This is a ready-to-use HACCP-style hazard analysis and critical control point (CCP) determination worksheet, adapted for sterile and aseptic pharmaceutical, biologic, and cell and gene therapy manufacturing rather than food production. Replace every <<FILL: ...>> placeholder with your own specifics, set your document numbers and dates, and route it through your normal document control, review, and approval. A worked filled specimen follows the template. Verify each cited regulation against the current source before you rely on it.
Document control header
| Field | Entry |
|---|---|
| Document title | HACCP Hazard Analysis and CCP Determination for <<FILL: PROCESS / PRODUCT>> |
| Document number | <<FILL: RA-ID, e.g. RA-QA-018>> |
| Version | <<FILL: version, e.g. 1.0>> |
| Effective date | <<FILL: effective date>> |
| Supersedes | <<FILL: prior version or "New">> |
| Document owner | <<FILL: role, e.g. Quality Assurance Manager, Sterility Assurance>> |
| Process / product in scope | <<FILL: process description, product, site>> |
| Linked documents | <<FILL: process flow diagram, contamination control strategy, EM program>> |
1. Purpose and methodology
This worksheet identifies the hazards present in a defined process, determines which process steps are critical control points (CCPs), specific points where a control must hold because loss of control there cannot be corrected by anything downstream, and sets the critical limit, monitoring, corrective action, and verification for each CCP found. It follows the general HACCP method (hazard analysis, CCP determination, critical limits, monitoring, corrective action, verification, record-keeping) referenced as an example risk management tool in ICH Q9(R1), applied here to a GxP manufacturing context rather than food production.
HACCP complements, rather than replaces, a process FMEA. Use an FMEA (/templates/assessment-validation-risk-fmea or a process FMEA) to surface failure modes across a whole process; use this worksheet to decide which of those steps carry non-negotiable, non-recoverable risk and therefore need dedicated monitoring and a defined critical limit, rather than spreading monitoring effort evenly across every step.
2. Scope
This worksheet covers <<FILL: the process, unit operations, and boundary, e.g. "component preparation through final container closure for the aseptic filling line">>. It assesses hazards to sterility assurance, product quality, and, where relevant, patient safety. It does not cover facility qualification or utility system risk, which are addressed in <<FILL: cross-reference>>, and it assumes prerequisite programs, cleaning validation, gowning and personnel qualification, incoming material control, calibrated environmental monitoring, are already in place and current; this worksheet does not substitute for them.
3. Responsibilities
| Role | Responsibility |
|---|---|
| HACCP team lead / facilitator | Runs the hazard analysis and CCP determination sessions, keeps the team working through the decision path consistently. |
| Process / manufacturing SME | Provides the process flow, the operating conditions, and the technical basis for hazard likelihood and severity. |
| Quality Assurance / sterility assurance | Confirms CCP determinations, critical limits, and monitoring plans meet the contamination control strategy, and approves the worksheet. |
| Microbiology / environmental monitoring | Provides the technical basis for microbial hazards, critical limits, and the monitoring methods credited at each CCP. |
| CCP owner (named per CCP) | Confirms monitoring is performed at the CCP as defined and escalates any deviation immediately. |
4. Definitions
- Hazard: a biological, chemical, or physical agent, or a process condition, with the potential to cause harm to product quality, sterility assurance, or the patient.
- Critical control point (CCP): a step at which control can be applied and is essential to prevent, eliminate, or reduce a hazard to an acceptable level, and where a lapse cannot be corrected by any later step.
- Critical limit: the measurable value (a temperature, a time, a pressure differential, a particle count, an integrity test result) that separates acceptable from unacceptable at a CCP.
- Prerequisite program: the underlying GMP controls, facility qualification, cleaning validation, gowning, personnel qualification, incoming material control, general environmental monitoring, that control routine hazards without needing a dedicated CCP.
- Monitoring: the planned sequence of observations or measurements at a CCP to confirm the critical limit is met, timely enough to correct a drift before harm occurs.
5. Hazard analysis
List every process step in the defined scope. For each, identify the hazard(s), judge whether the hazard is significant enough to warrant a CCP determination, and record the basis.
| Step | Potential hazard | Hazard type (biological / chemical / physical) | Significant? (Y/N) | Basis for judgment |
|---|---|---|---|---|
<<FILL: e.g. component washing>> | <<FILL: e.g. residual bioburden on components>> | <<FILL>> | <<FILL>> | <<FILL: e.g. controlled by validated cleaning cycle and pre-use bioburden testing>> |
<<FILL>> | <<FILL>> | <<FILL>> | <<FILL>> | <<FILL>> |
Carry forward only the steps judged significant to section 6.
6. CCP determination path
Apply this decision path to every significant hazard from section 5, one hazard per step at a time. Work top to bottom and stop at the first answer that resolves the question.
| Step | Hazard | Q1 | Q2 | Q3 | Q4 | CCP? | Rationale |
|---|---|---|---|---|---|---|---|
<<FILL>> | <<FILL>> | <<FILL: Y/N>> | <<FILL: Y/N>> | <<FILL: Y/N>> | <<FILL: Y/N>> | <<FILL: Y/N>> | <<FILL: one-line reasoning>> |
7. Critical limits, monitoring, corrective action, and verification
Complete this section only for steps determined to be CCPs.
| CCP | Hazard controlled | Critical limit | Basis for the limit | Monitoring method | Monitoring frequency | Who monitors | Corrective action if the limit is exceeded | Verification activity | Verification frequency |
|---|---|---|---|---|---|---|---|---|---|
<<FILL: e.g. CCP-1>> | <<FILL>> | <<FILL: measurable value>> | <<FILL: validation study, compendial requirement, or engineering basis>> | <<FILL>> | <<FILL>> | <<FILL: role>> | <<FILL: immediate action, hold/quarantine, disposition path>> | <<FILL: e.g. periodic requalification, data trend review>> | <<FILL>> |
8. Residual risk and approval
For each CCP, state the residual risk once the critical limit, monitoring, and corrective action are in place, and record who accepts it. A CCP with monitoring defined but no corrective action path, or no named accountable role, is not complete.
| CCP | Residual risk statement | Accepted by |
|---|---|---|
<<FILL>> | <<FILL>> | <<FILL: QA / sterility assurance role>> |
9. Acceptance criteria
- Every step in the defined scope was assessed for hazards; steps excluded as non-significant have a recorded basis.
- The four-question decision path in section 6 was applied consistently to every significant hazard, with the answers recorded, not just the conclusion.
- Every CCP has a critical limit with a stated basis, a monitoring method and frequency capable of detecting a deviation in time to act, a named corrective action, and a verification activity.
- Residual risk at each CCP is stated and accepted by Quality or sterility assurance, not by the process team alone.
- The worksheet is reviewed on change to the process, on a CCP deviation, or at the periodic cycle stated in the header.
10. References
ICH Q9(R1), Quality Risk Management, naming HACCP as an example risk management tool. EU GMP Annex 1 (2022), Manufacture of Sterile Medicinal Products, contamination control strategy expectations. 21 CFR Part 211 (current good manufacturing practice for finished pharmaceuticals), production and process control requirements. 21 CFR Parts 600 to 680, biological products, where the scope includes biologics manufacturing.
Confirm the current version of each reference before issue. The seven-principle HACCP method and its CCP decision-tree logic originate in Codex Alimentarius food-hygiene guidance; this worksheet adapts the underlying logic for a GxP pharmaceutical, biologic, or cell and gene therapy process, it does not reproduce the Codex text.
11. Revision history
| Version | Date | Author | Summary of change |
|---|---|---|---|
<<FILL: 1.0>> | <<FILL: date>> | <<FILL: author>> | Initial issue. |
12. Approvals
| Role | Name | Signature | Date |
|---|---|---|---|
| Author | <<FILL>> | ||
| Reviewer (Microbiology / Sterility Assurance) | <<FILL>> | ||
| Approver (QA) | <<FILL>> |
Filled specimen
The following shows the worksheet completed for an illustrative terminal sterilization and aseptic finishing line, so you can see the level of detail expected. The company, process, and numbers are illustrative; replace them with your own.
Scope: component washing through autoclave terminal sterilization and Grade A aseptic filling of a small-volume parenteral.
Hazard analysis (excerpt):
| Step | Potential hazard | Hazard type | Significant? | Basis |
|---|---|---|---|---|
| Component washing | Residual bioburden on vials and stoppers | Biological | No | Controlled by a validated wash cycle and a qualified washer, covered by the cleaning validation prerequisite program |
| Autoclave terminal sterilization cycle | Non-sterile units if lethality is not achieved | Biological | Yes | No downstream step can correct an under-processed load; direct patient-safety consequence |
| Grade A filling zone, open container exposure | Microbial or particulate ingress during fill | Biological, physical | Yes | Product has no terminal sterilization after this point; environmental control at this step is the only barrier |
CCP determination (excerpt):
| Step | Hazard | Q1 | Q2 | Q3 | Q4 | CCP? | Rationale |
|---|---|---|---|---|---|---|---|
| Component washing | Residual bioburden | Y | - | - | - | N | Fully addressed by the qualified wash cycle prerequisite program |
| Autoclave sterilization cycle | Non-sterile load | N | Y | Y | N | Y (CCP-1) | Lethality delivered here is the sole barrier; no later step can sterilize an under-processed load |
| Grade A filling zone | Microbial/particulate ingress during open exposure | N | Y | Y | N | Y (CCP-2) | No terminal step follows; control must hold at the point of exposure |
Critical limits, monitoring, and corrective action (excerpt):
| CCP | Hazard | Critical limit | Basis | Monitoring | Frequency | Who | Corrective action | Verification |
|---|---|---|---|---|---|---|---|---|
| CCP-1, autoclave cycle | Non-sterile load | Minimum delivered F0 of <<FILL: e.g. 8 minutes>> per the validated cycle, confirmed by biological indicator and validated temperature mapping | Sterilization validation study and periodic requalification | Continuous chamber temperature and pressure recording, biological indicator on every load, F0 calculated per cycle | Every cycle | Sterilization operator, verified by QA | Load quarantined, non-conforming material investigation opened, no release until F0 and BI results confirm the cycle met the limit | Annual thermal requalification, BI positive-control trend review |
| CCP-2, Grade A filling zone | Microbial/particulate ingress | Zero colony-forming units at Grade A viable limit; particle counts within the qualified ISO 14644 classification for the zone during fill | EU GMP Annex 1 grade requirements and the site’s environmental monitoring program | Continuous non-viable particle monitoring, active air sampling per session, personnel and settle-plate monitoring per the EM program | Continuous (particles), per fill session (viable) | Filling line operator, EM technician, verified by QA | Immediate stop of fill on an adverse trend or excursion; affected units quarantined pending investigation and sterility/EM trend review | EM program periodic review, annual smoke study, media fill |
Residual risk (excerpt): CCP-1 residual risk, an under-processed load reaching product, is judged low given continuous parametric monitoring plus a biological indicator on every load; accepted by Sterility Assurance QA. CCP-2 residual risk, a transient microbial or particulate event between sampling points, cannot be reduced to zero by monitoring alone; accepted by QA with the explicit acknowledgment that environmental monitoring is a trend and investigation tool, not a real-time release test, consistent with the contamination control strategy for the line.
Common inspection findings this worksheet prevents
- HACCP or CCP language is used in a contamination control strategy narrative with no worksheet showing how the CCPs were actually determined.
- A step is called a CCP with no critical limit defined, or a critical limit with no stated basis (no link to a validation study or a compendial requirement).
- Monitoring frequency at a CCP is not fast enough to catch a deviation before the affected material moves on.
- A corrective action exists on paper but no one is named as accountable for executing it when a critical limit is exceeded.
- Environmental monitoring is treated as if it were a real-time control rather than a trend and investigation tool, overstating what CCP-2-type monitoring can actually catch.
How to adapt this worksheet
- Set your document number, owner, process, and effective date in the header, and link your actual process flow diagram and contamination control strategy.
- Build the hazard analysis in section 5 from your real process steps; do not reuse the specimen steps if your process differs.
- Apply the decision path in section 6 to every significant hazard individually; do not shortcut by assuming a step is or is not a CCP from experience elsewhere.
- Set critical limits from your own validation data and compendial requirements, never from the specimen numbers.
- Confirm every regulation in section 10 against the current published version before issue.