Manufacturing Barriers to Biologics Competition and Innovation

As finding breakthrough small-molecule drugs gets harder, drug companies are increasingly turning to “large molecule” biologics. Although biologics represent many of the most promising new therapies for previously intractable diseases, they are extremely expensive. Moreover, the pathway for generic-type competition set up by Congress in 2010 is unlikely to yield significant cost savings. In this Article, we provide a fresh diagnosis of, and prescription for, this major public policy problem. We argue that the key cause is pervasive trade secrecy in the complex area of biologics manufacturing. Under the current regime, this trade secrecy, combined with certain features of FDA regulation, not only creates high barriers to entry of indefinite duration but also undermines efforts to advance fundamental knowledge. In sharp contrast, offering incentives for information disclosure to originator manufacturers would leverage the existing interaction of trade secrecy and the regulatory state in a positive direction. Although trade secrecy, particularly in complex areas like biologics manufacturing, often involves tacit knowledge that is difficult to codify and thus transfer, in this case regulatory requirements that originator manufacturers submit manufacturing details have already codified the relevant tacit knowledge. Incentivizing disclosure of these regulatory submissions would not only spur competition but it would provide a rich source of information upon which additional research, including fundamental research into the science of manufacturing, could build. In addition to provide fresh diagnosis and prescription in the specific area of biologics, the Article contributes to more general scholarship on trade secrecy and tacit knowledge. Prior scholarship has neglected the extent to which regulation can turn tacit knowledge not only into codified knowledge but into precisely the type of codified knowledge that is most likely to be useful and accurate. The Article also draws a link to the literature on adaptive regulation, arguing that greater regulatory flexibility is necessary and that more fundamental knowledge should spur flexibility. A vastly shortened version of the central argument that manufacturing trade secrecy hampers biosimilar development was published at 348 Science 188 (2015), available online

A structural, spectroscopic and theoretical study of the triphenylphosphine chalcogenide complexes of tungsten carbonyl, [W(XPPh3)(CO)5], X=O, S, Se

The series [W(XPPh3)(CO)5], X=O, S, Se has been structurally determined by X-ray crystallography and fully characterised spectroscopically to provide data for comparing the bonding of the Ph3PX ligands to the metal. The P-X-W angles are 134.3°, 113.2° and 109.2°, respectively, for X=O, S, Se. The bonding has been analysed using EHMO calculations which suggest that lower P-X-W angles depend on the relative importance of σ-bonding, which in turn depends on the chalcogen in the order X=Se > S > O. The effect is enhanced by lower energies of the metal σ and π orbital energies

Substituted phenylarsonic acids; structures and spectroscopy

Full NMR and ESI-MS spectra, and differential scanning calorimeter data are presented for 15 substituted phenylarsonic acids, including two new fluoro-substituted examples. X-ray crystal structure determinations of five examples (phenylarsonic acid and the 4-fluoro-, 4-fluoro-3-nitro-, 3-amino-4-hydroxy- and 3-amino-4-methoxy-substituted derivatives) were determined and the H-bonding crystal-packing patterns analysed

The Deepwater Horizon Oil Spill: Potential Insurance Coverage Implications

More than 300 lawsuits have already been filed in Louisiana, Florida, Texas, Mississippi, and Alabama against BP and other corporations involved in the Deepwater Horizon oil spill, including Transocean, Halliburton, and Cameron, with thousands more anticipated. This article briefly addresses the contours of the coverage lawsuit already filed against BP and other coverage disputes we may see in the future

Fluoride release and uptake in enhanced bioactivity glass ionomer cement (“glass carbomer™”) compared with conventional and resin-modified glass ionomer cements

Objectives: To study the fluoride uptake and release properties of glass carbomer dental cements and compare them with those of conventional and resin-modified glass ionomers. Materials and Methods: Three materials were used, as follows: glass carbomer (Glass Fill), conventional glass ionomer (Chemfil Rock) and resin-modified glass ionomer (Fuji II LC). For all materials, specimens (sets of six) were matured at room temperature for time intervals of 10 minutes, 1 hour and 6 weeks, then exposed to either deionized water or sodium fluoride solution (1000 ppm in fluoride) for 24 hours. Following this, all specimens were placed in deionized water for additional 24 hours and fluoride release was measured. Results: Storage in water led to increase in mass in all cases due to water uptake, with uptake varying with maturing time and material type. Storage in aqueous NaF led to variable results. Glass carbomer showed mass losses at all maturing times, whereas the conventional glass ionomer gained mass for some maturing times, and the resin-modified glass ionomer gained mass for all maturing times. All materials released fluoride into deionized water, with glass carbomer showing the highest release. For both types of glass ionomer, uptake of fluoride led to enhanced fluoride release into deionized water. In contrast, uptake by glass carbomer did not lead to increased fluoride release, although it was substantially higher than the uptake by both types of glass ionomer. Conclusions: Glass carbomer resembles glass ionomer cements in its fluoride uptake behavior but differs when considering that its fluoride uptake does not lead to increased fluoride release