Cleaning Validation — ISO 17664 / AAMI TIR30 · Pharmaceutical Analysis

What Is Cleaning Validation?

Cleaning validation proves that the manufacturer's cleaning instructions for a reusable medical device reduce real-use soiling to an acceptable level. It is a mandatory step before sterilisation: a device with organic residue on it cannot be reliably sterilised.

Purpose of Cleaning Validation

The purpose is to show that the cleaning method in the instructions for use is effective even in the worst-case soiling scenario, and to fulfil the information obligation under ISO 17664.

Which Products Is Cleaning Validation Applied To?

Reusable surgical instruments
Endoscopes and lumened devices
Orthopaedic instruments and sets
Dental hand instruments
Reusable device accessories

In Which Sectors Is Cleaning Validation Used?

Medical DeviceHealthcarePharmaceuticals

Standards Related to Cleaning Validation

ISO 17664-1
ISO 15883 series
AAMI TIR30
AAMI ST98
ISO 11737-1determination of microbial load in medical devices test

Cleaning Validation Conditions

Test soil: Artificial soil representing clinical use, as defined in the standards, is applied
Worst case: The hardest-to-clean points of the device (lumen, hinge, blind hole) are targeted
Markers: Residue indicators such as protein, haemoglobin, TOC, carbohydrate and endotoxin are measured

Equipment for Cleaning Validation

Washer-disinfector
Ultrasonic cleaner
Residue-extraction rig
Spectrophotometer and TOC analyser
Microbiology laboratory infrastructure

Sample Requirements for Cleaning Validation

Real devices, in a configuration representing the worst case
The number of specimens must be determined with statistical justification
Device design details (lumen diameter, hinge, disassembly) must be shared
The recommended cleaning instructions and chemicals must be provided

Duration of Cleaning Validation

Typically several weeks, including method development and repeat cycles.

Cleaning Validation Procedure

1The device's hardest-to-clean points are identified.
2The residue-extraction method is developed and recovery efficiency is determined.
3The test soil defined in the standard is applied to the device and left to dry.
4The cleaning cycle in the manufacturer's instructions is applied.
5Residues are extracted from the device.
6Protein, haemoglobin, TOC and other markers are measured.
7The residue level is calculated, corrected by the recovery factor.
8The cycle is repeated to demonstrate consistency.

Cleaning Validation Acceptance Criteria

Acceptance criteria are determined and justified by the organisation; residue thresholds commonly used in technical reports such as AAMI TIR30 (e.g. values on the order of micrograms per unit area for protein) are used as reference. The standard does not impose a single universal limit.

Evaluation of Results

Results are evaluated at the worst-case points. If recovery efficiency is low, the measured residue appears lower than it really is; validation of the extraction method is therefore essential for the reliability of the result.

Cleaning Validation Report

Device description and worst-case rationale
Test-soil composition and application method
Cleaning-cycle parameters
Extraction method and recovery efficiency
Residue-marker results
Acceptance criteria and rationale

Accreditation

EUROLAB holds internationally recognised accreditation obtained from accreditation bodies party to the IAF and ILAC multilateral recognition arrangements, under ISO/IEC 17025 for laboratory testing, ISO/IEC 17020 for inspection and surveillance, and ISO/IEC 17021-1 and ISO/IEC 17065 for system and product certification. This chain ensures the reports and certificates issued are accepted worldwide.

Whether this test can be offered within accredited scope depends on your product and the standard applied; since accreditation is method-based, the scope is confirmed in writing at the quotation stage.

Scope and authorisations

Related Regulations

MDR (EU) 2017/745
ISO 17664 information requirements

Pharmaceutical Analysis — What Does This Testing Field Cover?

The section below describes the field that the Cleaning Validation test belongs to; the conditions and acceptance criteria of this particular test are given in the sections above. The scope specific to your product is confirmed in writing at the quotation stage.

Pharmaceutical analysis determines the identity, purity, quantity and behaviour of an active substance and of the finished product. What sets this family apart is that the methods are largely defined in PHARMACOPOEIAS: the European Pharmacopoeia (Ph. Eur.) and the United States Pharmacopeia (USP) give both the method and the acceptance framework together.

The binding nature of the pharmacopoeial method shapes how the field works. In other sectors a laboratory can choose a suitable method, whereas here the method in the monograph governs; if an alternative method is to be used, its equivalence must be demonstrated. This is what makes results comparable worldwide.

Analyses are carried out in several groups. Identity and assay (HPLC, UV, titration) show what the product is and how much active substance it contains. The impurity profile and residual solvents look for unwanted compounds arising from the manufacturing process. Elemental impurities address metals originating from catalysts and equipment. Dissolution and disintegration behaviour is the most important in vitro indicator of how the drug will be released in the body.

The DISSOLUTION TEST is one of the most critical measurements in the field. It is not enough for a tablet to contain the right amount of active substance; that substance must dissolve at a suitable rate. The dissolution profile is used to assess the effect of formulation changes on bioavailability and holds a central place in generic drug licensing.

METHOD VALIDATION is a mandatory step in this family. If a pharmacopoeial method is used, it is verified that the method works properly under that laboratory's conditions. If an in-house method has been developed, it is validated against parameters such as linearity, precision, accuracy, specificity, limits of detection and quantification, and robustness. A result produced with an unvalidated method cannot be used in a licence dossier.

Stability studies determine shelf life and are the longest-running work in the field. The product is held under defined temperature and humidity conditions, analysed at set intervals, and the results become the basis of the shelf life and storage condition claims. Accelerated conditions give preliminary information but real-time data is what counts.

The microbiological side is a separate body of work: microbial enumeration, testing for specified microorganisms, sterility testing for sterile products and the bacterial endotoxin test. For sterile products, packaging integrity and sterilisation validation also come into play.

Data integrity has moved to the centre of inspections in recent years. It is not enough for the result to be correct; the raw data must be traceable, unalterable and auditable. Validation of electronic record systems has therefore become an inseparable part of analysis.

Method groups in this field

Identity and assay
HPLC, UPLC, UV-Vis spectrophotometry, titration, identity confirmation by FTIR.
Impurities and residues
Related impurities, degradation products, residual solvents (GC headspace), nitrosamine screening.
Elemental impurities
Determination of elemental impurities by ICP-MS and ICP-OES and the associated risk assessment.
Physicochemical
Dissolution and disintegration, hardness, friability, uniformity of dosage units, water content (Karl Fischer), particle size.
Microbiological
Microbial enumeration, specified microorganisms, sterility, bacterial endotoxin, preservative efficacy.
Stability
Real-time and accelerated stability studies; photostability and in-use stability.

Commonly confused in this field

The pharmacopoeial method is binding; an alternative method may be used only by demonstrating its equivalence.
A result produced without method validation cannot be used in a licence dossier.
Accelerated stability does not replace real-time data; shelf life is supported by real-time results.
The dissolution profile is sensitive to apparatus type, agitation rate and medium; the conditions must be complete in the report.
A shortcoming in data integrity produces a non-conformity in an inspection even when the result is correct.
A change of formulation or supplier requires analytical comparison and, where necessary, a new stability study.

Which decisions these results support

The licence dossier and batch release
Determining shelf life and storage conditions
Method transfer and method validation
Incoming raw material acceptance control from suppliers
Assessing the effect of a formulation change on bioequivalence

Related Tests

Frequently Asked Questions About Cleaning Validation

Why is a worst-case device selected?

Validating every device in a product family separately is impractical. If the hardest-to-clean geometry (the narrowest lumen, the most complex hinge) is validated, the more easily cleaned members of the family are also covered. The selection must be justified.

Does cleaning validation substitute for sterilisation validation?

No; the two are sequential steps. Cleaning is a precondition for sterilisation to be effective. Organic residue protects microorganisms from the sterilant; both must therefore be validated separately.