Process Simulation for Aseptically Filled Products
A widely-used PDA Technical Report providing detailed industry guidance on designing, executing, and evaluating aseptic process simulations (media fills). TR 22 operationalises the media-fill expectations of EU GMP Annex 1 and FDA aseptic guidance.
What this does not cover
stated in the document's own scope- Is voluntary industry guidance, not a regulation; the binding requirement is EU GMP Annex 1 / FDA aseptic-processing guidance.
- Covers aseptic process simulation for filled products, not terminal-sterilisation validation, which follows its own sterilisation standards.
- Addresses the media-fill study, not the full contamination-control strategy or the environmental-monitoring programme, which are broader Annex 1 topics.
Always verify against the current published text before relying on it for a submission or inspection.
Overview
PDA Technical Report No. 22, Process Simulation for Aseptically Filled Products, is the industry’s detailed reference for designing, executing, and evaluating aseptic process simulations — the "media fills" used to demonstrate that an aseptic filling process can reliably exclude microbial contamination. It addresses how to represent worst-case conditions and interventions, how many units to fill, how long the simulation should run, how to incubate and read the filled units, how to set and interpret acceptance criteria, and how to investigate and act on any contaminated units. It translates high-level regulatory expectations for aseptic processing into practical study design.
Scope & applicability
Sterile manufacturers running aseptic process simulations. An industry best-practice reference — used to implement Annex 1 / FDA aseptic expectations, not a regulation.
Legal basis & how it acquires force
TR 22 is a Technical Report published by the Parenteral Drug Association (PDA); it is voluntary industry best-practice guidance and carries no independent legal force. The binding requirements it operationalises sit in the aseptic-processing rules of the relevant GMP framework — EU GMP Annex 1 and the FDA Guidance for Industry on sterile drug products produced by aseptic processing. A manufacturer’s obligation runs to those instruments; TR 22 is a recognised, detailed way to meet the media-fill expectations they set.
Document structure
| Part | Covers |
|---|---|
| Purpose and programme design | Objectives of process simulation and the overall media-fill programme, including initial qualification and periodic re-qualification |
| Simulation design | Representing the process, worst-case conditions, interventions, container/closure, and line speed |
| Number of units and duration | Fill quantities and run length needed to represent routine production |
| Incubation and inspection | Growth media selection, incubation conditions, and reading of filled units |
| Acceptance criteria and interpretation | Setting acceptance limits and interpreting results |
| Investigation and response | Investigating contaminated units and the actions that follow a failed simulation |
Key requirements
- Design media fills that challenge the aseptic process realistically
- Define run size, incubation, and acceptance criteria
- Investigate any positive units thoroughly
Implementation tips
- Align TR 22 media-fill design with the intervention list in your Annex 1 contamination control strategy
Revision notes
PDA Technical Reports are periodically revised; align the version with the current Annex 1 (2022) expectations.
Where this control fails
live FDA enforcementLive FDA recalls SPEQ maps to this standard’s topics — a SPEQ interpretation, not an FDA classification.
International alignment
TR 22 operationalises the media-fill expectations of EU GMP Annex 1 (Manufacture of Sterile Medicinal Products) and the FDA aseptic-processing guidance, and it is consistent with the environmental-monitoring and contamination-control principles that surround aseptic manufacture. It complements — rather than substitutes for — those primary sources, and works alongside compendial microbiology chapters and the Contamination Control Strategy expected by Annex 1.
PDA TR No. 22: frequently asked questions
Quick answers to common questions about PDA TR No. 22.
What is a media fill, as described in PDA TR 22?
A media fill (aseptic process simulation) substitutes a sterile growth medium for product and runs the filling process under representative, often worst-case, conditions to demonstrate the process can exclude microbial contamination. TR 22 details how to design, run, and evaluate one.
Is PDA TR 22 mandatory?
No. It is a voluntary PDA Technical Report — industry best practice. The mandatory requirements it helps satisfy are EU GMP Annex 1 and the FDA aseptic-processing guidance.
What regulatory expectations does TR 22 support?
It operationalises the aseptic process-simulation (media-fill) expectations of EU GMP Annex 1 and the FDA Guidance for Industry on sterile drug products produced by aseptic processing.
This standard in practice
Recall domain is a SPEQ mapping of this standard’s topics, not an FDA classification.