White Paper: PAT And TOC Analysis With An Onboard Automated Standards Introduction System (OASIS™)

By Steven Smith, Hach Ultra Analytics

Historically, product quality in the pharmaceutical industry was ensured through quality inspections at various stages in the procurement, production and packaging processes. Because pharmaceutical processes are defined and prescribed out of the product development process, and are carefully crafted to produce the desired pharmacological outcome, little room has existed to apply engineering principles to improve the process, and establish real-time quality control. This converts the production process to more art than science with the goal of simply reproducing the desired outcome, with rejections through quality inspection.

PAT is intended to support innovation and efficiency in pharmaceutical development, manufacturing, and quality assurance. The PAT framework is founded on process understanding to facilitate innovation and risk-based regulatory decisions by industry and the US Food and Drug Administration(FDA).

In accordance with the FDA, the United States Pharmacopoeia (USP 31) is the accepted guide (compendia) for producing pharmaceutical products in the United States. The USP specifies standards of quality, purity, packaging, and labelling for many pharmaceutical products and the ingredients used in the manufacture of these products. The guide specifies two grades of bulk ingredient water used in the preparation of compendia dosage forms, USP Purified Water (PW) and USP Water for Injection (WFI). The adoption of USP <643> in 1998 defined the usage and measurement of TOC in USP pharmaceutical waters. The USP Total Organic/Oxidizable Carbon (TOC) standards have helped in the international harmonization of TOC monitoring for all pharmaceutical waters, including the adoption of European Pharmacopoeia (EP) Method 2.2.444 and methods in Japan Pharmacopeia XV (2.59)