Forward-flow pressure test

The integrity of the filter assembly should be checked by an appropriate method, such as bubble-point pressure test or forward flow pressure test immediately before and after use. Results of these filter-integrity checks should be recorded in the batch record. 

Perform pressure hold test or a forward flow test. 

It is essential that the microbiological particle passage test is performed as part of the development of new sterile formulations. Because of its very specialized nature, the test is normally performed only by the filter manufacturers, who then provide limits for secondary physical tests (e.g., bubble point, pressure decay, forward flow, etc.), which can be applied to verify the pore size rating and integrity of the membrane filters. 

The integrity of sterilizing fillers is most often validated and routinely monitored by nondestructive methods. The U.S., European, and U.K. guidelines on sterile filtration refer to four methods of integrity measurement filtration flow rate, bubble point tests, diffusion (forward flow) tests, and pressure hold tests. Each of these has its uses in determining that routinely used filters are per-forming to the same standards as those validated for the particular products and processes. 

Hydrophobic gas filter can be tested with the water intrusion test (WIT). Hydrophilic liquid filter are usually tested with water, the often used test method is the pressure decay test (PDT) a variation of the forward flow test (FFT). 

When a test gas (for example ambient air) is applied over a water moistened filter, just below the pressure level of the bubble point, test gas diffusion will occur through the water in the wetted membrane filter. This diffusion happens in all water filled pores, not only in the largest. This principle is the basis for two tests, which use different approaches to measure gas diffusion the pressure hold test and the diffusive-flow (forward flow) test. Other names for the same principle tests exist. These tests are performed at a pressure of about 80 % of the theoretical bubble point pressure of the filter. It is important that the largest pores are still filled with liquid. In this phase, diffusion occurs more or less linearly with the pressure drop over the... 

In the diffusive-flow test, also called the forward flow test, the filter membrane or candle in its tightly closed case is set under continuous test gas pressure. The amount of air that diffuses through the filter membrane per time unit is measured downstream, on the sterile side of the filter. The pressure drop over the membrane should be constant during the test to prevent variations in diffusion rate. Collection and measurement of the air on the sterile side often require actions that may lead to contamination of the setup, and thus these actions should be performed aseptically. Furthermore, for small filter surface areas the volume of air that diffuses through the filter is small and therefore no accurate measurements are possible for these small filters. 

After catalyst charging and the flow vs. RPM measurement is done, the reactor should be closed and flushed out with nitrogen while the impeller runs, until O2 drops below a few tenths of a percent. Then a static pressure and leak test should be made by turning off the forward pressure controller and the flow controller. If an observable drop of pressure occurs within 15 minutes, all joints and connections should be checked for leaks and fixed before progressing any fijither. 

Reversible reactions. Many solid-gas reactions are reversible, e.g., dehydration of crystal hydrates, so that rate equations for such processes should include terms for the rate of the reverse reaction. If the rates of contributing forward and reverse reactions are comparable, the general set of kinetic models (Table 3.3.) will not be applicable. The decomposition step in a reversible reaction thus needs to be studied [94] under conditions as far removed from equilibrium as possible (e.g. low pressures or high flow rates of carrier gas) and sensitive tests are required for determining whether the kinetics vary with the prevailing conditions. Sinev [95] has calculated that, for the decomposition of calcium carbonate, the rate of the reverse reaction is comparable with that of the forward reaction even when small sample masses (10 mg) and high flow rates (200 cm s ) of inert gas are used. Interpretation of observations becomes more difficult and the reliabihty of conclusions decreases if local inhomogeneities of kinetic behaviour develop within the reactant mass. 

The conservation equations for matter (2.4.3) and energy (2.4.10) provide constraints on quantities, and therefore they allow us to test for consistency in the specifications of a proposed process. For example, with these conservation laws we may be able to test whether the proposed outputs of matter or energy are consistent with the proposed inputs. However, the entropy balance (2.4.21) is not a conservation law, and therefore it does not provide a check on quantities or consistency. Instead, it provides a constraint on the direction of a proposed process. Some proposed processes can be performed in both forward and reverse directions, but many others can be performed in only one way. In the latter cases, the entropy balance can be used to identify the ranges of operating variables (temperatures, pressure, flow rates) that must be used to make a proposed process proceed in the desired direction. 

---