Abstract

A unique approach to maintaining the quality of the pharmaceutical product is called Quality by design, or QbD. Quality means customer satisfaction like service of the product, design of the product and process of the product. This article tells anotice about the pharmaceutical Quality by design. The main utilization of the (QbD) is to develop the Quality of the pharmaceutical analysis. Under this article tells the growth of the product. To recognize the product capabilitieslike Quality Target Product Profile (QTPP), Critical Quality Attributes (CQAs), Design Space, about Pharmaceutical Analysis, Risk Assessment,the establishment of Quality by design is ICH Guidelines.ICH Guidelines Q8 (Pharmaceutical Development), Q9 (Quality Risk Management), and Q10 (Pharmaceutical Quality System) are the foundation for quality by design. QbD can also be applied to pharmaceutical product manufacture and quality.

Keywords

Quality by design, Quality Target Product Profile, Critical Quality Attributes, Design Space, Risk Assessment, Process Analytical Technology, Control strategy.

Introduction

The Latin term "qualities," which means "general excellence" or "distinctive feature," is where the word "quality" originated.The International Conference on Harmonization (ICH) and the Food and Drug Administration (FDA) established quality by design as a pharmaceutical science [4]The basic idea of Quality by design is Quality means not only product test, but also built into it. Pharmaceutical development studies are conducted in order to obtain skills, information and manufacturing experience as well as to understand the installation of manufacturing controls and design space [3, 4].

Definition

Quality: [5]Quality is an essential word in Quality by Design, Quality is defined as the acceptable or suitable to ensure the identity, purity, potency of the product for intended purposes. [4]

Quality by design:

QbD is the advanced software technique applicative many pharmaceutical industries. The main focus of QbD is to verify the product's efficacy, safety, and quality. [1]. QbD to show the results of the final product [6]. The manufacturing of the product development is high efficient and different methods are used to developed the quality of the product. QbD was implemented the scientific tools by the increasing of the product quality. [1, 3, 4]  In industry the standard formulas were accomplishes developed by the QbD. Always the regulatory authorities are advanced application of ICH quality requirements, including Q8, Q9, and Q10.

History of the QbD

Dr. Joseph M. Juran was the first to realize quality by design, and the mechanized industry additionally utilized it. Since 1986, w Edwards Deming also discuss the concept of Quality by design. In2002 FDA was proposed a new inventiveness (cGMP for the 21st century a risk based approach) [3] . The concepts of quality by design can be applied to new product development, industry quality processes, and automated drug research, development, and manufacture.

Objectives of QbD

The most important objective of the QbD is to realize the product quality:

• To be maintain the high quality of the product.
• To be decrease the cost.
• During the process development time to be gain the practical knowledge.
• To be increases the product potentiality and can be decrease the product variability and deficiency by increasing the product process and process design understanding the control.
• To reach the positive performance testing.
• Foundation of QbD

ICH guidelines Q8, Q9, and Q10 related to pharmaceutical development, quality risk management, and under-structuring of the quality system by QbD. 

Benefits ofQbD

The main advantages involved in the QbD is

• QbD assist the enhancement of the product quality and easily understanding of the method.
• QbD is a upstanding sciences.
• QbD is high rating of business. [12]
• To learn the technical skills.
• To developed the higher quality of the product.
• QbD will be cost effective.
• It will remove the batch failures.
• Good development decisions.
• Empowerment of technical skills.
• To eliminate entire bath. [13]
• Toavoid regulatory compliance problems. [14]

Opportunities of QbD

• To increase the manufacturing potency, and scale back prices and project rejections and waste.
• To Build knowledge based on the all products
• Sciences problem on higher business
• Economical, agile, versatile system
• To include the risk management

Steps involved in QbD / Elements of QbD

1. Clinical development

• Preclinical research
• Nonclinical research
• Clinical research
• Scale up
• Market approval submission

2. Manufacturing

• Design space
• Real time quality control
• Process analytical technologies

3. Control strategy

• Risk based decision- marking
• Continuous improvement and
• Product performance

The following seven steps comprise the QbD start-up plan: [1, 3, and 6]

1. Employ a contracting Quality by Design Specialist
2. Examine your company and procedures with a professional gap analysis audit
3. Organize a fundamental Quality by Design session for your entire staff
4. Examine the experts finding and suggestions
5. Create schedules, an implementation strategy, and a cost estimate.
6. Assign the work and / or hire come one else to
7. Keep the impartial specialist on staff as your “project assurances advisor”

Important attributes about QbD

1. Quality Target Product Profile (QTPP) [1,2,3]

Quality target product profile means to development the basis layout of the product. QTPP emphasizes mainly on the product's safety and effectiveness.

• Dosage form
• Appearance
• Identity
• Strength
• Assay
• Uniformity
• Purity/impurity
• Stability and Dissolution
• Disintegration of pharmacokinetics and Bioequivalence as well as the
• Dosage and administration

Taking into account the intended use and mode of administration, QTPP identifies the characteristics that are essential to the drug product's quality.For the patient and/or customer, it may be necessary or vital to ease identification in the Quality target product profile (such as critical quality attributes, or CQAs) [1].

Advantages of the QTPP: [1, 2]

1. To identify the risk and best advanced to lead of risk.
2. The complete life cycle process of an abrupt decision that results in therapeutic action helps the patient.
3. To create and authorize the knowledge sharing.
4. The medication product is developed and manufactured to meet the quality target product profile while adhering to release/dissolution acceptance standards and other parameters that align with the desired in vivo performances of the product.

2. Critical Quality Attributes (CQAs) [2,3]

The terms "physical, chemical, biological, and microbiological properties" (CQAs) refer to these characteristics. [2, 3]CQAs must be maintained within the parameters of the product quality distribution, range, or restrictions. CQAs are basically similar within the drug substances, excipients and intermediates of the drug products. In some cases, product will be directly effects like quality and safety of the product and also impact on the method development and it is examining the critical quality attributes can be also developed the HPLC method to the specific drug product. The quantity of accurately may be vary for an API production company processes associated to a drug product and manufacturing process.

3. Design Space [3,7]

It is possible to relate the relationship between the critical quantity attributes and process inputs to the design space. [3]The entire design process can be constructed for both single- and multi-unit operations. The FDA guidelines state that design space is not necessary for understanding the product and process or for having total control over the system [20].

4. Risk Assessment

Risk Assessment means combination and expectation of experience of harm and the dangerous of that harm. Risk Assessment is an analysis and establishment of risk which is associated to a situation and accept as a threat. Technical expertise and patient safety should be the foundation of any investigation on the danger to quality.  ICHQ9 is a quality risk management suitable manufacturing and usage of the drug products and it will be recognizing the control strategy for the process, Raw materials of the final testing. Risk Assessment tools can be used to recognize and rank parameters. Threat assessment is helpful for the improve communication when the procedures involves the FDA, Experts, and R&D, mock-up-model (prototyping) and various manufacturing spots.

This technique for a control threat as follows a so many threat assessment styles are represented in ICHQ9.

• Analysis of Failure Mode Effects
• The Analysis of Failure Mode Effect and Criticality
• Analysis of Fault Trees
• Analysis of Hazards and Crucial Control Point
• Analysis of Hazard Operability
• Initial Hazard Assessment
• Filtering and Risk Ranking

5. Process Analytical Technology

PAT is defined as the system designing, analysing controlling measurements and manufacturing process of critical quality and process attributes of in- process materials verify the final product. [2] PAT is using continuous manufacturing technologies can be consequence is an improved product quality and remove the waste. In the pharmaceutical industry, PAT refers to change from batch production additional dynamic approach. Since the CAQ of the final product is an affected the instrumentation of CPPs at defined intervals after refining the high quality product and reduced the waste and lower costs. In the principle, real-time PAT assessment could be providing fundamental continuous response and feedback in enhances process robustness [18, 19]. The main tool of PAT is useful for Realm time of release testing (RTRT) recorder the particle size blend uniformity, granulation, content uniformity, polymorphism and dissolution.

There are three main Tools of PAT

1. Real/Time/ in-line tools
2. Downstream process application
3. Multivariate statistical methods.

6. Control strategy

During the drug product development time based on the process and product different source of variability are identified the product.

Control strategy mainly impact on process development, in-process materials, drug product materials and components, facility and equipment, operating condition, in-process control, final product specification, and product quality to maintain consistent quality of the drug product during entire product life cycle.

Elements on effective strategy [5, 6]

• Method examination testing
• Batch release testing
• Consistency testing
• In-Process control &
• Procedural control

Applications of Quality by Design (QbD) [1, 2, 9]

QbD is widely applicable in following cases

• Drug substances Development
• In clinical trails
• Bioequivalence studies
• Pharmaceutical manufacturing
• Formulation Development and
• Analytical Development

Regarding the chromatographic method                                                                                              

• To identify contaminants
• In a chromatography column for screening
• Design and development of HPLC procedures
• Capillary electrophoresis
• Stability studies and
• UHPLC
• QbD also used for the Nano suspensions preparations

CONCLUSION

Quality-based drug development (QbD) primarily focuses on eliminating unpredictability and continuously improving the building and product production processes.[2,13]The fundamental ideas and instruments of quality by design are crucial to the information and process development and control strategies.[2]QbD is mainly provided to the golden opportunity for greater regulatory and flexibility.[2]Additionally, QbD is able to register for the development and assessment of the analytical techniques. The connection between all prospective parameters and all crucial analytical answers is excellent during the technique development process. Critical analytical factor is identified the process development in ICH Q8 and Q9.Robust manufacturing method can be developed.  In the pharmaceutical business, the development and validation of analytical methods heavily relies on QbD. Understanding from product development to commercial production is the outcome of QbD. QbD enhances the quality of medicines for manufactures and regulators. Internal change of control procedures may apply to any modifications made to this operation.

CONFLICT OF INTEREST

There is no conflict of interest among authors

ACKNOWLEDGEMENT

Hereby heart fully acknowledged to Shri Vishnu College of pharmacy management and staff for their encouragement in research activities.

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