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Automated compounding device (ACD) are increasingly used for parenteral nutrition (PN) bag production, and their acquisition must be sufficiently thought. The law requires the qualification of these ACD, but did not specify the tests to be performed. The quality by design (QbD) risk based approach allowed to define the quality target product profile in order to acquire the best ACD for each unit, and thanks a risk analysis permitted to define the critical quality attributes (CQA). These CQA will allowed to define tests performed during qualification. The ACD qualified was a 12 pump volumetric system. The CQA for PN bags consisted in sterile, precisely and accurately production with enough stability. During operational qualification volumetric accuracy test was performed, and during the performance qualification: flush volume, media fill, microbiological integrity of environment, sterility of control bag and production test were performed. At the end, all tests were conclusive (excepted for some results mostly due to analytical bias) and the ACD was considered to produce sterile bags in a control environment, precisely (relative standard deviation < 4%) and accurately (mean bias < 1% for weight and < 7% for other controls) with a sufficient stability. The QbD risk based approach allowed to acquire the best ACD for our need, and qualify relevant elements regarding the production process. [Display omitted] [ABSTRACT FROM AUTHOR]

Cardiovascular diseases, including fatal myocardial infarctions from atheromatous plaques, are the primary global mortality cause. Detecting stenotic atheromatous plaques is possible through coronary angiography, but vulnerable plaques with eccentric remodeling are undetectable with current diagnostic methods. Addressing this challenge, our group developed a radiopharmaceutical drug targeting vascular cell adhesion molecule 1 (VCAM-1), radiolabeled with technetium-99m. Given the absence of a monograph in the European Pharmacopoeia, and in order to draft the investigational medicinal product documentation, analytical methods had to be validated by high performance liquid chromatography (HPLC) and thin layer chromatography (TLC) to determine the radiochemical purity (RCP) of 99mTc-cAbVCAM1–5. This study therefore presents the results of the validation of analytical methods obtained in this context. The method validation followed the European Association of Nuclear Medicine (EANM) recommendations adapted from ICH Q2(R1), ensuring conformity with specificity, accuracy, repeatability and intermediate precision, linearity, robustness, quantification limit (LoQ), and range criteria. Regarding the results of specificity, both HPLC and TLC methods demonstrated excellent separation of 99mTc-cAbVCAM1–5 from impurities 99mTcO4-. Accuracy results indicated recovery percentages within the range of 99.52–101.40% for the HPLC and 99.51–101.97% for TLC, ensuring reliable measurements for each concentration of 99mTcO 4 -. Precision of the methods was validated by assessing repeatability and intermediate precision. Linearity was determined over the usual concentrations range and the correlation coefficient was greater than 0.99 for both methods. The limit of quantification was measured by diluting the 99mTcO 4 - to obtain a signal-to-noise ratio of around 10:1. Under these conditions, we obtained an LOQ of 2.10 MBq/mL for HPLC and 2Mbq/mL for TLC. In conclusion, the analytical methods developed in this study comply with EANM recommendations. This therefore allows us to correctly assess the radiochemical purity of 99mTc-cAbVCAM1–5, a new radiotracer targeting inflammation in vulnerable plaques. • 99mTc-cAbVCAM1–5 is a new radiopharmaceutical targeting a marker of inflammation found in vulnerable atheromatous plaques in cardiac diseases. • A validation of the analytical method to evaluate the radiochemical purity (RCP) by HPLC and TLC was carried out. • Specificity, accuracy, precision, linearity, robustness, quantification limit, and range criteria were assessed. • The results demonstrate that the analytical methods are suitable for assessing the RCP of this new radiopharmaceutical. [ABSTRACT FROM AUTHOR]