What you’ll learn
Introduction: Why QbD, what is QbD? FDA objectives, the QbD approach
The QbD process: QTPP, assessing risk, working through unit operations to determine CPPs and CMAs
QbD in development of formulation, method development, and manufacturing
Drug properties: setting your QTPP, risk assessment, risk management, risk assessment questions
Identifying CQAs: drug product QAs, drug substance QAs, raw material QAs
Determining CPPs and CMAs
Product or Process design
Control strategies: different levels, monitoring and control, post-approval changes
QbD and continuous processing: FDA perspective, advantages, challenges
DoE in QbD: introduction to DoE, where does DoE fit in QbD
Chemists, engineers, analysts and formulators in pharmaceutical development
Curiousity about learning
Become Certified Professional in Quality by Design (QbD)
The certification covers all the statistical tools for QbD framework. The certification features with industry specialists and experts facilitating quality implementation in various industries. QBD implementation can give manufacturers much more confidence in the robustness of their product, potentially increases the efficiency and quality of their development and manufacturing process as well as reduces profit leakages.
QbD elements include the following: (QbD elements include the following:
(1) a quality target product profile (QTPP) that identifies the critical quality attributes (CQAs) of the drug product;
(2) product design and understanding including identification of critical material attributes (CMAs);
(3) process design and understanding including identification of critical process parameters (CPPs), linking CMAs and CPPs to CQAs;
(4) a control strategy that includes specifications for the drug substance(s), excipient(s), and drug product as well as controls for each step of the manufacturing process; and
(5) process capability and continual improvement. QbD tools and studies include prior knowledge, risk assessment, mechanistic models, design of experiments (DoE) and data analysis, and process analytical technology (PAT).
This certification will provide insight into the key principles of QbD covering quality risk management and formal experimental design. The certification is intended as continuing professional development (CPD) for professionals in the pharmaceutical industry, particularly in production, regulatory affairs and quality functions. The certification will offer an excellent introduction for those less familiar with QbD and provide those with more experience with QbD, new ideas on how to further implement the QbD programme.
The case study based approach in certification programme is designed for working professionals in full time employment who want to update their knowledge and gain required skills and attitude in the area in order to become a certified GMP professional in the domain. This certification is also beneficial for professionals from different streams to help them intensify their knowledge. This is an advanced certification having rigorous case studies based methodology throughout the duration.
While quality by design principles have been used to advance product and process quality in industry, and particularly the automotive industry, they have also been adopted by the U.S. Food and Drug Administration (FDA) for the discovery, development, and manufacture of drugs.
QbD Overview – a US FDA initiative and its advantages
Since the introduction of Quality-by-Design (QbD) concepts, it has been accepted that quality of pharmaceutical products should be designed and built during the manufacturing process. Most of quality problems are related to the way in which a pharmaceutical product was designed. A poor-designed pharmaceutical product will show poor safety and efficacy, no matter how many tests or analyses have been done to verified its quality. Thus, QbD begins with the recognition that quality will not be improved by merely increasing testing of pharmaceutical products. In other words, quality must be built into the product.
Quality by Design (QbD) is one of the most important initiative by US FDA. “Pharmaceutical Quality for the 21st Century: A Risk-Based Approach in 2002 by FDA was the first step towards this goal of QbD compliance. Same period FDA issued another guideline on “Process Analytical Technology” (PAT) to guide the Generic Industry about the advantages of PAT in Real Time Release. This was the beginning of the journey towards implementing QbD. The concept is based on enhancement of Process & Product understanding with the help of Risk assessments, identifying Critical Quality Attributes & Critical Process Parameters to be monitored thru right control strategy. Customers are benefitted thru consistency in commercial manufacturing. FDA recommended the implementation since 2013.
US FDA initiative on QbD
QbD principles have been adopted by the US Food and Drug Administration (FDA) for the discovery, development, and manufacture of drugs.
The FDA initiative is outlined in its report “Pharmaceutical Quality for the 21st Century: A Risk-Based Approach (1). FDA has taken this initiative to guide the Pharmaceutical Industry on how to implement the concepts of QbD into its processes. The focus is on quality should be built into a product with an understanding of the product and process by which it is developed and manufactured with understanding risks involved in manufacturing the product and how best to manage those risks. This is improvement is over “Quality by Testing” (QbT), traditional approach, by the Industry.
QbD facilitates design of products and processes that enhances the product’s Qurity, Efficacy and Safety in the interest of Patients.
While QbD will provide design space (DS), the scale-up and commercial manufacturing experience provides knowledge about the process and the interactions of raw materials used therein with excipients. FDA’s Process Validation (2) guidance in January 2011 is for companies to continue benefiting from knowledge gained, and continually improve throughout the process lifecycle by making adaptations to assure root causes of manufacturing problems are addressed.
International Conference on Harmonization (ICH) Guidelines
Working with regulators in the European Union (the European Medicines Agency) and Japan, the US FDA has improved Quality by Design objectives through the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. ICH introduced the guidelines:
ICH Q8 (Pharmaceutical Development), ICH Q9 (Quality Risk Management), and ICH Q10 (Pharmaceutical Quality System).
These ICH guidelines improve understanding to build “Quality by Design” into Formulation development. This will ensure that “Quality Risk Management and Knowledge Management” are used to monitor the lifecycle management that maintain process control and product quality. The difference between QbD for New Drug Application (NDA) and Abbreviated New Drug Application (ANDA) products is most apparent at the first step of the process(4).
US FDA defines QbD as “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”.
QbD is a systematic process to generate Robust processes with the help of Quality Risk Management (ICH Q9). It is important to control the “Variability” of Raw materials as well as in Manufacturing process by identifying Critical Quality Attributes (CQA) / Critical Material Attributes (CMA) and Critical Process Attributes (CPP) through Risk Management process. It helps to have better understanding of Process & Product thus helping Life Cycle Management of the product (LCM) as explained in diagram no.1
Elements of QbD
1. Quality Target Product Profile (QTPP) that identifies CQAs of the drug product.
2. Product design and understanding including the identification of Critical Material Attributes (CMAs).
3. Process design and understanding including the identification of Critical Process Parameters (CPPs) and a thorough understanding of scale-up principles, linking CMAs and CPPs to CQAs.
4. A control strategy that includes specifications for
the drug substance(s), excipient(s), and drug product as well as controls for each step of the manufacturing process.
5. Process capability and continual improvement.
Regulatory agencies objectives (7) for QbD initiatives are to:
“Encourage early adoption of new technological advances by the pharmaceutical industry. Facilitate industry application of modern quality management techniques, including implementation of quality systems approaches, to all aspects of pharmaceutical production and quality assurance. Encourage implementation of risk-based approaches that focus both industry and the agency attention on critical areas. Ensure regulatory review and inspection policies are based on state-of-the-art pharmaceutical science. Enhance consistency and coordination of the FDA’s drug quality regulatory programs, in part, by integrating enhanced quality systems approaches into the agency’s business processes and regulatory policies concerning review and inspection activities”.
By obtaining increased process & product understanding in order to identify and monitor critical sources of variability helps to achieve Right First Time Performance. Therefore it is essential we shift from Compliance to improved Process & product understanding , which will allow QbD of effective and efficient manufacturing process as well as Real Time Quality Assurance.
One of the important goals of QbD is to ensure that all Sources of Variability affecting a process are identified, explained and managed by appropriate measures.This enables the finished medicine to consistently meet its predefined characteristics from the start to achieve ”Right first time”. QbD focuses on the use of multivariate analysis, often in combination with modern process-analytical chemistry (PAT) methods and knowledge-management tools to enhance the identification and understanding of critical attributes of materials and critical parameters of the manufacturing process. This enhanced understanding of product and process is used to build quality into manufacturing and provide the basis for continuous improvement of products and processes. Knowledge gained through such process and product understanding helps to monitor Life Cycle Management of the product. process & product understanding to support Continual Improvement.
Advantages of QbD to the Generic Industry
Better understanding of the process and the product.
- Minimum batch failures.
- Better understanding of risks involved & mitigation.
- Minimising variations to achieve consistency in manufacturing quality.
- An enhance QbD approach to pharmaceutical development provides opportunities for more flexible regulatory approaches for example: Manufacturing changes within the approved design space can be without regulatory review or approval.
- Reduction of post-approval submissions.
- Greater regulator confidence of robust products.
- Innovative Process Validation approaches.
- More drug availability and less recalls from market.
- Improved yields, lower cost, less investigations, reduced testing, etc.
- Timely launch of products.
- Right first time & every time concept.
- Continuous improvement over the total product life cycle.
- Real time Release thru PAT implementation.
- Return on investment / cost savings.
- More efficient technology transfers.
QbD Applications Scope: It can be applied to Drug substance development (ICH Q11); Drug Product (ICH Q8 R2) , Analytical method development. FDA strongly recommends to include QbD elements in ANDA submissions since January
- Robust product and processes
- Reduce Production losses
- Reduce deviations and recalls
Who this course is for:
- Chemists, engineers, and in pharmaceutical development
- Anyone involved with the development of new or existing drug products; changes or improvements to existing or generic drugs are subject to QbD principals.
- Pharma Research Scientists
- Pharmacy students
- Pharma professionals
- Pharma industry professionals