IMPLEMENTING PHARMACEUTICAL QUALITY BY DESIGN FOR ENHANCED PRODUCT DEVELOPMENT
Korna Devamani
Asst. Professor, Department of Pharmaceutical Analysis, Princeton College of Pharmacy, Hyderabad, Telangana, India
Kurma Kirankumar
Asst. Professor, Department of Pharmaceutical Analysis, Princeton College of Pharmacy, Hyderabad, Telangana, India
Abstract - The term "Quality by Design" (QbD) refers to a novel approach to product development that has the potential to boost productivity, provide flexibility and relief from regulations, and provide significant business advantages throughout the product life cycle.
It encourages the pharmaceutical industry and FDA to adopt a risk-based, holistic, and proactive approach to drug development. A company must define the desired product performance profile (Target Product Profile (TPP) and Target Product Quality Profile (TPQP)) and identify critical quality attributed (CQA) during product design and development in QbD. The company then creates the product's formulation and manufacturing procedures to meet the product's characteristics. This lets you know how the CQAs are affected by the raw materials (Critical Material Attributes, or CMAs), as well as where variability comes from and how to control it. The traditional, heavily empirical approach to product development and manufacturing has greatly influenced this systematic approach. QbD is required by regulatory requirements as well as for the implementation of novel ideas like design space, the guidelines of the International Conference on Harmonization for Q8 pharmaceutical development, Q9 quality risk management, and the FDA's process analytical technology (PAT).
Keywords: Product Profile, Design, Quality, and Experimentation.
1 INTRODUCTION
A drug product of high quality is free of contamination and consistently delivers the therapeutic benefit promised to the consumer on the label. "The suitability of either a drug substance or drug product for its intended use" is the definition of quality in ICH Q8. The terms "identity,"
"strength," and "purity" are all included.
"Delighting the customer by fully meeting their needs and expectations" is a common definition of quality.
Performance, appearance, availability, delivery, dependability, maintainability, cost-effectiveness, price, and total customer satisfaction may all fall under this category. It is essential that quality be incorporated into the design. To accomplish the elevated degree of value there is need of Value by Plan.
1.1 Quality by Design
Joseph M. Juran, a well-known quality expert, first presented this idea in Quality by Design (J.M. : " Juran on "Designing for Quality" The internal FDA discussion began in the latter half of the 1990s, and in 2002, a concept paper on 21st-century Good Manufacturing Practice was published. Pilot programs to investigate the application and understandings of Quality by Design were initiated with the assistance of a number of biopharmaceutical companies.
1.2 Definition
"A systematic approach to development that begins with predefined objectives and emphasizes product and process understanding and process control, based on sound science and quality risk management," according to ICH Q8 (R2) Pharmaceutical Development 2009, is the
definition of QbD. It entails developing formulations and manufacturing procedures to meet predetermined quality goals. From the perspective of patients, quality by design (QbD) identifies characteristics that are essential to the quality of a drug product, translates these characteristics into the characteristics that the drug product ought to have, and establishes the key process parameters that can be varied to consistently produce a drug product with the desired characteristics.
1.3 Advantages of QbD
It gives a more significant level of confirmation of medication item quality.
The pharmaceutical industry can benefit from cost savings and increased efficiency.
It makes the sponsor's understanding of the control strategy for the drug product's
approval and eventual
commercialization more
transparent.
It makes scaling up, validating, and commercializing transparent, logical, and predictable.
It encourages new ideas to address unmet medical needs.
It lowers manufacturing costs and product rejects while also improving the efficiency of pharmaceutical manufacturing processes.
It reduces or eliminates drug recalls, costly penalties, and potential compliance actions.
It provides opportunities for ongoing advancement.
It improves regulatory oversight efficiency:
It smoothes out post endorsement fabricating changes and administrative cycles.
It makes it easier to get approval for the first cycle;
It makes CGMP inspections after approval more focused.
It works with consistent improvement and lessens the CMC supplement.
It speeds up CMC review time and improves CMC quality.
2 ELEMENTS OF QUALITY BY DESIGN a. Defining the target product quality profile
A "prospective and dynamic summary of the quality characteristics of a drug product that ideally will be achieved to ensure that the desired quality, and thus the safety and efficacy of a drug product are realized" is the definition of a Target Product Profile (TPP). This includes the dosage form, the route of administration, the strength of the dosage form, the release or delivery of the therapeutic moiety, and the pharmacokinetics characteristics (such as dissolution and aerodynamic performance) necessary to develop the drug dosage form and the drug product-quality criteria for the intended marketed product.
The term "TPQP" for "target product quality" is a natural extension of
"TPP" for "product quality." The drug product ought to have the qualities necessary for reproducibly delivering the therapeutic benefit promised on the label.
The TPQP directs formulation scientists in the development of formulation strategies and the maintenance of focused and effective formulation efforts. Identity, assay, dosage form, purity, and label stability are all related to TPQP. The physical, chemical, and biological properties of a drug are all biopharmaceutical properties.
b. Identifying critical quality attributes The next step is to find the appropriate CQAs after TPP is found. According to ICH guidance Q9, a CQA is defined as "a physical, chemical, biological, or microbiological property or characteristic that should be within an appropriate
limit, range, or distributed to ensure the desired product quality." Risk assessment is used to identify CQAs. The key to these risk assessments is prior product knowledge, which can be gleaned from previous laboratory, nonclinical, or clinical experience with a particular product-quality attribute. Relevant data from similar molecules and data from literature references may also be included in this knowledge. The connection between the CQA and product safety and efficacy is supported by this data. The QbD paradigm is unique in that robust risk assessment methods are used to identify CQAs.
c. Performing Risk Assessment
It simply involves connecting CQAs to material attributes and process parameters. According to ICH Q9 Quality Risk Management, the production and use of a drug product always involve some risk. The link between the patient's therapeutic benefit and the risk of quality should be the basis for the assessment.
The level of risk should be proportional to the level of effort, formality, and documentation of the quality risk management process. Before developing a pharmaceutical, manufacturers can choose which studies to conduct by conducting a risk assessment.
Concentrate on results figure out which factors are basic and which are not, which then guide the foundation of control techniques for in-process, unrefined substance, and last testing.
3 TOOLS OF QUALITY BY DESIGN a. Design of Experiments (DOE)
A structured and organized approach to determining the relationship between factors that influence a process's outputs is known as design of experiments (DOE).
DOE may be able to provide returns four to eight times greater than the cost of running the experiments in a fraction of the time, it has been suggested. In his groundbreaking book The Design of
Experiments (1935), Ronald A. Fisher proposed a method for designing experiments. When DOE is used in QbD, it helps to get the most information from the fewest number of experiments. When DOE is applied to a pharmaceutical process, the raw material characteristics (like particle size) and the process parameters (like speed and time) are the factors. On the other hand, the critical quality characteristics (like blend uniformity, tablet hardness, thickness, and friability) are the outputs. It is impossible to experimentally investigate all of the input and output variables and process parameters of each unit operation. The key input and output variables as well as the process parameters that will be investigated by DOE must be identified by scientists using risk management and prior knowledge. DOE results can assist with recognizing ideal circumstances, the basic factors that most impact CQAs and the individuals who don't, as well as subtleties, for example, the presence of collaborations and cooperative energies between factors, Each Calculate turn and Plan of analyses.
b. Process Analytical Technology (PAT)- PAT has been described as "a system for designing, analyzing, and controlling manufacturing through measurements, during processing of critical quality and performance attributes of raw and in- process materials and processes, with the goal of ensuring the quality of the final product." This definition was provided by the definitions group. "Enhance understanding and control of the manufacturing process, which is consistent with our current drug quality system:" is the objective of PAT. Products cannot be tested for quality; It ought to be included by default or be built in. The key and critical process parameters, as determined by process characterization studies, along with their acceptable ranges, define the design space. On-line,
in-line, or at-line PAT applications focus primarily on these parameters. Real-time PAT assessments could theoretically serve as the foundation for ongoing feedback and enhance process robustness.
Because it monitors the particle size, blend uniformity, granulation, content uniformity, polymorphism, dissolution, and the process online, at the line, and offline, NIR serves as a tool for PAT and is useful in RTRT (Real Time Release Testing). As a result, it reduces the product's release testing.
4 CHALLENGES OF IMPLEMENTING QBD WITH FDA PERSPECTIVE
Problems with implementation include:
• Implementing novel ideas and methods (Quality by Design, Design Space, Quality Risk Management)
• A wide range of products
• Expectation for QbD-based submission while meeting traditional requirements (dual process)
• Integration of ongoing review and inspection work, a broad range of approaches to development, manufacturing, and quality operations across the industry implementing, harmonizing
• Changes in culture, application information, and the role of an industry scientist in regulatory discussions are implementation challenges for the industry.
Business challenges include removing budgeting silos across business units, removing silos across business units, and making additional investments during development to improve efficiency and reduce manufacturing costs over the lifecycle. Management support is also a challenge.
5 CONCLUSION
Quality by design is a common understanding of the ICH Q8, Q9, and Q10 concepts that will be crucial to the
formulation process. The review clarifies the concept of critical process parameters, implements the control strategy, continues monitoring and updating the process, and explains the use of the target product profile, risk assessment, and critical material attributes. In addition, it explains how QbD principles and tools can be used in the development of drug products and processes. It is possible to draw the conclusion that the principles and tools of Quality by Design (QbD) play a significant role in facilitating a higher level of understanding of the process and creating opportunities for investigation and the development of control strategies for formulation and process development.
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