A German hospital-pharmacy study argues blister-machine cleaning is a mandatory duty of care, and shows UV-Vis spectroscopy can replace HPLC as the analytical method.
What happened
A study in the European Journal of Hospital Pharmacy by Dominic Fenske and Lilly Zerrenner (Helios Klinikum Erfurt) with Stephanie Zergiebel (Friedrich Schiller University Jena, corresponding author) asks a question most cleaning-validation programmes never reach: how do you validate the cleaning of a blister packaging machine?
The authors report that validation of a cleaning process for blister machines is "essential" to ensure quality-assured care for patients, but that high-performance liquid chromatography (HPLC), the workhorse for this analysis, carries operating costs high enough to discourage routine use. Their answer was a new, quick and cost-effective method based on UV-Vis spectroscopy.
In the design, metamizole (dipyrone) and paracetamol tablets served as marker substances and were packed in blisters. Test tablets were then packaged before and after cleaning the machine and examined for contamination by UV-Vis spectroscopy — a before/after bracketing that preserves classic carryover logic.
The authors report that UV-Vis spectroscopy "has been shown to be superior to HPLC analysis for cleaning validation of blister machines," being much faster and cheaper, requiring less equipment and personnel effort "while maintaining the same reliability and sensitivity." They conclude that unit-dose blistering is increasingly popular in hospital pharmacies worldwide, and that this UV-Vis method is the first innovative method suitable for the purpose to date.
Why it matters
Packaging equipment sits on the same GMP footing as the vessels, mixers and tablet presses in a manufacturing suite: it contacts product, sheds residues, and must be shown clean by evidence rather than assertion. Yet blister lines are frequently outside the scope of a site's cleaning-validation master plan — treated as secondary packaging when, in unit-dose repackaging, they are the last surface a tablet touches before the patient.
The cost argument is the practically important one. Where an analytical method is expensive to run, sampling tends to shrink, acceptance criteria get justified by precedent rather than measurement, and revalidation lags behind product changeover. A cheaper, faster method does not lower the scientific bar — it changes what is affordable to measure routinely, which is where validated status is either maintained or quietly lost.
What is particularly interesting
The method does not abandon carryover testing. It keeps marker substances, pre- and post-clean sampling and a contaminant-specific measurement, then swaps the detector — a useful model for resource-limited settings: preserve the validation rationale, re-engineer the burden of proof. A pharmacy that cannot justify routine HPLC can now defend routine measurement.
Limitations
The study is single-site and confined to two marker substances with convenient UV chromophores; it does not establish that UV-Vis generalises to actives without suitable absorbance, nor to highly potent products. Specificity, swab recovery and linearity must be established per product family. The abstract reports no numerical residue values, MACO derivation, hold times or acceptance criteria.
Questions for our programme
- Which of our equipment is excluded from the cleaning-validation master plan purely by convention — blister lines, cartoners, cap sealers, transfer conveyors?
- If analytical cost is the real constraint on sampling density, would an adapted spectroscopic method let us sample more locations rather than fewer?
- What is our justified rationale for sampling locations on packaging equipment, and is it documented from a residue-risk assessment?
- Are our acceptance criteria derived from a health-based exposure or dose-based limit, rather than inherited from the previous validation?
- Do our protocols state explicitly when visual inspection, not analysis, is the deciding evidence?
Sources
Fenske D, Zerrenner L, Zergiebel S. Cleaning validation for blister packaging machines in hospital-supplying pharmacies. European Journal of Hospital Pharmacy. doi:10.1136/ejhpharm-2024-004232. PMID 39043561. https://pubmed.ncbi.nlm.nih.gov/39043561/
Validation takeaway
Packaging equipment belongs in the cleaning-validation master plan, and analytical method cost is a design variable: a validated UV-Vis method can make routine residue testing affordable where HPLC economics force sampling to shrink.
Questions worth asking in our own programme
- Which of our equipment is excluded from the cleaning-validation master plan purely by convention — blister lines, cartoners, cap sealers, transfer conveyors?
- If analytical cost is the real constraint on sampling density, would an adapted spectroscopic method let us sample more locations rather than fewer?
- What is our justified rationale for sampling locations on packaging equipment, and is it documented from a residue-risk assessment?
- Are our acceptance criteria derived from a health-based exposure or dose-based limit, rather than inherited from the previous validation?
- Do our protocols state explicitly when visual inspection, not analysis, is the deciding evidence?
