Quality by design in pharmaceutical development

Quality By Design In pharmaceutical Development

1. Quality by design in pharmaceutical development PRESENTED BY GUIDE MR. SHUBHAM GAJANAN WAGH PROF. S.C.ATRAM M.pharm (pharmaceutics) 1 st year VIDYA BHARATI COLLEGE OF PHARMACY, AMRAVATI-444602 2021-22

2. INDEX Sr. No. Contents Page No. 1 Introduction 3 2 Benefits of quality by design 4 3 Approaches to pharmaceutical development 5 4 Flow of quality by design 6 5 Product profile 7 6 Critical Quality Attributes (CQAs) 8-9 7 Risk assessment 10 8 Design space 11 9 Control strategy 12 10 Life cycle management and continuous improvement 13 11 References 14 2

3. Introduction Definition of quality by design 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 Quality by Design is a concept first outlined by Joseph M. Juran in various publications. He supposed that quality could be planned. The concept of QBD was mention in ICH Q8 guidelines, which states that, “To identify quality can not be tested in products, i.e. Quality should be built in to product by design .” Objective of QbD The main objective of QbD is to achieve the quality products. To achieve positive performance testing. Ensures combination of product and process knowledge gained during development. From knowledge of data process desired attributes may be constructed . 3

4. Benefits of quality by design Benefits of QBD for Industry Eliminate batch failures. Minimize deviations and costly investigations. Empowerment of technical staff. Increase manufacturing efficiency, reduce costs and project rejections and waste. Better understanding of the process. Continuous improvement. Ensure better design of product with less problem .   Benefits of QBD for FDA Provide better consistency. More flexibility in decision making. Ensure scientific base of analysis. Ensures decisions made on science and not on empirical information. Improves quality of review . 4

5. Approaches to pharmaceutical Development 5 Aspects Traditional Quality by design Pharmaceutical development Empirical Systematic and multivariate experiments Manufacturing process Fixed Adjustable with experiment design space Process control Offline and has wide or slow response PAT (process analytical technique) utilized for feedback Product specification Based on batch data Based on the desired product performance Control strategy By end product testing Risk based, controlled shifted up stream, real time release Life cycle management Post approval changes needed Continual improvement enable within design space

6. Flow of quality by design 6 Product profile Identify critical quality attributes (CQA) Carry out risk assessment Establish the design space Describe control strategy Life cycle management and continuous improvement

7. Product Profile Target Product Profile (TPP ) “ A prospective summary of the quality characteristics of drug product that ideally will be achieved to ensure the desired quality, taking in to account safety & efficacy of drug product.”(ICH Q8) Target product profile should includes- Dosage form, Route of administration, Dosage strength, Pharmacokinetics, Stability The TPP is a patient & labeling centered concepts, because it identifies the desired performance characteristics of the product, related to the patient’s need & it is organized according to the key section in the drug labeling. Quality Target Product Profile ( QTPP) QTPP is a quantitative substitute for aspects of scientific safety & efficacy that can be used to design and optimize a formulation and mfg. process. QTPP should only include patient relevant product performance. The Quality Target product profile is a term that is an ordinary addition of TPP for product quality QTPP is related to identity, assay, dosage form, purity, stability in the label . 7

8. Critical Quality Attributes (CQAs) Definition A CQA has been defined as “a physical, chemical, biological or microbiological property or characteristics that should be within an appropriate limit, range, or distribution to ensure the desired product quality. Critical Quality Attributes are generally associated with the drug substance, excipients , intermediates and drug product. The quality attributes of a drug product may include identity, assay, content uniformity, degradation products, residual solvents, drug release, moisture content, microbial limits. physical attributes such as color, shape, size, odor, score configuration , and friability. These attributes can be critical or not critical . Critical Material Attributes ( CMA) A CMA of a drug substance, excipient , and in-process materials is a physical, chemical, biological, or microbiological characteristic of an input material that should be consistently within an appropriate limit to ensure the desired quality of that drug substance, excipient , or in-process material. The CMA is likely to have an impact on CQA of the drug product. A material attributes can be an excipients raw material, drug substances, reagents, solvents, packaging & labeling materials. 8

9. Critical Process Parameter (CPPs) Critical process parameters (CPPs) are defined as “parameters whose variability have an impact on a CQA and therefore should be monitored or controlled to ensure the process produces the desired quality” Process robustness is defined as the ability of a process to demonstrate acceptable quality and performance and tolerate variability in inputs at the same time . A CPP of manufacturing process are the parameters which, when changed, can potentially impact product CQA and may result in failure to meet the limit of the CQA 9 Critical Quality Attributes (CQAs)

10. Risk assessment Quality risk management is a systematic process for the assessment, control, communication and review of risks to the quality of the drug (medicinal) product across the product lifecycle. Risk assessment is a valuable science-based process used in quality risk management that can aid in identifying which material attributes and process parameters potentially have an effect on product CQAs. Risk assessment is typically performed early in the pharmaceutical development process and is repeated as more information becomes available and greater knowledge is obtained. Risk assessment is the linkages between material attributes & process parameters. It is performed during the lifecycle of the product to identify the critical material attributes (CMA) & critical process parameters (CPP ). 10

11. Design Space As per ICH Q8- Design Space is the multidimensional combination and interaction of input variables (e.g., material attributes) and process parameters that have been demonstrated to provide assurance of quality. The relationship between the process inputs (material attributes and process parameters) and the critical quality attributes can be described as the design space A design space may be built for a single unit operation or for the ensure process . Design space is proposed by the applicant and is subject to regulatory assessment and approval (ICH Q8 ). A design space can be described in terms of ranges of material attributes and process parameters. It can also be described through more complex mathematical relationships. It is possible to describe a design space as a time dependent function (e.g., temperature and pressure cycle of a lyophilisation cycle), or As a combination of variables such as components of a multivariate model. 11

12. Control Strategy Control strategy is defined as “a planned set of controls, derived from current product and process understanding that assures process performance and product quality ”. The ability to evaluate and ensure the quality of in- process and/or final product based on process data which typically include a valid combination of measured material attributes and process controls. ICH Q8(R2 ). The control strategy can include the following elements: procedural controls, in process controls, lot release testing, process monitoring, characterization testing, comparability testing and stability testing . Control strategy Based on process and product understanding, during product development sources of variability are identified . Understanding the sources of variability and their impact on processes, in-process materials, and drug product quality can enable appropriate controls to ensure consistent quality of the drug product during the product life cycle. Elements of a Control Strategy Procedural controls In-process controls batch release testing Process monitoring Characterization testing Comparability testing Consistency testing 12

13. Life cycle management and continuous improvement 13 In the QbD paradigm, process changes within the design space will not require review or approval. Therefore, process improvements during the product life cycle with regard to process consistency and throughput could take place with fewer post approval submissions. In addition to regulatory flexibility, the enhanced understanding of the manufacturing process would allow more informed risk assessment as per ICH Q9 regarding the affects of process changes and manufacturing deviations on product quality. Manufacturing , the experience grows and opportunities for process improvement identified are operating space could be revised within the design space without the need for post-approval submission. Over the lifetime of a product, process changes may be required to be made and may require process characterization, validation and filing of the changes to the approved process design space. The quality system needs to provide adequate oversight during QbD implementation of changes that will not go through regulatory approval. Robustness of the quality system would need to be demonstrated with respect to the following four elements: process performance/product quality monitoring preventative/corrective action, change management and management review of process performance and product quality

14. Reference https:// www.slideshare.net/ManishRajput58/quality-by-design-in-pharmaceutical-development-141388093 https://learnaboutgmp.com/good-validation-practices/pharmaceutical-quality-by-design-qbd-an-introduction-process-development-and-applications / https:// www.google.com/amp/s/www.pharmatutor.org/articles/quality-by-design%3Famp 14