Industry perspective on a holistic container closure integrity approach to parenteral combination products.

Biologics are being developed more and more as parenteral combination products with drug delivery devices. The maintenance of sterility is imperative for such medical devices throughout their life cycle. Therefore, the container closure integrity (CCI) should, preferably, be built into the overall process, and not just demonstrated during the final testing of the combination product. The integrity is an important Critical Quality Attribute (CQA) and in the scope of specific considerations and studies during the combination product life cycle i.e., design robustness, assembly processes, storage (to end of shelf life), and shipping prior to patient use. The goal of this paper is to summarize an industry holistic approach to ensure CCI, for a combination product, and to build a scientifically based justification that Quality (in terms of CCI) is built into the overall process. Current analytical approaches used for characterization or Good Manufacturing Practice (GMP) CCI testing during combination product development will be described. However, the use of quality by design (QbD) during product development can reduce or eliminate routine batch level or stability testing of the combination product.

3D analysis of congenital scoliosis due to hemivertebra using biplanar radiography.

INTRODUCTION: This study aims to investigate the use of biplanar radiography for assessing congenital scoliosis due to hemivertebra in 3D. MATERIALS AND METHODS: A reconstruction method was developed to model 3D spines with congenital scoliosis from biplanar radiography. 3D measurements quantifying the global posture, scoliotic deformities and imbalance and describing the shape and pose of the hemivertebra were automatically computed. Five cases of congenital scoliosis were analyzed and the accuracy of the method was evaluated by comparing 3D reconstructions from biplanar radiography with 3D segmentations generated from CT. RESULTS: The mean shape accuracy was 1.8 mm (1.5 mm for the vertebral bodies and pedicles and 2.2 mm for the posterior arches). CONCLUSION: Biplanar radiography can be considered an interesting tool for clinical follow-up of congenital scoliosis as it overcomes some limitations of the analyses based on CT or anteroposterior X-ray: head to feet acquisition, low radiation dose and provides a set of automatically computed postural and morphological parameters in 3D.

Angle measurement reproducibility using EOS three-dimensional reconstructions in adolescent idiopathic scoliosis treated by posterior instrumentation.

STUDY DESIGN: A reproducibility study was conducted in preoperative and postoperative three-dimensional (3D) measurements for patients operated for adolescent idiopathic scoliosis (AIS). OBJECTIVE: To assess the reliability of preoperative and postoperative 3D reconstructions using EOS in patients operated for AIS. SUMMARY OF BACKGROUND DATA: No prior reliability study of 3D measurements has been performed in the literature for severe scoliosis and for operated patients. METHODS: This series included 24 patients (62° ± 11) operated for Lenke 1 or 2 AIS, using either all-pedicle screw constructs (group 1) or hybrid constructs, with universal clamps at thoracic levels (group 2). All patients underwent low-dose standing biplanar radiographs, pre- and postoperatively. Three operators performed the 3D reconstruction process two times preoperatively and two times postoperatively (total 288 reconstructions). Intraoperator repeatability and interoperator reproducibility were calculated and compared between groups. RESULTS: The preoperative reproducibility was between 4° and 6.5° for parameters dedicated to scoliosis (Cobb and apical vertebral rotation), between 4° and 7° for kyphosis and lordosis values, and between 1° and 5° for pelvic measurements. The postoperative reproducibility was between 5° and 8° for values of kyphosis and lordosis, between 1° and 5.5° for pelvic parameters, and between 6.5° and 10.5° for the scoliotic parameters. The reproducibility of the scoliotic parameters was slightly better in the hybrid construct group, but the difference was not significant (P = 0.8). No difference was found between groups for the other parameters. CONCLUSION: 3D postoperative reconstructions are as reproducible as preoperative ones. The reproducibility is not influenced by the type of implant used for correction. Mean difference between operator was higher than previously reported for the apical rotation measurement, but this difference can be explained by the severity of the curves and the lower visibility of the anatomical landmarks due to the implants.

3D postural balance with regard to gravity line: an evaluation in the transversal plane on 93 patients and 23 asymptomatic volunteers.

Relevance of posture assessment has been reported in case of spine disorders. This study explores the interest in quantifying posture using 3D reconstruction from biplanar X-rays in free standing position and a force plate. 93 patients consulting for spine disorders were divided ('3D deformity', 'sagittal imbalance' and 'mild deformity') and compared with 23 asymptomatic volunteers. Registration of the gravity line (GL) in reconstruction yielded transversal position of the center of acoustic meati (CAM) T1, T4, T9, L3, S1 and hip axis (HA) with regard to GL. Transversal position of CAM and L3 appeared as relevant parameters to discriminate patients from volunteers. Sagittal inclination of the axis linking the CAM to HA was correlated with position of the CAM to GL (r = 0.92 for patients). In conclusion, observing posture in 3D with regard to GL provides clinical relevant information. CAM-HA inclination may improve postural evaluation without force plate.