scholarly journals Biosimilar Biologic Drugs: A Systematic Approach to Development, Manufacturing and Clinical Applications

2020 ◽  
Vol 10 (6) ◽  
pp. 191-194
Author(s):  
Kaiser Jay Aziz-Andersen
Keyword(s):  
Quality By Design ◽  
Systematic Approach ◽  
Reference Product ◽  
Drug Product ◽  
Clinical Use ◽  
Biological Characterization ◽  
Biologic Drugs ◽  
Drug Products ◽  
Risk Benefit Assessment ◽  
System Approaches

This publication addresses biosimilar biologic drugs development and future innovations. Emphasis is placed on quality system approaches to the development and availability of new biosimilar drug products presented in premarket applications. For approvals of new biosimilars, the sponsors of premarket applications must present analytical and biological characterization to demonstrate that a proposed biosimilar drug is highly similar to the licensed reference product. The premarket application protocol requires a sponsor to describe the biosimilar product’s PK/PD clinical data comparing its safety, efficacy, and immunogenicity to that of the licensed reference product. Emphasis is placed on Quality by Design (QbD), Validation, Verification, and c-GMP risk-based monitoring criteria. A brief discussion is presented on risk-benefit assessment that guides the clinical use of the new biosimilar drug product by providing patients organized data and appropriate labeling information in conformance with the new biosimilar drug’s intended clinical use. Keywords: biosimilar biologic drugs, safety, efficacy and immunogenicity, Quality by Design (QbD)

Inspecting Insulin Products Using Water Proton NMR. I. Noninvasive vs Invasive Inspection

2021 ◽  
pp. 193229682110238
Author(s):  
Marc B. Taraban ◽  
Yilin Wang ◽  
Katharine T. Briggs ◽  
Yihua Bruce Yu
Keyword(s):  
Quality Control ◽  
Relaxation Rate ◽  
Drug Product ◽  
Proton Nmr ◽  
Water Proton ◽  
Proton Relaxation ◽  
Content Uniformity ◽  
Biologic Drugs ◽  
Insulin Solution ◽  
Insulin Pens

Background: There is a clear need to transition from batch-level to vial/syringe/pen-level quality control of biologic drugs, such as insulin. This could be achieved only by noninvasive and quantitative inspection technologies that maintain the integrity of the drug product. Methods: Four insulin products for patient self-injection presented as prefilled pens have been noninvasively and quantitatively inspected using the water proton NMR technology. The inspection output is the water proton relaxation rate R2(1H2O), a continuous numerical variable rather than binary pass/fail. Results: Ten pens of each product were inspected. R2(1H2O) displays insignificant variation among the 10 pens of each product, suggesting good insulin content uniformity in the inspected pens. It is also shown that transferring the insulin solution out of and then back into the insulin pen caused significant change in R2(1H2O), presumably due to exposure to O2 in air. Conclusions: Water proton NMR can noninvasively and quantitatively inspect insulin pens. wNMR can confirm product content uniformity, but not absolute content. Its sensitivity to sample transferring provides a way to detect drug product tampering. This opens the possibility of inspecting every pen/vial/syringe by manufacturers and end-users.

scholarly journals Comparative Analysis of the QbD Approach in the Pharmaceutical Industry

2019 ◽  
Vol 8 (4) ◽  
pp. 20-26 ◽  
Author(s):  
S. A. Rozhnova ◽  
A. V. Tsypkina
Keyword(s):  
Comparative Analysis ◽  
Drug Development ◽  
Systematic Approach ◽  
New Drugs ◽  
Pharmaceutical Development ◽  
Drug Products ◽  
New Drug ◽  
Eurasian Economic Union ◽  
Pharmaceutical Manufacturers ◽  
Economic Union

Introduction. In the development and introduction of medicines into production, the aim of pharmaceutical manufacturers is to comply with the principle of «Quality-by-Design» (QbD). The International Council for Harmonisation (ICH) has created a number of GxP standards, which have become the regulatory framework for the development of documentation regulating the requirements for the development and production of drug products for countries focused on bringing their products to the world pharmaceutical market. The analysis of the system of regulation of pharmaceutical stages of development of new drugs in the territory of the Eurasian Economic Union was not considered, but for the formation of a systematic approach to the management of the process of pharmaceutical development it is necessary to describe them.Aim. To analyze the possibility of applying the QbD principle to the process of drug development at domestic pharmaceutical enterprises.Materials and methods. Content analysis of scientific publications, system and comparative analysis, sociological methods of research in the field of pharmaceutical development.Results and discussions. Regulatory state requirements to the organization and conduct of drug development procedures are analyzed and described. A number of systemic and sectoral problems typical for domestic pharmaceutical manufacturers in the organization of the development and implementation of new drug products. It is established that one of the main problems for Russian enterprises was the organization of the process as a whole and its individual procedures. To solve the problem of organization of procedures for the development and implementation of new medicines, we formed a methodological support, developed on the basis of a systematic approach and international requirements from the quality system.Conclusion. The main problem identified by the manufacturers is the lack of methodological support for the organization of the processes of pharmaceutical development and the introduction of new drugs in the part of research going to the stage of preclinical and clinical development. The decisions adopted by the Eurasian Economic Union do not affect such aspects of pharmaceutical development regulation as the organization of processes, their management and methodological support aimed at the implementation of the QbD principle. To solve this problem, we have developed guidelines for the implementation of the processes of pharmaceutical development and the introduction of new drug products, which allowed us to apply unified and formalized approaches to their organization. 

scholarly journals Container Closure and Delivery Considerations for Intravitreal Drug Administration

2021 ◽  
Vol 22 (3) ◽  
Author(s):  
Ashwin C. Parenky ◽  
Saurabh Wadhwa ◽  
Hunter H. Chen ◽  
Amardeep S. Bhalla ◽  
Kenneth S. Graham ◽  
...  
Keyword(s):  
Adverse Events ◽  
Product Development ◽  
Drug Product ◽  
Healthcare Providers ◽  
Standard Of Care ◽  
Volume Determination ◽  
Common Procedure ◽  
Drug Products ◽  
Fill Volume ◽  
Container Closure

AbstractIntravitreal (IVT) administration of therapeutics is the standard of care for treatment of back-of-eye disorders. Although a common procedure performed by retinal specialists, IVT administration is associated with unique challenges related to drug product, device and the procedure, which may result in adverse events. Container closure configuration plays a crucial role in maintaining product stability, safety, and efficacy for the intended shelf-life. Careful design of primary container configuration is also important to accurately deliver small volumes (10-100 μL). Over- or under-dosing may lead to undesired adverse events or lack of efficacy resulting in unpredictable and variable clinical responses. IVT drug products have been traditionally presented in glass vials. However, pre-filled syringes offer a more convenient administration option by reducing the number of steps required for dose preparation there by potentially reducing the time demand on the healthcare providers. In addition to primary container selection, product development studies should focus on, among other things, primary container component characterization, material compatibility with the formulation, formulation stability, fill volume determination, extractables/leachables, and terminal sterilization. Ancillary components such as disposable syringes and needles must be carefully selected, and a detailed administration procedure that includes dosing instructions is required to ensure successful administration of the product. Despite significant efforts in improving the drug product and administration procedures, ocular safety concerns such as endophthalmitis, increased intraocular pressure, and presence of silicone floaters have been reported. A systematic review of available literature on container closure and devices for IVT administration can help guide successful product development.

scholarly journals Rotulagem de medicamentos industrializados: uma análise das diretrizes legais brasileiras e contribuições para a qualidade de produtos

2020 ◽  
Vol 20 (81) ◽  
Author(s):  
Márcia Lombardo
Keyword(s):  
Drug Product ◽  
Regulatory Agencies ◽  
Quality And Safety ◽  
Sources Of Information ◽  
Normative Documents ◽  
Drug Products ◽  
Legal Provisions ◽  
Product Surveillance ◽  
Study Results ◽  
Regulatory Knowledge

RESUMOObjetivos: a rotulagem é um aspecto de qualidade fundamental no uso de medicamentos, seja pelo profissional de saúde, seja pelo paciente. Este trabalho propôs uma análise crítica do tema com base na legislação em vigor, bem como a triagem de documentos normativos úteis no processo de elaboração ou de avaliação da conformidade da rotulagem de medicamentos. Métodos: foi realizada uma pesquisa documental empregando-se como fonte de informações os sítios eletrônicos oficiais do Ministério da Saúde e da Agência Nacional de Vigilância Sanitária. Os documentos contendo itens pertinentes a rotulagem de medicamentos e classificados como vigentes ou vigentes com alteração foram selecionados para a realização do estudo. Resultados: os quesitos mais relevantes das disposições gerais e das disposições específicas da norma vigente para rotulagem de medicamentos foram sistematizados, verificando-se suas contribuições na qualidade e segurança de produtos. Embora a padronização da rotulagem de medicamentos seja necessária, a ocorrência de elevados graus de semelhança entre rótulos, embalagens ou mesmo nomenclaturas é discutida no âmbito da prática clínica e esta questão merece atenção especial. A busca de material complementar à legislação vigente resultou no levantamento de um total de 20 documentos, incluindo normas, guias, bancos de consulta e planilhas, que podem auxiliar no cumprimento dos requisitos de rotulagem de medicamentos. Conclusão: rótulos de medicamentos são recursos técnicos que contribuem na eficácia e na segurança do tratamento. Os esforços das Agências Reguladoras têm permitido a consolidação de diretrizes legais para que informações e formatos adequados de rotulagem sejam aplicados nas embalagens de medicamentos industrializados. A elaboração ou a análise da rotulagem de medicamentos requer amplo conhecimento regulatório, o qual é dinâmico e, portanto, um grande desafio.Palavras-chave: Rotulagem de Medicamentos. Legislação de Medicamentos. Vigilância de Produtos Comercializados. Segurança do Paciente. ABSTRACTObjectives: the labeling of drug products is an aspect of quality that is fundamental to the use of medicines, whether by the health professional or by the patient. This work proposed a critical analysis of the current legislation on the labeling of drug products, as well as the screening of normative documents useful for the process of preparing or assessing the conformity of labels. Methods: a documentary research was carried out using the official websites of the Ministry of Health and the National Health Surveillance Agency (Brazil) as sources of information. The documents containing relevant items on labeling of drug products and classified as current or current with changes were selected for the study. Results: the most important requirements of the general and specific provisions from the current legislation have been systematized, and their contributions to the quality and safety of products have been verified. Although the standardization of the labeling is necessary, the occurrence of high degrees of similarity between labels, packaging or even nomenclatures is discussed in the context of clinical practice and this issue deserves special attention. The search for material complementary to the current legislation resulted in the collection of a total of 20 documents, including normative documents, guides, databases and spreadsheets, which might help in complying with the requirements for the labeling of drug products. Conclusion: the labeling of drug products are technical resources that contribute to the effectiveness and safety of treatment. The efforts of the Regulatory Agencies have allowed the consolidation of legal provisions for the dissemination of appropriate information and labeling formats in the packaging of drug products. The drafting or analysis of the labels requires extensive regulatory knowledge, which is dynamic and, therefore, a great challenge.Keywords: Drug Labeling. Legislation, Drug. Product Surveillance, Postmarketing. Patient Safety.

scholarly journals Rapid microbiological testing method

2020 ◽  
Vol 11 (3) ◽  
pp. 3927-3932
Author(s):  
Raghuprakash P ◽  
Gowrav M P ◽  
Gangadharappa H V ◽  
Hemanth Kumar S
Keyword(s):  
Clinical Laboratory ◽  
Drug Product ◽  
Free Products ◽  
Hygienic Condition ◽  
Cycle Times ◽  
Drug Products ◽  
Microbiological Methods ◽  
Wide Range ◽  
Microbiological Testing ◽  
Microorganism Identification

Classical microbiological methods currently have unacceptably long cycle times. Rapid microbiological strategies are accessible within the marketplace for about 10 years and are mostly used in the clinical laboratory and in food industries. However, their reapplication in the pharma industry has wide range of advantage. A comparison with ancient strategies to be conjointly performed. During this review, data concerning the validation of RMM strategies described within the document was given in addition as proof of the issue of validation of those strategies. A comparison with ancient strategies is additionally mentioned. This data is beneficial to the industries and in the labs which will doubtless be adopted. These strategies for microorganism free products. This methodology for microorganism identification will be delicate, accurate and fast. How the laboratory should be maintained for carrying out different tests, there should be good hygienic condition maintained. This article also includes different methods for identifying bacteria which is present in drug products as well as the material which are used for doing test. Presence of bacteria may affect the activity of drug product and bio availability may decreases and potency the drug may loss. How the laboratory should be maintained for carrying out different tests, there should be good hygienic condition maintained.

scholarly journals Liposome Characterization, Applications and Regulatory landscape in US

2021 ◽  
Vol 9 (2) ◽  
pp. 81-89
Author(s):  
Amit Kumar ◽  
Madhu Gupta ◽  
Simran Braya
Keyword(s):  
Drug Product ◽  
Drug Carrier ◽  
Current Status ◽  
Liposomal Drug ◽  
Drug Products ◽  
Target Drug Delivery ◽  
Target Drug ◽  
Conventional Drug ◽  
Regulatory Guidelines ◽  
Reduced Toxicity

Liposomes are lipid based drug carrier whose therapeutic performance depends on their structure. Liposomes offer several advantages over the conventional drug like target drug delivery, reduced toxicity, and extended pharmacokinetics. Characterization and Identification of critical attribute of liposomal formulation and suitable strategies for control during product development is important for quality of the liposomal drug product. This paper discusses the current status of the liposomal drug product and strategy used in regulating liposome product. Despite of lack of regulatory guidelines many liposome formulations get approved which shows the potential of liposome drug products.

scholarly journals Development of the Minimum Equipment List: Current Practice and the Need for Standardisation

Aerospace ◽  
2020 ◽  
Vol 7 (1) ◽  
pp. 7
Author(s):  
Solomon O. Obadimu ◽  
Nektarios Karanikas ◽  
Kyriakos I. Kourousis
Keyword(s):  
Present State ◽  
Environmental Conditions ◽  
Systematic Approach ◽  
Current Practice ◽  
Prior Experience ◽  
Technical System ◽  
Related Literature ◽  
Aircraft Systems ◽  
Tailored Approach ◽  
System Approaches

As part of the airworthiness requirements, an aircraft cannot be dispatched with an inoperative equipment or system unless this is allowed by the Minimum Equipment List (MEL) under any applicable conditions. Commonly, the MEL mirrors the Master MEL (MMEL), which is developed by the manufacturer and approved by the regulator. However, the increasing complexity of aircraft systems and the diversity of operational requirements, environmental conditions, fleet configuration, etc. necessitates a tailored approach to developing the MEL. While it is the responsibility of every aircraft operator to ensure the airworthiness of their aircraft, regulators are also required to publish guidelines to help operators develop their MELs. Currently, there is no approved standard to develop a MEL, and this poses a challenge to both aviation regulators and aircraft operators. This paper reviews current MEL literature, standards and processes as well as MEL related accidents/incidents to offer an overview of the present state of the MEL development and use and reinstate the need for a systematic approach. Furthermore, this paper exposes the paucity of MEL related literature and the ambiguity in MEL regulations. In addition, it was found that inadequate training and guidance on the development and use of MEL as well as lack of prior experience in airworthiness topics can lead to mismanagement and misapplication of the MEL. Considering the challenges outlined above, this study proposes the combination of system engineering and socio-technical system approaches for the development of a MEL.

Does a coxib-associated thrombotic risk limit the clinical use of the compounds as analgesic, antiinflammatory drugs?

2006 ◽  
Vol 96 (10) ◽  
pp. 413-416 ◽  
Author(s):  
Thomas Hohlfeld ◽  
Sebastian Harder ◽  
Artur-Aron Weber
Keyword(s):  
Clinical Practice ◽  
Therapeutic Option ◽  
Benefit Assessment ◽  
Clinical Use ◽  
Antiinflammatory Drugs ◽  
Thrombotic Risk ◽  
Risk Benefit Assessment ◽  
Inflammatory Drugs ◽  
Cox 2 ◽  
Cox 2 Inhibitors

SummaryThe issue of the risk-benefit assessment of cyclooxygenase-2 (COX-2) inhibitors, as compared to traditional non-steroidal anti-inflammatory drugs (tNSAIDs), is far from being resolved. These compounds need to be carefully re-evaluated in order to avoid hasty conclusions, as it happened when COX-2 inhibitors were introduced into clinical practice. Several arguments support the concept, that COX-2 inhibitors remain a valuable therapeutic option at least for selected patients.

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