Understanding Pharmaceutical Quality by Design

Yu, Lawrence X.; Amidon, Gregory E.; Khan, Mansoor A.; Hoag, Stephen W.; Polli, James E.; Raju, G.; Woodcock, Janet

doi:10.1208/s12248-014-9598-3

Cited by 1,034 publications

(602 citation statements)

References 19 publications

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“…One crucial element of QbD is the generation of a Quality Target Product Profile (QTPP) and enhanced process control strategies to assure the product quality (17)(18)(19)(20)(21)(22)(23). These concepts have been debated, discussed, piloted, and reflected in regulatory guidance documents (17)(18)(19)(20)24); however, the implementation and transition to such manufacturing models has been difficult to attain and has not been fully realized.…”

Section: Regulatory Landscape and Mammentioning

confidence: 99%

A View on the Importance of “Multi-Attribute Method” for Measuring Purity of Biopharmaceuticals and Improving Overall Control Strategy

Rogers

Abernathy

Richardson

et al. 2017

AAPS J

127

122

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Abstract.Today, we are experiencing unprecedented growth and innovation within the pharmaceutical industry. Established protein therapeutic modalities, such as recombinant human proteins, monoclonal antibodies (mAbs), and fusion proteins, are being used to treat previously unmet medical needs. Novel therapies such as bispecific T cell engagers (BiTEs), chimeric antigen T cell receptors (CARTs), siRNA, and gene therapies are paving the path towards increasingly personalized medicine. This advancement of new indications and therapeutic modalities is paralleled by development of new analytical technologies and methods that provide enhanced information content in a more efficient manner. Recently, a liquid chromatography-mass spectrometry (LC-MS) multi-attribute method (MAM) has been developed and designed for improved simultaneous detection, identification, quantitation, and quality control (monitoring) of molecular attributes (Rogers et al. MAbs 7(5): 2015). Based on peptide mapping principles, this powerful tool represents a true advancement in testing methodology that can be utilized not only during product characterization, formulation development, stability testing, and development of the manufacturing process, but also as a platform quality control method in dispositioning clinical materials for both innovative biotherapeutics and biosimilars.KEY WORDS: biotherapeutic; mass spectrometry; multi-attribute method; quality by design.To date, multi-attribute method (MAM) has been applied to several early stage clinical programs with different classes of protein therapeutics and compared to current practices. This experience shows that the MAM technology can be utilized for different types of protein therapeutics delivering highly specific and quantitative information, which is invaluable during process development and essential for molecular characterization. Data has also been generated to support its use for release and stability in alignment with Quality by Design (QbD) principles. Utilizing recent advances in the technology, research, and development labs, in industry, has generated convincing data that MAM would be highly beneficial in a cGMP environment. This article will summarize the advantages of MAM relative to conventional product testing approaches. We recommend that MAM, unlike conventional purity methods, be used to specifically monitor and quantify molecular product quality attributes and product/process-related impurities. This increased specificity for attributes with increased relevance to safety and efficacy can lead to better product/process understanding, shorter process and product development timelines, and an improved control strategy by improving specificity of the measurement. MAM OVERVIEWReduced LC-MS-based peptide mapping methods have been used in academia and the industry for several decades. Biopharmaceutical companies are increasingly using quantitative LC-MS-based peptide mapping methods for clinical material characterization, as well as release and stability testing (1-7). Quantit...

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Section: Regulatory Landscape and Mammentioning

confidence: 99%

A View on the Importance of “Multi-Attribute Method” for Measuring Purity of Biopharmaceuticals and Improving Overall Control Strategy

Rogers

Abernathy

Richardson

et al. 2017

AAPS J

127

122

View full text Add to dashboard Cite

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“…Adaptado de Yu e cols, 2014 (11) As "FERRAMENTAS" da Quality By Design "Planejamento Experimental" (Design of Experiments, DoE). O Planejamento Experimental (DoE) tem como objetivo fornecer informações dos dados experimentais considerando, racionalmente o sistema e os recursos disponíveis.…”

Section: Figuraunclassified

Quality by Design (Qbd) Como Ferramenta Para Otimização Dos Processos Farmacêuticos

Bezerra

Rodrigues

2017

Infarma

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The pharmaceutical industry is constantly evolving. The harmonization of production standards, with the aim of guaranteeing efficacy, safety and quality of medicines, is one of the greatest challenges. The concept of "Quality by design" (QbD) proposes a systematic approach, based on scientific knowledge and risk management associated with the manufacturing process. In this approach, quality is inversely proportional to variability. The implementation of the QbD concept is a promising tool for pharmaceutical production, since it allows the production of medicines by means of risk prediction, increasing the possibility of generating products with efficiency, safety and quality assured, together with the reduction of costs. The implementation of this concept requires not only new technologies, but the change in the concept of quality.Keywords: pharmaceutical processes; quality by design; process analytical techniques. RESUMOO setor farmacêutico está em constante evolução. A harmonização de normas de produção, com o intuído de garantir eficácia, segurança e qualidade dos medicamentos, consiste em um dos maiores desafios. O conceito "qualidade baseada no projeto" (Quality by design, QbD) propõe uma abordagem sistemática, fundamentada no conhecimento científico e no gerenciamento do risco associado ao processo de fabricação. Nesta abordagem, qualidade é inversamente proporcional a variabilidade. A implementação do conceito de QbD constitui uma ferramenta promissora para a produção farmacêutica pois permite a produção de medicamentos por meio da previsão de riscos, ampliando a possibilidade de gerar produtos com eficácia, segurança e qualidade assegurados, aliado a redução de custos. A implementação deste conceito exige não somente novas tecnologias, mas a mudança no conceito de qualidade.Palavras-chave: processos farmacêuticos; qualidade baseada no projeto; técnicas analíticas de processo INTRODUÇÃO A produção de medicamentos inclui uma série de processos farmacêuticos, caracterizados por uma sequência de operações unitárias, que realizam transformações químicas ou físicas em matérias-primas, com o fim de gerar produtos com eficácia, segurança e qualidade assegurados (1). Estabelecidos durante o desenvolvimento dos produtos, os processos farmacêuticos devem ser submetidos a aprovação por órgãos regulatórios para concessão de registro de comercialização, o qual assegura que a empresa comprovou ter condições de fornecer produtos de qualidade desejada de forma consistente, conforme as exigências regulatórias (2,3).Apesar do rigor das agências regulatórias na elaboração de normas e guias para a produção farmacêutica, estes requerimentos apresentam limitações, e falhas nos processos farmacêuticos são comumente observadas, o

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“…As defined in ICH Q8 (Pharmaceutical Development), [21][22][23] QTPP should be defined to meet patients' needs and the intended product performance. QTPP for the DPM gastroretentive floating tablets is defined in Table 1.…”

Section: Qtpp Of Dpm Gastroretentive Floating Tabletsmentioning

confidence: 99%

Untitled

Shah

2017

AJP

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Introduction: This research focuses on development and optimization of dipyridamole (DPM) gastroretentive (GR) floating matrix tablets through risk-based approach using combination of rate controlling hydrophilic polymers. Materials and Methods: A 3 2 full factorial design was deployed to optimize ratio of polymers and polymer concentration in the formulation. Dissolution studies, Buoyancy studies, swelling index studies, kinetic modelling, drug content, and differential scanning calorimetry studies were performed to effectively assess developed gastroretentive dosage form. Estimation of related substances was also done for optimized formulations to check the stability of dosage form during shelf life. Results and Discussion: Buoyancy studies suggested that concentration of PanExcea™ GR polymer should be at least 25% w/w or more to get better floating and swelling capabilities if used alone as rate controlling polymer. Selection of optimum batches was done using constraintbased graphical optimization technique. The optimum batches exhibited desired extended drug dissolution profile, minimal floating lag time, and total floating time of >12 h. Thermal characterization studies also preclude any drug polymer interaction and change in polymorphic form of drug during manufacturing process. Stability studies indicated optimized formulations are stable under selected packaging configurations. Conclusion: The present research exemplifies successful application of quality by design approach in designing gastroretentive dosage form of DPM. From the present study, it can be concluded that selection of appropriate ratio and concentration of hydrophilic polymers play a pivotal role in matrix integrity, buoyancy, swelling potential as well as drug release profile of GRDDS.

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Understanding Pharmaceutical Quality by Design

Cited by 1,034 publications

References 19 publications

A View on the Importance of “Multi-Attribute Method” for Measuring Purity of Biopharmaceuticals and Improving Overall Control Strategy

A View on the Importance of “Multi-Attribute Method” for Measuring Purity of Biopharmaceuticals and Improving Overall Control Strategy

Quality by Design (Qbd) Como Ferramenta Para Otimização Dos Processos Farmacêuticos

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