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 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.

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.

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.

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.

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.

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.

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.

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.

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.

Rapid differentiation of Australian, European and American ranaviruses based on variation in major capsid protein gene sequence.

Epizootic haematopoietic necrosis virus (EHNV), Bohle iridovirus (BIV) and Wamena virus (WV) cause serious diseases in fish, amphibians and snakes, respectively but are restricted to Australasia. European catfish virus (ECV) and sheatfish virus (ESV) have caused epizootics in fish on farms in continental Europe. Currently there are no simple or readily available methods to distinguish these viruses, which are in the Iridoviridae.

Rescue of the colony-stimulating factor 1 (CSF-1)-nullizygous mouse (Csf1(op)/Csf1(op)) phenotype with a CSF-1 transgene and identification of sites of local CSF-1 synthesis.

Colony-stimulating factor 1 (CSF-1) regulates the survival, proliferation, and differentiation of mononuclear phagocytes. It is expressed as a secreted glycoprotein or proteoglycan found in the circulation or as a biologically active cell-surface glycoprotein. To investigate tissue CSF-1 regulation, CSF-1-null Csf1(op)/Csf1(op) mice expressing transgenes encoding the full-length membrane-spanning CSF-1 precursor driven by 3.

The role of platelet alpha-granular proteins in the regulation of thrombopoietin messenger RNA expression in human bone marrow stromal cells.

Thrombopoietin (TPO), the specific cytokine that regulates platelet production, is expressed in human bone marrow (BM), kidney, and liver. There appears to be no regulation of TPO in the kidney and liver, but TPO messenger RNA (mRNA) expression can be modulated in the stromal cells of the BM. In this study, we used primary human BM stromal cells as a model to study the regulation of TPO mRNA expression in response to various platelet alpha-granular proteins.

hFOG-2, a novel zinc finger protein, binds the co-repressor mCtBP2 and modulates GATA-mediated activation.

We have identified a novel human zinc finger protein, hFOG-2, which is related to but distinct from the murine transcription factor Friend-of-GATA-1 (mFOG-1). The hFOG-2 gene was initially detected in K562 cells using a polymerase chain reaction approach with degenerate primers corresponding to zinc finger regions of mFOG-1. A murine homologue of hFOG-2 was also identified in the mouse expressed sequence tag data banks, indicating that a family of FOG genes exists in mammals.

Absence of colony-stimulating factor-1 in osteopetrotic (csfmop/csfmop) mice results in male fertility defects.

Previous studies have shown that the mononuclear phagocyte growth factor, colony-stimulating factor-1 (CSF-1), has an important role in female reproduction. Mating experiments with osteopetrotic (csfmop/csfmop) mice, which possess an inactivating mutation in the CSF-1 gene, suggested that there are male, as well as female, reproductive defects. In the present study, we have shown that male csfmop/csfmop mice have a sevenfold lower concentration of circulating testosterone (T) and a significantly lower intratesticular T concentration than wild-type mice.

Osteopetrotic (op/op) mice deficient in macrophages have the ability to mount a normal T-cell-dependent immune response.

The osteopetrotic (op/op) mouse possesses an inactivating mutation in the CSF-1 gene that is associated with a lack of certain mononuclear phagocyte populations. To examine the effects of these deficiencies on T-cell-dependent immune functions, the responses of op/op and normal mice to a T-cell-dependent antigen, ovalbumin, and to a foreign histocompatibility antigen were compared. The ability of op/op mice (1) to induce antigen-specific proliferation of naive T-cells, (2) to generate cytotoxic T-lymphocytes, (3) to supply spleen cells to serve as stimulators in a mixed lymphocyte reaction, and (4) to produce IgM and IgG antibodies was indistinguishable from normal mice.

Role of colony stimulating factor-1 in the establishment and regulation of tissue macrophages during postnatal development of the mouse.

Colony stimulating factor-1 (CSF-1) regulates the survival, proliferation and differentiation of mononuclear phagocytes. The osteopetrotic (op/op) mutant mouse is devoid of CSF-1 due to an inactivating mutation in the CSF-1 gene and is deficient in several mononuclear phagocyte subpopulations. To analyze more fully the requirement for CSF-1 in the establishment and maintenance of mononuclear phagocytes, the postnatal development of cells bearing the macrophage marker antigens F4/80 and MOMA-1, in op/op mice and their normal (+/op or +/+) littermates, were studied during the first three months of life.

Delayed hematopoietic development in osteopetrotic (op/op) mice.

Changes in structure, cellularity, hematopoietic progenitor cell and macrophage content, and osteoclast activity were investigated in the hematopoietic organs of the colony-stimulating factor 1(CSF-1)-less osteopetrotic (op/op) mouse. The data indicated that op/op mice undergo an age-related hematopoietic recovery and resolution of osteopetrosis, suggesting that the hematopoietic system has the capacity to use alternative mechanisms to compensate for the absence of an important multifunctional growth factor, CSF-1. In young animals, op/op femurs were heavily infiltrated with bone, and marrow cellularity was significantly reduced.

Constitutive expression of exogenous myc in myelomonocytic cells: acquisition of a more transformed phenotype and inhibition of differentiation induction.

The effects of deregulated expression of the human c-myc and MC29 v-myc oncogenes have been examined in a murine myelomonocytic cell line J774 (c-myc) and in a variety of myelomonocytic cell lines of different degrees of maturity generated from primary hematopoietic tissue (v-myc). Introduction of a Moloney murine leukemia virus long terminal repeat (LTR) c-myc construct into J774 cells resulted in constitutive expression of the exogenous myc gene and a concomitant increase in the degree of transformation and tumorigenicity of the cells. In addition, constitutive expression of exogenous myc inhibited induced differentiation of these cells by a variety of treatments including addition to the medium of lipopolysaccharide (LPS) or the phorbol ester 12-O-tetradecanoyl phorbol 13-acetate (TPA) as well as complete withdrawal of serum from the medium.

An in vitro fibroblast model system to study myc-driven tumour progression.

We have utilized fibroblast cell lines to investigate myc-mediated cell transformation and tumour progression. Deregulated myc alleles were introduced into the rat fibroblast cell line, Rat-1, and a partially-transformed derivative of this cell line termed Rat-1 (PT). A human c-myc gene coupled to the Moloney murine leukemia virus long terminal repeat was introduced into both cell lines by transfection.

Inducible transformation of fibroblasts using a metallothionein-v-myc gene construct.

An inducible oncogene construct has been engineered by coupling the MC29 v-myc oncogene to the sheep metallothionein promoter. Transfection of this plasmid, which also contains the neomycin resistance gene, into Rat-1 cells, has resulted in the isolation of independent clones resistant to G418. Certain of these clones were found to exhibit inducible transformation in response to ZnSO4.