For decades, Quality and Manufacturing teams have accepted manual data review as the necessary safeguard between testing and release. Today, it has become one of the most expensive operating models in biopharma.
At modern scale, the cost of maintaining an “eyes-on-everything” review process can exceed $50 million over three years, not because of exceptions in the data, but because highly trained experts are spending their time reviewing data that is already good.
In modern biopharma, a single QC site can generate 10,000 to 20,000 tests per year. As organizations scale high-throughput platforms and lab automation, this translates into millions of injections and audit trail events annually — a volume that industry guidance explicitly notes does not scale with exhaustive manual review (ISPE GAMP 5, Risk-Based Approach, 2022). Yet, most QC organizations remain tethered to an “eyes-on-everything” two-person, fully manual review process designed for the era of paper notebooks–not today’s digital volume and complexity enabled by modern Chromatography Data Systems (CDS).
We have reached a breaking point. Under constant pressure to release faster, most QC leaders have quietly accepted a false trade-off: you can have speed, or you can have rigorous compliance, but never both. At today’s scale, this trade-off is no longer a safety net; it is a structural tax on your entire portfolio.
The Bottleneck: Why The “Eyes-on-Everything” Model is a Multi-Million Dollar Liability
The traditional Analyst + Reviewer model was designed to prevent errors through redundancy. In practice, it has become a systemic drain on capacity, cost, and risk posture. Based on industry benchmarks and customer data, maintaining this approach creates three structural drains that quietly erode the bottom line.
- The Labor Capacity Drain: Analysts and reviewers currently spend 40-50% of their time processing and reviewing data and audit trails rather than running experiments, investigating exceptions or method improvements.
- The Outsourcing Trap: As internal teams drown in routine manual review volume, organizations turn to outsourced partners at a 20–30% premium just to keep up (DrugPatentWatch, The Ultimate Guide to CDMO Pricing).
- The Cost of Speed: Manual review cycles are iterative and slow. Simpler drug modalities (e.g. small molecules) may require two to three review iterations, while complex biologics can exceed five or more rounds of back-and-forth between the analyst and the reviewer. Every day of delay in batch release can cost over $800,000 to over $1 million per day in lost revenue (Tufts CSDD – cost of delay summary).
Taken together, these factors turn manual QC review into a $50M anchor—dragging down release velocity, consuming expert capacity, and increasing operational risk year over year.
The Solution: Review by Exception (RbE) Assistant for High-Volume Workflows
The Review by Exception Assistant breaks the manual review bottleneck by operationalizing expertise through a human-in-the-loop, risk-based framework. Rather than replacing human judgment, RbE encodes existing expertise into repeatable, auditable controls that scale with data volume.
The RbE Assistant targets the two most time-intensive and subjective components of chromatography review across release and stability testing.
- Chromatogram Profiler leverages an organization's historical batch data to establish a golden batch profile. A golden batch can be a single example of a best in-class integration or a curated set of best in-class examples. Next, RbE incorporates contextualized, historical batch data to train AI classification models that measure chromatogram profile similarities and flags meaningful anomalies like peak integration changes or retention time shifts, while letting conforming data pass automatically.
- Intelligent Audit Trail Review converts static PDF data verification checklists into digitized, enforceable rules mapped to Tetra Data models. RbE continuously evaluates audit trail events against these rules and flags only meaningful compliance exceptions where the users have the ability to determine appropriate steps for alert resolution. Importantly, these interactions are logged back into RbE so that the system is continuously improving and refining its rules for exception flagging. This accelerates review cycles and directs reviewers to known compliance rule violations.
Strategic Human Oversight
Modernizing QC does not remove the human; it focuses them.
- Coded Exceptions: Every flagged exception is assigned a specific error code, ensuring standardized terminology across the network.
- Mandatory Human Review: Each exception requires a Subject Matter Expert (SME) to review the flag, investigate the root cause, and add a mandatory comment for resolving the alert.
- Immutable Documentation: Expert comments and dispositions are captured directly within the digital record, creating a robust, defensible audit trail that is far superior to manual signature logs.
Based on our work with biopharma partners with RbE, quality and manufacturing organizations can reclaim over 198,000 hours of high-value labor time by automating review of conforming data and prioritizing expert time on critical exceptions.
The Compliance Case: Why Regulators Favor Modernized Oversight
There is a pervasive myth that 100% manual review is the "safe" option. In reality, it is often a risk multiplier. When reviewers are forced to check thousands of compliant chromatograms and audit trail lines, review fatigue and cognitive overload sets in – conditions shown to increase inconsistency and human error. True risks such as anomalies, out-of-trend patterns, and unexplained integration changes may be missed in the noise of "good" data.
Regulators are not asking for more manual checks; they are asking for smarter ones.
- Regulatory Support: Frameworks like EU GMP Annex 11 and 21 CFR Part 11 explicitly permit electronic systems and technical controls to support risk-based, exception-driven oversight.
- Industry Standards: The International Society for Pharmaceutical Engineering (ISPE) defines RbE as a method to surface only critical process exceptions for disposition, ensuring SMEs are focused on high-risk data, not routine system logs.
The Path to Real-Time Batch Release
The move to the Review by Exception Assistant represents a rare convergence where the most profitable path is also the most compliant.
For the Heads of Quality, Review by Exception Assistant removes subjectivity and enforces consistent exception logic across sites and products. For the Head of Digital Quality, it represents the first concrete, high-ROI step toward the ultimate goal: Real-Time Batch Release.
Adhering to the legacy manual review model is no longer neutral. Every day spent manually reviewing compliant chromatograms and scrolling through pages of audit logs is a day of lost revenue, wasted expert capacity, and missed risk signals.
The cost of doing nothing is compounding—quarter after quarter—into a $50M anchor that modern QC organizations can no longer afford to carry.