Stability Operating Procedures establishment

Stability Operation Practices are guided by SOPs. Each company has its own set of procedures, which describe all activities that are deemed critical. SOPs will help to establish consistency, and thus quality of company stability operations. Therefore, they should be written precisely, based on FDA regulations. Unfortunately, most common deficiencies result from inadequate SOPs. 

Failure to establish yields or acceptable levels of rejects for both in-process and finished product Failure to conduct stability studies Manufacturing equipment not identified and/or qualified Inadequate training of employees working in aseptic operations Inadequate process change procedures Validation protocols that lack acceptance criteria Incomplete investigations of laboratory failures Failure to follow United States Pharmacopeia (USP) procedures for the bacterial endotoxin test... 

A review of these publications reveals a host of misstatements such as "After evaluation of the various lamps, none could be declared superior to others in terms of variability or operating conditions" (30) or "Although acceptable lamps may have different SPDs, these differences should not effect the yes/no outcome of the testing procedure..(30), the previously cited quotation from Beaumont (3) or the statement of Wooton that "If a material is going to be exposed to different light sources it is unlikely that a single test will provide sufficient data to establish the stability of a material to all sources (32)."... 

The requirements for chemical actinometers, listed in the previous sections [such as sensitivity, reproducibility, (thermal) stability, ease of analytical procedure, etc.], reduce the seemingly unlimited number of actinometers reported over the years (9) to a short list of well-established and highly recommended chemical actinometers. In this section, we first present a selected list of such reliable actinometers, which all operate in the liquid phase. After that, a few controversial systems are described and their potential error sources discussed. Finally, actinometric procedures suitable for solid-state applications, polychromatic sources, and laser irradiation will be introduced in section "Special Applications."... 

At the same time, internal quality control must be carried out to verify the performance stability of the limited-scope performance of the method. Triply redundant verification methods are carried out with regard to control of first, second and/or third line, each set of methods applied to a particular type of test. The first line of verification involves pro forma repetition of all the steps of the test, in order to establish repeatability or reproducibility for quantitative tests, and to verify the range of sensitivity or detection for qualitative tests. This verification is performed by the experimenter himself, as part of the proper performance of the test. A second line of verification is put into operation by administrative decision, and includes testing with blind samples, repetition of samples, internal audit procedures, etc. If necessary, a third line of verification can be set up by the use of certified reference materials (or spiking materials), or through collaborative trials. These procedures are based on external cooperation. External audit procedures and complaints handling procedures are also part of this third line of verification. 

The quality control department as a whole will also have other duties, such as to establish, validate, and implement all quality control procedures, to evaluate, maintain, and store the reference standards for substances, to ensure the correct labelling of containers of materials and products, to ensure that the stability of the active pharmaceutical ingredients and products is monitored, to participate in the investigation of complaints related to the quality of the product, and to participate in environmental monitoring. All these operations should be carried out in accordance with written procedures and, where necessary, recorded. 

A covalent bond is established between the functional groups in the activated carrier and the functional groups in the amino acid residues of the enzyme, like —OH, —SH, —NH2, and —COOH. Covalent immobilization has been thoroughly studied and detailed information on methods and procedures can be found in several publications devoted to it (Zaborsky 1973 Cao 2005b Guisan 2006). It is a rather complex method where the carrier is hardly recoverable after enzyme exhaustion, immobilization yield is rather low and the kinetic properties of the enzyme can be severely altered. However, operational stability is high and it is quite flexible, so that directed immobilization can be done to suit the particular characteristics of the process. 

In the most recent iteration of the feedback loop which relates molecular structure to solid-state device performance, the fast bistable [2]rotaxane 11" has been superseded " by the modified and improved version shown in Fig. 1.15, namely, the [2]rotaxane The impetus for this iteration was at least two-fold (1) to produce a molecular switch in which the bistable rotaxane starts off exclusively in one, and only one, of its two possible co-conformations and (2) to incorporate into this all-or-nothing switch enhanced oxidative stability by removing all of the phenolic residues from the hydrophilic stopper. The rotaxane, which was obtained (Fig. 1.15) by the now well-established templation protocol, has been incorporated by the familiar fabrication procedures into an 8 x 8 crossbar device (Fig. 1.16(a)). Fig. 1.16(b) demonstrates one of these 64-bit devices in operation with the exception of one of the wires, i.e., 56 out of the 64 bits can be switched. This device has been used to store (Fig. 1.16(c)) the letters DARPA in ASCII code the lifetime of the switch-closed state of this devices is about 10 minutes. The proposed electromechanical switching mechanism for the bistable [2]rotaxane which is outlined in Fig. 1.17, merits comparison with that already discussed in Fig. 1.16 for the bistable [2]rotaxane In the case of it is proposed that oxidation of the TTF unit to its radical cation (TTF ) occurs when a +2 V bias is applied across the bistable [2]rotaxane and the tetracationic cyclophane moves to encircle the... 

Laguna Verde unit one during a startup after a scram in cycle four, experienced such kind of instabilities, with peak to peak of the order of 10% of rated power, this unexpected performance, required an analysis of the core stability in the power flow map. Consequences such reduction of the operational area in the power flow map was established, changes to the procedures for shift speed of re-circulation pump were launched. Specific operator training was developed. 

Operability and maintainability. The control system of the plant was designed and checked fbr plant stability with no significant oscillation or deviation for 10% stepwise changes and 5% ramp changes in reactor power. ISI of the primary major components was implemented for the structural concept based on the ISI policy(draft) established for the DFBR. It is confirmed that the major components and main piping in the primary loop can be repaired and maintained. Maintenance methods and procedures were examined using 3-dimensional CAD simulation. It was confirmed that regular maintenance and inspection works can be carried out within 60 days. 

The mass inventory for the primary loop stabilizes at about 80% and 93% of the initial value in the two operational configurations calculated by code runs ND03 and NI03, respectively. This includes the fluid in the pressuriser. Stable liquid level in the pressuriser, i.e. buoyant fluid in a dynamic condition, establishes as the result of the procedure considered for power rise. The level value is such to allow the operation of heaters, though they are not called into operation in the present framework. 

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