Global regulatory considerations for unified assay specifications.

When developing a biotechnology product for global registration, there are several aspects to evaluate in an effort to unify specifications. These include differences between the United States, Europe and Japan, and Rest-of-World (ROW) countries with regard to the respective regulatory guidelines and pharmacopoeias in force, the state-of-the-art of product testing analytical methods, and the interval between submitting a registration dossier to different countries. In terms of regulatory guidelines, one country may have a monograph or required specifications for particular tests, for example the potency that a product has to meet before clinical trials can be initiated. For pharmacopoeias, different assay methods are required for sterility, general safety, and pyrogen testing, so that one may have to test a specific lot of a product at two or three different times to evaluate the same parameter, because of specific testing differences required for each country's pharmacopoeia. In addition, the state of analytical methods is always evolving and better analytical techniques become available. Sometimes, from starting with one set of tests, and based on the time in development, new tests may be added to the existing list of release specifications, because new analytical techniques have become available. Examining the global registration approval process for Betaseron, (interferon beta-1b) illustrates when specifications were able to be unified and when they were not.

Immunoglobulin E to cow's-milk protein in breast-fed atopic children.

Over a 3-yr period, 18 children , ages 10 mo to 5 yr, were discovered to have IgE to cow's-milk protein (CMP). They were compared with 18 age-matched patients for having been primarily breast fed during the first 6 mo of life. All were new allergy clinic asthmatic patients with a strong family history of atopy and evidence of IgE to multiple allergens. Analysis of the data on this allergic population revealed that both a history of breast feeding and of milk-induced immediate reaction in patients with CMP-specific IgE was significantly higher (p is less than 0.03) than in those patients without IgE to CMP. Inadvertent sensitization to food antigens can occur in some atopic breast-fed infants.

Polymer distribution in human serum albumin powders prepared by lyophilization or acetone drying.

Various lots of human serum albumin, prepared by the Cohn alcohol procedure, were assayed for polymer distribution after lyophilization or acetone drying of the albumin paste. Sodium dodecyl sulfate polyacrylamide gel electrophoresis revealed that powders obtained by acetone drying of the pastes contained significantly higher amounts of monomeric albumin.