The value and benefits of the International Conference on Harmonisation to drug regulatory authorities: advancing harmonization for better public health.

The International Conference on Harmonisation (ICH) is an unparalleled undertaking, which has brought together drug regulatory authorities and pharmaceutical trade associations from Europe, Japan, and the United States, to discuss the scientific and technical aspects of medical product registration. Launched in 1990, the value and benefits of ICH to regulators are being realized. ICH has harmonized submission requirements and created a harmonized submission format that is relieving both companies and regulatory authorities of the burdens of assembling and reviewing separate submissions for each region.

The common technical document: the changing face of the New Drug Application.

Drug approval is the goal of the long process of drug development. Once preclinical and clinical trial data have been collected, a New Drug Application must be submitted to the regulatory authority for approval. Although the requirements for this submission have similarities around the world, until now, the applications have been different.

A methacholine challenge dose-response study for development of a pharmacodynamic bioequivalence methodology for albuterol metered- dose inhalers.

Background: With the expiration of the patent on albuterol metered-dose inhalers (MDIs) in 1989, methods to assess in vivo bioequivalence of generic formulations required investigation.

Objective: In an effort to develop a sensitive method to document bioequivalence, bronchoprovocation with methacholine chloride was used to assess the dose-response relationship of albuterol as delivered by MDI. Sensitivity was assessed in terms of magnitudes of ED(50), the estimated albuterol dose required to achieve 50 % of the fitted maximal value of the pharmacodynamic effect above baseline, and change in response as a function of dose, with emphasis on 1 and 2 actuations.

Development of in vivo bioequivalence methodology for dermatologic corticosteroids based on pharmacodynamic modeling.

Background: Dermatologic corticosteroid products produce skin blanching that is related to clinical potency and dose. (For application of the vasoconstrictor assay to bioavailability and bioequivalence assessment, dose is defined in terms of duration of treatment exposure [dose duration], so the terms dose and dose duration have been used interchangeably). The vasoconstrictor assay is the method of choice to assess dermatologic corticosteroid products bioequivalence if dose-response is validated.

Solubility of calcium oxalate in 1-alkanols and ethanol--water mixtures.

Solubility profiles for calcium oxalate were determined in pure 1-alkanols and ethanol--water mixtures at 20 degrees. The magnitude of solubility in the aliphatic alcohols was highest in methanol and decreased in a nonlinear fashion as the dielectric constant decreased, going to n-decanol. In ethanol--water mixtures, the solubility increased nonlinearly with water content or increasing dielectric constants.