Validation, defined

The FDA guidance on IVIVC development and validation defines a number of circumstances where an IVIVC can be used to justify a biowaiver request in support of (1) level 3 process changes, (2) complete removal or replacement of non-release-controlling excipients, (3) level 3 changes in release-controlling excipients, (4) approval of lower strengths, and (5) approval of new strengths. Additionally, use of the IVIVC to justify biorelevant dissolution specifications is cited as the optimal approach. 

In performing the validation, defining the quality attributes—that is, gaining a clear understanding of the required quality and intended use—is the most important issue, and should be determined before starting the validation. Without defining required quality attributes we cannot establish validation protocols, which are the basis of all validation studies. 

The World Health Organization GMP [6] concept requires that critical processes should be validated, with validation defined as the documented act of proving... 

Thermal optima Can we validly define thermal optima for physiological systems If so, what are these thermal optima, and how much change in temperature is adequate to create a sub optimal state of function Do all physiological systems of a species display similar thermal optima ... 

Validation plans are documents that tailor a firm s overall philosophies, intentions, and approaches to be used for establishing performance adequacy to a specific project. They state who is responsible for performing development and validation activities. They identify which systems are subject to validation, define the nature and extent of inspection and testing expected to be done on each system, and outline the protocols to be followed to accomplish the validation. 

A validation team member from the Maintenance department participates in performing the validation defining the necessary equipment specifications, limitations, capacity, calibration, and maintenance requirements and providing the necessary training on the proper operation and maintenance of the equipment. The Maintenance department should be responsible for providing the necessary utilities and equipment accessories. 

The most fruitful approach steers the middle course of establishing simple theoretical models of the complex in terms of suitable transferable parameters which may be calculated, or determined empirically by some other technique which is, in itself independent of the chirality of the complex. The empirical rules may then be assessed theoretically, and the range of their validity defined explicitly in terms of such parameters. The critical discussion of such a simple, unified model in terms of transferable, well-defined parameters is the main aim of this paper. 

Pre-study validation defines that the method produces reliable results. During pre-study validation, fundamental parameters such as selectivity, assay calibration, accuracy, precision, linearity, and stability are evaluated. 

External validity Defining the domain to which a study s finding can be generalized. 

Safety Validation Defining a test/validation plan and executing and assessing the results of... 

The American standard ASTM 6400 provides standard specifications for compostable plastics and products manufactured from these materials. ASTM 6400, like all other standards, states its scope of validity, defines its concepts, and states the specific requirements (here for compostable materials and/or products). Similar to DIN EN 13432, subsection 6 (Detailed Requirements) describes the chemical tests as well as the general proof of general biodegradability, followed by the test for total disintegration. However, ASTM 6400 provides little detailed information, but rather refers repeatedly to ASTM D6002 regarding test execution. 

A specification or standard for product characteristics is valid only if it is matched with references to well defined and recognized test methods, such that quality control tests conducted by the parties involved —client and supplier, for example— are comparable even if they are performed at different locations. 

The previous equation is only valid as long as there is no compositional change of the gas between the subsurface and the surface. The value of E is typically in the order of 200, in other words the gas expands by a factor of around 200 from subsurface to surface conditions. The actual value of course depends upon both the gas composition and the reservoir temperature and pressure. Standard conditions of temperature and pressure are commonly defined as 60°F (298K) and one atmosphere (14.7 psia or 101.3 kPa), but may vary from location to location, and between gas sales contracts. 

The above approximation, however, is valid only for dilute solutions and with assemblies of molecules of similar structure. In the event that concentration is high where intemiolecular interactions are very strong, or the system contains a less defined morphology, a different data analysis approach must be taken. One such approach was derived by Debye et al [21]. They have shown tliat for a random two-phase system with sharp boundaries, the correlation fiinction may carry an exponential fomi. 

Let H and L be two characteristic lengths associated with the channel height and the lateral dimensions of the flow domain, respectively. To obtain a uniformly valid approximation for the flow equations, in the limit of small channel thickness, the ratio of characteristic height to lateral dimensions is defined as e = (H/L) 0. Coordinate scale factors h, as well as dynamic variables are represented by a power series in e. It is expected that the scale factor h-, in the direction normal to the layer, is 0(e) while hi and /12, are 0(L). It is also anticipated that the leading terms in the expansion of h, are independent of the coordinate x. Similai ly, the physical velocity components, vi and V2, ai e 0(11), whei e U is a characteristic layer wise velocity, while V3, the component perpendicular to the layer, is 0(eU). Therefore we have... 

Alternatively, authors have repeatedly invoked the internal pressure of water as an explanation of the rate enhancements of Diels-Alder reactions in this solvent ". They were probably inspired by the well known large effects of the external pressure " on rates of cycloadditions. However, the internal pressure of water is very low and offers no valid explanation for its effect on the Diels-Alder reaction. The internal pressure is defined as the energy required to bring about an infinitesimal change in the volume of the solvents at constant temperature pi = (r)E / Due to the open and... 

A somewhat dilferent way to define a molecule is as a simplified molecular input line entry specification (SMILES) structure. It is a way of writing a single text string that defines the atoms and connectivity. It does not define the exact bond lengths, and so forth. Valid SMILES structures for ethane are CC, C2, and H3C-CH3. SMILES is used because it is a very convenient way to describe molecular geometry when large databases of compounds must be maintained. There is also a very minimal version for organic molecules called SSMILES. 

If the magnitudes of the dissipative force, random noise, or the time step are too large, the modified velocity Verlet algorithm will not correctly integrate the equations of motion and thus give incorrect results. The values that are valid depend on the particle sizes being used. A system of reduced units can be defined in which these limits remain constant. 

Fig. 3. Comfort 2ones at 6% of population predicted dissatisfied from ref 4. RH lines are valid only when the air temperature equals the average temperature of the surfaces, (a) Operative temperature range where ET is effective temperature as defined in text, (b) Comfort 2one detail. To convert...

In order to see why, we need to look at our car in a bit more detail (Fig. 5.2). We start by assuming that it is surrounded by a large and thermally insulated environment kept at constant thermodynamic temperature Tq and absolute pressure po (assumptions that are valid for most structural changes in the earth s atmosphere). We define our system as (the automobile -1- the air needed for burning the fuel -1- the exhaust gases... 

It is really rather meaningless to talk about a nucleus containing only two or three atoms To define a b.c.c. crystal we would have to assemble at least 20 or 30 atoms. But it will still be far easier to fluctuate 30 atoms into position than to fluctuate 100. Our argument is thus valid qualitatively, if not quantitatively. 

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