Compatibility of immunogenicity guidance by the EMA and the US FDA

Bioanalysis ◽  
2019 ◽  
Vol 11 (17) ◽  
pp. 1619-1629 ◽  
Author(s):  
Pekka Kurki
Keyword(s):  
Multidisciplinary Approach ◽  
Reference Product ◽  
Therapeutic Protein ◽  
European Medicines Agency ◽  
Fda Guidance ◽  
Antidrug Antibody ◽  
The Us ◽  
Antibody Assays ◽  
Us Fda

The guidelines for immunogenicity studies by the European Medicines Agency and the US FDA are based on different legislations and regulatory philosophies. In spite of the different background, the main guidelines are compatible on the scientific level, especially for new innovative therapeutic protein products. The importance of sensitive and drug-tolerant antidrug antibody assays and multidisciplinary approach to development and assessment are highlighted by both agencies. The main differences are in the field of biosimilars. The nonclinical in vivo immunogenicity studies are seen more useful by the FDA than by the European Medicines Agency. The draft FDA guidance on interchangeability will complicate global biosimilar development by requiring clinical switch studies with US sourced reference product.

scholarly journals Responder Definition of a Patient-Reported Outcome Instrument for Laryngopharyngeal Reflux Based on the US FDA Guidance

2015 ◽  
Vol 18 (4) ◽  
pp. 396-403 ◽  
Author(s):  
Han-Chung Lien ◽  
Chen-Chi Wang ◽  
Shou-Wu Lee ◽  
Jeng-Yuan Hsu ◽  
Hong-Zen Yeh ◽  
...  
Keyword(s):  
Laryngopharyngeal Reflux ◽  
Patient Reported Outcome ◽  
Fda Guidance ◽  
Outcome Instrument ◽  
Patient Reported ◽  
The Us ◽  
Us Fda ◽  
Definition Of

scholarly journals UHPLC–MS/MS method for iohexol determination in human EDTA and lithium-heparin plasma, human urine and in goat- and pig EDTA plasma

Bioanalysis ◽  
2020 ◽  
Vol 12 (14) ◽  
pp. 981-990
Author(s):  
Jasper Stevens ◽  
Mireille A Wessels ◽  
Jan Roggeveld ◽  
Remco A Koster ◽  
Claire CJ Dekkers ◽  
...  
Keyword(s):  
Human Urine ◽  
Pharmacokinetic Profile ◽  
European Medicines Agency ◽  
Simple Method ◽  
The Us ◽  
Heparin Plasma ◽  
Thermo Fisher Scientific ◽  
Tandem Quadrupole Mass Spectrometer ◽  
Edta Plasma ◽  
Us Fda

Aim: Iohexol plasma clearance is used as an indicator of kidney function in clinical and preclinical settings. To investigate the pharmacokinetic profile of iohexol, a rapid, simple method for measurement of iohexol in different matrices and species was needed. Materials & methods: Iohexol was separated on an Accucore C18 column (Thermo Fisher Scientific, CA, USA). Detection was performed on a Thermo Scientific Quantiva tandem quadrupole mass spectrometer. The method was validated according to the requirements for bioanalytical methods issued by the US FDA and European Medicines Agency. Conclusion: We developed and validated a fast and efficient analytical method, suitable for analyzing iohexol in human EDTA plasma, human lithium-heparin plasma, human urine and goat- and pig EDTA plasma, using only one calibration line prepared in human EDTA plasma.

scholarly journals Structural and Functional Characterization of Low-molecular-weight Heparins: Impact on the Development of Guidelines for Generic Products

2009 ◽  
Vol 15 (2) ◽  
pp. 137-144 ◽  
Author(s):  
Cafer Adiguzel ◽  
Walter P. Jeske ◽  
Debra Hoppensteadt ◽  
Jeanine M. Walenga ◽  
Vinod Bansal ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Functional Characterization ◽  
Current Data ◽  
European Medicines Agency ◽  
Low Molecular Weight ◽  
Low Molecular Weight Heparins ◽  
Biological Drugs ◽  
Biologic Drugs ◽  
The Us ◽  
Us Fda

Low-molecular-weight heparins (LMWHs) are poly-pharmacologic drugs used to treat thrombotic and cardiovascular disorders. Recently, several generic versions of branded LMWHs have been introduced. Although generic versions of LMWHs exhibit similar profiles, marked differences in their biological and pharmacologic properties have been demonstrated. Several studies have demonstrated differences in terms of anti-Xa activity and tissue factor pathway inhibitor release. The current data emphasize the need to consider multiple functional parameters when defining bioequivalence of biologic drugs and also underscore the importance of further pharmacologic studies involving animal and human clinical trials. The US Food and Drug Administration (FDA) and the European Medicines Agency (EMEA) are currently developing guidelines for the acceptance of complex biological drugs including LMWHs. The US FDA considers these drugs as follow-on agents whereas the EMEA classifies these drugs as biosimilar agents. Until clear guidelines are developed, generic interchange of LMWHs may not be feasible.

Simultaneous quantification of dexamethasone and 6β-hydroxydexamethasone in rabbit plasma, aqueous and vitreous humor, and retina by UHPLC–MS/MS

Bioanalysis ◽  
2021 ◽  
Author(s):  
Jianghong Gu ◽  
Jiang Wang ◽  
Ashok Krishna ◽  
Lin Xu ◽  
Sharron Stewart ◽  
...  
Keyword(s):  
Rabbit Plasma ◽  
Distribution Profile ◽  
Bioanalytical Method Validation ◽  
Simultaneous Quantification ◽  
In Vivo Release ◽  
The Us ◽  
Fit For Purpose ◽  
Us Fda

Aim: To develop and validate a fit for purpose method for the simultaneous determination of dexamethasone and its major metabolite, 6β-hydroxydexamethasone, in rabbit plasma and ocular matrices to measure the in vivo release and distribution profile of dexamethasone from intravitreal implants. Materials & methods: An UHPLC–MS/MS system was employed to perform the bioanalysis. The method was validated according to the US FDA Bioanalytical Method Validation Guidance for Industry. Results & conclusion: The method was found to be fit-for-purpose for the described biological matrices and had a LLOQ of 0.1 ng/ml.

Analysis of regulatory guidance on antidrug antibody testing for therapeutic protein products

Bioanalysis ◽  
2019 ◽  
Vol 11 (24) ◽  
pp. 2283-2296 ◽  
Author(s):  
Nazneen Bano ◽  
Troy McKelvey ◽  
Nathan Spear ◽  
Tong-Yuan Yang ◽  
Gopi Shankar ◽  
...  
Keyword(s):  
Immune Responses ◽  
Antibody Testing ◽  
Regulatory Guidance ◽  
Antidrug Antibody ◽  
Antibody Assays ◽  
Guidance Documents ◽  
Potential Impact ◽  
Us Fda ◽  
Key Aspects ◽  
Development And Validation

Therapeutic proteins have the potential to induce unwanted immune responses. The potential impact of immunogenicity on pharmacokinetics, pharmacodynamics, safety and efficacy are well established. Here, we analyze key aspects of current US FDA and EMA guidelines on the development and validation of antidrug antibody assays. Although FDA and EMA guidance documents are in harmony on most points, EMA allows greater leeway for scientific judgement, while FDA recommends specific approaches that may not be appropriate in some situations. Many white papers suggest approaches different from the guidance documents, however, these can conflict with each other and are themselves only scientifically valid in certain situations. Here, we indicate when alternatives to guidance may be needed and what those approaches might be.

scholarly journals A Mixture of Tocopherol Acetate and L-Menthol Synergistically Promotes Hair Growth in C57BL/6 Mice

Pharmaceutics ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1234
Author(s):  
Seunghyun Ahn ◽  
Jung Yeon Lee ◽  
Sang Mi Choi ◽  
Yujeong Shin ◽  
Seyeon Park
Keyword(s):  
Hair Growth ◽  
Dorsal Side ◽  
In Vivo Experiments ◽  
Forkhead Box ◽  
Tocopherol Acetate ◽  
The Us ◽  
Topical Minoxidil ◽  
Fibroblast Growth Factor 10 ◽  
Us Fda

Oral finasteride and topical minoxidil are single components approved by the US FDA for treating hair loss. Some other compounds originating from natural products are also traditionally used for promoting hair growth. In this study, observations of treated keratinocyte cells were used to demonstrate that tocopherol acetate, L-menthol, and stevioside exert an effect on cell regeneration. Furthermore, these were topically applied to the shaved skin of C57BL/6 mice to observe their effects on hair growth. A mixture of tocopherol acetate, L-menthol, and stevioside showed the highest potential for promoting hair growth in vivo. In in vivo experiments, the mixture of tocopherol acetate, L-menthol, and stevioside was more effective than tocopherol acetate or L-menthol alone in promoting hair growth. The transcriptome analysis of skin from the dorsal side of a mouse treated with tocopherol acetate or L-menthol versus vehicle revealed key changes in keratin, keratin-associated protein, forkhead box, sonic hedgehog, fibroblast growth factor 10, desmoglein 4, deoxyribonuclease 1-like 2, and cadherin 3, known to play roles in promoting hair growth.

An updated review of infliximab biosimilar, CT-P13, in the treatment of immune-mediated inflammatory diseases

Immunotherapy ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 609-623
Author(s):  
Seung Wook Hong ◽  
Yong-Gil Kim ◽  
Byong Duk Ye
Keyword(s):  
Clinical Trials ◽  
Clinical Outcomes ◽  
Real World ◽  
Inflammatory Diseases ◽  
European Medicines Agency ◽  
Immune Mediated ◽  
The Us ◽  
Us Fda ◽  
The Cost

The introduction of anti-TNFs, such as infliximab (IFX), has revolutionized the treatment of immune-mediated inflammatory diseases. Anti-TNF agents have shown outstanding efficacy and long-term improvement of clinical outcomes, but the cost has been relatively high. Out of this concern, several ‘biosimilar’ drugs of anti-TNF agents have been developed. CT-P13, the first biosimilar of reference IFX, was approved by the European Medicines Agency and licensed by the US FDA for use in all indications of IFX. This updated review summarizes all aspects of CT-P13, including pharmacology and pharmacokinetics, and evaluates its efficacy, safety and immunogenicity for all indications based on the results of the latest clinical trials as well as on real-world experiences.

Quantitative bioanalytical LC–MS/MS assay for S130 in rat plasma-application to a pharmacokinetic study

Bioanalysis ◽  
2019 ◽  
Vol 11 (16) ◽  
pp. 1469-1481 ◽  
Author(s):  
Yanping Guan ◽  
Yuanyuan Fu ◽  
Yao Liu ◽  
Siyi Wang ◽  
Man Zhao ◽  
...  
Keyword(s):  
Rat Plasma ◽  
Negative Influence ◽  
Selected Reaction Monitoring ◽  
Toxicological Evaluation ◽  
Colorectal Cancer Cells ◽  
The Us ◽  
Us Fda

Aim: An innovative Atg4B inhibitor, S130, exhibited a negative influence on colorectal cancer cells in vitro and in vivo. To assist reliable toxicodynamic and pharmacokinetic evaluation, an LC–MS/MS assay of S130 in rat plasma must be necessary. Results: An LC–MS/MS assay for determination of S130 in rat plasma has been first developed and fully verified whose values met the admissible limits as per the US FDA guidelines. Chromatographic separation was achieved by using an isocratic elution after 3 min. MS was conducted under the ESI+ mode fitted with selected reaction monitoring. The calibration curve proved acceptable linearity over 0.50–800 ng/ml. Conclusion: The developed LC–MS/MS assay of S130 in rat plasma is easily applicable in pharmacokinetics study and the further toxicological evaluation.

Regulatory Framework and Challenges in Developing Biosimilar Monoclonal Antibodies and Related Biological Products

1970 ◽  
Vol 5 (3) ◽  
pp. 1765-1774
Author(s):  
Bobby George
Keyword(s):  
Monoclonal Antibodies ◽  
Anticancer Agents ◽  
Repeated Administration ◽  
European Medicines Agency ◽  
Dominant Component ◽  
Regulatory Strategy ◽  
The Us ◽  
Us Fda ◽  
New Guidelines ◽  
The Right

Monoclonal antibodies (mAbs) were initially used as laboratory reagents, later they were adopted as clinical diagnostic reagents, and eventually as therapeutic agents. The develop-ment of therapeutic mAbs commenced in the early 1980s and by 1986 the first mAb for human use “Orthoclone OKT3®” was approved by the US Food and Drug Administration (FDA). The next wave of antibody products were mostly anticancer agents which were approved in the US and Europe in the 1990s. The technological evolution from murine-based therapeutic mAbs to chimeric (part murine part human protein), humanized, and fully human antibodies has led to a reduction in immune-mediated clearance and hypersensitivity, improved the safety and feasibility of repeated administration making them therapeuti-cally viable.Since the commercialization of the first therapeutic mAb, these products have become a dominant component of the biopharmaceutical marketgenerating revenues of several billion dollars.The area of biosimilar antibody development is positioned for substantial growth with regulatory agencies like the European Medicines Agency (EMA) coming up with new guidelines on similar biological medicinal products followed by Health Canada, the US FDA and others, addressing biosimilar product development. With few of the blockbuster mAbs going off-patent in the next decade, companies with expertise in manufacturing biosimilar mAbs with the right kind of business and regulatory strategy are likely to have good value proposition.

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