Clean-in-place and clean-out-of-place systems
CIP skid · COP washer · Parts washer · Automated cleaning system
The skids and washers that clean product-contact equipment by a validated recipe, and the residue sampling that shows the next product is not contaminated by the last.
What this page does not claim
An equipment family page teaches how a kind of equipment works and how it is assured. It is not a qualification of any site’s equipment, sets no universal limits, and was checked by SPEQ against the sources it lists, not by an independent engineer.
WHAT IT DOES
Clean-in-place (CIP) circulates rinse water and cleaning solutions through fixed vessels and lines via spray devices, without dismantling; clean-out-of-place (COP) washes removable parts in a washer. Chapter 3 asks that equipment be designed to be "easily and thoroughly cleaned", cleaned to written procedures and stored clean and dry (3.36).
Annex 15 asks that cleaning be validated for all product-contact equipment, with residue limits from a toxicological evaluation, worst cases as the basis of the studies, and the normal operating range of an automatic process validated (10.1, 10.4–10.6). Visual cleanliness is part of acceptance but "it is not generally acceptable for this criterion alone to be used" (10.2).
Where it sits: Between batches and campaigns on formulation vessels, transfer lines, filling equipment parts and other product-contact equipment.
WHERE YOU FIND IT
- Formulation and holding vessels
- Transfer lines and filter housings
- Filling machine parts, tools and containers (COP)
In the reference facility: Processing & formulation suite, Equipment wash & parts preparation
Not covered on this page: Disinfection of cleanroom surfaces; Single-use equipment that is not cleaned.
MAJOR COMPONENTS
- Supply tanks and pump. Prepare and deliver rinse water and cleaning solutions.
- Heat exchanger and chemical dosing. Set solution temperature and concentration.
- Spray devices and supply/return circuits. Cover every surface of the vessel and drain it.
- Return pump and instruments. Return the solution and measure conductivity, temperature and flow.
- Parts washer (COP). Cleans removable parts in racks of defined configuration.
- Recipe controller. Runs the validated sequence of rinses, washes and final rinse.
Connects to: Purified water or WFI (final rinse); Formulation vessels and lines; Steam-in-place after cleaning; Batch and equipment logbooks.
INSTRUMENTS AND WHAT THEY MEASURE
- Conductivity sensor. Solution concentration in wash phases and the end of the final rinse. Watch for: compensated and uncompensated readings compared as if they were the same.
- Temperature sensor (RTD or thermocouple). Wash and rinse temperature. Watch for: sensor not at the location that matters (cold spot, load centre).
- Flow meter. Supply flow, which sets spray coverage. Watch for: flow measured at the supply while the low point is at the return.
- Total organic carbon (TOC) analyser. Organic residue in final rinse samples, where a specific test is not feasible (Annex 15, 10.6.2). Watch for: system suitability not shown for the analyser and method.
- Swab and rinse sampling with residue analysis. Residues at defined worst-case locations during validation (Annex 15, 10.11, 10.12). Watch for: recovery not shown for the surface material and method (annex 15, 10.12).
PARAMETERS
SETPOINT · MEASURED · LIMIT · ATTRIBUTE- Cleaning residue (limit, µg/swab or µg/cm² or ppm in rinse). At validated locations, against limits from the site’s toxicological evaluation, including cleaning agents (Annex 15, 10.6, 10.11).
- Temperature (setpoint, °C). Of each wash phase, within the validated range (Annex 15, 10.4).
- Distribution loop flow (setpoint, m/s or L/min). Supply flow within the validated range for spray coverage (Annex 15, 10.4).
- Conductivity (measured, µS/cm). Solution strength and end-of-rinse criterion, as validated.
- Dirty and clean hold time (limit, h or days). Dirty and clean hold times defined by the site in validation (Annex 15, 10.8).
SPEQ publishes no universal alarm or acceptance values: they depend on the process, the product and the site’s own qualification.
CONTROLS, ALARMS AND INTERLOCKS
- Control loop: Recipe sequence control. Runs each phase to its validated time, temperature, flow and concentration.
- Alarm: Phase out of range. Fails the cycle when a critical parameter leaves its range.
- Procedure: No retesting to a pass. Repeated cleaning and retesting until results pass is not an acceptable approach (Annex 15, 10.2).
- Procedure: Manual cleaning confirmation. Effectiveness of manual cleaning confirmed at a justified frequency (Annex 15, 10.15).
An alarm asks for a response; an interlock stops an action; a safety function protects people and has its own risk basis.
HOW IT FAILS
- Spray device blocked or misaligned. Shadowed surfaces left uncleaned.
- Dead legs or poor drainage. Residue and solution trapped in the circuit.
- Dirty hold time exceeded. Residues harder to remove than validated (Annex 15, 10.8).
- Parts loaded differently in the washer. Surfaces not reached by the validated configuration.
ASSURANCE ACROSS THE LIFECYCLE
EXAMPLES, NOT A MANDATORY LIST- Design. Cleanable design and drainability (Chapter 3, 3.36); Spray coverage (riboflavin) test.
- Cleaning validation (Annex 15, § 10). Worst-case product and conditions (10.5, 10.10); Residue limits from a toxicological evaluation (10.6); Sampling locations and recovery (10.11, 10.12); Microbial and endotoxin risk (10.7); Repeat runs justified by risk (10.13).
- Routine. Cycle records against validated ranges; Visual inspection; Hold time records.
- Change. Assessment of new products against the worst case (10.10).
WHAT THIS DOES NOT PROVE
- Equipment that looks clean is not shown to be below residue limits. Instead: Validated residue results (Annex 15, 10.2).
- A final rinse at low conductivity does not prove product residue was removed. Instead: Specific or TOC residue results at worst-case locations.
- A validated cycle for one product does not prove it cleans a new one. Instead: Assessment of the new product against the worst-case model (Annex 15, 10.10).
SOURCES
2 CITED- EU GMP Annex 15: Qualification and Validation — European Commission (EudraLex Volume 4), 2015. EU / EEA; in force. Supports: Cleaning validation: scope and grouping (10.1), visual checks (10.2), automated processes (10.4), worst cases (10.5), toxicological limits and TOC/conductivity (10.6), microbes and endotoxin (10.7), hold times (10.8), campaigns (10.9), worst-case product (10.10), sampling and recovery (10.11, 10.12), repeat runs (10.13), manual cleaning (10.15).
- EU GMP Part I, Chapter 3: Premises and Equipment — European Commission (EudraLex Volume 4), 13 August 2014, in operation 1 March 2015. European Union; in force. Supports: Cleanable design, written cleaning procedures and clean dry storage (3.36); cleaning equipment not a source of contamination (3.37).
HOW THIS PAGE WAS CHECKED
Researched and checked against the sources above by SPEQ (Claude) on 2026-10-21. It has not been reviewed by an independent engineer. It teaches how this kind of equipment works and is assured; it does not say any site, asset or process is qualified, validated or compliant.
- The EMA guideline on health-based exposure limits, which Annex 15 references for residue limits, is not yet cited.
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