrating planning of production scale-up and associated automation early and throughout the design process will increase the likelihood of a seamless transfer to manufacture and successful market launch. Focus and execution of these activities will build your organization’s confidence to successfully supply high-quality reliable product. It will also enable the organization to rapidly respond to changes in demand in those critical early days of market adoption.

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