This is a ready-to-use readiness checklist to run before a media fill so the simulation is set up to be a genuine test, not an accidental easy pass. Work each item, mark it Ready, Gap, or N/A, and resolve every Gap before execution. Replace every <<FILL: ...>> placeholder, set your document numbers, and route it through document control. A filled specimen follows. This is general guidance to adapt and verify, not legal or regulatory advice; confirm each cited regulation against the current source before you rely on it.
Document control header
| Field | Entry |
|---|---|
| Checklist title | Media Fill (APS) Pre-Execution Readiness |
| Document number | <<FILL: CHK-ID>> |
| Version | <<FILL>> |
| Line / process | <<FILL>> |
| Protocol reference | <<FILL: PROT-ID>> |
| Planned run date | <<FILL>> |
1. Protocol and design
| # | Item | Ready / Gap / N/A | Note |
|---|---|---|---|
| 1 | Protocol approved (all signatures) before execution | ||
| 2 | Purpose defined (initial run x of 3 / requalification / directed change) | ||
| 3 | Worst-case conditions set: line speed, campaign duration, operator count, shift change | ||
| 4 | Intervention matrix enumerates every permitted inherent and corrective intervention | ||
| 5 | Simulated intervention counts meet or exceed worst-case routine frequency | ||
| 6 | Interventions distributed across the run, not clustered | ||
| 7 | Fill quantity sufficient for the process (production-representative, statistically defensible) |
2. Medium and materials
| # | Item | Ready / Gap / N/A | Note |
|---|---|---|---|
| 8 | Medium selected, sterile-filterable, growth-promoting type (<<FILL: TSB>>) | ||
| 9 | Growth promotion plan defined (compendial organisms plus in-house isolates, <=100 CFU) | ||
| 10 | Container-closure format and components correct and sterile | ||
| 11 | Filter and integrity-test approach defined for the run |
3. Line, personnel, and facility
| # | Item | Ready / Gap / N/A | Note |
|---|---|---|---|
| 12 | Line qualified and set up as for production | ||
| 13 | Grade A protection confirmed (isolator / RABS integrity, airflow, current smoke study) | ||
| 14 | Every operator gowning-qualified and media-fill-current | ||
| 15 | Actual production crew running the fill (not a hand-picked easy crew) |
4. Monitoring and incubation
| # | Item | Ready / Gap / N/A | Note |
|---|---|---|---|
| 16 | Concurrent EM plan in place (viable air, settle, contact, glove; non-viable particle) | ||
| 17 | Incubation scheme defined (<<FILL: 7d 20-25 C then 7d 30-35 C, 14 days>>) | ||
| 18 | Incubator capacity and qualification sufficient for all units | ||
| 19 | Read schedule and reader assignment defined |
5. Reconciliation and handling
| # | Item | Ready / Gap / N/A | Note |
|---|---|---|---|
| 20 | Unit reconciliation method defined (filled, rejected, incubated, read all accounted for) | ||
| 21 | Rules for cosmetic/defective rejects documented (no turbid unit reclassified as reject) | ||
| 22 | Deviation and positive-unit investigation path known to the crew | ||
| 23 | Video recording available if the line is monitored |
6. Overall readiness
| Field | Entry |
|---|---|
| Total Gaps open | <<FILL>> |
| All Gaps resolved before execution | Yes / No |
| Cleared to execute | Yes / No |
Do not execute with an open Gap on any protocol, medium, line-protection, or personnel-currency item.
7. References
FDA Guidance, Sterile Drug Products Produced by Aseptic Processing (2004). EU GMP Annex 1, Manufacture of Sterile Medicinal Products (effective 25 August 2023). USP General Chapters on microbiological control and monitoring of aseptic processing environments.
Confirm the current version and clause numbers of each reference before issue.
8. Signoff
| Role | Name | Signature | Date |
|---|---|---|---|
| Prepared by (Process) | <<FILL>> | ||
| Microbiology / QC | <<FILL>> | ||
| QA cleared to execute | <<FILL>> |
Filled specimen
Illustrative excerpt for a semi-annual requalification.
| # | Item | Ready / Gap / N/A | Note |
|---|---|---|---|
| 1 | Protocol approved before execution | Ready | PROT-APS-14 v3 signed 18 Aug |
| 3 | Worst-case conditions set | Ready | 8 h campaign, one shift change, max operators |
| 5 | Intervention counts meet worst-case | Gap | Jam-clear simulated 2x, routine worst case is 3x; corrected to 3x before run |
| 13 | Grade A protection confirmed | Ready | RABS integrity checked, smoke study current |
| 14 | Operators gowning-qualified and media-fill-current | Gap | One operator’s media-fill currency lapsed; swapped for a current operator |
Two gaps were found and resolved before the run: the jam-clear frequency was raised to the true worst case, and a lapsed operator was replaced. Catching those before execution is the point; both would have weakened the simulation or invalidated an operator’s participation if found afterward.
Common inspection findings this checklist prevents
- A media fill run “clean” with the fewest interventions and a hand-picked crew.
- An operator with lapsed gowning or media-fill currency working the simulation.
- Interventions simulated below the true worst-case production frequency.
- Growth promotion not planned, so a “no growth” result would be uninterpretable.
- Reconciliation method undefined, so units cannot be fully accounted for afterward.
How to adapt this checklist
- Set your document number and link the protocol.
- Fill the medium type, incubation scheme, and limits to match your program.
- Keep the worst-case and intervention-frequency items strict; they are what make the fill a real test.
- Wire items 14 and 15 to your actual gowning and media-fill currency records.
- Confirm every regulation in section 7 against the current published version before issue.