Building Sustainable Theranostics Programs: Operational Models, Access, and Equity.

A comprehensively designed Pharmaceutical Quality System (PQS) incorporating Good Manufacturing Practice and Quality Risk Management implemented, maintained and continuously improved, allows a consistent delivery of products with appropriate quality attributes. The manufacturer in the third country and the batch certification and release site in EU belong to the same organization operating under a corporate Pharmaceutical Quality System. A signed Quality Agreement between both parties provides improvement of the Pharmaceutical Quality System and continual maintenance of the quality of the medicinal product throughout its shelf life. This paper outlines the role and the challenges of the manufacturing site in third country within the process of batch certification and release in EU (by EU QP) and also highlights the importance of the technically justified approach including Quality Risk Management process regarding sampling in third country. Through a Technical justification for sampling including Quality Risk Assessment, it is considered that the samples taken from the manufacturing site in third country ensure representation of the whole batch. Technical justification is performed periodically to identify and manage any risks associated with this approach, thus ensuring the quality, safety and efficacy according Marketing Authorization. Keywords: batch release in EU, third country, Pharmaceutical Quality System, QP

Targeted Next-Generation Sequencing Reveals Heterogenous Genomic Features in Viscerally Metastatic Prostate Cancer.

International quality management standard (QMS) ISO 9001 became widely accepted as a framework for product and/or services quality improvement. There are recent research conducted in order to define relationships and effects between the applied QMS and financial and/or non-financial business parameters. The effects of the applied pharmaceutical quality system (PQS) on the business performances in Serbian pharmaceutical-chemical industry are analyzed in this paper using multivariate linear regression analysis. The empirical data were collected using a survey that was performed among experts from Serbian pharmaceutical-chemical industrial sector during 2010. An extensive questionnaire was used in the survey, grouping the questions in eight groups: Implementation of pharmaceutical quality system (AQ), Quality/strategy planning (QP), Human resource management (HR), Supply management (SM), Customer focus (CF), Process management (PM), Continuous improvement (CI), and Business results (BR). The primary goal of the research was to analyze the effects of the elements of first seven groups (AQ, QP, HR, SM, CF, PM, and CI) that present various aspects of the implementation of PQS, on the elements of business results (BR). Based on empirical data, regression relations were formed to present the effects of all considered elements of PQS implementation on the business performance parameters (BR). The positive effects of PQS implementation on the business performances such as the assessment of performance indicators, continual products and/or services quality improvement, and efficient problem solving, are confirmed in the presented research for the Serbian pharmaceutical-chemical industrial sector. The results of the presented research will create a room for the improvement of the existing models in application, and for attracting interested parties that aim to commence this business standardization process. Hence, implementation of PQS is not only the regulatory requirement or advertising movement, but very important issue for the development and improvement of business performances.

The integrity of data within pharmaceutical quality systems is crucial to ensuring product quality, patient safety, and regulatory compliance. This paper presents a risk-based approach to safeguarding data integrity across pharmaceutical quality systems. It discusses the regulatory frameworks, industry best practices, and the potential risks associated with data manipulation, loss, or corruption. By applying risk assessment tools, the paper outlines strategies for identifying vulnerable points in data management processes and proposes corrective actions to mitigate these risks. Furthermore, it emphasizes the importance of a robust culture of data integrity and continuous monitoring to maintain system reliability. The approach helps pharmaceutical companies comply with Good Manufacturing Practices (GMP) and other regulatory standards while ensuring the accuracy and trustworthiness of critical data.

Aim. To determine the areas of the risk-based approach to the development and implementation of the pharmaceutical quality system with the emphasis on the production of in-bulk finished products, identify the main factors affecting the stability of the functional characteristics of drugs in order to provide their compliance with the international quality standards, Good Manufacturing Practice and quality risk management. Results. 29 pharmaceutical companies with the license in Ukraine for dispensing and packing of medicines from in-bulk products have been identified. The control strategy for the production of medicines for in-bulk products has been developed as a set of measures covering the incoming control of in-bulk products, the primary, secondary packing and their labeling, patient information leaflets, finished drug at release and shelf life, control of operating conditions of premises and equipment, parameters of dispensing and packing stages. The analysis of the specificity of the production of finished drugs from in-bulk products has been performed, and the areas of the risk-oriented approach have been determined to the development and implementation of the pharmaceutical quality system in this type of production based on the risk assessment of significant factors affecting the pharmaceutical production and the use of the appropriate risk management methods for quality in the production of medicines from in-bulk products. Conclusions. It has been determined that the risk-oriented approach to the development and implementation of the pharmaceutical quality system in the production of medicines from in-bulk products is a strategic direction. It allows increasing the effectiveness of the quality management system at a qualitatively new level, achieving goals in order to prevent adverse effects on quality and safety, and it means the best possible customer satisfaction. In our research, the quality guarantees that the pharmaceutical quality system should provide in the production of medicines from in-bulk products have been identified, and the control strategy has been developed. Key words: in-bulk products; medicines; drug quality; risk-based approach; pharmaceutical quality system; Good Manufacturing Practice; quality risk assessment

Nursing and Residential CareVol. 17, No. 3 EditorialCancer treatment: at what cost?Beverley AndersonBeverley AndersonSearch for more papers by this authorBeverley AndersonPublished Online:18 Feb 2015https://doi.org/10.12968/nrec.2015.17.3.173AboutSectionsView articleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareShare onFacebookTwitterLinked InEmail View article References Aapro MS (2012) Management of advanced prostate cancer in senior adults: the new landscape. Oncologist 17(Suppl 1): 16–22 Crossref, Google ScholarAttard G, Reid AHM, Yap TA et al. (2008) Phase I clinical trial of a selective inhibitor of CYP17, abiraterone acetate, confirms that castration-resistant prostate cancer commonly remains hormone driven. J Clin Oncol 26(28): 4563–71. doi: https://doi.org/10.1200/JCO.2007.15.9749 Crossref, Google ScholarCancer Research UK (2011) Where did abiraterone come from? http://tinyurl.com/mg39ml9 (accessed 27 January 2015) Google ScholarCancer Research UK (2014) Prostate cancer. http://tinyurl.com/l7aru6y (accessed 27 January 2015) Google Scholarde Bono JS, Logothetis CJ, Molina A, Fizazi K et al. (2011) Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med 364(21): 1995–2005. doi: https://doi.org/10.1056/NEJMoa1014618 Crossref, Google ScholarFizazi K, Scher HI, Molina A, Logothetis CJ et al. (2012) Abiraterone acetate for treatment of metastatic castration-resistant prostate cancer: final overall survival analysis of the COU-AA-301 randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol 13(10): 983–92. doi: https://doi.org/10.1016/S1470-2045(12)70379-0 Crossref, Google ScholarGravanis I, Lopez AS, Hemmings RJ, Jiménez JC et al. (2013) The European medicines agency review of abiraterone for the treatment of metastatic castration-resistant prostate cancer in adult men after docetaxel chemotherapy and in chemotherapy-naive disease: summary of the scientific assessment of the committee for medicinal products for human use. Oncologist 18(9): 1032–42. doi: https://doi.org/10.1634/theoncologist.2013-0092 Crossref, Google ScholarLogothetis CJ, Basch E, Molina A, Fizazi K et al. (2012) Effect of abiraterone acetate and prednisone compared with placebo and prednisone on pain control and skeletal-related events in patients with metastatic castration-resistant prostate cancer: exploratory analysis of data from the COU-AA-301 randomised trial. Lancet Oncol 13(12): 1210–7. doi: https://doi.org/10.1016/S1470-2045(12)70473-4 Crossref, Google ScholarMacmillan Cancer Support (2014) Abiraterone acetate (Zytiga). http://tinyurl.com/p6b5apk (accessed 27 January 2015) Google ScholarMulders PFA, Molina A, Marberger M, Saad F et al. (2014) Efficacy and safety of abiraterone acetate in an elderly patient subgroup (aged 75 and older) with metastatic castration-resistant prostate cancer after docetaxel-based chemotherapy. Eur Urol 65(1): 875–83. doi: https://doi.org/10.1016/j.eururo.2013.09.005 Crossref, Google ScholarNational Cancer Institute (2012) Abiraterone Improves Survival in Metastatic Prostate Cancer. http://tinyurl.com/3m4orwt (accessed 27 January 2015) Google ScholarNational Institute of Health and Care Excellence (2011) Prostate cancer (metastatic, hormone relapsed, not treated with chemotherapy) – abiraterone acetate (with prednisolone) [ID503]: appraisal consultation document. http://tinyurl.com/nvx4tgv (accessed 27 January 2015) Google ScholarNational Institute of Health and Care Excellence (2014a) Prostate Cancer: diagnosis and treatment, NICE Clinical Guideline 175. http://tinyurl.com/pu6ccrm (accessed 27 January 2015) Google ScholarNational Institute of Health and Clinical Excellence (2014b) NICE appraisal of earlier treatment with abiraterone for prostate cancer. http://tinyurl.com/kmhrnz7 (accessed 27 January 2015) Google ScholarParker C, Sartor O (2011) Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med 365(8): 767. doi: https://doi.org/10.1056/NEJMc1107198#SA3 Google ScholarPezaro CJ, Mukherji D, De Bono JS (2012) Abiraterone acetate: redefining hormone treatment for advanced prostate cancer. Drug Discov Today 17(5–6): 221–6. doi: https://doi.org/10.1016/j.drudis.2011.12.012 Crossref, Google ScholarProstate Cancer UK (2014) Abiraterone should definitely be an option for men who haven't had chemotherapy. http://tinyurl.com/k7b9dy9 (accessed 27 January 2015) Google ScholarRathkopf DE, Smith MR, De Bono JS et al. (2013) Updated interim analysis of COU-AA-302, a randomized phase III study of abiraterone acetate in patients with metastatic castration-resistant prostate cancer (mCRPC) without prior chemotherapy. http://tinyurl.com/pr5ocav (accessed 27 January 2015) Google ScholarScher, HI., Logothetis, C., Molina, A., Goodman, OB., Sternberg, CN., Chi, KN., Kheoh, TS., Itagg, CM., Fizazi, de Bono, JS. et al. (2010) Improved Survival outcomes in clinically relevant patient subgroups from COU-AA-301, a phase III study of abiraterone acetate plus prednisone in patients with metastatic castration-resistant prostate cancer after docetaxel-based chemotherapy, http://tinyurl.com/oph44n5 (accessed 27 January 2015) Google ScholarSmith R (2014) Prostate cancer patients ‘unjustly’ denied drug, The Telegraph. http://tinyurl.com/pvchebo (accessed 27 January 2015) Google ScholarThe Institute of Cancer Research (2014a) Abiraterone: a story of scientific innovation and commercial partnership. http://tinyurl.com/m2ehlpy (accessed 27 January 2015) Google ScholarThe Institute of Cancer Research (2014b) NICE pauses abiraterone decision for further price discussions. http://tinyurl.com/oeg3s5c (accessed 27 January 2015) Google Scholar FiguresReferencesRelatedDetailsCited byA Perspective on Uro-Oncology Management and the Macmillan Uro-Oncology CNS (MUCNS) Role in this Management23 March 2022 2 March 2015Volume 17Issue 3ISSN (print): 1465-9301ISSN (online): 2052-2932 Metrics History Published online 18 February 2015 Published in print 2 March 2015 Information© MA Healthcare LimitedPDF download

Second-line treatment options in metastatic castration-resistant prostate cancer: A comparison of key trials with recently approved agents

To establish a novel quantitative method that automatically excludes the red bone marrow and accurately quantifies the tumor volume on whole-body magnetic resonance imaging using updated imaging software. To also evaluate the association between the quantified tumor volume and the prognosis of patients with metastatic prostate cancer. This prospective analysis included patients diagnosed with metastatic hormone-sensitive or metastatic castration-resistant prostate cancer between 2017 and 2022. We developed an imaging software (Attractive BD_Score) that analyzed whole-body diffusion-weighted and in-phase and opposed-phase T1-weighted images to automatically exclude the red bone marrow. The quantified tumor volume was compared with that quantified by traditional whole-body diffusion-weighted imaging without red bone marrow exclusion. Prostate-specific antigen progression-free survival, time-to-pain progression, and overall survival were evaluated to assess the prognostic value of the quantified tumor volume. The quantified tumor volume was significantly smaller than that quantified by the traditional method in metastatic hormone-sensitive (median: 81.0 ml vs. 149.4ml) and metastatic castration-resistant (median: 29.4 ml vs. 63.5ml) prostate cancer. A highly quantified tumor volume was associated with prostate-specific antigen progression-free survival (p= 0.030), time-to-pain progression (p=0.003), and overall survival (p= 0.005) in patients with metastatic hormone-sensitive prostate cancer and with poor prostate-specific antigen progression-free survival (p= 0.001) and time-to-pain progression (p= 0.005) in patients with metastatic castration-resistant prostate cancer. Our imaging method could accurately quantify the tumor volume in patients with metastatic prostate cancer. The quantified tumor volume can be clinically applied as a new prognostic biomarker for metastatic prostate cancer.

Knowledge management (KM) is identified in ICH Q10 (Pharmaceutical Quality System), as a key enabler to the pharmaceutical quality system (PQS). ICH Q8 (Pharmaceutical Development), ICH Q11 (Development and Manufacture of Drug Substances), and ICH Q12 (Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management) each build on the expectation that knowledge will be managed effectively in order to support and improve the product and process across the pharmaceutical product life cycle. However, in spite of the fact that KM was introduced in ICH Q10 over 10 years ago, there is ample evidence that it is not yet a mature discipline within the biopharmaceutical sector, and the authors suggest that this could hinder full realization of the potential benefits of ICH Q8, ICH Q11, and ICH Q12. The Pharmaceutical Regulatory Science Team (PRST), a research team based at the Dublin Technological University (TU Dublin) in Ireland, has been conducting research on KM for several years, and this paper presents the next phase in this research. Specifically, the focus of this current research was to explore ways to offer practical solutions to improve the management of knowledge across the pharmaceutical product life cycle, starting with a focus on enhancing knowledge transfer during technology transfer projects. The typical challenges associated with ineffective knowledge transfer were presented and the high-level requirements needed to address these were identified through the research. From these requirements, a four-step framework was developed as a systematic means to enhance knowledge transfer. Accompanying the framework was a KM toolkit consisting of a range of KM practices (tools, processes, and behaviors) to facilitate more effective knowledge flow during technology transfer. It was then illustrated how such a framework can be extended across the entire pharmaceutical product life cycle, supporting the advancement of KM from an enabler in ICH Q10 to a key consideration (both technical and regulatory) in ICH Q12.

Metastatic Burden in Hormone-Naive Prostate Cancer: A Tale of Two Subgroups

Advanced Prostate Cancer: AUA/ASTRO/SUO Guideline PART II.

In 2015, American Cancer Society predicts that 220,800 men will be diagnosed with prostate cancer (PC). Patients diagnosed with metastatic PC are first treated with androgen deprivation therapies (ADT) in order to lower testosterone to castration levels. Unfortunately, it is only a matter of time before becoming metastatic castration resistant prostate cancer (mCRPC). Subsequent treatments include combined androgen deprivation therapies such as (abiraterone, enzalutamide), immunotherapies, investigational drugs, and/or chemotherapy (docetaxel and cabazitaxel). Individualizing therapy for prostate cancer patients is an overarching goal of research. Currently, no valid practical biomarkers exist that can predict resistance to the taxane in PC. Identifying a marker that predicts taxane sensitivity would delineate patients who would benefit from taxane regimens from those who would suffer from added side-effects without any improved response. Previous studies have confirmed TLE3 is associated with a response to taxane therapy in breast and ovarian cancers. Preclinical studies have also shown that TLR4, RAGE, and HMGB1 confers chemo resistance to docetaxel on PC-3 human PC cells. After obtaining IRB approval (protocol IUCRO-0499), 8 metastatic castration resistant prostate cancer samples and 6 control samples were pulled for this study after scrutinous review of the H&E slides from clinical cases. This study then consisted of investigating the proteins TLE3, TLR4, RAGE, and HMBG1. Immunostaining was performed using the automated immunostainer, Dako FLEX System, and the slides were scanned into the whole slide Aperio Scanscope CS digital imaging system. Computer-assisted morphometric analysis of digital images was then performed using the Aperio ImageScope software. Review of the TLE3 and TLR4 expression in metastatic castration resistance prostate cancer samples showed a difference between the expressions of these two proteins. TLR4 positivity was found to be 43.88% higher than the expression of TLE3. This is suggestive of resistance to docetaxel treatments. Review of the RAGE and HMGB1 expression in metastatic castration resistance prostate cancer samples compared to normal prostate epithelium showed a 32.9% increase in RAGE and 36.6% increase in HMGB1 expression. The findings of this study are suggestive that there is a possible correlation between the overexpression of these protein biomarkers and the patient's response to a specific drug treatment. Citation Format: Greg A. Rothchild, George Sandusky, Constance J. Temm, Costantine Albany. Identifying a predictive biomarker for chemotherapy (taxane) in patients with metastatic castration resistance prostate cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 426.

Post-approval changes (PACs) are inevitable and necessary throughout the life of a drug product. Because many PACs require prior approval by individual regulatory agencies each having their own reporting requirements and approval timelines, this results in companies having to manage several versions of a manufacturing process at the same time. The global regulatory complexity increases risk of drug shortages. Chief quality officers and heads of quality from more than 20 global pharmaceutical companies have come together to speak with One-Voice-of-Quality (1VQ) and develop solutions to this problem by developing a science and risk-based approach to manage more PACs in the pharmaceutical quality system (PQS) rather than submitting these as prior approval supplements. Pharmaceutical companies already conduct management review (MR) according to the International Conference on Harmonization (ICH) Q10. This One-Voice-Of-Quality paper is a practical guide on how companies can expand the MR to also evaluate and demonstrate the effectiveness of their PQS in specifically managing PACs to achieve regulatory flexibility as stated in ICH Q10, Annex 1. Examples of PQS key performance indicators (KPIs) that may be used to assess, plan, implement, and monitor PACs are described. The intent is to provide assurance through MR that PACs can be managed effectively in the PQS, thereby resulting in a reduced need for regulatory prior approval of certain low risk changes that enhance product availability, reduce the risk of drug shortages, and/or facilitate timely innovation and continual improvement in the pharmaceutical industry. This document is endorsed by 1VQ chief quality officers and heads of quality.

The publication discusses the theoretical and regulatory aspects of a pharmaceutical quality system (PQS) design at the manufacturers, including its discussion through the prism of historical and foreign experience, and specifies the significance of single PQS design for the formation of the EAEU single pharmaceutical market. It is substantiated that the quality assurance of pharmaceutical products under current conditions should be based on an integral approach, the most important element of which is PQS, universal guidelines contained in the current GMP regulations. The authors propose the solutions of the problem, among which an important role is played by the further harmonization of PQS requirements and the unification of management and control systems in the market.

Continuing enzalutamide with docetaxel in castration-resistant prostate cancer.