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October , 2018 Vol 10 issues 5
Mini Review
Quality by Design in Pharmaceutical Formulation: A risk minimization and multidisciplinary approach to manufacturing of medicines

Chukwuma Agubata1

1  Department of Pharmaceutical Technology and Industrial Pharmacy, University of Nigeria, Nsukka.


Abstract

The concept of Quality by Design (QbD) was incorporated into pharmaceutical manufacturing protocol in 2004 after the pharmaceutical cGMP for the 21st century initiative. This concept in pharmaceutical production provides opportunities for enhancing efficiencies, encouraging safety and reducing cost. Quality by Design was implemented by the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) and United States Food and Drugs Administration.

The concept of Quality by Design (QbD) was incorporated into pharmaceutical manufacturing protocol in 2004 after the pharmaceutical cGMP for the 21st century initiative. This concept in pharmaceutical production provides opportunities for enhancing efficiencies, encouraging safety and reducing cost. Quality by Design was implemented by the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) and United States Food and Drugs Administration.

Keywords: Quality by Design (QbD), pharmaceutical manufacturing protocol, pharmaceutical manufacturing.


Introduction

The concept of Quality by Design (QbD) was incorporated into pharmaceutical manufacturing protocol in 2004 after the pharmaceutical cGMP for the 21st century initiative. This concept in pharmaceutical production provides opportunities for enhancing efficiencies, encouraging safety and reducing cost. Quality by Design was implemented by the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) and United States Food and Drugs Administration.

The initiative on pharmaceutical cGMPs for the 21st century was a risk-based approach to protect the patient and deliver high quality drug product. The ICH, thereafter, established a series of guidance including Q8 (Pharmaceutical Development), Q9 (Quality risk management), Q10 (Pharmaceutical Quality System). All these guidance are related, however, Q8 encompasses the fundamentals of QbD. The benefits of QbD implementation include increase in product quality, reduction in defects, elimination of rejects or recalls, reduction in development time, minimization of product cost and facilitation of better regulatory supervision.

The key five steps in QbD:

  1. Define the Quality Target Product Profile (QTPP) elements
  2. Highlight the Critical Quality Attributes (CQAs)
  3. Identify the Critical Material Attributes (CMAs) and the Critical Process Parameters (CPP)
  4. Map out the design space
  5. Establish a control strategy and continuously provide improvement

Quality is dynamic and is a moving target that needs to be established from time to time and across different formulations and product categories

The QTPPs involve the quality characteristics of the target product. QTPP basically includes product features such as dosage form, dose, pharmacokinetics, stability and these characteristics need to be frequently evaluated and monitored throughout the product development [1]. For generics, it is expected that the drug content should be identical to that of the innovator product or standard. Furthermore, generic products should be biopharmaceutically equivalent to innovator product or standard. It is important to note that as new technologies and equipments emerge, the innovator product may no longer present the best product for an active pharmaceutical ingredient.

The CQAs are potential indicators of the product quality performance and are directly related to QTPP [2,3]. CQAs are actually subsets of QTPPs. CQAs include physical, chemical, biological or microbiological properties of the product that are affected by formulation and/or process variables [4]. These CQAs should be monitored to maintain quality within specifications for consistency or reproducibility [5].

Figure 1: USP standards for disintegration time test  Click to view

Critical process parameters are simply those critical processes that the input materials undergo until the final product is obtained. In tableting, these processes would include blending, lubrication, compression and coating, and they would affect the following critical quality attributes; in vivo performance, dissolution, drug content, content uniformity, friability and stability. The CQA depends on the product. For production of monoclonal antibodies, CQAs include fragmentation, aggregation, glycosylation, conformation, host cell proteins, formulation buffer components, culture media residues etc. In the production of active pharmaceutical ingredient (API), the particle size is a quality attribute and the process of crystallization of the drug molecule becomes a critical process that needs to be controlled to maintain quality!

In achieving effective Pharmaceutical Development and Quality by Design in pharmaceutical production, experts from different fields would have to work together. The quality of the API from extraction, chemical synthesis or modification need to be established and robust formulation studies should be performed. Quality should be guaranteed physically, chemically and biologically.

The scope of this journal emphasizes the need for interdisciplinary collaboration in Pharmaceutical Development and Industrial Pharmacy. These converging areas include Pharmaceutical Technology, Industrial Pharmacy, Pharmaceutics, Pharmacognosy, Pharmaceutical Microbiology and Biotechnology, Medicinal Chemistry, Pharmaceutical Chemistry and Analysis, In silico Modeling and Bioinformatics, Pharmaceutical Development, Quality by Design (QbD), Optimization, Good Manufacturing Practice and Formulation Science.

Figure two: This is a test table Click to view in full

References

[1] Yu LX, Amidon G, Khan MA, Hoag SW, Polli J, Raju GK, Woodcock, J. Understanding pharmaceutical Quality by Design. AAPS J. 2014; 16(4); 771-783

[2] Singh B, Raza K, Beg S. Developing “optimized” drug product employing “Designed” experiments. Chem Ind Digest. 2013: 70-76

[3] Lionberger RA, Lee SL, Lee L, Raw A, Yu LX. Quality by Design: concepts for ANDAs. AAPS J 2008; 10: 268-276

[4] Jain S. Quality by Design (QbD): A comprehensive understanding of implementation and challenges in pharmaceuticals development. International Journal of Pharmacy and Pharmaceutical Sciences. 2014; 6(1): 29-35

[5] ICH Harmonized Tripartite Guideline. Q8 (R2)- Pharmaceutical Development. 2004

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