This commentary outlines a proposed approach for navigating remediation (non-routine sanitization) of contaminated affinity-based resins. The methodology for collection of relevant information and for subsequent decision-making is presented, along with a tool for determining risk to the process associated with proposed return-to-use of remediated resin.

The sterility test has been utilized for many years to formally support the sterile release of products terminally sterilized by moist heat and other sterilization modalities. It is well-known that the sterility test is severely limited in providing a meaningful scientific and statistical basis to support the sterility of finished products. Accordingly, parametric release was developed as a sterility assurance release program that defines critical manufacturing process and sterilization control parameters that are essential for sterile product release, thereby eliminating the use of the sterility test. This article examines the limitations and shortcomings of the sterility test and reviews the findings from a case study to illustrate the risks associated with the overreliance on this test for the disposition of sterile products. The history of parametric release of products terminally sterilized with moist heat is presented with a summary of the current status, including a listing of global regulatory standards and guidances along with a discussion of applicable results from an industry survey of moist heat sterilization practice. This article is intended to be the initial step to establish a basic understanding of the parametric release concept and practices that can be leveraged as a baseline for future promotion and expanded implementation.

Interventions performed by personnel during an aseptic process can be a key source of microbiological contamination of sterile biopharmaceutical products, irrespective of the type of manufacturing system used. Understanding the relative risk of this source of contamination provides valuable information to help make decisions for the design, qualification, validation, operation, monitoring, and evaluation of the aseptic process. These decisions can be used to improve the aseptic process and provide assurance of the sterility of the products. To achieve these goals, an assessment of the contamination risk is needed. This risk assessment should be objective, accurate, and useful. This article presents an Intervention Risk Evaluation Model (IREM) philosophy and an objective, accurate, and useful method for intervention risk determination. The IREM uses a key word approach to identify, obtain, measure, and evaluate intervention risk factors. This article presents a general discussion of the method with the help of a case study to illustrate the development of the model, whereas subsequent parts would focus on application of this model with practical examples. This not only attempts to create objectivity of the entire process, but it develops awareness of the associated risks among shop floor operators, which can lead to a reduction of the overall risk level of the process and an improvement in the sterility assurance level.

Elagolix is a GnRH receptor antagonist, approved for treatment of endometriosis-associated pain at 150mg QD or 200mg BID, in the US, Canada, and Israel. This study examined the real-world impact of elagolix on woman’s health-related quality of life and treatment tolerability, as self-reported by women with endometriosis. This was a 6-month (M) interim analysis of the LOTUS study, an ongoing 24M observational study, collecting data via monthly electronic surveys administered through a patient support program, utilized by women in the US. Patients were pre-menopausal women, 18-49yrs. Analysis focused on women who confirmed they were taking elagolix (150mg QD or 200mg BID) every month until evaluation at 3M or 6M. Significance of the mean change from baseline for each of 6 domains of the Endometriosis Health Profile-30 questionnaire (EHP-30) at 3M (n=70) and 6M (n=44) was determined using paired t-tests. Responders for each domain were determined using published thresholds for a clinically meaningful response1. Treatment tolerability satisfaction was determined through the Endometriosis Treatment Satisfaction Questionnaire (ETSQ) and descriptive analysis was included. EHP-30 scores were statistically significantly reduced (i.e., improvement in EHP-30 domains) from baseline to 3M and 6M, respectively, for all 6 domains (See Table 1). Women with baseline moderate to severe (NRS≥4) dysmenorrhea, NMPP, or dyspareunia and completed the ESTQ (n=42, 36 and 26, respectively) responded “Somewhat Satisfied”, “Satisfied”, or “Extremely Satisfied” with 6M tolerability (lack of bothersome side effects) at 64.3%, 61.1%, and 42.3%, respectively. This real-world, patient-reported data demonstrates that elagolix had a positive impact on women’s quality of life at 3M and 6M, aligning with the results reported in elagolix phase 3 clinical trials2.

In the design, control, and regulation of the manufacturing and supply of microbiologically controlled devices (including sterile devices) and drug products (including cleaning, disinfection, and sterilization processing and/or aseptic process manufacturing), different terms and/or definitions are often used internationally for similar processes or applications. With product innovations (including combination products and cell-based therapy) and global regulatory influences, there is a growing need to harmonize these definitions. The objective of the Kilmer Regulatory Innovation microbiological quality and sterility assurance glossary is to clarify and harmonize the practical use of terms employed by the different parts of regulated health care product industries internationally and by regulators of the manufacturing and supply of microbiologically controlled health care products internationally. The glossary is expected to continue to evolve; and further industry, academic, and regulatory input is encouraged.

In clinical trials, dabrafenib plus trametinib improved overall survival (OS) compared with single-agent BRAF inhibitors (BRAFi) in patients with BRAF V600-mutant unresectable or metastatic melanoma. We investigated dabrafenib plus trametinib therapy in a compassionate-use setting [Named Patient Program (NPP); DESCRIBE II]. A retrospective chart review of patients with BRAF V600-mutated unresectable stage III/IV melanoma receiving dabrafenib plus trametinib as compassionate use was conducted. Treatment patterns and duration, clinical outcomes, and tolerability were evaluated. Of 271 patients, 92.6% had stage IV melanoma, including 36.5% with brain metastases. Overall, 162 patients (59.8%) were BRAFi naive and 171 (63.1%) received first-line dabrafenib plus trametinib. Among BRAFi-naive patients, the overall response rate (ORR) was 67.3%, median OS (mOS) was 20.0 months, and median progression-free survival (mPFS) was 7.5 months. In BRAFi-naive patients with known brain metastases (n = 62), ORR was 61.3%, mOS was 15.5 months, and mPFS was 6.2 months. Eighty-four patients received BRAFi monotherapy for >30 days and switched to dabrafenib plus trametinib prior to progression. Of these 84 patients, 63 had known disease status at the time of switch, and 22 improved with the combination therapy. No new safety signals were identified, and dabrafenib plus trametinib was well tolerated. Dabrafenib plus trametinib showed substantial clinical activity in NPP patients with BRAF V600-mutated unresectable or metastatic melanoma. Analysis of treatment patterns demonstrated the effectiveness of the combination in patients with brain metastases and across lines of therapy with a well tolerated and manageable safety profile.

Individuals with bipolar disorder are at greater risk for cardiovascular disease and are less likely to adhere to lifestyle interventions than the general population. To decrease cardiovascular risk and improve adherence to lifestyle interventions, we developed the Nutrition Exercise and Wellness Treatment (NEW Tx). NEW Tx is an 18-session, 20-week cognitive behavioral therapy-based treatment comprising 3 modules: Nutrition, Exercise, and Wellness. To evaluate the feasibility and acceptability of this intervention as well as predictors of treatment satisfaction and expectations, 38 adult outpatients with bipolar disorder were randomized to either NEW Tx or a waitlist control condition. There was no statistically significant difference in dropout rates between the groups (26.3% in NEW Tx, 31.6% in the control condition). In the NEW Tx condition, participants attended a mean of 66.7% of sessions and reported moderate to high satisfaction. There were no study-related adverse events. We also found that expectations, but not perceived credibility (or believability), of NEW Tx (as measured by the Credibility/Expectancy Questionnaire) at baseline predicted treatment satisfaction (as measured by the Care Satisfaction Questionnaire) posttreatment. Manic symptoms at baseline predicted treatment satisfaction, and marital status predicted one's expectations of lifestyle interventions. Data suggest that NEW Tx is a feasible and acceptable intervention for individuals with bipolar disorder and that further research is warranted to explore potential moderators of treatment expectations and credibility in this clinical population.

INSIGHTVolume 22, Issue 2 p. 76-76 Book Review Advances in Manufacturing and Processing of Materials and Structures Lawrence D. Pohlmann, Lawrence D. Pohlmann pohlmann@incose.org Founding member of INCOSE (member #9) passed away on July 3, 2019.Search for more papers by this author Lawrence D. Pohlmann, Lawrence D. Pohlmann pohlmann@incose.org Founding member of INCOSE (member #9) passed away on July 3, 2019.Search for more papers by this author First published: 21 August 2019 https://doi.org/10.1002/inst.12249 He served in several appointed and elected positions, including leading all of INCOSE's technical operations from 1991 to 1993 (NCOSE at the time). He was a frequent book reviewer for INSIGHT. He was a retired systems engineering and software engineering manager. Dr. Pohlmann was a part-time consultant using and applying systems engineering concepts to help clients develop solutions and proposals for large-scale programs. Since 2013, he focused his INCOSE support activities primarily on involvement with the Natural Systems Working Group. AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume22, Issue2August 2019Pages 76-76 RelatedInformation