Application Example: Feeder Selection For Pharmaceutical Extrusion Applications
Introduction: The pharmaceutical industry continues to implement continuous production techniques, including hot melt extrusion, to realize the benefits of:
Hot melt extrusion is presently one of the most widely applied techniques in the plastics industry.
Currently more than half of all plastic products, including plastic bags, sheets and pipes, are manufactured by this process.
The largest potential in the pharmaceutical industry resides with the processing of active or excipient materials to produce products such as:
Due to the tight tolerances demanded by the industry in general and the need for process integrity, the loss-in-weight feeder must be considered as an upstream device to ensure consistent mass flow of material(s) into the inlet throat of the extruder.
The Use of Feeders
The primary functions of the feeder are to regulate the mass transfer properties of the process, ensure constant material throughput, maintain formulation consistency, and introduce ingredients in proper order, and data collection and acquisition to enable process validation and lot traceability.
Multiple feeders are used to proportion multiple ingredients based on weight.
Considerations in Choosing the Proper Feeder for a Pharmaceutical Extrusion Process
There are 12 considerations to make when selecting the proper feeder for the application.
1. Process Accuracy Requirement
Feeder accuracy is typically described as linearity and repeatability expressed in percent of set rate.
Gravimetric feeders are used for performance in the ¼ to 1% range and utilize a load cell based weigh system
A control algorithm based upon measured weight lost as material flows out of the feeder hopper regulates the feeder speed.
Gravimetric feeders can also be used to provide a record by weight of the amount of material introduced into the system over time, thus helping with lot control issues
Feeder Accuracy Defined
To fully define feeder accuracy it is necessary to address three separate and distinct areas of feeder performance: repeatability, linearity, and stability.
Figure 1: Volumetric Feeder
Figure 2: Gravimetric Feeder
Figure 3: Gravimetric Feeding Principle
Figure 4: Repeatibility
Figure 5: Linearity
Figure 6: Stability
2. Process Operation - Batch vs. Continuous
The downstream process must be defined as either batch or continuous. The feeder equipment used will be mechanically identical, however, the selection of control software will be different.
Hot melt extrusion will utilize feeders which operate continuously at the extruder inlet, however, similar equipment will be used elsewhere in the pharmaceutical plant for batching applications as well.
3. Material Characteristics
Depending upon the characteristics of the material to be handled, numerous feeder selections can be made. The different types of feeding equipment include gravity gates, belt feeders, vibratory feeders, rotary valves, disk feeders, flow meters, liquid pumps, single screw and twin screw feeders.
Screw feeders are utilized extensively in the pharmaceutical industry due to their ability to handle most of the dry solid feeder applications and their ability to be provided in sanitary designs (See Figure 7).
The main material characteristics which are considered when configuring the feeder are bulk density, particle distribution, angle of repose, and flow characteristics such as cohesiveness, adhesiveness, floodability, ability to cake or pack, etc.
4. Feed Rate
|Given the material characteristics, a suitable screw selection is made for the required feed rate (See Figure 8) stated in units of cubic feet per hour (or pounds per hour).
The feeder hopper is sized as well based upon refill requirements and space available.
Figure 8: Feed Rate Chart
5. Product Change Over / Cleanability
Equipment with modular designs and/or self cleaning features should be used to minimize downtime caused by product change over. The equipment should be easy to clean and breakdown without the use of special tools.
6. Sanitary Designs
It is important to select a vendor who understands the guidelines set forth by cGMP standards. A vendor’s standard sanitary designs may not always be in alignment with cGMP, therefore, it is important to differentiate and be specific.
Only FDA approved materials should be used for construction. 316 or 316L stainless steel are typically used on product contact surfaces and 304 or 304L are commonly used on frames or non-contact areas. Gaskets and seals are typically white and FDA approved polymers.
Surface finish requirements vary, but typically a #8 finish with electropolish is used for contact and a 2B or #4 finish is used for exterior surfaces. Welds are always sanitary continuous, ground smooth and free of pits, cracks, burrs or inclusions. Welds must be passivated to avoid the possibility of rust or contamination.
7. Space for Installation
The space available for installation will have an impact on equipment selections. Considerations such as length of screws and hopper shape and size will be necessary.
8. Factory Environment
Depending upon placement within the plant, three levels of equipment construction can be provided; equipment designed to meet cGMP requirements (used in the process area), equipment designed to the manufacturer's sanitary standards (used in bulk unloading areas), and equipment designed per the manufacturer's normal standard (used in mechanical spaces).
Also, the area classification must be defined along with climate controls, plant elevations, sound requirements, vibration limits, and dust containment requirements.
When selecting feeding equipment, calibration features must be considered such as:
The ability to quickly tare the feeder weigh system allows for corrections based upon gross weigh changes as a result of operating and material conditions.
Figure 9: Digital Loadcell Design
Span of the feeder control system enables an adjustment to the system so that the feeder output matches the desired set rate. Feed Factor is a parameter in a material dependant value which allows the operator to understand the maximum mass flow rate of a feed system when running at 100% drive command.
Look for equipment that features factory calibrated components, such as digital load cells with built in temperature compensation, which will not require any additional field calibration (See Figure 9).
Typical control considerations include the choices of volumetric vs. gravimetric, batch vs. continuous, single feeder vs. multiple feeder, operator interfaces, recipe storage, and interfaces to other controllers. When standard off the shelf controllers and OIT’s are used, they are typically considered to be black box controls which do not have to be subject to the stringent requirements of hardware and software development as described in GAMP.
If these controls are customized in any way, or if a hybrid controller is designed for the application, then these controls must be developed and tested in accordance with the Life Cycle Approach as defined in the GAMP guidelines. Always choose a vendor who has documented experience in this area to avoid unforeseen costs. In all cases, the responsibilities of the user and the vendor must be stated in the URS published by the user.
11. Data Acquisition
The interface between the feeder controls and the supervisory control system must be clearly defined with regards to protocol, software and drivers to be used. The data and commands should be defined in the URS as well as any alarm, fault or shutdown conditions, which are to be exchanged. Using Loss-in-Weight feeding equipment facilitates lot control and process validation by accurately reporting material usage by weight.
12. Quality and Value
Selecting a vendor who has experience and a proven track record in the industry will provide the best value. Choose a vendor who has systems and project management expertise and who can clearly demonstrate an understanding of the overall process and interface requirements.
A vendor who is implementing an ISO or similar quality system will have the ability to produce the necessary Quality Plan to assist in the equipment validation process and will usually succeed in the audit process.
The selected manufacturer must be able and willing to conduct a FAT to satisfy the equipment validation plan. Manufacturer's that offer formalized training programs and aftermarket support will have the ability to provide the support necessary to complete IQ and OQ programs required for successful commissioning.
About Feeder Refill Systems
The feeder will require that a suitable refill system be implemented. Refill can be manual or automated to varying degrees. A variety of devices are available to transfer bulk materials from the receiving area to the process equipment. Equipment which falls into this category includes:
The same criteria for selecting and configuring the feeder will be applied to the equipment that makes up the refill system.
Vacuum pneumatic conveying (See Figure 10) offers many advantages such as distance to convey, managing dust levels, and capital investment, low cost of installation, cleanability.
Volumetric and Gravimetric Feeders are used extensively in many facets of the pharmaceutical industry. Besides continuous hot melt extruder applications, the feeder is used elsewhere in the pharmaceutical plant including:
The specific application requirements must be addressed to properly select and configure the optimum feeder. The process engineer must assess the process functions and performance requirements to match the feeder to the process.
There are numerous design options from which to choose. Integration of feeders within the plant can be a powerful tool to accurately deliver and provide a record of the pharmaceutical materials needed for an optimized process.
cGMP: current Good Manufacturing Practice
FAT: Factory Acceptance Test
FDA: Food and Drug Administration
GAMP: Good Automated Manufacturing Practice
ISO: International Standards Organization
IQ: Installation Qualification
OIT: Operator Interface Terminal
OQ: Operational Qualification
URS: User Requirement Specification
United States Food and Drug Administration, current Good Manufacturing Practices, 21CFR Part 210 and Part 211
Wilson, David H; Top Ten Frequently Asked Questions on Feeder Accuracy, Training Materials for Coperion K-Tron America. New Jersey, 2001.
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Wilson, David H; Feeding Technology for Plastics Processing; Munich; Carl Hanser Verlag, 1998
Willis, Fred, Keegan, Pat - Sanitary Feeders Minimize Product Contamination.Chemical Engineering. 1999.
Winski, John - Addressing Feeding Performance. Chemical Processing. Sept. 2001