Ester Lovsin Barle¹*, Andrew Walsh²
*Corresponding Author
1. Global HSE& BCM, Novartis, Basel, Switzerland
2. Center for Pharmaceutical Cleaning Innovation, Hillsborough, USA

Abstract

The terms highly hazardous, highly active and highly potent are often used in mixed or inconsistent contexts regarding good manufacturing practice and worker safety. This article provides an overview of definitions and criteria used for classifying active pharmaceutical ingredients (APIs) and the use of these terms for identification of risks in cleaning validation. While competent toxicological evaluation is required to identify and characterize the health hazards for each drug substance and then calculate a health based exposure limit, further steps in risk assessment for cross-contamination include batch size, maximal daily dose of subsequent products, equipment surface areas, cleaning process parameters and process capability. Risks presented by drug substances cannot be managed by simple classification into highly potent and highly hazardous categories.

INTRODUCTION

Although the terms hazard and potency are thought to be well understood, they are often mixed or used in inconsistent contexts. It is acknowledged that the hazards, as qualitative aspects are much easier to assess, communicate and perceive by the general public, but hazards alone are insufficient to assess the risks for populations and define the risk mitigation strategies that should follow. Scales that include the qualitative and quantitative aspects of hazards and potency that can be used in setting priorities of concern have been proposed for decades. One such example is ranking of possible carcinogenic hazards by an index that relates to potency of each carcinogen in rodents to the exposure in humans (Ames, 1987). In this article we have looked at the common definitions of human health hazards and potency of substances, and the possibility for the consistent use of these terms in risk assessment for cross-contamination of pharmaceuticals in multipurpose manufacturing facilities.

HIGHLY HAZARDOUS, TOXIC, POTENT AND ACTIVE

Human health hazard assessment is defined as “evaluation of the inf ...