This is a ready-to-use risk assessment for the critical starting materials and raw materials a CDMO’s process depends on: plasmid DNA, viral seed stock, master and working cell banks, and any specialized, thinly-sourced media component. Its job is narrow and specific: name every material a single supply or characterization failure could stall the program on, and score it, rather than letting starting-material risk hide behind a general equipment and quality-system assessment that never asks the question directly. Replace every <<FILL: ...>> placeholder with your own specifics and route it through your normal document control, review, and approval. A worked filled specimen follows. Verify each cited reference against the current source before you rely on it.
Document control header
| Field | Entry |
|---|---|
| Document title | Critical Starting Material Sourcing Risk Assessment for <<FILL: product / process>> at <<FILL: CDMO name>> |
| Document number | <<FILL: e.g. CSM-RA-2026-01>> |
| Version | <<FILL>> |
| Effective date | <<FILL>> |
| Linked technical assessment | <<FILL: document number>> |
| Document owner | <<FILL: e.g. Technical Operations Lead>> |
1. Purpose
This assessment identifies every critical starting material and specialized raw material the CDMO’s process depends on, evaluates each for single-source exposure and characterization maturity, and decides whether a documented mitigation, a second source, a confirmed inventory buffer, an accelerated characterization plan, is required before the program commits to a manufacturing schedule built on that material.
2. Scope
| Dimension | Decision |
|---|---|
| Process / product in scope | <<FILL>> |
| CDMO and site assessed | <<FILL>> |
| Materials assessed | <<FILL: plasmid DNA, viral seed stock, cell banks, cytokines, growth factors, specialized media components>> |
| Out of scope | <<FILL: e.g. commodity raw materials with a broad, verified supplier base, covered under routine vendor qualification>> |
3. Responsibilities
| Role | Responsibility |
|---|---|
| Technical operations / MSAT lead | Performs the assessment, drafts the risk table and conclusion. |
| CDMO technical contact | Provides sourcing, characterization, and inventory data for each material in scope. |
| Quality Assurance | Reviews and approves the conclusion, confirms any accepted single-source risk carries a documented risk acceptance. |
| Regulatory / CMC | Confirms whether a material’s characterization gap could affect a filing commitment or a comparability claim. |
4. Material sourcing risk table
| Material | Sole or dual source | Characterized to a named standard (state which) | Confirmed remaining inventory vs. program batch plan | Risk score (High/Medium/Low) | Mitigation |
|---|---|---|---|---|---|
| Plasmid DNA | <<FILL>> | <<FILL: e.g. USP <1040> quality considerations, or the CDMO's own internal specification>> | <<FILL>> | <<FILL>> | <<FILL>> |
| Viral seed stock, master | <<FILL>> | <<FILL>> | <<FILL>> | <<FILL>> | <<FILL>> |
| Viral seed stock, working | <<FILL>> | <<FILL>> | <<FILL>> | <<FILL>> | <<FILL>> |
| Master cell bank | <<FILL>> | <<FILL: e.g. ICH Q5D>> | <<FILL: N/A, single bank>> | <<FILL>> | <<FILL>> |
| Working cell bank | <<FILL>> | <<FILL: e.g. ICH Q5D>> | <<FILL: vials remaining vs. program need>> | <<FILL>> | <<FILL>> |
| Specialized media / cytokine / growth factor | <<FILL>> | <<FILL>> | <<FILL>> | <<FILL>> | <<FILL>> |
Add one row per material actually in use; do not compress two distinct materials with different suppliers into one row. Score High where a material is sole-sourced, has no confirmed inventory buffer against the batch plan, and has no documented second-source or re-derivation path; score Low only where a genuine second source or a validated, sufficient inventory buffer is confirmed, not assumed.
5. Characterization gap assessment
| Material | Characterization complete for intended use? | Gap identified | Closure plan | Owner | Target date |
|---|---|---|---|---|---|
<<FILL>> | <<FILL: Yes/No>> | <<FILL>> | <<FILL>> | <<FILL>> | <<FILL>> |
Leave this section stated as “none identified” rather than omitted if every material in section 4 is fully characterized; a reviewer checking this assessment against the CDMO’s own material files is checking for exactly this kind of silent gap.
6. Conclusion and decision
| Field | Entry |
|---|---|
| Materials scored High risk | <<FILL>> |
| Materials scored High risk with an open, undated mitigation plan | <<FILL: this blocks sign-off>> |
| Overall recommendation | <<FILL: proceed / proceed with conditions / hold pending mitigation>> |
| QA risk acceptance reference, for any accepted single-source risk | <<FILL>> |
7. References
ICH Q5D, Derivation and Characterisation of Cell Substrates Used for Production of Biotechnological/Biological Products. ICH Q7, Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients. USP General Chapter <1040>, Quality Considerations of Plasmid DNA as a Starting Material for Cell and Gene Therapies (in development; confirm current status before citing as an official standard).
Confirm the current version and status of each reference before issue.
8. Revision history
| Version | Date | Author | Summary of change |
|---|---|---|---|
<<FILL: 1.0>> | <<FILL>> | <<FILL>> | Initial issue. |
9. Approvals
| Role | Name | Signature | Date |
|---|---|---|---|
| Author (Technical Operations) | <<FILL>> | ||
| Reviewer (CDMO technical contact, informational) | <<FILL>> | ||
| Approver (Quality Assurance) | <<FILL>> |
Filled specimen
Extract for an example AAV gene therapy program assessing a candidate CDMO. Company and product are illustrative.
| Material | Sole or dual source | Characterized to a named standard | Confirmed remaining inventory vs. program batch plan | Risk score | Mitigation |
|---|---|---|---|---|---|
| Plasmid DNA (triple-plasmid transfection) | Sole source, CDMO’s affiliated plasmid manufacturer | Internal specification; not yet mapped against USP <1040>‘s quality considerations | Sufficient for 4 of 6 planned PPQ and commercial batches | High | Require a second qualified plasmid source or a documented capacity commitment covering the full batch plan before PPQ protocol approval |
| Viral seed stock, master | Single bank, no backup | ICH Q5D-aligned characterization on file | N/A, single bank by design | Medium | Confirm banking redundancy (split storage locations) and a re-derivation contingency plan documented, even though a second independent bank is not practical for this program |
| Master and working cell bank (producer cell line) | Single bank pair | ICH Q5D-aligned characterization on file, reviewed | Working bank vials sufficient for 9 planned batches against a 6-batch plan | Low | None required; inventory buffer confirmed sufficient |
| Cytokine/growth factor for producer cell expansion | Sole source, one vendor | Certificate of analysis on file, no gap identified | Vendor-confirmed allocation for the program’s full duration | Medium | Confirm vendor allocation commitment in writing and identify a qualified alternate vendor as a documented contingency, even if not immediately qualified |
Section 5, characterization gaps: plasmid DNA mapping against USP <1040>‘s quality considerations is not yet complete; closure plan owned by the CDMO’s analytical lead, target date before PPQ protocol approval.
Conclusion: one material, plasmid DNA, scored High risk with an open mitigation plan; recommendation is proceed with conditions, holding PPQ protocol approval until the plasmid second-source or capacity commitment and the USP <1040> mapping are both closed.
Common findings this risk assessment prevents
- A single-source starting material identified only after a supply interruption already affects the manufacturing schedule.
- Viral seed stock or a cell bank’s characterization basis assumed adequate with no named standard checked against.
- A confirmed inventory count never compared against the actual program batch plan, so a shortfall is discovered mid-campaign instead of during diligence.
- A high-risk material accepted informally with no documented QA risk acceptance a future reviewer or inspector can find.
How to adapt this risk assessment
- Build the material list in section 4 directly from the process flow diagram and bill of materials, not from memory; a material left off the list is a material this assessment cannot protect the program from.
- Score every material honestly against sole-source exposure, characterization maturity, and confirmed inventory, not against how inconvenient a “High” score would be for the schedule.
- Route every High-risk row with an open plan through section 5 with a real owner and date.
- Revisit this assessment before PPQ protocol approval and again before any commercial launch, since inventory and sourcing status both change over a program’s life.