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Health Informatics Journal 2021Pharmaceutical supply chain (PSC) consists of multiple stakeholders including raw material suppliers, manufacturers, distributors, regulatory authorities, pharmacies,... (Review)
Review
Pharmaceutical supply chain (PSC) consists of multiple stakeholders including raw material suppliers, manufacturers, distributors, regulatory authorities, pharmacies, hospitals, and patients. The complexity of product and transaction flows in PSC requires an effective traceability system to determine the current and all previous product ownerships. In addition, digitizing track and trace process provides significant benefit for regulatory oversight and ensures product safety. Blockchain-based drug traceability offers a potential solution to create a distributed shared data platform for an immutable, trustworthy, accountable and transparent system in the PSC. In this paper, we present an overview of product traceability issues in the PSC and envisage how blockchain technology can provide effective provenance, track and trace solution to mitigate counterfeit medications. We propose two potential blockchain based decentralized architectures, Hyperledger Fabric and Besu to meet critical requirements for drug traceability such as privacy, trust, transparency, security, authorization and authentication, and scalability. We propose, discuss, and compare two potential blockchain architectures for drug traceability. We identify and discuss several open research challenges related to the application of blockchain technology for drug traceability. The proposed blockchain architectures provide a valuable roadmap for Health Informatics researchers to build and deploy an end-to-end solution for the pharmaceutical industry.
Topics: Blockchain; Hospitals; Humans; Pharmaceutical Preparations; Privacy; Technology
PubMed: 33899576
DOI: 10.1177/14604582211011228 -
Advanced Drug Delivery Reviews Jun 2018Nanomedicines and follow-on versions (also called nanosimilars in the EU) have been on the market partially for decades although without recognition of their nano... (Review)
Review
Nanomedicines and follow-on versions (also called nanosimilars in the EU) have been on the market partially for decades although without recognition of their nano properties in the beginning; a substantial number is in clinical development. Nanomedicines are typically synthetic and belong to the non-biological complex drugs. They show a high variability in form, structure, and size. Additionally large molecule biologics show nano-characteristics meaning nano-dimension in size (1-100 nm) or specific properties related to these dimensions. The high complexity of nanomedicines with their heterogeneous structures do not allow a full physicochemical quality characterization, challenging the regulatory evaluation especially for follow-on versions upon comparison with the reference product. The generic paradigm with the sameness approach for quality and bioequivalence in blood plasma is not appropriate for nanomedicines where a similar approach is needed. After experiencing non-equivalence of authorized parenteral colloidal iron follow-on versions, EMA and FDA issued reflection papers and draft guidances for industry to present their current thinking on the evaluation of such complex products. A stepwise approach to evaluate the extent of similarity, from quality, including critical quality attributes (CQA) and assessment of nano properties, to a non-clinical biodistribution assay, required in the the EU but not in the US, and to clinical evaluation makes sense. The cumulated totality of evidence for the authorization of nanomedicine follow-on versions goes case-by-case. Interchangeability, or substitutability, is a challenge. However, a defined or even harmonized approval pathway for these follow-versions is still missing and causes potential differences in approval. To progress, a science-based discussion platform among stakeholders and experts in the field is necessary. An agenda has been agreed [5], namely CQA assessment, publication of scientific and clinical findings, consensus on nomenclature and labelling, and regulatory actions on substandard complex drug products. Consensus created in a public private approach will support progress towards a defined and harmonized regulatory pathway for nanomedicines and their follow-on versions. This will provide drug innovation but also larger access to follow-on versions of nanomedicines, both a benefit for the patient.
Topics: Drugs, Generic; Humans; Nanomedicine; Particle Size
PubMed: 29966685
DOI: 10.1016/j.addr.2018.06.024 -
Journal of Hepatology Apr 2023Biomarkers have the potential to accelerate drug development, as early indicators of improved clinical response, to improve patient safety, and for personalised... (Review)
Review
Biomarkers have the potential to accelerate drug development, as early indicators of improved clinical response, to improve patient safety, and for personalised medicine. However, few have been approved through the biomarker qualification pathways of the regulatory agencies. This paper outlines how biomarkers can accelerate drug development, and reviews the lessons learned by the EU IMI2-funded LITMUS consortium, which has had several interactions with regulatory agencies in both the US and EU regarding biomarker qualification in patients with non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. Sharing knowledge of such interactions with the scientific community is of paramount importance to increase the chances of qualification of relevant biomarkers that may accelerate drug development, and thereby help patients, across disease indications. A qualified biomarker enables a decision to be made that all understand and support in a common framework.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Biomarkers; Drug Development
PubMed: 36526000
DOI: 10.1016/j.jhep.2022.11.028 -
Toxicology Communications 2020The media have featured the antimalarials chloroquine (CQ) and hydroxychloroquine (HCQ) to treat coronavirus (COVID-19). Political leaders have touted their use and...
The media have featured the antimalarials chloroquine (CQ) and hydroxychloroquine (HCQ) to treat coronavirus (COVID-19). Political leaders have touted their use and recommended availability to the public. These anti-inflammatory agents have substantial human toxicity with a narrow therapeutic window. CQ and HCQ poisoning cause myocardial depression and profound hypotension due to vasodilation. Bradycardia and ventricular escape rhythms arise from impaired myocardial automaticity and conductivity due to sodium and potassium channel blockade. With cardiotoxicity, ECGs may show widened QRS, atrioventricular heart block and QT interval prolongation. CQ may also cause seizures, often refractory to standard treatment. Of concern is pediatric poisoning, where 1-2 pills of CQ or HCQ can cause serious and potentially fatal toxicity in a toddler. The treatment of CQ/HCQ poisoning includes high-dose intravenous diazepam postulated to have positive ionotropic and antidysrhythmic properties that may antagonize the cardiotoxic effects of CQ. Infusions of epinephrine titrated to treat unstable hypotension, as well as potassium for severe hypokalemia may be required. Current scientific evidence does not support treatment or prophylactic use of these agents for COVID-19 disease. Regulatory and public health authorities recognize that CQ/HCQ may offer little clinical benefit and only add risk requiring further investigation before wider public distribution.
PubMed: 32457932
DOI: 10.1080/24734306.2020.1757967 -
Journal of Pharmaceutical Sciences May 2022Recent advancements in data engineering, data science, and secure cloud storage can transform the current state of global Chemistry, Manufacturing, and Controls (CMC)... (Review)
Review
Recent advancements in data engineering, data science, and secure cloud storage can transform the current state of global Chemistry, Manufacturing, and Controls (CMC) regulatory activities to automated online digital processes. Modernizing regulatory activities will facilitate simultaneous global submissions and concurrent collaborative reviews, significantly reducing global licensing timelines and variability in globally registered product details. This article describes advancements made within the pharmaceutical industry from theoretical concepts to utilization of structured content and data in CMC submissions. The term Structured Content and Data Management (SCDM) outlines the end-to-end scientific data lifecycle from capture in source systems, aggregation into a consolidated repository, and transformation into semantically structured blocks with metadata defining relationships between scientific data and business contexts. Automation of regulatory authoring (termed Structured Content Authoring) is feasible because SCDM makes data both human and machine readable. It will offer health authorities access to the digital data beyond the current standard of PDF documents and, for a review process, SCDM would "enrich the effectiveness, efficiency, and consistency of regulatory quality oversight" (Yu et al., 2019). SCDM is a novel solution for content and data management in regulatory submissions and can enable faster access to critical therapies worldwide.
Topics: Commerce; Data Management; Drug Industry; Humans
PubMed: 34610323
DOI: 10.1016/j.xphs.2021.09.046 -
Journal of Cutaneous Medicine and... 2022Soft Tissue Filler (STF) Therapy for cosmetic facial rejuvenation is associated with known complications. The manifestation of these known complications can lead to... (Review)
Review
Soft Tissue Filler (STF) Therapy for cosmetic facial rejuvenation is associated with known complications. The manifestation of these known complications can lead to patients commencing civil litigation actions or making complaints to provincial regulatory authorities and alleging that the practitioner failed to obtain the patient's informed consent to the therapy. Data provided by the Canadian Medical Protective Association (CMPA) on medical-legal cases arising from the provision of STF therapy between 2005 and 2019 are presented. Select reported case law decisions from Canadian courts and regulatory bodies addressing the concept of informed consent are reviewed. Insights about the risk factors pertaining to the process of obtaining informed consent for STF therapy are presented to increase an understanding of the elements of communication and documentation needed to ensure patients are aware of the consequences of this treatment.
Topics: Canada; Cosmetic Techniques; Dermal Fillers; Face; Humans; Informed Consent; Malpractice
PubMed: 34310242
DOI: 10.1177/12034754211032542 -
Frontiers in Sociology 2022This article discusses similarities between the finance industry and the gambling industry. It considers empirical studies from both fields and compares both industries...
This article discusses similarities between the finance industry and the gambling industry. It considers empirical studies from both fields and compares both industries with regard to possible substitution effects. Afterwards, the current regulatory approach to gambling and financial markets is discussed. Based on this literature review, the author points out that regulators need to acknowledge the fact that both markets possess addictive properties and attract certain risk-seeking individuals. Moreover, the regulators need to find a way to align their fundamentally different objectives to find common solutions to cross-industry problems. Finally, an increased cooperation between (state) authorities is necessary. This cooperation could help to protect traders from developing gambling-related problems, provide significant insights for industry-wide and product-specific regulation and lead to a more informed use of technology for harm prevention purposes. The most important similarities and differences of both markets and the resulting regulatory implications are briefly summarized.
PubMed: 36479159
DOI: 10.3389/fsoc.2022.1023307 -
Bundesgesundheitsblatt,... Nov 2020Allergen immunotherapy (AIT) is the only causally effective, disease-modifying form of therapy that, in addition to alleviating allergic symptoms, counteracts disease... (Review)
Review
Allergen immunotherapy (AIT) is the only causally effective, disease-modifying form of therapy that, in addition to alleviating allergic symptoms, counteracts disease progression.This article provides an up-to-date overview of immunological, regulatory and practical aspects of AIT. Current literature was included and recent conceptual regulatory developments from the Division of Allergology at the higher federal authority (Paul-Ehrlich-Institut) are presented.The 62 AIT products currently approved in Germany and further 61 AIT products under the development program of the Therapy Allergen Ordinance (TAO) include 95 products for subcutaneous (SCIT) and 28 for sublingual (SLIT) treatment of birch/alder/hazel pollen, grass pollen, weed pollen, house dust mite and insect venom allergies. Native and chemically modified allergen extracts (allergoids) adsorbed to aluminium, tyrosine (partly monophosphoryl lipid A-adjuvanted) or lactose or based on lyophilisates are used as active ingredients.These 123 AIT products are subject to official state batch release testing. This does not apply to named patient products (NPPs) available for the treatment of less prevalent allergies (e.g. to olive pollen, animal hair, storage mites or moulds). There is a particular need for development of AIT products for children.As a new class of active ingredients, food allergens are in clinical phase II and III studies. A first food preparation for oral AIT of peanut allergy in children is currently undergoing a central European marketing authorization (MA) procedure. MA can only be granted if the benefit-risk balance is positive. Science and regulation are in continuous exchange on the development of AIT products that correspond to the current state of clinical research and regulation in the EU and enable early causal treatment of widespread allergies.
Topics: Allergens; Animals; Asthma; Child; Desensitization, Immunologic; Germany; Humans; Pollen
PubMed: 33140209
DOI: 10.1007/s00103-020-03224-6 -
Frontiers in Medicine 2020In recent years inhaled systems have shown momentum as patient-personalized therapies emerge. A significant improvement in terms of therapeutic efficacy and/or reduction... (Review)
Review
In recent years inhaled systems have shown momentum as patient-personalized therapies emerge. A significant improvement in terms of therapeutic efficacy and/or reduction adverse systemic effects is anticipated from their use owing these systems regional accumulation. Nevertheless, whatever safety and efficacy evidence required for inhaled formulations regulatory approval, it still poses an additional hurdle to gaining market access. In contrast with the formal intravenous medicines approval, the narrower adoption of pulmonary administration might rely on discrepancies in pre-clinical and clinical data provided by the marketing authorization holder to the regulatory authorities. Evidences of a diverse and inconsistent regulatory framework led to concerns over toxicity issues and respiratory safety. However, an overall trend to support general concepts of good practices exists. Current regulatory guidelines that supports PK/PD (pharmacokinetics/pharmacodynamic) assessment seeks attention threatening those inhaled formulations set to be approved in the coming years. A more complex scenario arises from the attempt of implementing nanomedicines for pulmonary administration. Cutting-edge image techniques could play a key role in supporting diverse stages of clinical development facilitating this pharmaceutics take off and speed to patients. The ongoing challenge in adapting conventional regulatory frameworks has proven to be tremendously difficult in an environment where market entry relies on multiple collections of evidence. This paper intention is to remind us that an acceptable pre-clinical toxicological program could emerge from, but not only, an accurate and robust data imaging collection. It is our conviction that if implemented, inhaled nanomedicines might have impact in multiple severe conditions, such as lung cancer, by fulfilling the opportunity for developing tailored treatments while solving dose-related toxicity issues; the most limiting threat in conventional lung cancer clinical management.
PubMed: 32181253
DOI: 10.3389/fmed.2020.00050 -
Clinical Therapeutics Aug 2022For more than a decade, the World Health Organization, Pan American Health Organization, Pan-American Network or Drug Regulatory Harmonization, and the International... (Review)
Review
For more than a decade, the World Health Organization, Pan American Health Organization, Pan-American Network or Drug Regulatory Harmonization, and the International Conference of Drug Regulatory Authorities, have encouraged regulators to adopt reliance and recognition pathways to reduce duplication, improve efficiency and efficacy, and strengthen regulatory capabilities, in order to facilitate marketing authorization approval, thereby maintaining supply chain integrity. Several factors have limited the more widespread implementation of reliance pathways in Latin America, among which is having the appropriate legal tools in place between and among agencies. Key among these tools are the Memorandum of Understanding (MOU) and cooperation agreements. Herein we have reviewed the content and the characteristics of MOUs and cooperation agreements available on the official websites of the regulatory agencies of the region (we found 11 multilateral MOUs and 8 cooperation agreements published), signed by Latin American agencies and interregional organizations. In this commentary, common characteristics are identified and recommendations for further implementation are made to promote communication, information sharing, and trust, thereby supporting the broader use of reliance pathways in the region.
Topics: Humans; Latin America; Organizations; Pan American Health Organization
PubMed: 35798570
DOI: 10.1016/j.clinthera.2022.06.005