Kilo Lab – Scale-Up Manufacturing

This topic is part of the SG Systems Global manufacturing, quality, and scale-up glossary.

Updated October 2025 • Process Development & Tech Transfer • cGMP Readiness & Digital Evidence

A kilo lab is a development and bridge-manufacturing environment that takes a proven bench process and scales it to multi-hundred-gram through multi-kilogram output with industrially relevant equipment, controls, and documentation. In pharma, APIs and key intermediates move through kilo lab before pilot plant and commercial. The point is not just bigger batches; it’s where process understanding, operability, safety, quality, and data integrity are hardened so the recipe can survive real hardware, human factors, and regulatory scrutiny. Typical operations include jacketed glass/steel reactors (5–100 L), contained charging, controlled additions, vacuum distillation, filtration/drying, and in-line analytics (PAT). Output often supplies tox studies, early clinical supply, or engineering lots used for IQ/OQ/PQ of downstream equipment.

The kilo lab is where development teams translate chemistry or formulation into capable unit operations with defined ranges, proven robustness, and documented risks. It is also where digital execution begins to mirror cGMP expectations: controlled masters under Document Control, contemporaneous entries in eBMR/eMMR, enforced identities and Audit Trails, and controlled release of materials and instructions. For regulated programs, frameworks such as ICH Q7, ICH Q10, and GAMP 5 shape how evidence is created and reviewed—even if the facility is not yet a full commercial GMP plant.

“Scale-up isn’t a multiplier; it’s a maturity test for process physics, safety, quality, data, and people—run on real equipment with real consequences.”

1) What It Is

A kilo lab sits between bench R&D and the pilot plant. Equipment mimics commercial unit ops but in smaller, more flexible form: jacketed reactors with precise temperature control; pressure/vacuum capability; inline pH, conductivity, turbidity, or Raman for PAT; contained powder/liquid handling; Nutsche filters and tray/vacuum dryers; and explosion-rated utilities where solvents or dusts demand it. The environment blends development agility with production discipline: change logs, training records, digital travelers, line clearances for cross-contamination risk, and reconciliation of labeled containers. Output feeds material needs and de-risks the recipe for scale.

Beyond equipment, a kilo lab is a system: master recipes, materials specifications, and sampling plans live under Document Control; people execute steps with Dual Verification where risk warrants; data is captured directly from instruments into eBMR with role-based e-signatures per Part 11. It’s the proving ground for continued process verification: are we actually in control at meaningful scale?

2) Scope, Regulatory Anchors & Governance

Scope ranges from synthetic steps (reactions, workups, crystallizations) to formulation (granulation, blending, coating, filling) and device assembly of subcomponents for combination products. Where output supports clinical supply or stability studies, expectations align to ICH Q7 for API, 21 CFR 210/211 for drug product, and lifecycle/quality system thinking from ICH Q10. Software and instruments follow GAMP 5 risk-based validation appropriate to intended use. Even when classified as “development,” regulators expect traceable decisions, controlled changes, and defensible data.

Governance includes Document Control, Change Control, periodic data review, and defined release states for materials and instructions. Equipment must demonstrate fitness for intended use through IQ/OQ/PQ or fit-for-purpose checks; utilities (HVAC, gases, purified water) are documented; and cleaning is validated or verified with scientific rationale (see Cleaning Validation).

3) Process Design: DoE, PAT & Defining Proven Ranges

The kilo lab is where ranges stop being guesses. Teams run structured Design of Experiments to map critical parameters—temperature, addition profiles, agitation, solvent ratios, seeding, drying endpoints—to critical quality attributes (CQA) like assay, purity, particle size, blend uniformity, or dissolution. Inline PAT (e.g., FT-Raman for crystallization, torque/power draw for granulation) reduces blind spots and supports closed-loop control in later scales. Outputs are proven acceptable ranges, design spaces, and control strategies suitable for pilot/commercial automation and monitoring (SPC/CPV).

Material science is locked down here: polymorph control, solvent selection for safety and sustainability, hold times bounded by Hold Time Studies, and raw-material variability addressed with tighter specs or Identity Testing. Sampling plans are statistically sound; results are captured in eBMR with instrument links for traceability.

4) Process Safety & Operability

Kilo scale exposes hidden hazards. Teams run calorimetry and gas-evolution tests to characterize adiabatic temperature rise, maximum technically feasible rates, and pressure relief needs. HAZOP and task-level JHA/JSA (see JHA) identify credible mis-operations: wrong charge order, blocked vents, incompatible washes, static/sparks during powder transfers. Mitigations include interlocks via the HMI, inerting, dosing controls, ATEX/NFPA compliant equipment, and poka-yoke fittings and labeling.

Human factors matter. Human Factors Engineering is applied to charge sequences, scale readability, line clearance prompts, and alarm handling. Emergency stops, eyewash placement, and escape paths are verified during FAT/site shakedowns; training is role-based and recorded.

5) Materials Readiness, Labeling & Genealogy

Every input should be traceable, approved, and staged. Intake runs through Goods Receipt, Incoming Inspection, and status under Component Release. Bin rules (Bin Location Management) and FEFO/FIFO (FEFO/FIFO) prevent aging. All vessels and containers carry controlled labels; quantities are verified with Gravimetric Weighing and Barcode Validation. Full Batch Genealogy ties inputs, intermediates, and outputs so results can be traced bi-directionally.

Where toxic or allergenic substances are used, segregation and verified cleaning are non-negotiable. Methods and acceptance criteria live under Cleaning Validation; swab/rinse limits and campaign rules are enforced at Job Release.

6) Execution, Evidence & Review

Work is executed against a controlled Job Ticket and Job Traveler. Release gates confirm materials, equipment status, and training are aligned. Devices (balances, thermocouples, PAT) integrate directly to the record; manual entries require reasons for changes and may invoke Dual Verification. Deviations (Deviation/NC) trigger containment and root-cause; systemic issues flow to CAPA. QA reviews by exception with audit-trail scrutiny and renders release/hold decisions.

Data integrity is absolute: attributable, legible, contemporaneous, original, accurate (ALCOA+). Version links must show which master recipe and label template were in force. If records support stability or filings, retention and archival follow defined policy (see Data Retention & Archival).

7) Tech Transfer Dossier: What “Ready” Looks Like

A credible transfer from kilo lab to pilot/commercial includes: master recipe with parameter ranges and alarms; DoE/validation evidence; hazard studies and relief sizing; cleaning validation strategy; sampling/IPC plan; materials specifications; inspection/test methods; qualification and calibration status; training plans; and examples of executed, reviewed eBMR. It should also include an issues log with mitigations and open risks, and a proposal for CPV metrics post-transfer.

For supply chains with external CMOs, digital exchange (recipes, parameters, label masters) occurs under change control with clear responsibilities and release mechanics. Where traceability is needed, serialized identifiers and shipping documentation integrate with WMS (EDI or structured hand-offs).

8) Practical Walkthrough (API Crystallization to Dried Cake)

An API lab scales a crystallization from 2 L bench to a 50 L glass-lined reactor. Beforehand, the team runs reaction calorimetry and defines a safe addition profile. The Job Ticket references the controlled recipe and sampling plan. Materials are kitted per Directed Picking and released. During execution, PAT monitors supersaturation; the traveler prompts seed charge and hold. A deviation opens when PAT shows a slower nucleation rate; a reason code is captured and temperature is adjusted within the proven range. After reaching endpoint, slurry moves to a Nutsche filter; wash volumes are verified by gravimetric checks. Drying proceeds under vacuum; residual solvent is tested per method. All steps, scans, and signatures land in the eBMR. QA reviews by exception; lots are dispositioned and samples dispatched to stability. The issues log recommends a tighter seed window and a revised hold-time bound for the mother liquor, then flows to Change Control and the next engineering run.

9) How This Fits with V5

V5 by SG Systems Global turns kilo lab intent into controlled execution. In V5 MES, master recipes live under Document Control; parameters and IPC checks compile into a digital traveler; Job Release enforces prerequisites (materials, equipment status, training). Device connectors capture primary data; Dual Verification gates risky actions; exceptions open Deviations with photos and reason codes. In V5 WMS, Directed Picking, FEFO, and Bin Location rules manage staging and returns. Audit Trails, Data Integrity, and analytics support rapid, defensible review and feed the tech-transfer dossier automatically.

10) FAQ

Q1. When does a development lab become a “kilo lab”?
When equipment and controls support kilogram outputs with industrially relevant unit ops, safety systems, digital records, and governed masters—sufficient to de-risk pilot transfer and, where applicable, cGMP expectations.

Q2. Do we need full Part 11 and GxP validation in a kilo lab?
If data supports filings, clinical supply, or quality decisions, follow Part 11 expectations proportionate to risk and apply GAMP 5 principles to systems and spreadsheets used as records.

Q3. What qualifies equipment: IQ/OQ/PQ or “fit-for-purpose”?
For regulated outputs, perform risk-appropriate IQ/OQ/PQ. For pure development use, document fitness for intended use with calibration and safety checks, but plan full qualification before pilot/commercial.

Q4. How do we prevent cross-contamination at small scale?
Enforce line clearance, dedicated/cleanable tooling, contained transfers, and validated or verified cleaning methods with acceptance limits; use label reconciliation and barcode checks on vessels and samples.

Q5. What are the success metrics for kilo lab readiness?
On-time starts, deviation rate at start-up, first-pass yield, genealogy completeness, successful reproduction of results in pilot runs, time-to-review eBMRs, and closure time for transfer actions/CAPAs.

Related Reading
• Governance & Validation: Document Control | Change Control | GAMP 5 | Audit Trail (GxP) | Data Integrity
• Execution & Records: Electronic Batch Record (eBMR) | Job Ticket | Job Traveler | Gravimetric Weighing | Batch Genealogy
• Quality & Safety: ICH Q7 | ICH Q10 | HAZOP | Cleaning Validation | Deviation/NC | CAPA