This is a preview of "PDA TR 62-2013". Click here to purchase the full version from the ANSI store.

Technical Report No. 62

Recommended Practices for
Manual Aseptic Processes

Bethesda Towers
4350 East West Highway
Suite 200
Bethesda, MD 20814 USA
Tel: 1 (301) 656-5900
This is a preview of "PDA TR 62-2013". Click here to purchase the full version from the ANSI store.

PDA Recommended Practices for Manual Aseptic Processes Technical Report Team
Authors

Olivia A. Henderson, Ph.D., Biogen Idec (co-Chair) John M. Lindsay, Aseptic Solutions, Inc.

Carol Lampe, J.M. Hansen & Associates, Inc. (co-Chair) Jeanne E. Moldenhauer, Excellent Pharma Consulting

James Agalloco, Agalloco and Associates, Inc. Robert J. Nolly, University of Tennessee,
Pharmaceutical Sciences
Edward A. Fitzgerald, Fitzgerald Consulting
Laura A. Thoma, Pharm. D., University of Tennessee,
Thomas Genova, Ph.D., Johnson & Johnson Pharmaceutical Sciences
John W. Levchuk, Food and Drug Administration
(retired)

Contributors

Mark Birse, Medicines and Healthcare Products Ian Jackson, Medicines and Healthcare Products
Regulatory Agency Regulatory Agency
Mark Ellison, Medicines and Healthcare Products Terry E. Munson, PAREXEL Consultants
Regulatory Agency
Michelle Rowson, Medicines and Healthcare Products
Andrew Hopkins, Medicines and Healthcare Products Regulatory Agency
Regulatory Agency

Disclaimer: The content and views expressed in this Technical Report are the result of a consensus achieved by the
Task Force and are not necessarily views of the organizations they represent.
This is a preview of "PDA TR 62-2013". Click here to purchase the full version from the ANSI store.

Recommended Practices for

Manual Aseptic Processes
Technical Report No. 62

ISBN: 978-0-939459-57-5
© 2013 Parenteral Drug Association, Inc.
All rights reserved.

Bethesda Towers
4350 East West Highway
Suite 200
Bethesda, MD 20814 USA
Tel: 1 (301) 656-5900
Fax: 1 (301) 986-0296
E-mail: info@pda.org
Web site: www.pda.org
This is a preview of "PDA TR 62-2013". Click here to purchase the full version from the ANSI store.

Table of Contents

1.0 INTRODUCTION...................................................1 8.1.1 Compositing/Assembly Activities............ 16

8.1.2 Formulation/Compounding Activities....... 16
2.0 GLOSSARY OF TERMS.........................................3 8.1.3 Filling/Subdivision Activities
3.0 BUILDINGS AND FACILITIES...............................6 (Including Lyophilization if Needed) ........ 16
8.1.4 Manual Manipulation Steps Performed in
4.0 OPERATIONAL PERSONNEL TRAINING AND Conjunction with Other Processes .......... 16
QUALIFICATION....................................................8 8.2 Media Sterilization ....................................... 17
4.1 Personnel Training and Qualification............... 8 8.3 Frequency and Number of APS Runs ........... 17
4.2 Gowning Qualification .................................... 8 8.3.1 Duration of Runs ..................................... 17
4.3 Risk Management........................................... 8 8.3.2 Size of Runs............................................. 17
4.4 Aseptic Handling Challenges.......................... 9 8.4 Observation of the Process Simulation......... 17
8.5 Media Fill Volume......................................... 18
5.0 EQUIPMENT, COMPONENTS 8.6 Anaerobes/Inert Gassing ............................. 18
AND CONTAINER/CLOSURE...............................10 8.7 Environmental Monitoring............................. 18
6.0 PROCESS TIME LIMITATIONS............................11 8.8 Execution of the Simulation.......................... 18
8.9 Pre-Incubation Inspection............................. 18
7.0 DESIGN OF MANUAL ASEPTIC PROCESSES.....12 8.10 Incubation Time/Temperature ...................... 19
7.1 Manual Aseptic Process Design Principles in 8.11 Post-Incubation Inspection .......................... 19
Unidirectional Air Flow Hoods...................... 12 8.12 Growth Promotion........................................ 19
7.2 Manual Aseptic Process Design Principles 8.13 Interpretation of Test Results ....................... 19
in Isolators and RABS................................... 14 9.0 CONCLUSION......................................................21
8.0 EVALUATION OF MANUAL ASEPTIC
PROCESSING–PROCESS SIMULATION..............16 10.0 REFERENCES....................................................22
8.1 Simulation Design ........................................ 16 11.0 ADDITIONAL READING....................................23

TABLE INDEX

Table 3.0-1 Cleanroom Standards Airborne Particulate Limits��������������������������������������������������������������������������������6

This is a preview of "PDA TR 62-2013". Click here to purchase the full version from the ANSI store.

1.0 Introduction

The purpose of this technical report is to outline methods and approaches for control and evalua-
tion of aseptic processing operations for drug products/medicinal products which use all or partially
manual procedures. The goal of aseptic processing is to prevent the contamination of sterile materials
during their processing. The goal of evaluating any aseptic process is to demonstrate that aseptic pro-
cessing can be achieved and maintained successfully under the specified operational configuration,
activities, and conditions. These goals are the same for manual or automated aseptic operations, and
for small-scale or large-scale operations.

Manual aseptic processing (MAP) operations differ from automated operations in several ways. These
differences pose unique operational and evaluation challenges not generally encountered with auto-
mated operations. These challenges must be considered thoroughly when designing the evaluation
procedure or protocol for the MAP operation. MAP involves a human operator performing, at a mini-
mum, the container and/or closure movements. Some semi-automated equipment may be used, but
the process is not fully automated. For this reason MAP relies heavily on individual operator’s basic
understanding of microbiology proficiency where personnel must be individually qualified.

The greatest source of microbial contamination during MAP is generally recognized to be the op-
erational personnel and their activities. Aseptic processes that rely on manual operations are inher-
ently subject to performance or procedural drift over time. Furthermore, reproducible human perfor-
mance cannot be assumed, especially where there are significant time gaps between aseptic processing
events. The likelihood of human performance deviations or failures is linked to:
• Complex aseptic processing tasks
• The continuous span of time during which an operator carries out repetitive aseptic activities
• The expected rate of activity
• Change in personnel

This technical report has value for hospital and formulation pharmacies where manual aseptic pro-
cessing may occur. The guidance provided in this report may be applicable to various operations,
including: vaccine preparation, cell culture, gene therapy, IND/IMP manufacturing, clinical and com-
mercial manufacturing, and pharmacy formulation and dispensing. When manual aseptic processing
of sterile dosage forms is required, special consideration must be given to sterility and verification of
processing accuracy, as the administration of these products into the vascular and nervous system of
human subjects poses the greatest risk of harm. As applicable, the 2004 FDA guidance on aseptic pro-
cessing, EU GMP–Annex 1, Ph Eur 5. 1. 1, and USP Chapters <797> and <823> provide procedures
and the requirements for (1-5):
• Training of personnel involved in sterile preparation processes
• Environmental control and monitoring requirements
• Specifications for sterile and non-sterile ingredients and components
• Release criteria for sterility and pyrogen testing

Compliance with these requirements is paramount to ensure the safety of human recipient.

Some of these processes require aseptic steps subsequent to sterilization but prior to filling, such as
volume or pH adjustments, which present their own contamination risks.

This report is not intended to address the brief, relatively infrequent, human interventions into an
otherwise automated filling process. Examples include reach-ins to remove a toppled vial from the
filling line or to obtain a container for a fill-weight check, aseptic connections made during set-up, cor-
rective activities during line stoppages, and so on. Operator activities and interventions of this nature

Technical Report No. 62 © 2013 Parenteral Drug Association, Inc. 1