REGULATORY AND INDUSTRY VIEWS ON QbD (1).pptx

REGULATORY AND INDUSTRY VIEWS ON QbD

1. REGULATORY AND INDUSTRY VIEWS ON QbD PRESENTED BY NIVEDITHA G 2 nd sem Mpharm(Pharmaceutics) NARGUND COLLEGE OF PHARMACY 15-08-2023 Niveditha G (Nargund college of Pharmacy) 1

2. REGULATORY AND INDUSTRY VIEWS ON QbD Quality by Design (QbD) is one of the most important initiatives 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. 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. 15-08-2023 Niveditha G (Nargund college of Pharmacy) 2

3. A poor-designed pharmaceutical product will show poor safety and efficacy, no matter how many tests or analyses have been done to verify 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. QbD concept can lead to cost savings and efficiency improvements for both industry and regulators. 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. 15-08-2023 Niveditha G (Nargund college of Pharmacy) 3

4. 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. 15-08-2023 Niveditha G (Nargund college of Pharmacy) 4

5. Continuous improvement over the total product life cycle. • Real time Release thru PAT implementation. • Return on investment / cost savings. • More efficient technology transfers. QbD can also be applied to Drug substance development (ICH Q11); Drug Product (ICH Q8 R2), Analytical method development. FDA strongly recommends including QbD elements in ANDA submissions since January 2013. It can be implemented for Biopharmaceuticals products too. US FDA has published two QbD implementation case studies Quality by Design for ANDAs: An Example for Immediate-Release Tablets April 2012. 2. Quality by Design for ANDAs: An Example for Modified Release Tablets December 2011. 15-08-2023 Niveditha G (Nargund college of Pharmacy) 5

6. Regulatory Agencies like EMA also initiated the QbD concepts implementation. EU has also released a document for “Real Time Release”. The European Medicines Agency (EMA) welcomes applications that include quality by design. Quality by design is an approach that aims to ensure the quality of medicines by employing statistical, analytical and risk-management methodology in the design, development and manufacturing of medicines. EMA, FDA, and ICH working groups have appointed the ICH quality implementation working group (Q-IWG), which prepared various templates, workshop training materials, questions and answers, as well as a points- to-consider document (issued in 2011) that covers ICH Q8(R2), ICH Q9, and ICH Q10 guidelines. 15-08-2023 Niveditha G (Nargund college of Pharmacy) 6

7. In a QbD context, the model is defined as a simplified representation of a system using mathematical terms. Models are expected to enhance scientific understanding and possibly predict the behavior of a system under a set of conditions. ICH QIWG document classifies the models according to their relative contribution in assuring the quality of a product and the following is an example of such a categorization: Low-Impact Models: These models are typically used to support product and/or process development (e.g., formulation optimization). Medium-Impact Models: Such models can be useful in assuring quality of the product but are not the sole indicators of product quality (e.g., most design space models, many in-process controls). High-Impact Models: A model can be considered high impact if prediction from the model is a significant indicator of quality of the product (e.g., a chemometric model for product assay, a surrogate model for dissolution). 15-08-2023 Niveditha G (Nargund college of Pharmacy) 7

8. Development and implementation of models include definition of the model purpose, decision on the type of modeling approach (e.g. mechanistic or empirical), selection of variables for the model, understanding of the model assumptions limitations, collection of experimental data, development of model equations and parameters estimation, model validation, and documentation of the outcome of the model development . The ICH Q-IWG document also suggests that a design space can be updated over the product lifecycle, as additional knowledge is gained. It also notes that in development of design spaces for existing products, multivariate models can be used for retrospective evaluation of the production data. 15-08-2023 Niveditha G (Nargund college of Pharmacy) 8

9. Joint efforts of EMA and FDA resulted in a pilot program for parallel assessment of QbD applications in 2011 and discussed the following topic such as Level of detail in QbD containing applications ⇒ Verification of models for real time release testing (RTRT) and in-process Near Infrared (NIR) spectroscopy analytical methods ⇒ Strategies for scale-up and verification of design space ⇒ Post approval change protocols ⇒ Large sample size acceptance criteria 15-08-2023 Niveditha G (Nargund college of Pharmacy) 9

10. The services of the QbD concept for both industry and regulatory bodies are summarized as below. Industry Development of scientific understanding of critical process and product attributes. Controls and testing are designed based on limits of scientific understanding at development stage. Utilization of knowledge gained over the product’s lifecycle for continuous improvement. 15-08-2023 Niveditha G (Nargund college of Pharmacy) 10

11. Regulatory agency Scientifically based assessment of product and manufacturing process design and development. Evaluation and approval of product quality specifications in light of established standards (e.g. purity, stability, content uniformity, etc.). Evaluation of post- approval changes based on risk and science. 15-08-2023 Niveditha G (Nargund college of Pharmacy) 11

12. THANK YOU 15-08-2023 Niveditha G (Nargund college of Pharmacy) 12