TR70 Toc
TR70 Toc
70
Fundamentals of Cleaning and Disinfection
Programs for Aseptic Manufacturing Facilities
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PDA Fundamentals of Cleaning and Disinfection Programs for Aseptic Manufacturing Facilities
Technical Report Team
Authors
Arthur Vellutato Jr., Veltek Associates, Inc. (Chair) Peter Koger, Veltek Associates, Inc.
Cindy Adams, Northampton Community College Alison Livsey, Contec, Inc.
Barbara M. Andon, Merck and Company, Inc. Carol Molinaro, Sanofi Pasteur
Michael B. Dolan, Merck and Company, Inc. James N. Polarine Jr., Steris Corporation
Pamela D. Deschenes, Veltek Associates, Inc. Dona Reber, Pfizer, Inc.
Roger E. Deschenes, Cubist Pharmaceuticals Mike Sarli, Steris Corporation
Jayne Dovin, Sanofi Pasteur Michael A. Szymanski, GlaxoSmithKline Biologicals
Barry A. Friedman, Ph.D., Consultant Steve Trombetta, Hospira, Inc.
Jill K. Giulianelli, West-Ward Pharmaceuticals Brent Watkins, Veltek Associates, Inc.
PDA would like to recognize Glenn Wright of the PDA Science Advisory Board for supporting this technical report
as the SAB subject matter advisor.
DISCLAIMER: The content and views expressed in this Technical Report are the result of a consensus achieved by the
authorizing Task Force and are not necessarily the views of the organizations they represent.
www.pda.org/bookstore
Fundamentals of Cleaning
and Disinfection Programs
for Aseptic Manufacturing
Facilities
Technical Report No. 70
ISBN: 978-0-939459-77-3
© 2015 Parenteral Drug Association, Inc.
All rights reserved.
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Tel: 1 (301) 656-5900
Fax: 1 (301) 986-0296
E-mail: [email protected]
Web site: www.pda.org
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Table of Contents
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14.8 Aspects of a Disinfection Program���������������� 43 20.0 APPENDIX IV: OVERVIEW OF THE EU
14.9 Assessment of Understanding BIOCIDAL REGULATIONS���������������������������������53
and Qualification������������������������������������������� 44
21.0 APPENDIX V: EPA-RELATED SAFETY LABELING
15.0 CONDUCTING INVESTIGATIONS RELATED TO INFORMATION������������������������������������������������������� 54
CLEANING AND DISINFECTION�����������������������45
22.0 APPENDIX VI: AOAC PROTOCOL TESTING
16.0 CONCLUSION����������������������������������������������������47 FOR DISINFECTANT REGISTRATION����������������57
Table 5.2.1-1 Commonly Used Figure 10.0-1 Example Risk-Based Approach for
Neutralization Agents ���������������������� 11 Selection of Routine Cleaning and
Table 5.2.2-1 Recommended Acceptance Criteria�� 14 Disinfection Frequencies for Classified
Manufacturing Areas������������������������ 37
Figure 7.0-1 Considerations to Maintain
Low Levels of Contamination������������ 17 Table 21.0-1 Toxicity Categories��������������������������� 54
Table 9.1-1 Area Classifications: Cleanroom Table 21.0-2 Precautionary Statements
Standards–Airborne Particulate Limits�� 25 by Route of Entry������������������������������ 55
Table 9.1-2 Environmental Monitoring Table 23.0-1 Summary of EN Test Criteria for
Requirements/Guidance�������������������� 26 Registration for Established Claims��� 60
Table 9.4.3-1 Examples of Surfaces����������������������� 32
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1.0 Introduction
While sterile product manufacturing has the most stringent application, these concepts can also be
used to design a program for the manufacture of nonsterile products. To ensure a consistently con-
trolled production environment, a comprehensive cleaning and disinfection program together with a
contamination control program should be supported by the following:
• Sound facility design and maintenance
• Established documentation systems
• Validated/qualified disinfection procedures
• Reliable process controls
• Good housekeeping practices
• Effective area traffic and access controls
• Effective training, certification/qualification, and evaluation programs
• Quality assurance of materials and equipment
• Risk management mitigation
The purpose of the cleaning and disinfection program is not only to control microbial contamination,
but also to serve as a corrective action for the loss of control for viable excursions contamination.
While the destruction of viable cells are an integral part of the cleaning and disinfection program, the
use of disinfection as a singular focus without efforts to control contamination from entering the area
is without technical merit. Environmental monitoring (EM) evaluates the efficacy of controls on the
manufacturing environment. It is through control of bioburden levels entering the area, along with
cleaning and disinfection, that acceptable viable control of the manufacturing or appropriate testing
environment is achieved. This technical report provides comprehensive information and suggested
best practices as well as appropriate references to support such guidance.
For individuals wanting a historical perspective of disinfection, a summary can be found in Appendix I
(Section 17.0).
The technical report team consisted of members who are cleaning and disinfection experts from vari-
ous global pharmaceutical and biopharmaceutical companies, academia, and companies that manu-
facture agents used in disinfection.
1.1 Purpose
The purpose of this document is to identify systematic elements that are essential to assuring an
appropriate and compliant cleaning and disinfection program for aseptic and bioburden controlled
manufacturing facilities and classified environments.
1.2 Scope
The document covers cleaning and disinfection within controlled and noncontrolled environments
using chemical agents that reduce or destroy microorganisms. The document provides guidance for
non-product-contact surface cleaning and disinfection. This document is not intended to fully address
product-contact surface cleaning from a clean-in-place (CIP) or clean-out-of-place (COP) system which
is specifically addressed in PDA’s Technical Report No. 29 (Revised 2012): Points to Consider for Cleaning Vali-
dation and Technical Report No. 49: Points to Consider for Biotechnology Cleaning Validation (1,2).
This document should be considered as technical guidance; it is not intended to establish any manda-
tory or implied standard.
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Technical Report No. 70 © 2015 Parenteral Drug Association, Inc. 1