Critical Material Attributes in Wet Granulation

Question-based Review (QbR) is a format proposed by United States Food and Drug Administration (US FDA) enhancing the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use's Common Technical Document (ICH CTD) format to streamline the submission process. It is a question–answer format applied to Quality Overall Summary section of the submission. The format includes putting up questions under every section, so the applicant can submit precise and accurate data for approval of the respective application. The QbR format can be applied to NDA, ANDA, and Type II DMF applications. The companion document available with Manual of Policy and Procedures 5015.10 (MaPP 5015.10) allows the reviewer to inspect the critical information in the data provided. It encourages applicants to encompass Quality by Design (QbD) in their development process. QbR gives a structure through which the data collected by applying QbD can be presented. For effective application of QbR format, the submission should be backed with thorough scientific knowledge, risk assessment data, and data integrity. The questions asked compel the applicant to provide justification for the various decisions made in the development phase. Also, questions regarding quality target product profile, critical quality attributes, critical material attributes, critical process parameters and design of experiment are covered under the QbR format. MaPP 5015.10 finalized by US FDA in 2014 clarifies the concept of QbR. There is MicroQbR available which includes questions confirming the sterility of the product. QbR is a step towards speeding up the review process with an intention to motivate the applicants to implement QbD to the project.

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Applications of Statistical Tools for Optimization and Development of Smart Drug Delivery System

10.5772/intechopen.99632 ◽

2021 ◽

Author(s):

Pankaj Sharma

Keyword(s):

Dosage Form ◽

Quality By Design ◽

Process Analytical Technology ◽

Quality Attributes ◽

Critical Material ◽

Statistical Tools ◽

Pharmaceutical Dosage Form ◽

Critical Quality Attributes ◽

Critical Material Attributes ◽

Form Development

In the novel dosage form development, quality is the key criterion in pharmaceutical industry. The quality by design tools used for development of the quality products with tight specification and rigid process. The specifications of statistical tools are essentially based upon critical process parameters (CPPs), critical material attributes (CMAs), and critical quality attributes (CQAs) for the development of quality products. The application of quality by design in pharmaceutical dosage form development is systematic, requiring multivariate experiments employing process analytical technology (PAT) and other experiments to recognize critical quality attributes depend upon risk assessments (RAs). The quality by design is a modern technique to stabilize the quality of pharmaceutical dosage form. The elements of quality by design such as process analytical techniques, risk assessment, and design of experiment support for assurance of the strategy control for every dosage form with a choice of regular monitoring and enhancement for a quality dosage form. This chapter represents the concepts and applications of the most common screening of designs/experiments, comparative experiments, response surface methodology, and regression analysis. The data collected from the dosage form designing during laboratory experiments, provide the substructure for pivotal or pilot scale development. Statistical tools help not only in understanding and identifying CMAs and CPPs in product designing, but also in comprehension of the role and relationship between these in attaining a target quality. Although, the implementation of statistical approaches in the development of dosage form is strongly recommended.

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An Updated Risk Assessment as Part of the QbD-Based Liposome Design and Development

Pharmaceutics ◽

10.3390/pharmaceutics13071071 ◽

2021 ◽

Vol 13 (7) ◽

pp. 1071

Author(s):

Zsófia Németh ◽

Edina Pallagi ◽

Dorina Gabriella Dobó ◽

Gábor Kozma ◽

Zoltán Kónya ◽

...

Keyword(s):

Risk Assessment ◽

Active Pharmaceutical Ingredient ◽

Experimental Models ◽

Phospholipid Content ◽

Formulation Development ◽

Critical Material ◽

Critical Material Attributes ◽

Critical Process Parameters ◽

Saline Solutions ◽

Phosphate Buffered Saline

Liposomal formulation development is a challenging process. Certain factors have a critical influence on the characteristics of the liposomes, and even the relevant properties can vary based on the predefined interests of the research. In this paper, a Quality by Design-guided and Risk Assessment (RA)-based study was performed to determine the Critical Material Attributes and the Critical Process Parameters of an “intermediate” active pharmaceutical ingredient-free liposome formulation prepared via the thin-film hydration method, collect the Critical Quality Attributes of the future carrier system and show the process of narrowing a general initial RA for a specific case. The theoretical liposome design was proved through experimental models. The investigated critical factors covered the working temperature, the ratio between the wall-forming agents (phosphatidylcholine and cholesterol), the PEGylated phospholipid content (DPPE-PEG2000), the type of the hydration media (saline or phosphate-buffered saline solutions) and the cryoprotectants (glucose, sorbitol or trehalose). The characterisation results (size, surface charge, thermodynamic behaviours, formed structure and bonds) of the prepared liposomes supported the outcomes of the updated RA. The findings can be used as a basis for a particular study with specified circumstances.

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Impact of Critical Material Attributes (CMAs)-Particle Shape on Miniature Pharmaceutical Unit Operations

AAPS PharmSciTech ◽

10.1208/s12249-020-01915-6 ◽

2021 ◽

Vol 22 (3) ◽

Author(s):

Mohammad A. Azad ◽

Gerard Capellades ◽

Allison B. Wang ◽

David M. Klee ◽

Gregory Hammersmith ◽

...

Keyword(s):

Drug Product ◽

The United States ◽

Pharmaceutical Drugs ◽

Critical Material ◽

Unit Operations ◽

Custom Made ◽

Critical Material Attributes ◽

Powder Properties ◽

Tablet Manufacturing ◽

States Pharmacopeia

AbstractThe U.S. Food and Drug Administration (FDA) emphasizes drug product development by Quality by Design (QbD). Critical material attributes (CMAs) are a QbD element that has an impact on pharmaceutical operations and product quality. Pharmaceutical drugs often crystallize as needle-shaped (a CMA) particles and affect the process due to poor flowability, low bulk density, and high compressibility, and eventually the product performance. In this study, the product obtained from crystallization was needle-shaped Ciprofloxacin HCl (CIPRO), formed lumps during drying, and compacted during processing through feeders. To delump small amounts of materials and break the needles, multiple available devices (mortar-pestle, Krups grinder) and custom-made grinder were assessed before formulation. The processed CIPRO powder was then used to make tablets in the miniature tablet manufacturing unit developed by the team at MIT. The critical quality attributes (CQA) of the tablets, set by the United States Pharmacopeia (USP), were then assessed for the drug powder processed with each of these devices. Powder properties comparable to commercial CIPRO were obtained when the custom MIT-designed grinder was used, leading to tablets that meet the USP criteria, with comparable dissolution profiles of those for marketed CIPRO tablets. This study demonstrates how needle-shaped crystals have an impact on pharmaceutical operations, even if it is on a miniature scale, and how proper shape and subsequent flow properties can be obtained by processing the particles through the MIT team-designed grinder. Graphical Abstract

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