Stability chambers specifications

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. 

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. 

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. 

Preventative maintenance (and cleaning) for photo-stability chambers will depend on the type of chamber and variables such as (1) does the chamber control temperature or humidity, (2) does it have built-in radiation monitors and (3) is it Option I or Option II. The information provided for preventative maintenance of tempera-ture/humidity chambers (refer to Section 14.6) applies here. The chamber manufacturer will provide specific procedures and frequencies for preventative maintenance and these should be transferred to an internal SOP. 

A stability program SOP should define all general aspects of stability studies and serve as the basis for preparation of specific protocols. The SOP should include sections on (or reference other SOPs for) the procedures for the stability protocol, samples, testing, chambers or rooms, and final report. Items to be included in each section of a stability program SOP are outlined in Examples 9-15. 

The examples presented in this chapter [308 320] are illustrations of the concepts presented in the previous chapters. They correspond to recent numerical analysis of burners which are typical of most modern high-power combustion chambers, especially of gas turbines the flame is stabilized by strongly swirled flows, the Reynolds numbers are large, the flow field sensitivity to boundary conditions is high, intense acoustic/combustion coupling can lead to self-sustained oscillations. Flames are stabilized by swirl. Swirl also creates specific flow patterns (a Central Toroidal Recirculation Zone called CTRZ) and instabilities (the Precessing Vortex Core called PVC). 

In most amperometric cytochrome b2 electrodes the reaction is followed by anodic oxidation of ferrocyanide at a potential of +0.25 V or above. The first of such sensors was assembled by Williams et al. (1970), who immobilized the enzyme (from baker s yeast) physically at the tip of a platinum electrode within a nylon net of 0.15 mm thickness. The large layer thickness resulted in a response time of 3-10 min. Owing to the low specific enzyme activity used, the sensor was kinetically controlled. Therefore the linear measuring range extended only up to 0.1 Km-A similar sensor has been applied by Durliat et al. (1979) to continuous lactate analysis. The enzyme was contained in a reaction chamber of 1 pi volume in front of the electrode. This principle has also been employed in the first commercial lactate analyzer using an enzyme electrode (Roche LA 640, see Section 5.2.3.3X With a sensor stability of 30 days and a C V below 5%, 20-30 samples/h can be processed with this device. 

Various alternative precursor delivery processes have been designed specifically to circumvent the low volatility and low thermal stability problems associated with (Ba(dpm)2 (see Sect. 2.4.1.2). The first method involves the dissolution of Y(dpm)j, Ba(dpm)2 and Cu(dpm)2 precursors in solvents such as butylacetate [188], THF [153, 156], toluene [189], decane [190] and supercritical carbon dioxide [191]. According to this process, termed aerosol-assisted CVD (AACVD), the multicomponent precursor solution is atomized or vaporized into a carrier gas stream or directly into the reaction chamber, with deposition occurring on a heated substrate. Some attractive features of AACVD include deposition at atmospheric pressure, the ability to use thermally sensitive precursors, and a high precursor transport rate [189]. Figure 2-30 shows a sum-... 

In the last few years gas combustion technology has undergone important innovations especially in residential heating appliances. In particular, requirements on low emissions together with load modulation has led to the use of premixed combustion technologies besides traditional diffusive flames. Constant demand for smaller overall dimensions and cost optimization has led to design combustion chambers with higher combustion intensity and this has led to premixed surface burners, then to radiant burners, and then to metallic mat burners in particular. With the metallic mat combustion flame front stabilizes above a metallic mat and at specific power loads is located inside. It differs from porous matrix combustion where combustion takes place inside a solid. 

While there is not currently a temperature or relative humidity requirement for photo-stability studies, it is recommended that a specification (tolerance) be established. This requirement may not necessarily be as tight as that for a tempera-ture/humidity chamber. It should take into consideration the following ... 

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