Stability chambers chamber

Sensors are distributed equally in various areas of the stability chamber no less than 2 inches from any wall. A set of sensors should be placed near or at the temperature and/or humidity controller of the chamber, as the controller will maintain the set-point temperature and/or humidity within the chamber during normal use. For a typical walk-in chamber, a minimum of 24 thermocouples and six resistance-transmitting devices are recommended for use in the mapping study. For a benchtop or reach-in chamber, a reduced number of sensors may be used. It is important to note that regardless of the size of the chamber, the placement pattern of the sensors should be such that any potential hot or cold spots are mapped, particularly those areas near the door and comers of the chamber. Typical sensor placement patterns for a reach-in and walk-in chamber are shown in Figures 16.1 and 16.2, respectively. In these examples, the extremities of the chamber (i.e., top and bottom) have a larger number of sensors than the middle of the chamber, since these areas would have a greater probability of either hot or cold spots, due to the airflow pattern within the stability chamber. 

The acceptance criteria for a successful operation qualification are based on the current ICH tolerance limits of 2°C for temperature and 5% RH for humidity [6, 7]. As it is expected that the temperature and humidity uniformity of an empty chamber would be superior to that for a chamber containing product, the acceptance criteria for successful OQ is set tighter than the ICH tolerance limits to ensure that the chamber will meet the required specifications during normal use. Therefore, at each location within the stability chamber, it is recommended that the temperature and humidity should be within 1°C and 4% RH of the predefined chamber set point. 

Figure 16.1. Typical sensor placement pattern for a reach-in stability chamber.

In summary, a successfully executed qualification of a stability chamber will ensure that the chamber will perform within its intended range of operation and that stability studies are performed at the proper storage condition within specified tolerance limits and according to current regulatory expectations. 

All stability studies on clinical trial materials must be carried out in full accordance with cGMPs, even if a research department carries out the studies. All studies must be carried out by adequately trained personnel under adequate work conditions. The personnel must use properly qualified and calibrated stability chambers, instruments, reagents, and standards. They must follow validated analytical methods and approved written procedures, and they must properly document all work. There must be proper sample and data traceability, change control, and go on. 

Different companies define zero-time in different ways. It may be the date corresponding to the completion of the manufacture of the bulk product, the start or end of packaging, the release by quality assurance (QA), the placement of samples in the stability chambers, or other measures. These dates can differ significantly for a variety of reasons, such as scheduling conflicts in the manufacturing and packaging departments and the time required to initiate a stability program. 

Storage after removal from stability chamber Time between receipt of samples and start of testing Holding of samples and sample solutions for investigations of OOS Disposition of unused samples Documentation... 

EXAMPLE 12 STABILITY PROGRAM SOP—STABILITY CHAMBERS OR ROOM... 

Use of validated, stability-indicating methods Evaluation of forced degradation products Properly executed method transfer protocols Use of qualified and calibrated equipment by trained analyst Use of qualified and calibrated stability chambers or rooms Handling of OOS and OOT results Timely implementation of corrective actions Stability chambers/rooms... 

The process of determining the irradiation homogeneity as a function of a location on the exposure area is often referred to as "mapping," a term commonly used in the pharmaceutical stability field when referring to temperature homogeneity within a thermal stability chamber. It should be noted that such measurements do not provide any information about the SPD of the radiation impinging upon the samples. 

Figure 24 PSC062 Pharma-Safe". (A) Stability test chamber, photostability model (B) custom built walk-in unit (C) exposure equilization filter. Source. Courtesy of Weirs Gallenkarmup.

As mentioned above, veterinary dosage forms can be very large and packaging of multiple doses achieved through the use of large packages. This presents substantial demands upon stability test chambers due to the sheer volume of product that must be stored. Appropriate sampling-size protocols can aid in the solution of this issue. 

Therefore, admixture studies are performed on parenteral drugs with commonly used intravenous diluents. Studies are performed by preparing admixtures of the drug product with various diluents in an appropriate type of flexible intravenous bag. Initial samples are taken for analysis before the bags are stored in temperature-controlled stability chambers. Subsequent samples may be pulled at 6-, 12-, 24-, 48-, and 72-h time points. The analytical tests commonly performed include visual appearance, pH, and HPLC assay. Degradation products are not commonly tested unless the method has been previously evaluated for specificity and stability-indicating ability with a particular intravenous diluent. This is necessary because there may be differences in the stability profile of the product in its original formulation compared to the admixture solution. Formation of any particulate matter is detected by visual... 

Because the stability chambers are an integral part of the stability program and require continuous performance to specifications for long-term studies, all aspects of the chambers must be described in detail in an SOP. The SOP should include the procedures and the schedule for calibration of the chambers, the description and operating parameters, a routine maintenance schedule, inventory system, IQ/OQ procedures and a monitoring system (PQ), and emergency procedures for malfunctions or unusual occurrences. 

Table 6.3 Two protocols for accelerated stability studies of solid pharmaceutical products. In each case, samples are exposed to the environment of the stability chamber (open conditions) except for those at 5%RH where a desiccant is used with a closed container...

Abstract An important aspect of all stability studies is the stability chambers themselves. This chapter is intended to provide a description of the different sizes and types of chambers that are available, the chamber tolerances required, and to provide some practical information for qualification, calibration, maintenance and monitoring of the chambers. Temperature, humidity and photo-stability chambers are included. Also included are guidelines on how to handle chamber excursions. 

Stability chambers can be obtained in a wide variety of sizes from commercially available small bench top reach-in chambers to large custom-designed walk-in rooms. Today the chamber manufacturer can provide high quality chambers at almost any size, for use at just about any condition. 

Fig. 14.1 ES 2000 74 cu ft Reach-in stability chamber Photo Courtesy of Environmental...

Fig. 14.2 ESI Walk-in stability chamber with CCS Touchscreen control (Photo Courtesy of Metrics Inc.)...

When a chamber is set to a specified set-point, it must be demonstrated that the entire chamber interior is maintained at that set-point within a certain tolerance. The chamber specifications described here refer to these tolerances and all stability chambers should be tested to assure that these tolerances are met. The specification will vary depending on the set-point(s) of the chamber as shown in Table 14.1. 

As with most pieces of equipment used in a GMP operation, stability chambers must go through a qualification process prior to use. This process traditionally includes three stages identified as the Installation Qualification (IQ), Operation Qualification (OQ), and Performance Qualification (PQ). At each stage a qualification protocol is written, approved, and executed. After successful execution a qualification report is written and approved. Upon approval, the next qualification stage is performed. Many components of equipment qualification are common to all pieces of equipment. A brief definition of each stage of qualification will be provided along with what might be included that is unique to stability chambers. 

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