FDA Preliminary Concept Paper Sterile Drug Products Produced by Aseptic Processing This presentation summarizes the content of PDA’s official position, presented to the PSAC in the report “PDA Comments Prepared for the Pharmaceutical Science Advisory Committee Meeting on October 22, 2002 on FDA Preliminary Concept Paper Sterile Drug Products Produced by Aseptic Processing”

Introduction  Positives:  Revision of the aseptic processing guidance issued by FDA in 1987 is overdue  Supports advantages of isolators relative to conventional, manned aseptic processing  Provides the framework for open dialog with the agency  At this stage, is not intended for use by the field

Introduction  PDA’s Concerns Grouped into Categories  Best Practices and cGMP  Technical Issues/Unconventional Terminology  Scope  Harmonization

Best Practices and cGMP  Departures from Current Industry Practices  Media fills conducted in ‘worst case’ environmental conditions  Environmental sampling of critical surfaces that are terminally sterilized  Isolators do not normally employ unidirectional airflows or redundant HEPA filters  There is no evidence to support that isolators must be housed in classified areas

Technical Issues / Unconventional Terminology  References ISO for numerical values for particles per cubic foot, but does not agree with values published therein  Indicates that membrane filters are used for hot air sterilizer vents, when HEPA filters are used  States that container-closure systems that permit penetration of air are unsuitable, when many elastomeric closures permit transmission of air/gas  Defines alert/action limits, text refers to (alert/action) levels for environmental, but does not define the term

Scope (Omissions)  Does not clarify how many units should be filled or allowed positive for a media fill  Little guidance is provided outside of the APA critical processing zone  No guidance on CIP/SIP  Does not provide a systematic, rational approach to aseptic process control and risk assessment

Scope (Topics that should be Excluded)  Terminal Sterilization  Endotoxin Control  Equipment Qualification  Sterility Testing

Harmonization  The ISO convention for the use ‘should’ and ‘shall’ would greatly clarify requirements from guidance. Currently ‘should’ is used exclusively and clearly some points are requirements  Room classifications should be according to ISO standards instead of the obsolete FS209E  Non-viable particulate values could be harmonized with EU for sample size and limits

Recommendations  Concept paper reviewed by ad hoc committee composed of FDA headquarters, ORA and industry (or PQRI subcommittee) to resolve issues  Committee submits revised document to FDA for review and approval  Final draft issued for public comment  Revised aseptic processing guidance issued