Validation of fermentation processes.

The ability to prepare consistent biopharmaceutical products depends extensively on possession of banked and characterized cell substrates and on development of production processes which can be validated. While the attributes that define cell characterization have been extensively detailed by ICH and the regulatory agencies in the past decade, little has been specified regarding process validation for biological processes. The extent to which validation concepts can be applied to biological processes varies depending on the nature of the process, the nature of the product, and the level of knowledge regarding the relationship between process parameters and product quality. Expectations concerning the rigour of the validation programme should be adjusted accordingly. There is no single approach that is appropriate for all processes and products. At a minimum, there should be an attempt to define which process parameters are critical, and to focus the attention of validation efforts on these parameters.

Viral validation strategy for recombinant products derived from established animal cell lines.

For products derived from continuous cell lines, regulatory agencies worldwide require that the purification process be validated for its ability to remove or inactivate potential contaminants such as viruses and virus-like particles. New guidance suggests a requirement for statistical evaluation of these studies but the industry has yet to develop such standards. The task of estimating excess capacity is also complicated by variable assays, accumulation of variability in clearance estimates over unit operations, dependence of clearance capacity on operating parameters, and expense of experiments. We propose an experimental strategy to determine the excess clearance capacity of a biopharmaceutical process and to provide statistical estimation of excess capacity in an efficient way. Clearance estimates and their variances are calculated for each orthogonal unit operation and estimates are combined to form an interval estimate of overall process clearance capacity. Poisson regression is suggested as an efficient technique for data analysis of clearance studies. We believe that this approach should meet regulatory guidelines in a cost effective way, while clarifying the roles of qualitative and quantitative components in setting requirements.

Characterization of the research papers of U.S. medical schools.

An investigation of the relationship between National Institutes of Health (NIH) funding and the quantity and nature of biomedical publications is reported for 120 U.S. medical school complexes. A correlation of 0.95 was found between the amount of NIH funds received and the number of biomedical publications from the medical schools. Medical school ranks based on bibliometric measures were found to correlate at the 0.80-0.90 level with ranks based on peer assessments of the schools. The characteristics of the medical school papers varied with the type of school. The average citation influence per paper increased with the publication size of the schools. This was true even when factors such as public versus private control, geographic region, average research level (from basic to clinical), and subject emphasis were controlled. The positive relationship between number of papers from a school and its citation influence holds within individual research levels and within subfields.

Effects of phosphonium compounds on Schistosoma mansoni.

A new series of phosphonium salts was examined for effects on the cholinergic nervous system of Schistosoma mansoni. Studies were conducted using both an activity-monitoring and fluorescent-labeling technique. The activity method gave more definitive results, indicating that some poly(methylene)bis(triphenylphosphonium) salts and some [3-(alkylamino)propyl]triphenylphosphonium salts have strong anticholinergic effects. Hexyltriphenylphosphonium bromide has very marked effects both in the motility and the fluorescence test, but these effects cannot immediately be ascribed to cholinergic actions.

Juxtaposition of the atrial appendages.

Juxtaposition of the atrial appendages is a rare congenital cardiac anomaly almost universally associated with severe conotruncal abnormalities, especially transposition of the aorta. This presentation describes a case of right sided juxtaposition of the atrial appendages without concomitant conotruncal malformations. This finding contradicts previous hypotheses concerning the genesis of juxtaposition.