Crizanlizumab, a monoclonal antibody against P-selectin, has been shown to reduce vaso-occlusive crises (VOCs) compared to placebo in patients ≥ 16 years with sickle cell disease (SCD). However, there have been rare reports of patients experiencing severe pain and subsequent complications within 24 hours of crizanlizumab infusions. These events are defined as infusion-related reactions (IRRs). Informed by current literature and clinical experience, a group of content experts developed clinical guidelines for the management of IRRs in patients with SCD. We used the RAND/University of California, Los Angeles (UCLA) modified Delphi panel method, a valid, reproducible technique for achieving consensus. We present our recommendations for managing IRRs, which depend on patient characteristics including: prior history of IRRs to other monoclonal antibodies or medications, changes to crizanlizumab infusion rate and patient monitoring, pain severity relative to patient\'s typical SCD crises, and severe allergic symptoms. These recommendations outline how to evaluate and manage IRRs in patients receiving crizanlizumab. Future research should validate this guidance using clinical data and identify patients at risk for these IRRs.

Antibody-drug conjugates (ADCs) are a class of targeted biological agents that link cytotoxic drugs to monoclonal antibodies through linkers. The monoclonal antibody targets tumor cells and transports small-molecule cytotoxic drugs for specific delivery and minimal off-target side effects. September 30, 2022, 14 anti-tumor ADC drugs have been approved for marketing in the world, and four ADCs have been approved in China. With the improvement of the clinical accessibility of ADC drugs, clinicians urgently need to understand the molecular characteristics and mechanisms of ADCs, and clarify the indications for rational use of drugs. Patients\' survival mainly depends on the appropriate dose and course of treatment and also on proper management of adverse reactions. In view of this, on the basis of the \"Expert Consensus on the Clinical Application of Antibody-drug Conjugates for the Treatment of Malignant Tumors (2020 edition)\" , Professional Committee on Clinical Research of Oncology Drugs, Chinese Anti-Cancer Association fully combines the existing clinical research evidence and the feasibility of current ADC drugs in China to update the consensus content. This consensus aims to provide a systematic overview of ADC drugs, so as to provide practical and effective suggestions and references for clinicians to apply and manage ADC drugs more accurately.
抗体药物偶联物(ADC)是一类通过连接子将细胞毒性药物连接到单克隆抗体的靶向生物制剂，可高效靶向转运至目标肿瘤细胞而发挥抗肿瘤作用。截至2022年9月30日，全球已经有14种抗肿瘤ADC药物获得批准上市，中国获得批准上市的ADC有4种。随着ADC药物临床可及性的提高，临床医师亟需深入熟悉其分子特征和机制，明确适应证以合理用药。此外，选择合适的剂量和疗程，有效管理不良反应，可指导临床用药，甚至改善患者的预后转归。鉴于此，中国抗癌协会肿瘤药物临床研究专业委员会在《抗体药物偶联物治疗恶性肿瘤临床应用专家共识(2020版)》的基础上，基于临床研究证据，结合中国目前ADC药物的可及性，对共识进行更新，旨在对ADC药物进行系统性概述，从而为临床医师更精准地应用和管理ADC药物提供切实有效的建议和参考。.

Biologic therapies are known to reduce exacerbations and improve severe uncontrolled asthma management. The at-home administration of biologics has increased during the COVID-19 pandemic, but the characteristics of severe uncontrolled asthma patients who may benefit from at-home administration of biologic therapy have yet to be identified.
This project is based on the Delphi method, designed to reach an expert consensus through a multidisciplinary scientific committee addressing the following questions: clinical characteristics, treatment adherence, patient or caregiver administration ability, patient self-care, relationship with the healthcare professional, patient preference, and access to the hospital.
One hundred and thirty-one healthcare professionals (pulmonologists, allergists, nurses, and hospital pharmacists) completed two Delphi consensus questionnaires. Fourteen items were identified as priority characteristics, the first five being: 1. The patient follows the healthcare team\'s indications/recommendations to control their disease, 2. The patient is capable of detecting any deterioration in their disease and of identifying exacerbation triggers, 3. The patient receives biologic therapy and has stable disease with no vital risk, 4. The patient takes responsibility for their self-care, 5. The patient has occupational/educational obligations that prevent them from going to the hospital regularly.
Disease stability and control plus the ability to identify exacerbation triggers are the most important characteristics when opting for at-home administration for a patient with severe uncontrolled asthma on biologic therapy. These recommendations could be applicable in clinical practice.

UNASSIGNED: The use of Monoclonal Antibodies (MAbs) as therapeutics has been increasing over the past 30 years due to their high specificity and strong affinity toward the target. One of the major challenges toward their use as drugs is their low thermostability, which impacts both efficacy as well as manufacturing and delivery.
UNASSIGNED: To aid the design of thermally more stable mutants, consensus sequence-based method has been widely used. These methods typically have a success rate of about 50% with maximum melting temperature increment ranging from 10 to 32°C. To improve the prediction performance, we have developed a new and fast MAbs specific method by adding a 3D structural layer to the consensus sequence method. This is done by analyzing the close-by residue pairs which are conserved in >800 MAbs\' 3D structures.
UNASSIGNED: Combining consensus sequence and structural residue pair covariance methods, we developed an in-house application for predicting human MAb thermostability to guide protein engineers to design stable molecules. Major advantage of this structural level assessment is in significantly reducing the false positives by almost half from the consensus sequence method alone. This application has shown success in designing MAb engineering panels in multiple biologics programs.
UNASSIGNED: Our data science-based method shows impacts in Mab engineering.

X-linked hypophosphataemia (XLH), the most common inherited form of rickets, is caused by a PHEX gene mutation that leads to excessive serum levels of fibroblast growth factor 23 (FGF23). This leads to clinical manifestations such as rickets, osteomalacia, pain, lower limb deformity and overall diminished quality of life. The overarching aims in the management of children with XLH are to improve quality of life by reducing overall burden of disease, optimise an individual\'s participation in daily activities and promote normal physical and psychological development. Burosumab, a monoclonal antibody targeting FGF23, has been shown to improve biochemistry, pain, function and radiological features of rickets in children with XLH and has transformed management of XLH around the world. Burosumab has been recently approved for clinical use in children with XLH in Australia. This manuscript outlines a clinical practice guideline for the use of burosumab in children with XLH to assist local clinicians, encourage consistency of management across Australia and suggest future directions for management and research. This guideline also strongly advocates for all patients with XLH to have multidisciplinary team involvement to ensure optimal care outcomes and highlights the need to consider other aspects of care for XLH in the era of burosumab, including transition to adult care and the effective coordination of care between local health-care providers and specialist services.

The fast diffusion of the SARS-CoV-2 pandemic have called for an equally rapid evolution of the therapeutic options.The Human recombinant monoclonal antibodies (mAbs) have recently been approved by the Food and Drug Administration (FDA) and by the Italian Medicines Agency (AIFA) in subjects aged ≥12 with SARS-CoV-2 infection and specific risk factors.Currently the indications are specific for the use of two different mAbs combination: Bamlanivimab+Etesevimab (produced by Eli Lilly) and Casirivimab+Imdevimab (produced by Regeneron).These drugs have shown favorable effects in adult patients in the initial phase of infection, whereas to date few data are available on their use in children.AIFA criteria derived from the existing literature which reports an increased risk of severe COVID-19 in children with comorbidities. However, the studies analyzing the determinants for progression to severe disease are mainly monocentric, with limited numbers and reporting mostly generic risk categories.Thus, the Italian Society of Pediatrics invited its affiliated Scientific Societies to produce a Consensus document based on the revision of the criteria proposed by AIFA in light of the most recent literature and experts\' agreement.This Consensus tries to detail which patients actually have the risk to develop severe disease, analyzing the most common comorbidities in children, in order to detail the indications for mAbs administration and to guide the clinicians in identifying eligible patients.

BACKGROUND: Severe uncontrolled chronic rhinosinusitis with nasal polyps has a negative impact on an individual\'s quality of life. Therefore, new biologics have emerged for use in specific phenotypes of chronic rhinosinusitis, changing the paradigms of its treatment.
OBJECTIVE: To review the current status of biologic treatment indications in chronic rhinosinusitis.
METHODS: The Brazilian Academy of Rhinology brought together different specialists to suggest a course of action, considering its particularities and aspects related to the national reality.
RESULTS: Of particular interest for decision making will be the identification of subgroups of patients refractory to pre-existing treatment options and the construction of a strategy that improves their quality of life, with the best cost-benefit ratio.
CONCLUSIONS: The use of biologics is a valid option for treatment in more severe cases. This strategy must be better understood and improved in the future, with more studies and greater clinical experience.

Antibody-drug conjugate (ADC) is a type of targeted biological agent which connect cytotoxic drug to monoclonal antibody by a connector head, which enables monoclonal antibody acted as a carrier to efficiently transport small molecular cytotoxic drugs to target tumor cells. It is very important for clinicians to have an in-depth understanding of the molecular characteristics and mechanism of ADC drugs, rationally choose the appropriate dose, course of treatment and manage adverse reactions according to the indications during the clinical application of ADC drugs, which may even affect the survival of patients. Therefore, the consensus aims to conduct a systematic overview of commercially available ADC drugs, provide effective recommendations and references for clinicians to better apply and manage ADC drugs.
抗体药物偶联物(ADC)是一类通过连接头将细胞毒性药物连接到单克隆抗体的靶向生物药剂，以单抗作为载体将小分子细胞毒性药物以靶向方式高效地运输至目标肿瘤细胞中。深入了解ADC药物的分子特征和机制特点，并在ADC药物临床应用过程中根据适应证合理用药，选择合适的剂量和疗程，有效管理不良反应，对临床医师而言十分重要，甚至可能影响患者的生存转归。因此，共识旨在对市面可及的ADC药物进行系统概述，从而为临床医师更好地应用和管理ADC药物提供切实有效的建议和参考。.

Objective: The aim was to critically evaluate well-established regulatory agencies mAb biosimilar guidelines for development and marketing authorization about quality, efficacy and safety and compare to BRICS-TM regulations to identify challenges. Materials and Methods: The current valid guidelines of EMA, WHO, USFDA, BGTD/HC, ICH, and BRICS-TM were obtained from official websites and comparative qualitative review was performed. Results: The review revealed that Health Canada uses mAb specific guidelines from EMA or USFDA when necessary. The BRICS agencies (except Russia) have incorporated some or most of the WHO SBP TRS and related annexes in similar national biotechnological/biological guidelines; however, gaps or insufficient information have been identified. The Russian Federation has issued general product registration guideline/s with very brief information about mAbs. The TMMDA (Turkey) has published an updated biosimilar guideline which parallels those of the EMA and the ones from WHO; however, no mAb specific guidelines are published. COFEPRIS (Mexico) has published a biotechnological/biological product registration guideline with no information about mAb. The SAHPRA biosimilar guideline has an annex on mAbs which focuses on non-clinical and clinical aspects. The comparative evaluation of BRICS-TM agencies indicates a gap pertaining to clarification for physico-chemical characterization, manufacturing process, overages and compatibility requirements between biological substances and excipients specifically on mAbs. In vitro assay requirements seem quite aligned with those of WHO, whereas in vivo studies mostly have disparity in terms of necessity, type of studies as well as design and criteria. Clinical safety and efficacy studies are indicated in emerging regulatory agencies, however detailed information pertaining to design, size of populations, requirements for primary and secondary endpoints, clarity and evaluation criteria differ. In general, BRICS-TM agencies allow extrapolation of indications provided that pre-defined conditions are met. Interchangeability, switching and substitution of biosimilars are not defined in most of BRIC-TM guidelines whereas South Africa, by law, allows neither interchangeability nor substitution. Pediatric research remains questionable across BRICS-TM. Conclusions: EMA, USFDA guidelines are broadly aligned with WHO and in addition, they also contain specific requirements pertaining to their own region. BRICS-TM has considerably less defined mAb specific biosimilar development and comparability parameters in their published guidelines.

These consensus guidelines provide recommendations for the safe handling of monoclonal antibodies. Definitive recommendations are given for the minimum safe handling requirements to protect healthcare personnel. The seven recommendations cover: (i) appropriate determinants for evaluating occupational exposure risk; (ii) occupational risk level compared with other hazardous and non-hazardous drugs; (iii) stratification of risk based on healthcare personnel factors; (iv) waste products; (v) interventions and safeguards; (vi) operational and clinical factors and (vii) handling recommendations. The seventh recommendation includes a risk assessment model and flow chart for institutions to consider and evaluate clinical and operational factors unique to individual healthcare services. These guidelines specifically evaluated monoclonal antibodies used in the Australian cancer clinical practice setting; however, the principles may be applicable to monoclonal antibodies used in non-cancer settings. The guidelines are only applicable to parenterally administered agents.