TRICIN: A Phase II Trial on the Efficacy of Topical TRIchloroacetic Acid in Patients with Cervical Intraepithelial Neoplasia.

Data on non-surgical treatment approaching persistent cervical intraepithelial neoplasia (CIN) are scarce. Retrospective analysis suggest high efficacy of topical treatment with trichloroacetic acid (TCA). This prospective phase II study set out to investigate the efficacy of a single application of 85% TCA in the treatment of CIN I/II. Patients with CIN I/II were treated a single time with 85% TCA. After three and six months colposcopic, histologic, and HPV evaluation was performed. The primary endpoint was treatment efficacy defined as complete histologic remission six months after treatment. The secondary endpoint was HPV clearance six months after treatment. A total of 102 patients with CIN I/II were included into this trial. Complete histologic remission rates were 75.5% and 78.4% three and six months after TCA treatment, respectively. Clearance rates of HPV 16, 18 and other high risk types were 76.5%, 91.7%, 68.7% after six months, respectively. Side effects of TCA were mild and lasted usually less than 30 min. This is the first prospective trial reporting high histologic complete remission rates in patients with CIN I/II after a single 85% TCA treatment. In the future, TCA may represent an effective and feasible non-surgical treatment approach for CIN.

Cleaning validation for blister packaging machines in an Austrian pharmacy.

OBJECTIVES: Our pharmacy works in accordance with the Good Manufacturing Practice in the area of multidose individual blister repackaging. This required validating the cleaning procedure of the blister machines accounting for the characteristics of our setting and investigating worst possible production scenarios. METHODS: Visual clean: After machine cleaning we inspected surfaces for visible residues. Cross-contamination: A tablet vulnerable to contamination was analysed after blister packaging for residues of a medication with high contamination risk using. Critical medications in the machine were identified by their dust formation potential. Placebo tablets were blister-packaged and analysed for residues of these critical medications using mass spectrometry. We assessed pharmacological relevance of contamination from these two analyses by the dose criterion. Validity of results: Comparing production conditions and technical construction of the blister machines, validity of the validation results for the whole setting was investigated. RESULTS: After cleaning no residues were visible on the machine. No contamination was detected on the vulnerable tablet. In 80% of 280 analysed placebo tablets contamination was not measurable or below 1% of the cut-off limits according to the dose criterion, the highest value being 8.5%. Production volume and cleanability were comparable in the other machines. CONCLUSIONS: Blister machine cleaning was successfully validated: visual cleanliness was achieved; contamination values were clearly below the cut-off limits, ruling out relevant cross-contamination of copackaged drugs. The results proved valid for the whole site. The study contributes evidence to safety and quality of blister repackaging and may serve as reference for similar settings.