Minimum acceptable profile

Meets minimum acceptable profile (MAP) Does not have the desired effect and does not meet MAP Has desired effect but does not meet MAP Progress the drug into full development Terminate the project Bring forward back-up compounds. May be suitable to use as probe in man to evaluate basis for drug action or to develop methodology to be apphed to back-up compounds... 

With a clear understanding of this goal, what is the minimum acceptable profile ... 

Discussion of critical features of the minimum acceptable profile for go/no-go decisions... 

Specification of acceptable limits on extractables is preferred when possible by regulatory authorities. At a minimum, a profiling of extractables using appropriate solvents is expected of pharmaceutical manufacturers. 

Preference estimate Multiple regression techniques on the survey data are used to estimate the relative importance of each attribute level. CA allows estimation of the relative importance of each attribute such that the utility differences and values across all profiles can be evaluated. Several BR metrics can be derived such as minimum acceptable benefit for a given level of risk and maximum acceptable risk for a given level of benefit, net effective margin, and net safety margin, to be used in BRA. 

Maximum water reuse can be identified from limiting water profiles. These identify the most contaminated water that is acceptable in an operation. A composite curve of the limiting water profiles can be used to target the minimum water flowrate. While this approach is adequate for simple problems, it has some severe limitations. A more mathematical approach using the optimization of a superstructure allows all of the complexities of multiple contaminants, constraints, enforced matches, capital and operating costs to be included. A review of this area has been given by Mann and Liu21. 

Anyway, the first step toward any receptor-based COSMO-RS calculations is the calculation of qualitatively acceptable er-profiles of the receptor regions of enzymes. In a performance test of a highly parallel version of the TURBOMOLE program on the supercomputer at the Research Center Jiilich [141], we could show that TURBOMOLE presently can handle single point, i.e., fixed geometry, BP-SVP DFT-calculations of enzymes up to about 1,500 atoms. On the basis of preliminary data, an enzyme of 1,000 atoms requires about 6 CPU h on 32 CPUs of a supercomputer cluster with a minimum quadratic scaling of CPU-time with the number of atoms of the enzymes. Thus for medium-sized enzymes we would require a minimum of 600 h on such a supercomputer, which would be rather expensive, even if all the technical problems arising at these molecule sizes would be solved. Therefore, brute-force DFT calculations appear to be unfeasible at present, but they may be possible in the future. 

The SSE is an important and practical LCFR. We discussed the flow fields in SSEs in Section 6.3 and showed that the helical shape of the screw channel induces a cross-channel velocity profile that leads to a rather narrow residence time distribution (RTD) with crosschannel mixing such that a small axial increment that moves down-channel can be viewed as a reasonably mixed differential batch reactor. In addition, this configuration provides self-wiping between barrel and screw flight surfaces, which reduces material holdback to an acceptable minimum, thus rendering it an almost ideal TFR. 

Fig. 112 shows the temperature profile for the moment at which the dynamic equilibrium is established, when steam is injected into the bed without interruption at rates indicated above. We may accept 70°C to be the minimum temperature at which petroleum can still be actively displaced from the reservoir by the heat carrier. In that case, the maximum radial distance from the injection well at which steam still has some effect is about 180 m (Fig. 112). At that point, the thermal efficiency co-efficient does not exceed 0.15.

Chemical purity—Central to the preparation of BPCs are issues relative to the purity of the desired material. Until recently, the only concern was whether the material met the minimum potency requirements. A typical requirement would be a minimum potency specification of 98%. Any lot that had an assay higher than 98% would be acceptable. Awareness that the small amount of material that is not the desired molecule could cause adverse reactions led to the establishment of purity profiles for the molecule. Using a purity profile approach mandates that the firm identify the impurities present. Current FDA expectations are that firms should characterize all impurities that comprise more than... 

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