Barr ruling

The situation of the pharmaceutical industry is today governed by the Barr ruling. The foregoing suggestions concerning the use of outlier tests are expressly aimed only at those users and situations not subject to the Barr ruling. 

Since the 1993 court decision against Barr Laboratories, 5 tjjg elimination of outliers has taken on a decidedly legal aspect in the U.S. (any non-U.S. company that wishes to export pharmaceuticals or preciwsor products to the U.S. market must adhere to this decision concerning out-of-specifica-tion results, too) the relevant section states that ... An alternative means to invalidate an individual OOS result... is the (outlier test). The court placed specific restrictions on the use of this test. (1) Firms cannot frequently reject results on this basis, (2) The USP standards govern its use in specific areas, (3) The test cannot be used for chemical testing results. ... A footnote explicitly refers only to a content uniformity test, 5 but it appears that the rule must be similarly interpreted for all other forms of inherently precise physicochemical methods. For a possible interpretation, see Section 4.24. 

The Strictest Interpretation In the following, the language of the Barr decision (see notes at end of this section) is interpreted in the most restrictive sense, namely that each and every measurement has to comply with the rule no values outside the limits. ... 

Since the U.S. vs. Barr decision in 1993 (relevant to pharmaceuticals and related fields, rules applied by the Federal Food Drug Administration, FDA), outlier tests may no longer be applied to physicochemical tests, under the assumption that such test methods, having been optimized and validated for the particular set of circumstances, rarely produce outliers. These tests may not be applied to CU results at all. Good manufacturing practices mandate that operators work according to pre-set procedures and write down any observed irregularities as they... 

FDA s Summary of Judge Wollin s Interpretations of GMP Issues Contained in the Court s Ruling in USA vi. Barr Laboratories (2 -93f, http //www.fda.gov/ora/inspect ref/igs/pharm.html. 

Inhibition and stimulation of LOX activity occurs as a rule by a free radical mechanism. Riendeau et al. [8] showed that hydroperoxide activation of 5-LOX is product-specific and can be stimulated by 5-HPETE and hydrogen peroxide. NADPH, FAD, Fe2+ ions, and Fe3+(EDTA) complex markedly increased the formation of oxidized products while NADH and 5-HETE were inhibitory. Jones et al. [9] also demonstrated that another hydroperoxide 13(5)-hydroperoxy-9,ll( , Z)-octadecadienoic acid (13-HPOD) (formed by the oxidation of linoleic acid by soybean LOX) activated the inactive ferrous form of the enzyme. These authors suggested that 13-HPOD attached to LOX and affected its activation through the formation of a protein radical. Werz et al. [10] showed that reactive oxygen species produced by xanthine oxidase, granulocytes, or mitochondria activated 5-LOX in the Epstein Barr virus-transformed B-lymphocytes. 

Figure 3.4.6. VLE correlation of the 2-propanot and water binary system at 523 K with the IPVDW mixing rule and the PRS V equation of state and v are the experimental data. A binary interaction parameter fei2 = —0.1120 was used. (Points are the data of Barr-David and Dodge 1959 the data file for this system on the accompanying disk is 2PW250.DAT.)...

Figure 4.4.7. VLE correlations of the 2-propanol and water binary system at 523 K with various approximate EOS-C models. Clockwise from top left HVOS, MHV2, MHVl, and LCVM mixing rules combined with the van Laar excess free-energy model and the PRSV equation of state. Solid lines represent correlations with the van Laar parameters fit to experimental data, and the dashed hnes are predictions using van Laar parameters obtained from the DECHEMA tables at 303 K. Points are the VLE data at 523 K from Barr-David and Dodge 1959,...

The main photodissociation process for nitrous oxide is N20— N2 + O( D). It occurs with a quantum yield of nearly unity (Cvetanovic, 1965 Greiner, 1967a Paraskepopoulos and Cvetanovic, 1969). The photoproducts N2 + 0(5P) and NO + N(4S), although energetically allowed, would violate the spin conservation rule and are expected to be generated with low probability. For the second of these processes Preston and Barr (1971) have established a quantum yield of less than 2%. 

Equation 2.2 J = aE is not valid in anisotropic materials if a is a sealar. Tissue as a rule is anisotropic. Plonsey and Barr (2000) discussed some important eomplications posed by tissue anisotropy and also emphasized the necessity of introdueing the concept of the bidomain for cardiac tissue A hidomain model is useful when the eeUs are connected by two different types of junctions tight junctions and gap junctions with the cell interiors directly connected. The intracellular space is one domain and the interstitial space the other domain. Bidomain models have also been used for neural tissue (Sadleir, 2010). 

Nina J. Easton, Gang of Eive 236—37 (2000) (McIntosh) Joseph Alper, War Over the Wetlands Ecologists v. the White House, 257 Science 1043 (1992) Kriz, Swamp Fighting, 1919 Stephen Barr, Clinton to Revise Wetlands Policy, WP, August 25, 1993, at Ai John H. Gushman, Quayle, in hast Push for Landowners, Seeks to Relax Wetland Protections, NYT, November 12, 1992, at A16 Philip J. Hilts, U.S. Aides Retreat on Wetlands Rule, NYT, November 23, 1991, at Ai. 

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