Failures process related

There is considerable literature on material imperfections and their relation to the failure process. Typically, these theories are material dependent flaws are idealized as penny-shaped cracks, spherical pores, or other regular geometries, and their distribution in size, orientation, and spatial extent is specified. The tensile stress at which fracture initiates at a flaw depends on material properties and geometry of the flaw, and scales with the size of the flaw (Carroll and Holt, 1972a, b Curran et al., 1977 Davison et al., 1977). In thermally activated fracture processes, one or more specific mechanisms are considered, and the fracture activation rate at a specified tensile-stress level follows from the stress dependence of the Boltzmann factor (Zlatin and Ioffe, 1973). 

Lubricating-film instability is the dominant failure mode for sleeve bearings. This instability is typically caused by eccentric, or off-center, rotation of the machine shaft resulting from imbalance, misalignment, or other machine or process-related problems. Figure 44.48 shows a Babbitt bearing that exhibits instability. 

Fewer complaints about process-related failures... 

Ranky, P. G., and ChamyVelumani, S. (2003), An analytical approach, a tool (DFRA) and apphcation examples for assessing process-related failure risks, Int. I. CIM, 16(4-5), 326-333. 

The increasing use of high-performance fibrous composites in critical structural applications has led to a need to predict the lifetimes of these materials in service environments. To predict the durability of a composite in service environment requires a basic understanding of (1) the microscopic deformation and failure processes of the composite (2) the significance of the fiber, epoxy matrix and fiber-matrix interfacial region in composite performance and (3) the relations between the structure, deformation and failure processes and mechanical response of the fiber, epoxy matrix and their interface and how such relations are modified by environmental factors. 

Once the retesting protocol is executed successfully (i.e., no analytical deviations), the results will either support the OOS result and confirm a material failure or render the OOS result invalid and provide ample justification to pass the test specifications. If the OOS result is confirmed, the batch is rejected and the quality assurance department should take appropriate steps for batch disposal. Since confirmation of the OOS result strongly suggests an operator-related or process-related error, the onus is now placed on the formal or phase II investigation participants to identify a cause. If an operator-related error is found and batch rework is possible and prescribed in an approved batch record and approved regulatory submission, this may be the desired course of action. If no rework or reprocessing is possible, the batch is rejected and disposed of in an acceptable manner. 

Examination of product control charts is most useful in trying to distinguish between process-related or non-process-related causes.Trend analysis of key production parameters and attributes could assist in localizing a possible cause of the OOS. For example, if the potency of the product has been trending higher than usual for the last few batches produced (and the OOS resulted from an upper limit failure), this could be indicative of such causations as inaccurate moisture analysis or operator compensation error, error in the batch record, weighing error due to balance or scale bias, change in excipient purity which could impact functional characteristics or failure to maintain and/or calibrate apiece of equipment. 

The FDA expects the phase I and phase II investigation efforts to proceed beyond the batch in question and to other batches that were also manufactured under the same circumstances leading to failure of the OOS batch. If the investigation has revealed an operator-related or process-related error (e.g., ingredient test failure, equipment malfunction, calibration expiration, irregularity in process execution) and other batches were made using one or more common elements, they should also be investigated for compliance with all acceptance criteria. In the case above, dissolution results should be scrutinized. 

For each analytical test, the number and frequency of nonconforming batches should be tabulated. An explanation for the failure should be provided, in such a way as to distinguish between process- and non-process-related failures. 

As shown before, me is a function of stressed state ( > and an important parameter for the failure process, and the functional form cannot be introduced from theoretical considerations in this stage. However, we can determine it by experiment, particularly by creep failure experiment because of a simple relation between and mg as shown in eq(7). 

Halide anions have also been employed to facilitate the cyclization of weakly nucleophilic terminal vinyl ir-nucleophiles. For example, the butenylamine (85) undergoes Mannich cyclization in the presence of excess Nal to provide the 4-iodopiperidine (87) in excellent yield. The success of this cyclization should be contrasted with the failure of related amines to cyclize in formic acid with formaldehyde (Scheme 25). A detailed study " of the effect that nucleophile concentration has on the outcome of Mannich cyclizations provides deilnitive evidence that the cyclization of iminium ions with alkenes is not a concerted process, but rather proceeds via a cationic intermediate capable of partitioning between product formation and reversal to the starting iminium ion. A bridged cation or ir-complex, e.g. (86) in equation (8), is a reasonable description of this intermediate. 

Process performance qualification typically is conducted during the production of qualification lots using target set points for all process input parameters to demonstrate consistency and reproducibility of input and output parameters [32]. This process consistency is demonstrated by multiple full-scale batches, for example, three-to-five consecutive purification lots from three consecutive fermentation lots, during which yield and product concentration are monitored at each step [14]. A failed lot can occur without resetting the count if it is due to a known assignable cause that is not process-related (e.g., operator error or equipment failure) [33]. The cause of noncompliance must be determined and corrected, the noncompliant product disposition designated, and any corrective actions taken recorded [11]. At... 

The Court rejected FDA s position that a batch failure occurs when an individual test result doesn t meet specification. OOS results can be due to laboratory errors, non-process-related (operator) errors or process-related (manufacturing) errors. Only non-process or process-related errors are properly identified as failures. 

The Court ruled that re-testing is appropriate if the failure investigation has determined that re-testing is appropriate. Re-testing is not appropriate if the error was process-related, or for product failures. 

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