ConsiGma® Continuous Wet Granulation, Drying & Tabletting

Description

The FDA has been promoting continuous processing as a method to improve quality in pharmaceutical production since the publication of its Process Analytical Technology (PAT), highlighting the advantages of using the Quality by Design (QbD) and PAT philosophy. Manufacturing without interruption with a constant flow of materials fits very well within the concept of QbD. It provides many opportunities to adjust the process to meet the critical quality attributes and thus improve product quality.

A new generation of continuous wet granulation, drying & tableting technology

GEA Pharma’s ConsiGma^® continuous tableting line was developed in concurrence with the FDA’s QbD initiative and was designed to satisfy the industry’s need for continuous production to provide improved quality, flexibility, consistency for pharmaceutical processes and reducing cost per tablet. The ConsiGma^® continuous high-shear mixing, drying and tabletting line has been designed in such a way that both R&D and production can use the same size of equipment, thus eliminating scale-up. Further advantages are a higher yield and very stable, plug flow-based process leading to increased quality levels and higher efficiency. In addition, development times are shorter, the total cost of ownership is reduced and energy consumption is lower. So far, more than 50 companies have tested over 80 different formulations at the GEA Process Development Centre in Belgium.

Reduced scale up costs

One system can run 500g in R&D – but can also run clinical trial, launch and production size batches. As there is no process scale-up,  time is the only relevant factor in a continuous process – manufacturers are able to reduce development time dramatically, thereby reducing costs and bringing products to the market much faster.

Reduced Granulation and Tabletting Footprint

At one-third of the size of a classic granulation line (inclusive of the tablet press)  the system is very compact, while its modular construction allows it to fit perfectly into any R&D department or existing tablet production room. There is no need for any building alterations – the system is just wheeled in, connected to the power and air supply, and after a simple start-up period is ready to go. Installation time and cost are reduced to a fraction of the current benchmark. It is also possible to avoid high peak energy periods and run at continuous low energy consumption, helping companies meet their environmental obligations.

The ConsiGma^® system is capable of undertaking particle design and mimicking any traditional batch granulation process – with a much higher and consistent quality resulting from its continuous production set-up and ‘risk-based approach’ to GMP. The granules have generally a better intra-granular porosity, with improved compressibility characteristics that help tablet presses run more efficiently at maximum speed with hardly any weight adjustments being required.

Continuous Tabletting

The full tablet production line consists of the ConsiGma^® high-shear granulator and dryer, combined with the GEA rotary tablet press. A special in-line blender mixes in the external phase between the systems. The granulator and dryer section of the line has three modules: a wet high-shear granulation module, a segmented dryer module, and an evaluation module.

ConsiGma^® Continuous Wet Granulation, Drying and Tableting – from powder to tablet in 20 minutes

1. Continuous Powder Supply

• Dosing by means of loss-in-weight feeders
• Up to 4 different feeders installed on ConsiGma high-shear, in-line blender
• Optional: integration of low-shear, in-line blender (max. 6 additional feeders)

2. High shear mixing & granulation

• Twin screw granulator based on plug flow principle
• No risk for pressure built-up in granulator
• Liquid is accurately dosed for in-line control of the torque
• Optional: second liquid dosing when binder is dissolved in liquid

3. Segmented fluid bed dryer

• Drying curve of each package is monitored
• Time or temperature based discharge

4. Granule conditioning unit

• Granule calibration
• Evaluation unit: on-line analysis of QCA’s (control – reject – stop)
• In-line External phase and Lubricant blending

Six Benefits of the ConsiGma^® Continuous Wet Granulation, Drying and Tabletting Technology

1. Plug flow: FiFo concept for each process step

• Proven & guaranteed by PEPT and tracing powder
• Full & comprehensive tracing of product
• Real time monitoring and process control
• Improved & guaranteed end product quality

2. System & control integration

• Seamless integration between all process units & peripheral equipment
• No need for intermediate storage in bins or expensive product transfer
• PAT tools for in-line measuring & control of Critical Quality Attributes: BU, CU, LOD & PSD
• Reduced GMP area, less QC activities/batch and simplified logistics

3. Modular approach & built-in versatility

• All modules fit into standard pharma doors
• Vertical or horizontal set-up depending on room dimensions
• Smooth integration of different OSD processes in ConsiGma-line
  melt granulation, direct compression, roller compaction
• Multiple use process line & fast deployment

4. No scale up and limited amount of active used for product transfer

• From ConsiGma 1 (R&D) to ConsiGma 25 (Clinical study, Product launch & Production)
• No scale-up for granulation & drying process
• Direct transfer of recipes & process parameters
• Each single DoE test involves approx. 1 kg of product (Production)
• Avoid intensive & expensive scale-up activities and corresponding trouble shooting

5. Processing of high potent drugs

• High containment execution with split valves and liner technology
• Wash in Place concept for maximum operator safety
• Reduced filter surface and product contact area for increased yield
• Single room operation to avoid cross-contamination

6. Upgradable from bin to bin solution to continuous line with Real Time Release (RTR)

• Modular integration of continuous tablet & coating suite
• PAT tools, process monitoring and control