This is a ready-to-use register that links every stage of a viral vector manufacturing chain, plasmid, cell bank vial, producer cell expansion, vector harvest, purification pool, fill finish, back to specific parent lots and their disposition. Replace every <<FILL: ...>> placeholder, keep one row per lot per stage, and maintain it under document control in a system with an audit trail rather than an uncontrolled spreadsheet. A filled specimen follows. Verify each cited regulation against the current source before you rely on it. This is general guidance to adapt, not legal or regulatory advice.
Register header
| Field | Entry |
|---|---|
| Register number | <<FILL: ID>> |
| Program / product | <<FILL>> |
| Vector system | <<FILL: e.g. AAV serotype, lentiviral, retroviral>> |
| Owner | <<FILL: role, e.g. MSAT / process owner>> |
| Last review / by | <<FILL>> |
Field definitions
| Field | Format | Required | Notes |
|---|---|---|---|
| Stage | Plasmid / cell bank / expansion / harvest / purification / fill finish / drug product | Yes | One row per lot at each stage |
| Lot ID | Unique lot number | Yes | Assigned at the point the lot is created, never after the fact |
| Parent lot(s) | Unique lot number(s) | Yes | Every source lot consumed to create this lot |
| Quantity / proportion from each parent | Amount or percent | Yes for pooling or splitting events | Captures exactly how much of each parent went into this lot |
| Disposition of parent lot(s) at time of use | Released / Qualified / In process, with basis | Yes | The status of the parent when it was actually consumed, not its current status |
| Date / time of event | Timestamp | Yes | Contemporaneous with the pooling, splitting, or consumption event |
| Recorded by | Name / ID | Yes | Attributable to the person present at the event |
| Reference batch record | Document / record ID | Yes | Links the genealogy entry back to its source batch record |
The genealogy record
| Stage | Lot ID | Parent lot(s) | Quantity / proportion | Parent disposition at use | Date/time | Recorded by | Reference batch record |
|---|---|---|---|---|---|---|---|
<<FILL>> | <<FILL>> | <<FILL>> | <<FILL>> | <<FILL>> | <<FILL>> | <<FILL>> | <<FILL>> |
<<FILL>> | <<FILL>> | <<FILL>> | <<FILL>> | <<FILL>> | <<FILL>> | <<FILL>> | <<FILL>> |
Add one row per lot at every stage. A single drug product lot will typically require multiple rows to fully reconstruct its upstream chain, especially at pooling stages where several harvest or purification lots combine.
How to handle pooling and splitting events
Viral vector genealogy is frequently many to one: a purification pool combining several harvests, or a fill finish lot combining several purification lots. At every such event, record each contributing parent lot separately with its own quantity or proportion, never a generic entry such as “prior harvests” or “combined lots.” Reconcile the total quantity consumed against the total quantity available from each parent lot; an unexplained gap between what was available and what was used is a signal to investigate before the resulting lot is dispositioned, not after.
Acceptance criteria
- Every drug product lot traces to specific, disposition-confirmed lots at every upstream stage, with no orphan link and no unexplained substitution.
- Every pooling or splitting event names its exact source lots and the quantity or proportion contributed by each.
- Entries are made contemporaneously with the event they record, attributable to the person present, not reconstructed later from memory or from disparate logs.
- The register is reviewed as part of batch disposition for the final drug product lot, confirming the complete chain, not only the immediate parent.
- Quantity reconciliation at each stage is documented, with any gap investigated and closed before the resulting lot is used further.
References
21 CFR 211.188 and 211.194 (batch production and laboratory records, completeness and traceability). 21 CFR Part 11 (electronic records; audit trail where the register is maintained electronically). ICH Q5E (comparability, where genealogy underpins the scope of a comparability exercise). FDA Data Integrity and Compliance With Drug CGMP Q&A (final, Dec 2018), for the attributability and completeness expectations applied here.
Confirm each reference against the current source before issue.
Filled specimen
Illustrative genealogy for one drug product lot of an AAV-based gene therapy. Replace with your own lot numbers, dates, and personnel.
| Stage | Lot ID | Parent lot(s) | Quantity / proportion | Parent disposition at use | Date/time | Recorded by | Reference batch record |
|---|---|---|---|---|---|---|---|
| Plasmid | PLM-2026-0087 | Bacterial MCB vial BC-014, WCB vial BC-014-W3 | 1 vial WCB-014-W3 | Released | 2026-03-02 08:10 | <<FILL: name>> | BR-PLM-0087 |
| Producer cell bank vial | PCB-014, passage 6 | MCB vial PC-002 | 1 vial | Qualified | 2026-03-04 09:05 | <<FILL: name>> | BR-PCB-014-P6 |
| Producer cell expansion | EXP-2026-0231 | PCB-014 (p6) | Full vial, two vessels | Confirmed viable, mycoplasma negative | 2026-03-06 07:40 | <<FILL: name>> | BR-EXP-0231 |
| Vector harvest | HRV-2026-0512, HRV-2026-0513 | EXP-2026-0231 (vessel 1, vessel 2) | 100 percent of each vessel | Both released to pool | 2026-03-10 15:20 | <<FILL: name>> | BR-HRV-0512, BR-HRV-0513 |
| Purification pool | PUR-2026-0198 | HRV-2026-0512, HRV-2026-0513 | 55 percent HRV-0512, 45 percent HRV-0513 | Both released | 2026-03-12 10:00 | <<FILL: name>> | BR-PUR-0198 |
| Fill finish / drug product | DP-2026-118 | PUR-2026-0198 | 100 percent | Released | 2026-03-15 13:45 | <<FILL: name>> | BR-DP-0118 |
Reading this specimen backward from DP-2026-118 answers, without contacting anyone, exactly which two harvest lots, in what proportion, and which producer cell expansion, plasmid lot, and cell bank vial ultimately contributed to this drug product lot. That is the reconstruction test a reviewer will apply.
Common inspection findings this register prevents
- A drug product lot genealogy that exists but has never been walked end to end before an inspector asks to see it done live.
- A pooled harvest lot’s individual contributing sub-lots recorded only as a summary total, so an investigation into one contaminated sub-lot cannot determine which finished lots it reached.
- Cell bank passage number known informally but not captured contemporaneously in the record consumers actually use.
- Genealogy maintained in a personal file with no audit trail, discovered to be inconsistent with the underlying batch records only during an investigation.
How to adapt this register
- Map your own manufacturing chain stage by stage before building the register; a shorter or longer chain than the specimen is normal and the register should mirror your actual process, not this example.
- Decide where the register lives, a LIMS, MES, or equivalent system with an audit trail is strongly preferred over a spreadsheet; if a spreadsheet is used, control it as a GxP record with version control, access control, and periodic review.
- Assign a named genealogy owner accountable for the complete chain, not only their own stage.
- Build the reconciliation step (quantity in versus quantity consumed versus quantity out) into the same review that disposition each lot, not as a separate exercise done later.
- Confirm every reference against the current source before issue.