Quality Issues Identified During the Evaluation of Biosimilars by the European Medicines Agency's Committee for Medicinal Products for Human Use.

The aim of this study was to identify trends in deficiencies raised during the EU evaluation of the quality part of dossiers for marketing authorisation applications of biosimilar medicinal products. All adopted day 120 list of questions on the quality module of 22 marketing authorisation applications for biosimilars submitted to the European Medicines Agency and concluded by the end of October 2015 was analysed. Frequencies of common deficiencies identified were calculated and summarised descriptions included. Frequencies and trends on quality deficiencies were recorded and presented for 22 biosimilar applications. Thirty-two 'major objections' for 9 products were identified from 14 marketing authorisation applications with 15 raised for drug substance and 17 for drug product. In addition, 547 'other concerns' for drug substance and 495 for drug product were also adopted. The frequencies and trends of the identified deficiencies together with their impact were discussed from a regulatory perspective and how these impact key manufacturing processes and key materials used in the production of biosimilars. This study provides an insight to the regulatory challenges prospective companies need to consider when developing biosimilars; it also helps elucidate common pitfalls in the development and production of biosimilars and in the submission of dossiers for their marketing authorisations. The results are expected to be of interest to pharmaceutical companies but also to regulators to obtain consistent information on medicinal products based on transparent rules safeguarding the necessary pharmaceutical quality of medicinal products.

Anonymization of DICOM electronic medical records for radiation therapy.

Electronic medical records (EMR) and treatment plans are used in research on patient outcomes and radiation effects. In many situations researchers must remove protected health information (PHI) from EMRs. The literature contains several studies describing the anonymization of generic Digital Imaging and Communication in Medicine (DICOM) files and DICOM image sets but no publications were found that discuss the anonymization of DICOM radiation therapy plans, a key component of an EMR in a cancer clinic. In addition to this we were unable to find a commercial software tool that met the minimum requirements for anonymization and preservation of data integrity for radiation therapy research. The purpose of this study was to develop a prototype software code to meet the requirements for the anonymization of radiation therapy treatment plans and to develop a way to validate that code and demonstrate that it properly anonymized treatment plans and preserved data integrity. We extended an open-source code to process all relevant PHI and to allow for the automatic anonymization of multiple EMRs. The prototype code successfully anonymized multiple treatment plans in less than 1min/patient. We also tested commercial optical character recognition (OCR) algorithms for the detection of burned-in text on the images, but they were unable to reliably recognize text. In addition, we developed and tested an image filtering algorithm that allowed us to isolate and redact alpha-numeric text from a test radiograph. Validation tests verified that PHI was anonymized and data integrity, such as the relationship between DICOM unique identifiers (UID) was preserved.