Quality Risk Management in Technology Transfer: Common Failures and Fixes

Technology transfer often looks complete on paper—protocols approved, documents signed, timelines met. Yet during execution, we often see deviations, rework, or delayed validation because risk was not fully understood or managed across sites.

Quality Risk Management (QRM) is not just a regulatory expectation under International Council for Harmonization (ICH) Q9, it is a practical tool to anticipate where transfer breakdowns occur and reduce downstream impact.

---

Where QRM Breaks Down in Tech Transfer

1. Superficial Risk Assessments

Risk assessments are completed as a formality, often too high-level to guide execution.

• Limited input from manufacturing, QC, or engineering
• No linkage to critical process parameters (CPPs) or critical quality attributes (CQAs)
• Generic risk scoring without site-specific context

Impact: Issues emerge during scale-up or validation, requiring late-stage fixes.

---

2. Incomplete Process Understanding Transfer

The sending site assumes process knowledge is fully captured in documents.

• Tacit knowledge not transferred (operator experience, unwritten adjustments)
• Scale-dependent risks not assessed
• Differences in equipment or utilities overlooked

Impact: Process variability increases at the receiving site.

---

3. Misaligned Risk Ownership

Risk ownership is unclear between sending and receiving sites.

• No defined accountability for mitigation actions
• Risks identified but not tracked through closure
• Cross-functional gaps (QA, MSAT, QC)

Impact: Known risks remain open and resurface during execution.

---

4. Poor Integration with Validation Strategy

QRM outputs are not effectively used to shape validation.

• Critical risks not translated into validation parameters
• Sampling plans not risk-based
• Continued process verification (CPV) not aligned

Impact: Validation gaps, unexpected deviations, and regulatory observations.

---

5. Static Risk Management Approach

Risk assessments are treated as one-time exercises.

• No updates after engineering runs or initial batches
• Deviations and learnings not fed back into risk models
• No lifecycle approach

Impact: Repeated issues across batches and delayed stabilization.

---

Practical Fixes That Strengthen QRM

1. Build Risk Assessments Around Process Reality

• Use structured tools like FMEA with cross-functional input
• Anchor risks to CPPs, CQAs, and process steps
• Include site-specific variables (equipment, environment, operators)

---

2. Transfer Knowledge, Not Just Documents

• Conduct detailed knowledge transfer sessions (KT workshops)
• Capture tacit knowledge through SMEs and operators
• Use process mapping and failure mode walkthroughs

---

3. Define Clear Risk Ownership

• Assign risk owners for each identified risk
• Track mitigation actions with timelines
• Integrate into project governance and reporting

---

4. Link QRM to Validation and CPV

• Translate high-risk areas into validation focus points
• Align sampling, IPCs, and acceptance criteria with risk levels
• Use early batch data to refine risk assessments

---

5. Apply a Lifecycle QRM Approach

• Update risk assessments after each key milestone
• Integrate deviation trends and batch data
• Maintain a live risk register through commercial scale

---

A Pattern We Often See

In one transfer, a biologics process moved smoothly through documentation review but failed initial PPQ batches due to variability in mixing performance. The root cause was not equipment failure but an unassessed difference in impeller design between sites.

The risk had been “identified” at a high level but never translated into a mitigation or validation requirement.

A revised QRM approach focused on equipment equivalency and process dynamics helped stabilize the process within two additional runs.

---

How BioBoston Consulting Supports Technology Transfer

We support pharma and biotech teams in strengthening QRM during technology transfer by:

• Facilitating risk assessments aligned with ICH Q9
• Connecting QRM outputs to validation and CPV strategies
• Supporting cross-site alignment and governance
• Helping teams build practical, inspection-ready risk documentation