Asian Journal of Biomedical and Pharmaceutical Sciences

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Review Article - Asian Journal of Biomedical and Pharmaceutical Sciences (2020) Volume 10, Issue 70

Review on comprehensive understanding of building an analytical quality by design for drug manufacturing process.

Shishir Kumar Prasad*, Kalpana Diwekar, Anita A

Department of Pharmaceutical Chemistry, Dayananda Sagar University, Bangalore 560078, India

Corresponding Author:
Shishir Kumar Prasad
Department of Pharmaceutical Chemistry
Dayananda Sagar University
Bangalore, India
E-mail: [email protected]

Accepted date: April 10, 2020


When knowledge based on pure scientific understanding and quality risk management is applied to product and process learning with regulation on process control along with a systematic approach for development of predefined objectives in analytical field then it is called as quality by design or QBD it follow ICH guidelines for quality in pharmaceutical product concept of QBD also extends to analytical methods, it is mandatory process in QBD to define a goal.
A protocol for the method which will continue monitoring the process throughout in a systematic way and working on alternate methods as well to get optimal performance, the methods given are carefully analyzed in structured pattern for risks and is put for a challenge of the validity of method which later on can be taken for the criteria, benefit of these studies.
The performances can be improved as well as clearly understood along with the risk management and desired performance methods which can also be validated later on, the review briefly gives an inside view of application of analytical QBD in industries and its current status with examples and principles of analytical methods in HPTLC ,titration for moisture content, determination of toxic impurities in mixtures, quantative colour measurement and various spectroscopic method for identification of chemical moiety.
QBD developed spectroscopic and chromatographic method is usually done as per ICH Q8 R2, the critical parameters are compared to principle observation and analysis, the HPTLC method employs solvent usage and detection of absorbance and wavelength comparison.


HPTLC, Toxic impurities, Analytical target, Design formulation.


As science is now based on quality management system, with quality to be built in QBD aims into looking into the quality of analytical process during development stage itself instead of waiting for final result for an integrated approach to development manufacturing and quality for both industry and regulators [1]. As per FDA guidelines for process validation at three step approach can be utilized (Figure 1).

Figure 1: The new widely accepted protocol for QBD include a systematic approach like.

Stage 1: Design of ATP {analytical target profile} the method and conditions required to control critical values

Stage 2: Qualification: the methods utilized is capable of its purpose

Stage 3: Continuous monitoring: the methods utilized are ensured to remain in monitoring for intended work

Various Elements of QBD

Product and process design and development [2], the products are identified as per critical quality assessments and it is up fronted for the desired performance. The design formulation and process are made to meet the product specific requirement. Risk assessment and risk control it includes the impact of material testing to be clearly understood, product eqas and process parameter with various attributes are explained well. The identification and control of variability in process and material management is followed, To assure the consistent quality all the process are continuously monitored and updated (Table 1).

Traditional approach QBD
Product develpoment Product development
Fixed batch manufacturing process Responsive batch or continuous
Fixed batch packagig process Manufacturing process
Product quarintine Reponsive pkg process
Product disrtibution Product distribution
Fixed parameters ranges Design- control dtrategy
In-process testing process Real Time Release

Table 1: System comparision of pharmacuetical supply and analytical system.

Quality target product profile

The perfect quality of a drug is ensured by all the acceptable control strategy and all the process with and formulation which are quite robust of the results. Critical quality attributes: A CQA is a characteristics that should be within an appropriate limit, range or distribution which can have physical, chemical biological or microbial property range or distribution to ensure the desire product quality as per the guidelines (ICH Q8 R2) CQ As which are generally associated with drug substance, intermediates, in processes, final products and excipients as well [3-7].

Quality risk managements

Q9 Describes systematic approach for assessment control communication review, it even applies for product lifecycle development manufacturing and distributions, it is also inclusive of principle methodologies and examples of tools for risk quality management and assessment of risk to quality should be linked to protection of patients based on scientific knowledge, and extend over the life cycle of the a pharmaceutical product [4].

Process parameters

A process parameters whose viability has an impact on a critical quality attribute and therefore should be monitored or controlled to ensure the process the desired quality (Q8 R2), cppc have a direct impact on CQAs, The examples in temperature, pH, agitation, dissolved ratte of oxygen are all measured parameters which can be easily adjusted which are controlled as well are measured parameters [9-12].

Quality Attribute Deemed Critical

A severity scale is used to assess relative magnitude of impact. A change is critical only when it is in severity (Figures 2 and 3).

Figure 2: Quality model of quality attribute deemed critical.

Figure 3: Model of material attributes and process parameters.

Design space approach

First principle approach is combination of experimental data and mechanical knowledge of chemistry physics and engineering to model and predict performance, next is non-mechanistic or empirical approach statistically designed experiments (DOES),along with linear and multiple linear regression, after that comes the scale up co-correlations which translates the operating condition between different scales or pieces of equipment’s, all steps are culminated into risk analysis which determines the significance of effects and any combination of above (Figure 4).

Figure 4: Design space example.

Continuous improvement of various process and the product

Various processes like manufacturing, performance, monitoring ,market variance are made to acceptable changes by continuous improvement to increase the product lifecycle with regular feedbacks which is the basis of expanded knowledge and results in management with original concept intact [9-20].


QBD is the developmental approach which should be adapted based on the complexity and specificity of product and design, FDA encourages these practices to be include in their application by the industry, using QBD does not bring about any change in the regional regulatory process but provides more of scientifically proven flexible approaches to them and for which in any case the adherence to GMP is any required. Various process like inspections and reviews, and the flexible regulatory approaches to facilitate these does prove that, opportunity does existto develop more appropriately factors depending on the level of understanding achieved and adapted quality system in place, the approved design space described within the manufacturing process movements without further regulatory views, with a reduction of post approval submissions, and a real time release testing leading to reduction of end product release testing.


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