Clean hold time

Finally, the dirty hold time and the clean hold time have to be established [17]. When a vessel is not cleaned immediately after use, the remnants may dry in so the vessel may not be cleanable using the normal procedure. The dirty hold time is the time for the cleaning to be completed to be sure that the validated cleaning procedure is still effective. The clean hold time is the time that the equipment may be considered clean after performing cleaning and sanitisation (if applicable) and can be safely used for the next production. 

Reaction times can be as short as 10 minutes in a continuous flow reactor (1). In a typical batch cycle, the slurry is heated to the reaction temperature and held for up to 24 hours, although hold times can be less than an hour for many processes. After reaction is complete, the material is cooled, either by batch cooling or by pumping the product slurry through a double-pipe heat exchanger. Once the temperature is reduced below approximately 100°C, the slurry can be released through a pressure letdown system to ambient pressure. The product is then recovered by filtration (qv). A series of wash steps may be required to remove any salts that are formed as by-products. The clean filter cake is then dried in a tray or tunnel dryer or reslurried with water and spray dried. 

For part 2, for 98% conversion, each batch will require a holding time of 3.54 ksec and a downtime of 1.80 ksec for emptying, cleaning, and start-up. The total time consumed in processing one batch is thus 5.34 ksec. In order to produce 2000 kg of zeolite A per day we require that each batch contain an amount of amorphous solids equal to... 

In situ infrared spectra were obtained using the set-ups described in the experimental section. The step potential sequence was applied to obtain clean surface. The electrode was pushed onto the window after the potential was held at 1050 mV. The potential was stepped to 100 mV and the spectra were recorded repeatedly until no change was seen. The potential was increased with steps of 20 mV each and held 3 min. An infrared spectrum was recorded at each potential in the final 2 min. of the holding time. 400 scans were accumulated each time, leading to a 4 cm l resolution. 

The sample holding assembly should be cleaned every time. 

In the basic system described above, if the temperature drops below the pasteurisation temperature or the flowrate exceeds that for the correct holding time there is no other choice than to shut down the process and to clean and resterilise the equipment before production can be restarted. The consequences of this may be limited by diverting the flow of insufficiently pasteurised product back to the balance tank forward flow may be resumed once correct conditions are restored. The divert valve should be placed sufficiently downstream of the temperature monitoring probe that the system response time (probe, controller and valve) is less than the time taken for the unpasteurised product to reach the valve. 

For continuous processes, the lowest possible system dead volume will enable the operation with low average holding times. This may be important in some applications, especially those involving bacteria-laden liquids. Low system dead volume is also desirable for batch or continuous processes to minimize the volumes of cleaning solutions required during a cleaning cycle. 

Scale-down studies have been used for a wide variety of process validation studies, including resin lifetimes, in-process stream hold times, buffer stability, virus clearance, harvest criteria, filter extractables, resin leachables, and cell age at harvest [14, 91, 92]. The ease of scale-down differs depending on step and should be considered in selecting those steps to be validated [5]. In fact, certain validation issues can be addressed only via small-scale models (e.g., virus clearance evaluation, nucleic acid and other impurities/additives removal, cleaning and storage procedure evaluation, and column lifetime estimation) because their use increases worker safety, reduces costs, and permits use of higher titer samples for improved... 

Figure 8.3 the precipitator is partially filled with the solution of the active substance. CO2 is then pumped up to the desired pressure and introduced in the vessel, preferably from the bottom to achieve a better mixing of the solvent and antisolvent. After a holding time, the expanded solution is drained under isobaric conditions to wash and clean the precipitated particles. 

Fugate T (2007) Hold time studies a lost parameter for cleaning validation. J Valid Technol 13(3) 206—209... 

Less stable parts of the sludge can be treated by holding in tanks for extended periods of time to allow the weaker emulsion to break and separate a clean product. The mote stable sludges can be broken by mechanical action in filters or centrifuges, by recycle to the furnace for redistillation, or by redistillation in auxiliary units. Chemical attack via oxidation or complexing agents that break the emulsion has also been employed. 

---