Quality by Design in Action 2: Controlling Critical Material Attributes during the Synthesis of an Active Pharmaceutical Ingredient

2015 ◽  
Vol 19 (11) ◽  
pp. 1645-1654 ◽  
Author(s):  
Abdul Qayum Mohammed ◽  
Phani Kiran Sunkari ◽  
Amjad Basha Mohammed ◽  
P. Srinivas ◽  
Amrendra Kumar Roy
Keyword(s):  
Quality By Design ◽  
Active Pharmaceutical Ingredient ◽  
Critical Material ◽  
Critical Material Attributes

Implementation of Question-based Review in support of Quality by Design streamlining the US FDA’s review process

2018 ◽  
Vol 14 (3) ◽  
pp. 129-134
Author(s):  
Alisha Desai ◽  
Jayanta Kumar Maji ◽  
Kanhoba Walavalkar ◽  
Priti J Mehta
Keyword(s):  
Quality By Design ◽  
Review Process ◽  
Critical Material ◽  
Technical Requirements ◽  
The Us ◽  
Product Profile ◽  
United States Food ◽  
Critical Material Attributes ◽  
States Food ◽  
Us Fda

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.

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

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.

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

Pharmaceutics ◽  
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.

scholarly journals Implementation of the Quality by Design approach for developing the composition and the manufacturing technology of an injectable drug for intra-articular introduction

2021 ◽  
pp. 28-37
Author(s):  
O. Saliy ◽  
O. Los ◽  
T. Palchevska ◽  
K. Nebylytsia
Keyword(s):  
Quality Indicators ◽  
Quality By Design ◽  
Experimental Studies ◽  
Active Pharmaceutical Ingredient ◽  
Number System ◽  
Manufacturing Technology ◽  
Solution Temperature ◽  
Critical Material ◽  
Factors Affecting ◽  
Injectable Drug

Aim. To implement the Quality by Design (QbD) approach in order to develop the composition and the manufacturing technology of injectable hyaluronate sodium (HS) in combination with chondroitin sulfate (CS) for intra-articularintroduction. Materials and methods. The composition of the solution for injection was developed using samples of the active pharmaceutical ingredient (API) of HS and CS. The approaches of the ICH international guidelines were used to create the QbD protocol. The quality target product profile (QTPP) was developed based on the literature review, analysis of similar drugs and the previous in-house experimental studies. Determination of critical quality assessment (CQA) product indicators was performed by risk analysis for all quality indicators listed in QTPP. The risk assessment of quality indicators was performed by assessing them according to the Risk Priority Number system (hereinafter – RPN) by a 9-point scale. When studying the composition and the manufacturing technology of the injectable solution the quality risk management (QRM) was developed according to the Ishikawa diagram. Results and discussion. It has been found that the QbD concept is a systematic approach to the drug development. At the first stage QTPP was developed. Based on the QTPP data the CQA indicators were determined, and quality risks were assessed. The critical process parameters (CPP) of the solution for injection based on HS and CS, their control methods, as well as the critical material attributes (CMA) were determined. Based on the data obtained the drug control strategy was proposed taking into account the need to minimize the repetition of control experiments. Using the Isikawa diagram the variability of the material and the process with the environmental factors affecting the qualityof the solution for injection with HS and CS was shown.Conclusions. Using the basic QbD approaches when developing the composition and the manufacturing technology of an injectable drug for intra-articular introduction it has been found that the route of administration, dose, potency, and consumer properties of the product are important aspects of QTPP. It has been proven that the quality indicators, such as transparency, viscosity, sterility and the quantitative content of API are determined as CQA to achieve the objectives defined in QTPP. The study shows that almost all stages of production are critical, therefore, they need to be constantly monitored and checked to obtain a quality product. In further experimental studies to confirm the composition developed and the manufacturing technology according to QRM it is necessary to focus on such indicators as the solution temperature, stabilization time, degassing mode and filtration conditions.

QUALITY BY DESIGN: AN OVERVIEW

INDIAN DRUGS ◽  
2015 ◽  
Vol 52 (02) ◽  
pp. 5-11
Author(s):  
S Suresh ◽  
◽  
S. Roy ◽  
B. K Ahuja
Keyword(s):  
Manufacturing Process ◽  
Quality By Design ◽  
Pharmaceutical Products ◽  
Point Of View ◽  
Assessment Tools ◽  
Successful Implementation ◽  
Critical Material ◽  
Road Map ◽  
Process Understanding ◽  
Critical Material Attributes

Quality by Design (QbD) is a systematic, scientific, holistic and proactive approach that begins with pre-defined objectives and emphasis on product, process understanding and process control. It essentially necessitates designing and developing the product and the manufacturing process to achieve the predefined product quality objectives. QbD identifies characteristics that are vital to quality from the patient’s point of view and converts them into critical quality attributes (CQAs) that the product should possess. Further, it establishes the limits, the design space, for critical process parameters (CPPs) and critical material attributes (CMAs) that affect the CQAs within which the process will be unaffected and consistently manufacture the desired product. This knowledge is then used to implement a flexible and robust manufacturing process that can adapt and yield a stable product. Risk assessment tools and design of experiments (DoE) are its integral components. This article gives a road map for successful implementation of QbD for pharmaceutical products.

scholarly journals Raw Material Variability and Its Impact on the Online Adaptive Control of Cohesive Powder Blend Homogeneity Using NIR Spectroscopy

Processes ◽  
2019 ◽  
Vol 7 (9) ◽  
pp. 568 ◽  
Author(s):  
Guolin Shi ◽  
Bing Xu ◽  
Zhiqiang Zhang ◽  
Chan Yang ◽  
Shengyun Dai ◽  
...  
Keyword(s):  
Latent Variable ◽  
Near Infrared ◽  
Process Analytical Technology ◽  
Nir Spectroscopy ◽  
Active Pharmaceutical Ingredient ◽  
Raw Material ◽  
Critical Material ◽  
Critical Material Attributes ◽  
Blending Process ◽  
Cohesive Powders

It is significant to analyze the blend homogeneity of cohesive powders during pharmaceutical manufacturing in order to provide the exact content of the active pharmaceutical ingredient (API) for each individual dose unit. In this paper, an online monitoring platform using an MEMS near infrared (NIR) sensor was designed to control the bin blending process of cohesive powders. The state of blend homogeneity was detected by an adaptive algorithm, which was calibration free. The online control procedures and algorithm’s parameters were fine-tuned through six pilot experiments and were successfully transferred to the industrial production. The reliability of homogeneity detection results was validated by 16 commercial scale experiments using 16 kinds of natural product powders (NPPs), respectively. Furthermore, 19 physical quality attributes of all NPPs and the excipient were fully characterized. The blending end time was used to denote the degree of difficulty of blending. The empirical relationships between variability of NPPs and the blending end time were captured by latent variable modeling. The critical material attributes (CMAs) affecting the blending process were identified as the particle shape and flowability descriptors of cohesive powders. Under the framework of quality by design (QbD) and process analytical technology (PAT), the online NIR spectroscopy together with the powder characterization facilitated a deeper understanding of the mixing process.

scholarly journals A Quality by Design Framework for Capsule-Based Dry Powder Inhalers

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1213
Author(s):  
Li Ding ◽  
Ashlee D. Brunaugh ◽  
Sven Stegemann ◽  
Scott V. Jermain ◽  
Matthew J. Herpin ◽  
...  
Keyword(s):  
Quality By Design ◽  
Drug Formulation ◽  
Dry Powder Inhalers ◽  
Critical Factors ◽  
Dry Powder ◽  
Critical Material ◽  
Depth Analysis ◽  
Product Profile ◽  
Critical Material Attributes ◽  
And Control

Capsule-based dry powder inhalers (cDPIs) are widely utilized in the delivery of pharmaceutical powders to the lungs. In these systems, the fundamental nature of the interactions between the drug/formulation powder, the capsules, the inhaler device, and the patient must be fully elucidated in order to develop robust manufacturing procedures and provide reproducible lung deposition of the drug payload. Though many commercially available DPIs utilize a capsule-based dose metering system, an in-depth analysis of the critical factors associated with the use of the capsule component has not yet been performed. This review is intended to provide information on critical factors to be considered for the application of a quality by design (QbD) approach for cDPI development. The quality target product profile (QTPP) defines the critical quality attributes (CQAs) which need to be understood to define the critical material attributes (CMA) and critical process parameters (CPP) for cDPI development as well as manufacturing and control.

scholarly journals Explicating the Applications of Quality by Design Tools in Optimization of Microparticles and Nanotechnology Based Drug Delivery Systems

2021 ◽  
Vol 12 (4) ◽  
pp. 4317-4336
Keyword(s):  
Drug Delivery ◽  
Drug Delivery Systems ◽  
Quality By Design ◽  
Process Analytical Technology ◽  
Delivery Systems ◽  
Design Parameters ◽  
Sampling Errors ◽  
Critical Material ◽  
Assessment Design ◽  
Critical Material Attributes

Quality by design (QbD) can also contribute to design, manufacturing, and producing highly finished goods. To better explain the manufacturing processes, the FDA focused QbD in the healthcare industry, based on a comprehensive understanding of how technology and design parameters affect the quality of the manufactured product. Various elements of QbD are critical quality attributes (CQA); critical material attributes (CMAs), and critical process parameters (CPPs). The tools generally applied in QbD are risk assessment, design of experiments, and process analytical technology. The various benefits of the QbD model are preventing sampling errors and variability in research studies, less experimentation, and enhanced productivity. Since the microparticles and nanotechnology-based formulations need complex experimentation and an extremely time-consuming process, the application of QbD tools in such investigations can intelligently conclude the research processes. This review article provides a brief outline of the fundamentals, elements, and tools of QbD. Furthermore, the recently published applications of QbD in the optimization of microparticles and nanotechnology-based drug delivery systems have been discussed in this review.

Quality by Design: Concept to Applications

2019 ◽  
Vol 16 (3) ◽  
pp. 240-250 ◽  
Author(s):  
Suryakanta Swain ◽  
Rabinarayan Parhi ◽  
Bikash Ranjan Jena ◽  
Sitty Manohar Babu
Keyword(s):  
Quality By Design ◽  
Pharmaceutical Products ◽  
Assessment Tools ◽  
Basic Knowledge ◽  
Target Product ◽  
Target Product Profile ◽  
Critical Material ◽  
Novel Approach ◽  
Product Profile ◽  
Performance Report

Background: Quality by Design (QbD) is associated with a modern, systematic, scientific and novel approach which is concerned with pre-distinct objectives that not only focus on product, process understanding but also lead to process control. It predominantly signifies the design and product improvement and the manufacturing process in order to fulfill the predefined manufactured goods or final products quality characteristics. It is quite essential to identify the desired and required product performance report, such as Target Product Profile, typical Quality Target Product Profile (QTPP) and Critical Quality Attributes (CQA). Methods: This review highlighted the concepts of QbD design space, for critical material attributes (CMAs) as well as the critical process parameters that can totally affect the CQAs within which the process shall be unaffected thus, consistently manufacturing the required product. Risk assessment tools and design of experiments are its prime components. Results: This paper outlines the basic knowledge of QbD, the key elements; steps as well as various tools for QbD implementation in pharmaceutics field are presented briefly. In addition to this, quite a lot of applications of QbD in numerous pharmaceutical related unit operations are discussed and summarized. Conclusion: This article provides a complete data as well as the roadmap for universal implementation and application of QbD for pharmaceutical products.

QBD BASED RP-HPLC METHOD FOR SCREENING AND ANALYSIS OF TELAPRAVIR AND 7 OTHER ANTIRETROVIRAL AGENTS

INDIAN DRUGS ◽  
2015 ◽  
Vol 52 (02) ◽  
pp. 20-33
Author(s):  
N. S Kumar ◽  
◽  
R Kumaraswamy ◽  
S. Shantikumar ◽  
D. Paul
Keyword(s):  
Quality By Design ◽  
Pharmaceutical Formulations ◽  
Active Pharmaceutical Ingredient ◽  
Hplc Method ◽  
Array Detector ◽  
Simultaneous Estimation ◽  
Rp Hplc ◽  
Ich Guidelines ◽  
Full Factorial

The present study describes the separation and simultaneous estimation of eight anti-retroviral drugs, namely, Telaprevir (TPV), Emtricitabine (ECB), Fosamprenavir (FANV), Tenofavir (TNF), Ritonavir (RNV), Raltegravir (RGV) and Oseltamivir (OSMV) and Zidovudine (ZDV) as an active pharmaceutical ingredient, by RP-HPLC method by applying the principles of Quality by Design (QbD). An application of DoE (Design of Experiments) full factorial design was used for initial screening and optimization. The final optimized method consists of separation being carried out on a Fortis C18 column (150 mm × 4.6 mm, 5μ particle size) using acetonitrile and 10 mm ammonium formate buffer (pH 3 adjusted with formic acid) using a gradient program. The quantitative evaluation was performed with a diode array detector at 251 nm and 230 nm with a flow rate of 1 mL min–1. Suitability of this method for the quantitative determination of the drugs was proved by validation in accordance with the International Conference on Harmonization (ICH) guidelines. The method is selective, precise, robust and accurate and can be used for routine analysis of pharmaceutical formulations in quality control and counterfeit screening.

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