Criticality/noncriticality

The calibration program ensures that instruments associated with manufacturing processes are calibrated and maintained. Instruments in the facility are typically classified as either critical, noncritical, or reference. Those instruments that are deemed either critical or noncritical are typically calibrated using NIST or other applicable standards on a routine basis. 

Critical Noncritical Input Output Controlled Uncontrolled ... 

Document the functions that are critical and noncritical in the system based on the... 

The last, but by no means the least, important of the military characteristics is availability under wartime conditions. Materials are classified as strategic, critical, and non-critical in this respect A strategic material is one that must be imported into the United States a critical material is one that is available in the United States but, because of either limited plant facilities or excessive demands, becomes nonavailable a noncritical material is one that is readily available in. sufficient amounts under wartime conditions. An insecticide to be of value to the military forces must be readily available under wartime conditions, must not be dependent upon the importation of certain essential materials, and must not impose a burden upon plant facilities in the United States. 

Determining the capacity of the noncritical steps (those steps that are not bottlenecks) may require some testing. If a step is not critical there is no reason for the operators or engineers to determine its maximum throughput. Yet, as has been illustrated, this must be known to properly expand or to design a new plant. 

Critical stenosis occurs when the obstructing lesion encroaches on the luminal diameter and exceeds 70%. Lesions creating obstruction of 50% to 70% may reduce blood flow, but these obstructions are not consistent, and vasospasm and thrombosis superimposed on a noncritical lesion may lead to clinical events such as MI. If the lesion enlarges from 80% to 90%, resistance in that vessel is tripled. Coronary reserve is diminished at about 85% obstruction due to vasoconstriction. 

It should be mentioned that the calculated entanglement here has a corresponding critical exponent ys = 0. This means that the entanglement is constant at the critical point over all sizes of the system. But it is not a constant over all values of U/t. There is an abrupt jump across the critical point as L —> oo. If we divide the regime of the order parameter into noncritical regime and critical... 

The QA SOP manual should describe QAU audit and inspection techniques with attached inspection checkhsts, if used. Statistically based methods for random selection of phases of studies for inspection and for random selection of data points during final report audits should be described and justified. Any designation of study phases as critical or noncritical used to estabhsh the frequency of study inspec-... 

Classification of equipment as critical or noncritical with regard to calibration necessities should be maintained. 

All critical items should be calibrated every 6 months. Noncritical items should be calibrated every 12 months. If necessary, recalibration frequency should be reviewed and revised. 

Identification of isolates from critical sampling points such as water used for preparation and areas immediate to these critical sampling points such as water used for CIP should take precedence over identification of microorganisms from noncritical sampling points. 

A software validation plan must take into account the risk analyses for the software therefore a critical software must have a high level of confidence and must be submitted to deep validation processes, whereas noncritical software may be submitted to less extensive validation processes. 

In contrast, a heterogeneous solution of noncritical composition (e.g., v < xc, as shown by the arrow and dashed line in Fig. 7.11) shows a qualitatively different behavior as it is rises through the coexistence boundary and into the homogeneous region near and above Tc. For each increase in temperature along the dashed line in Fig. 7.11, a horizontal tie-line yields both the compositions of the A-rich and B-rich liquids (from the two ends of the tie-line), as well as the relative amounts of each phase (from the lever rule). Clearly, the critical composition xc remains near the middle of the tie-line as T increases toward Tc, whereas a noncritical composition x xc moves toward one or other terminus of the tie-line as the temperature is raised. 

Figure 7.12 Successive snapshots of a binary A/B system in the immiscible region of coexisting A-rich (lighter) and B-rich (darker) liquid phases (Fig. 7.11), comparing the T-dependent behavior for noncritical (upper sequence cf. dashed line in Fig. 7.11) versus critical composition (lower sequence cf. dotted line in Fig. 7.11), and showing how the meniscus rises out of the container in the first case but vanishes at the critical point Tc in the second case. [Both solutions are taken to be fairly comparable in the starting low-71 snapshot, but their deviations are readily apparent in the second snapshot at the temperature Ttie of the horizontal tie-line in Fig. 7.11.]...

Once the computer system has been delivered to the pharmaceutical manufacturer s site and is installed and connected through field cabling and tubing to instrumentation (and possibly other systems) it is ready for site acceptance testing—this for both critical and noncritical parameters and functions. The in situ acceptance testing of the system under the SAT is a key element of engineering commissioning. For continuity, SAT test results should be analyzed and compared to the FAT results. 

In order to determine whether or not an operation is critical or noncritical, a set of consistent criteria must be used as a reference. The Food, Drug and Cosmetic Act makes this clear. 

Validation of critical operations is mandatory, whereas validation of noncritical operations is optional. 

Computer simulation is invariably conducted on a model system whose size is small on the thermodynamic scale one typically has in mind when one refers to phase diagrams. Any simulation-based study of phase behavior thus necessarily requires careful consideration of finite-size effects. The nature of these effects is significantly different according to whether one is concerned with behavior close to or remote from a critical point. The distinction reflects the relative sizes of the linear dimension L of the system—the edge of the simulation cube, and the correlation length —the distance over which the local configurational variables are correlated. By noncritical we mean a system for which L E, by critical we mean one for which L [Pg.46]

Compared to binary mixtures of low molecular fluids, the critical behavior of polymer blends has been much less explored so far. However, a number of interesting static and dynamic critical phenomena in polymer blends attract increasing attention [4, 5], Neutron, X-ray, and static light scattering experiments belong to the major techniques for characterizing the static properties of polymer blends. Photon correlation spectroscopy (PCS) has traditionally been the method of choice for the investigation of the dynamics of critical [6-9] and noncritical [10-12] polymer blends. 

A third important assumption relates to selecting the critical response. EPA assumes that if the dose is below that required to cause the most sensitive response, then other deterministic responses will not occur. However, if other responses have shallower slopes in the dose-response curves near their thresholds, estimating RfD on the basis of the critical response may not be sufficiently protective to preclude a noncritical response from occurring. For this reason, EPA may use information on the slopes of dose-response curves to determine the critical response and the number of safety factors to be applied, although EPA rarely does so. 

A batch or run listed as critical early in product development may later be determined to be noncritical if the course of development changes. In this case, these batches or runs can be deleted fromTable 1 in the next issue of the development report with a brief rationale. 

Nature of target Good specificity of therapeutic to target or disease Target is noncritical, has redundancy Poor specificity of therapeutic to target or disease Inherent risk of targeting specific structures, nonredundant systems Critical biological effect... 

FIGURE 3-2. A typical isocratic HPLC. Plumbing considerations involve understanding the critical and noncritical bandspreading regions. 

---