To select a ggood freeze Dryer (Lyophilizer) here are some important cosniderations:
Some considerations:
Shelf Size: square meters
Shelf style: bulk or stoppering
Condensing Rate: liters per hour
Condensing capacity: liters
Condenser location: Internal or external
Material: 304 vs 316SS
Advanced features:
- Vacuum instrumentation
- Isolation valve
- Sterilization
- 21 CFR Part 11 compliance
The freeze dryer manufacturer will also want to know what space is available for the freeze dryer and what utilities, such as: electrical, air, chilled water, and air conditioning are available.
Lab Freeze Dryer:
Laboratory freeze dryers are used for a large variety of applications which range from simple removal of solvent from a material to Phase 1 clinical trials to protocol development for scale-up production. A typical laboratory system will have a shelf area from 0.1 sq meters up to 1 sq meter with a condensing capacity of up to 30 liters.
Pilot and Production systems offer shelf areas from 1 sq meter up to and over 40 sq m. Production systems are used for Phase 2 and Phase 3 clinical trials and tend to be used for the same or a limited number of products in high volume production. Recently, there is a shift from 10ml to 50ml vials, to smaller volume high potency biotech and protein related products, in 2ml and 5 ml vials. The result is smaller freeze dryers with expensive payloads.
Pharmaceutical and other applications may require sterilization between cycles. Sterilizaton can add significant complication and cost to a freeze dryer. A freeze dryer is normally rated for vacuum and the most common method of sterilization is pressurized steam, which requires the freeze dryer chambers to be certified pressure vessels rated to 2 atmospheres at 131C.
An alternative sterilization technique uses Hydrogen Peroxide. Hydrogen peroxide (H2O2)sterilization is growing in popularity for Laboratory and small production systems. H2O2 does not require a pressure rated vessel, which keeps the cost down.
The most current demand on freeze dryers are validation and the ability to meet 21CFR Part11 compliance as required by the FDA. These are now a significant part of the cost of pharmaceutical processing freeze dryers.
For validation a full component catalog must be supplied. An IQOQ (installation qualification, operational qualification) document is generated which outlines the proper validation process and an FAT (factory acceptance test) and SAT (site acceptance test) are implemented to verify that the system is supplied as ordered and performs within the specifications required.
To aid in 21 CFR Part11 compliance, the software must encrypt all data to prevent tampering and must log every change and entry on the computer control system using user log-in’s and password protection.
304SS vs 316SS stainless steel – 304 can be used on food grade and industrial applications. 316 is used on pharmaceutical and biotech applications.
Cylindrical vs Rectangular product chambers – A cylindrical product chamber is less expensive than a rectangular chamber, however, it may take up more floor space depending on the configuration of the shelf assembly.
Internal vs External Condenser – An internal condenser is less expensive and provides unrestricted vapor flow. An external condenser is supplied with an isolation valve to separate the product from the condenser. This protects the product from reconstitution during power loss and keeps the condensate out of the clean room environment.