Building a Competency Framework to Integrate Inter-disciplinary Precision Medicine Capabilities into the Medical Technology and Pharmaceutical Industry.

INTRODUCTION: Integration of precision medicine (PM) competencies across the Medical Technology and Pharmaceutical industry is critical to enable industry professionals to understand and develop the skills needed to navigate the opportunities arising from rapid scientific and technological innovation in PM. Our objective was to identify the key competency domains required by industry professionals to enable them to upskill themselves in PM-related aspects of their roles. METHODS: A desktop research review of current literature, curriculum, and healthcare trends identified a core set of domains and subdomains related to PM competencies that were consistent across multiple disciplines and competency frameworks. A survey was used to confirm the applicability of these domains to the cross-functional and multi-disciplinary work practices of industry professionals. Companies were requested to trial the domains to determine their relevance in practice and feedback was obtained. RESULTS: Four PM-relevant domains were identified from the literature review: medical science and technology; translational and clinical application; governance and regulation and professional practice. Survey results refined these domains, and case studies within companies confirmed the potential for this framework to be used as an adjunct to current role specific competency frameworks to provide a specific focus on needed PM capabilities. CONCLUSION: The framework was well accepted by local industry as a supplement to role specific competency frameworks to provide a structure on how to integrate new and evolving technologies into their current workforce development planning and build a continuous learning and cross-disciplinary mindset.

A Survey of Industry Perceptions of Facilitated Regulatory Pathways in Drug Development in Australia.

BACKGROUND: In Australia, facilitated regulatory pathways (FRPs) became available with the introduction of priority review (PR) in 2017 and provisional approval (PA) in 2018, which aim to facilitate expedited review and approval for novel medicines. The pathways were developed in consultation with a wide range of stakeholders and have since been utilised by pharmaceutical companies for various therapeutic products. However, the perceptions of the firsthand users of these pathways have not been evaluated in Australia. OBJECTIVES: We have conducted a survey of Australian regulatory professionals aiming to solicit the perceived benefits, barriers to utilisation, shortcomings and proposed modifications to utilising these pathways. We have also solicited the users' perspective on key aspects of the pathways, including overall satisfaction, regulatory burden, availability and ease of use of guidelines, regulator support, impact on company strategy and recommendations for improvement. METHODS: A survey was developed and distributed to Australian regulatory professionals from the pharmaceutical industry who had submission experience of new medicine applications via either PR, PA or the standard registration pathway to the Therapeutic Goods Administration (TGA). The questionnaire consisted of 44 questions with a skip logic and the option for free text comments. RESULTS: We received responses from 16/42 companies that had utilised these new pathways. Nine respondents had experience with the PR pathway and ten with the PA pathway. The respondents were generally satisfied with the effectiveness of the PR process in expediting registration approvals, but they were ambivalent towards the PA pathway in terms of overall satisfaction and timelines. Respondents expressed a desire for further improvements in the speed of approval, earlier access for patients across various pathways and introduction of new Health Technology Assessment processes for medicines approved under PA. CONCLUSION: While the FRPs have been an important and positive development in the Australian regulatory landscape, there remain opportunities for further improvements, some of which have been highlighted by this study and may help inform future regulatory decisions.

Regulatory Reform Outcomes and Accelerated Regulatory Pathways for New Prescription Medicines in Australia.

National Regulatory Authorities (NRAs) globally are facing the challenge of evaluating pharmaceutical products in a speedy manner, whilst simultaneously ensuring adequate efficacy, safety and quality of approved products. Additionally, common expectations include that the evaluation process is competent, flexible, commensurate with risk, efficient and rapid. In 2014, the Australian regulatory system was out of step with global regulatory developments which led to a comprehensive regulatory review and reform process. As part of the reforms, two Facilitated Regulatory Pathways (FRP) were developed for prescription medicines: Priority Review (PR) and Provisional Approval (PA). Furthermore, regulatory reliance and recognition arrangements have been expanded with the Therapeutic Goods Administration (TGA) making increased use of evaluation reports by trusted NRAs. The new pathways have been utilised by the pharmaceutical industry in Australia since 2017, with the number of medicines going through these pathways gradually increasing. Additional facilitated pathways have been developed following the review, providing alternatives to the standard pathway for registration of prescription medicines in Australia. The reform is timely, helping to position Australia well in the current global regulatory climate.

Oncofertility Information Available for Recently Approved Novel Non Cytotoxic and Immunotherapy Oncology Drugs.

We reviewed the available animal and human reproductive function studies of recently approved noncytotoxic oncology drugs. We reviewed the oncofertility information in the prescribing information for the US Food and Drug Administration (FDA)-approved products and/or the product information and consumer medicine information for Therapeutic Goods Administration (TGA)-approved drugs of 32 novel oncology drugs approved between 2014 and 2018 in the United States and/or Australia supplemented by a literature review for additional reproductive effects. No human studies were available on the reproductive effects of all 32 drugs. A systematic literature review of animal reproductive toxicity studies provided only very limited data with nine drugs displaying impaired male fertility, three impaired female fertility, and nine producing impaired fertility in both male and female animals. Two drugs in the study are reported to have no demonstrable impact on fertility in animal reproductive toxicity studies and nine are reported to have unknown effects on fertility. Of the 32 newly listed drugs, only 4 had recommendations regarding potential human fertility risks and accordingly advised clinicians about fertility preservation procedures for patients. The lack of human data and limited animal reproductive toxicity data raises concerns about the potential impact of these novel oncology drugs on human fertility and reproductive function. Consequently, adequate oncofertility recommendations, including for fertility preservation procedures, counselling for psychological or cost implications, and future prognosis for fertility are hindered by this paucity of relevant data. More data on human reproductive effects of novel oncology drugs is urgently required to facilitate effective use of the growing array of oncofertility care options available.

Future directions in regulatory affairs.

The field of regulatory affairs deals with the regulatory requirements for marketing authorization of therapeutic products. This field is facing a myriad of forces impacting all aspects of the development, regulation and value proposition of new therapeutic products. Changes in global megatrends, such as geopolitical shifts and the rise of the green economy, have emphasized the importance of manufacturing and supply chain security, and reducing the environmental impacts of product development. Rapid changes due to advances in science, digital disruption, a renewed focus on the centrality of the patient in all stages of therapeutic product development and greater collaboration between national regulatory authorities have been accelerated by the COVID-19 pandemic. This article will discuss the various trends that are impacting the development of new therapies for alleviating disease and how these trends therefore impact on the role of the regulatory affairs professional. We discuss some of the challenges and provide insights for the regulatory professional to remain at the forefront of these trends and prepare for their impacts on their work.

Multi-Criteria Decision Analysis for Benefit-Risk Analysis by National Regulatory Authorities.

The approval process for pharmaceuticals has always included a consideration of the trade-offs between benefits and risks. Until recently, these trade-offs have been made in panel discussions without using a decision model to explicitly consider what these trade-offs might be. Recently, the EMA and the FDA have embraced Multi-Criteria Decision Analysis (MCDA) as a methodology for making approval decisions. MCDA offers an approach for improving the quality of these decisions and, in particular, by using quantitative and qualitative data in a structured decision model to make trade-offs in a logical, transparent and auditable way. This paper will review the recent use of MCDA by the FDA and EMA and recommend its wider adoption by other National Regulatory Authorities (NRAs) and the pharmaceutical industry.

Creeping Through the Backdoor: Disruption in Medicine and Health.

Can disruption happen when no one notices? Disruptive technologies and processes are fundamentally starting to up-end how medicines and health systems benefit patients but the question is whether health systems are ready for them. This paper will briefly review the business strategy and management literature on topics such as disruption and "black swan" theories of change, before turning to discuss some of the areas where change is affecting medicine and healthcare. Such areas include the emergence of cell and gene therapies, the economics of cures, digital technologies, mobile apps, social media, supply chain technologies such as drones and online distribution, universal health coverage and funding, and consumerisation of healthcare. The question to be asked is whether these sorts of changes are "disruptive" or whether they were coming for a long time and it is just that health systems are slow to change. It could be argued that while perhaps unexpected by day-to-day practitioners in healthcare, in fact, many of the changes now starting to affect the health and medicines sector have been affecting other sectors such as technology, finance and communications for decades.

Curriculum Transformation: From Didactic to Competency-Based Programs in Pharmaceutical Medicine.

As the complexity of the pharmaceutical industry increases and with the current disruptive forces affecting it, there is an increasing need for suitably-qualified personnel. Universities must respond to the need for graduates with the appropriate skills and knowledge to enable the transformation and future growth of this industry. Restructuring educational offerings to focus on graduate attributes, such as analytical and critical thinking, collaboration and problem solving, creativity, flexibility and self-direction in the context of the pharmaceutical industry facilitates the changes needed for future growth and viability. This paper discusses the process of program transformation to enable the development of graduates who can respond to these challenges in the pharmaceutical industry.

Postgraduate Education in Pharmaceutical Medicine in Australia: Evaluation and Evolution to a Global Program Over 20 Years.

BACKGROUND: The Pharmaceutical Medicine program at the University of New South Wales provides postgraduate education for students seeking employment relating to development of new medicines and medical technology. The objective of this study was to determine which changes to the program were required to meet future educational needs of students. METHODS: Responses to questions from 76 students, tutors, lecturers, and stakeholders were obtained via Qualtrics surveys. RESULTS: Most respondents would recommend the program because of scope and program emphasis, content, quality of teaching, flexibility, and availability of distance and online content. Students valued links to industry and the national regulatory authority. Respondents recommended program content be current, expanded to meet needs of the Asia-Pacific region, and structured to ensure opportunities for networking and collaboration. CONCLUSIONS: Recommended changes to the program are being implemented to optimize skills and knowledge of graduates for roles in global pharmaceutical, medical technology, and biotechnology industries.

Improvements in Clinical Trials Information Will Improve the Reproductive Health and Fertility of Cancer Patients.

There are a number of barriers that result in cancer patients not being referred for oncofertility care, which include knowledge about reproductive risks of antineoplastic agents. Without this information, clinicians do not always make recommendations for oncofertility care. The objective of this study was to describe the level of reproductive information and recommendations that clinicians have available in clinical trial protocols regarding oncofertility management and follow-up, and the information that patients may receive in clinical trials patient information sheets or consent forms. A literature review of the 71 antineoplastic drugs included in the 68 clinical trial protocols showed that 68% of the antineoplastic drugs had gonadotoxic animal data, 32% had gonadotoxic human data, 83% had teratogenic animal data, and 32% had teratogenic human data. When the clinical trial protocols were reviewed, only 22% of the protocols reported the teratogenic risks and 32% of the protocols reported the gonadotoxic risk. Only 56% of phase 3 protocols had gonadotoxic information and 13% of phase 3 protocols had teratogenic information. Nine percent of the protocols provided fertility preservation recommendations and 4% provided reproductive information in the follow-up and survivorship period. Twenty-six percent had a section in the clinical trials protocol, which identified oncofertility information easily. When gonadotoxic and teratogenic effects of treatment were known, they were not consistently included in the clinical trial protocols and the lack of data for new drugs was not reported. Very few protocols gave recommendations for oncofertility management and follow-up following the completion of cancer treatment. The research team proposes a number of recommendations that should be required for clinicians and pharmaceutical companies developing new trials.