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Feed droop & head-pressure exceedance on BR-UP-01

Q-DEV-031Major · Tier 2Root-cause investigation

BR-UP-01 (2,000L Fed-Batch Bioreactor) · Masterflex Peristaltic Feed Pump (PM-204) · lot MES-26073. This dossier assembles evidence for the investigation; the deviation record itself lives in Veeva Vault QMS.

QMS mode: READ_ONLY_SANDBOXOwner Priya Natarajan (QA)Due 2026-11-18 (30-day)Demo · read-only
Draft CAPA summary in workspace Request QA sign-off
Frame QUAL-02
  1. Initiated
  2. Triage & containment
  3. 3Root-cause investigation
  4. 4CAPA plan
  5. 5QA approval
  6. 6Closure

Stage mirrors Veeva QMS. Advancing a stage happens in QMS by the record owner, not here.

Event sequence

Chronological. “Event −48 h” is relative to the pressure spike; “T+” is elapsed batch time. Times UTC.

  1. Event −48 h2026-10-17 07:12Observation

    WO-8819 · PM-204 occlusion clamp torque 0.42 → 0.55 N·m

    Returned to service without the dynamic slip verification required by SOP-UP-014 §7.2 (fixture unavailable).

  2. T+182.0–182.7 h2026-10-15 14:00Unknown

    Historian gap · 42 min (PI buffer overflow)

    No PM-204 flow or pressure data for this window. Not used in any calculation.

  3. T+200–264 h2026-10-16 → 10-19Calculated

    Gradual feed-flow decline on MES-26073

    Mean delivered flow falls ~0.4 mL/min below MES-26071 over this window.

  4. T+264.4 h2026-10-19 08:26Observation

    Head-pressure spike to 1.48 bar (ceiling 1.20 bar)

    Feed flow drops to 14.48 mL/min (−14.2%) within two minutes.

  5. T+264.5 h2026-10-19 08:31Observation

    eBR step 05.4 · operator acknowledged feed deviation

    FEED_SP 16.90 vs FEED_PV 14.48 mL/min recorded by T. Reed.

  6. T+265.1 h2026-10-19 09:05Observation

    Q-DEV-031 opened · lot MES-26073 placed on QA hold

    Classified Major (Tier 2) by P. Natarajan.

  7. T+267.6 h2026-10-19 11:40Observation

    QC-948 harvest titer 3.42 g/L · OOT

    Below the 3.80 g/L alert limit. Second-person review pending.

Root-cause narrative

Draft by Root Cause agent (RUN-2026-1042), edited by Alex Rivera. Pending QA review.

DraftHypothesis

Most-likely hypothesis, not an established cause

QA has not accepted this explanation. The physical tubing from PM-204 has not yet been inspected, which is the most direct test.

Most-likely mechanism

Raising the occlusion clamp torque during WO-8819 without the required dynamic slip verification likely over-compressed the tubing. The OEM notes that increased occlusion shortens tubing life and raises discharge pressure . That is consistent with both the progressive flow decline and the T+264.4h pressure spike with −14.2% feed droop .

Contributing factor

The SOP requirement exists but is not enforced at work-order closure; the verification fixture was unavailable and the pump was returned to service anyway .

  • ContradictedFeed media lot quality: FM-2207 osmolality and glucose are within specification.
  • ContradictedDO probe drift driving a control response: redundant probes A/B agree within 0.6%.
  • UnknownTubing run-hours at the time of the spike are not recorded in CMMS, so the OEM 400–500 h service-life window cannot be checked directly.
  • Unknown42 minutes of historian data are missing at T+182h.

What would change this conclusion

  • Tubing teardown showing no wear or spallation beyond normal.
  • A gravimetric slip test on the removed spool within ±3% at operating RPM.
  • A comparable pressure/flow event on PM-204 before WO-8819.

Proposed CAPAs

Proposals only. CAPA records are created and approved in Veeva QMS by their owners.

  • CAPA-01ProposalStatus: Proposed

    Exchange PM-204 tubing spool and perform dynamic slip verification

    Replace pump-head tubing with a fresh Pt-cured silicone size 24 spool; verify gravimetric delivery at operating RPM (±3% of setpoint) before return to GMP service.

    Owner
    R. Chen · Engineering
    Due
    2026-11-07
    Approval
    Not yet requested

    Effectiveness check

    Next 3 batches: feed delivery within ±3% of setpoint and head pressure < 1.20 bar for the full fed-batch phase (historian review).

    1. Proposed
    2. Approved in QMS
    3. Implemented
    4. Effectiveness verified
  • CAPA-02ProposalStatus: Proposed

    Amend SOP-UP-014 §7.2 to make slip verification a hard hold point

    Add a CMMS work-order closure check: occlusion adjustments cannot be closed without an attached slip-verification record; add a spare verification fixture to Suite 3B.

    Owner
    Alex Rivera · MSAT
    Due
    2026-11-28
    Approval
    Not yet requested

    Effectiveness check

    90-day CMMS audit: zero occlusion adjustments returned to service without a slip-verification record.

    1. Proposed
    2. Approved in QMS
    3. Implemented
    4. Effectiveness verified

QMS handoff

Disabled: this workspace runs in READ_ONLY_SANDBOX mode. Veeva Vault QMS remains the system of record. In a configured deployment, an authorized QMS user would review and enter the CAPA there.

Draft CAPA summary Request QA sign-off

Record

Classification
Major · Tier 2
Opened
2026-10-19 09:05
Lot
MES-26073
Equipment
PM-204
SOP
SOP-UP-014 §7.2
Linked CC
CC-017

Impact assessment

Preliminary

ObservationHarvest titer QC-948 is OOT.
CalculatedYield index 75.9 vs target 82.0.
UnknownProduct quality impact (SEC monomer, glycan) not yet tested.
UnknownWhether MES-26071/26072 used the same tubing lot is not recorded.

Linked work