Acceptance Limits for Api
Acceptance limits for APIs
This article reviews the history of Cleaning Validation Acceptance Limits for Active Pharmaceutical Ingredients (APIs) and identifies where the currently used industry limits came from.
Cleaning Validation for the 21st Century: Acceptance Limits for Active Pharmaceutical Ingredients (APIs): Part I by Andy Walsh
P
Introduction
art I of this article reviews the history of Cleaning Validation Acceptance Limits for Active Pharmaceutical Ingredients (APIs) and identifies the origins of currently used industry limits. The current approaches to setting acceptance limits will be analyzed and some of the problems and weaknesses of these approaches will be discussed.
Early Ideas on Cleaning Validation Acceptance Limits
In the early 1980s, most companies were just beginning to grapple with the FDA’s shift to validation. This activity was of course more focused on Process Validation, but some companies took a wider view and began looking at cleaning processes as well. In 1984, Samuel Harder published an article, “The Validation of Cleaning Procedures,” and discussed many aspects of what he saw would be required to validate a cleaning process.1 Most, if not all, of the ideas he expressed can still be seen in practice in cleaning validation today. Concerning the setting of Acceptance Limits, Harder wrote that limits “...must be practical and achievable by a reasonable cleaning procedure... ...must be verifiable by analytical methodology existing in the company... ...and must be safe and acceptable and in line with residual limits set for various substances in foods.” (Note: The phrase “Practical, Achievable, and 74 PHARMACEUTICAL ENGINEERING July/August 2011
Verifiable” began to appear in many guidelines and literature subsequently.) Harder goes on to reference 21 CFR 193 “Tolerances for Pesticides in Food Administered by the Environmental Protection Agency” and showed a table of limits for a variety of hazardous pesticides and
This article reviews the history of Cleaning Validation Acceptance Limits for Active Pharmaceutical Ingredients (APIs) and identifies where the currently used industry limits came from.
Cleaning Validation for the 21st Century: Acceptance Limits for Active Pharmaceutical Ingredients (APIs): Part I by Andy Walsh
P
Introduction
art I of this article reviews the history of Cleaning Validation Acceptance Limits for Active Pharmaceutical Ingredients (APIs) and identifies the origins of currently used industry limits. The current approaches to setting acceptance limits will be analyzed and some of the problems and weaknesses of these approaches will be discussed.
Early Ideas on Cleaning Validation Acceptance Limits
In the early 1980s, most companies were just beginning to grapple with the FDA’s shift to validation. This activity was of course more focused on Process Validation, but some companies took a wider view and began looking at cleaning processes as well. In 1984, Samuel Harder published an article, “The Validation of Cleaning Procedures,” and discussed many aspects of what he saw would be required to validate a cleaning process.1 Most, if not all, of the ideas he expressed can still be seen in practice in cleaning validation today. Concerning the setting of Acceptance Limits, Harder wrote that limits “...must be practical and achievable by a reasonable cleaning procedure... ...must be verifiable by analytical methodology existing in the company... ...and must be safe and acceptable and in line with residual limits set for various substances in foods.” (Note: The phrase “Practical, Achievable, and 74 PHARMACEUTICAL ENGINEERING July/August 2011
Verifiable” began to appear in many guidelines and literature subsequently.) Harder goes on to reference 21 CFR 193 “Tolerances for Pesticides in Food Administered by the Environmental Protection Agency” and showed a table of limits for a variety of hazardous pesticides and