Quality-by-Design (QbD) by Mr. Nitin Kadam.

Views:
 
     
 

Presentation Description

No description available.

Comments

Presentation Transcript

PowerPoint Presentation:

QUALITY – by – DESIGN (QbD) Implementation in Formulation Development For (ANDAs) By Mr. Nitin M. Kadam M. Pharm. QbD Team (Formulation Development Compliance) Global Scientific & Regulatory Affairs Wockhardt Research Center, Aurangabad.

PowerPoint Presentation:

What is QbD ??? QbD Definition as per ICH in ICH-Q8R “ A systematic approach to pharmaceutical development that begins with predefined objectives and emphasizes product and process understanding based on sound science and quality risk management.” It means designing and developing formulations and manufacturing processes to ensure predefined product quality objectives.

PowerPoint Presentation:

What is QbD ??? A more systematic approach to development can include, for example, incorporation of prior knowledge, result of studies using design of experiments, use of quality risk management and use of knowledge management through out life cycle of the product. Product quality life cycle is all about the practical means for the implementation of ICH guidance’s on ICH Q8 (Pharmaceutical Development), Q9 (Quality Risk management) and Q10 (Pharmaceutical Quality System), based on sound scientific, engineering and business principles.

PowerPoint Presentation:

What QbD dose in product development ??? QbD identifies characteristics that are critical to quality from the perspective of patients, translates them into the attributes that the drug product should possess, and establishes how the critical process parameters can be varied to consistently produce a drug product with the desired characteristics. For this the relationships between formulation & manufacturing process variables (i.e. CMAs of API and excipient and CPPs) and product characteristics (QTPP) are established and sources of variability identified (CQAs). This knowledge is then used to implement a flexible and robust manufacturing process that can adapt and produce a consistent product over time.

PowerPoint Presentation:

QbD principles increase product understanding and process knowledge. The increased process knowledge and product understanding resulting from QbD can increase the efficiency of manufacturing processes; reduce product recalls and compliance actions, resulting in cost savings for pharmaceutical companies. By reducing uncertainty and risk, QbD can allow industry and regulators to focus their resources in the most critical areas. Because much more process understanding has been demonstrated and expressed in the dossier. What QbD dose in product development ???

PowerPoint Presentation:

QbD filings also can help facilitate GMP inspections by the regulators and decrease the number of post-approval regulatory submissions required to make process changes. What QbD dose in product development ???

PowerPoint Presentation:

The QbD-based pharmaceutical manufacturing process will be adjustable within a design space , providing a robust process that is managed with a control strategy developed using modern statistical process control methods (DOE) and enabling a lifecycle approach to validation/continuous process verification . Product specifications will be based on desired product performance characteristics and will be part of a risk-based quality control strategy. What QbD dose in product development ???

PowerPoint Presentation:

Pharmaceutical QbD is a systematic, scientific, risk-based, holistic and proactive approach to pharmaceutical development that begins with predefined objectives and emphases product and processes understanding and process control. In my words …. A systematic and knowledge based scientific approach of maintaining CQAs by well defined control strategy and design space by establishing combination and interaction of CMAs and CPPs to provide predefined QTPP. What is QbD in brief ???

PowerPoint Presentation:

What is Design Space ??? It is a multidimensional combination and interaction of input variables ( CMAs – c ritical m aterial a ttributes) and process parameters ( CPPs – c ritical p rocess p arameters ) that have been demonstrated to provide assurance of quality. Most Important…. Out of Design Space Initiation of Post Approval Changes

PowerPoint Presentation:

A quality target product profile (QTPP) and a list of critical quality attributes (CQAs). A demonstration of product understanding through the identification of critical material attributes (CMAs) of the drug substance and excipients . 1. 2. A QbD based ANDA should include…….

PowerPoint Presentation:

A demonstration of process understanding through the identification of critical process parameters (CPPs) Development of a Control Strategy that ensures the product reliably meets the predefined objectives 4. 3. A QbD based ANDA should include…….

PowerPoint Presentation:

Defining Quality Target Product Profile (QTPP) Identification of Critical Quality Attributes (CQAs) : Critical/Non Critical Identification of Critical Material Attributes (CMAs) Initial Risk Assessment for Drug Substance Attributes Justification for Initial Risk Assessment for Drug Substance Attributes Selection of Excipients (Provide Rationale / Justification) Excipients Compatibility Studies Development of Q&Q formula for initial Formulation Development Initial Risk Assessment for Formulation Components Important QbD Aspects & Development Flow…

PowerPoint Presentation:

Designing Development Strategies DOE for Optimization of Formulation Defining Design Space for CQAs, CMAs or Formulation Components Pilot Bioequivalence Studies Update of Initial Risk Assessment for Drug Substance Attributes Update of Initial Risk Assessment for Formulation Components Justify the Levels of Risks changed Well Defined Control Strategy Important QbD Aspects & Development Flow…

PowerPoint Presentation:

Important QbD Aspects & Development Flow… Development of Manufacturing Process Initial Risk Assessment for Manufacturing Process DOE for Optimization of Manufacturing Process Defining Design Space for identified CQAs or CPPs Pilot Bioequivalence Study Justify the Levels of Risks changed Well Defined Control Strategy

PowerPoint Presentation:

Scale-up from Lab to Pilot Scale & then Commercial Scale Pre-exhibit / Exhibit Batch Update of Initial Risk Assessment for Manufacturing Process Pivotal Bioequivalence Control Strategy for Drug Product Container Closure System Development Studies to be supported with Stability Studies Important QbD Aspects & Development Flow…

PowerPoint Presentation:

Defining Quality Target Product Profile (QTPP) It contains prospective summary of the desired product features with respect to quality, safety, efficacy. QTPP Element Target Justification Dosage form, Route of Administration, Strength, Pharmacokinetics, Stability, Drug product quality attribute, Container Closure system, etc. Product Specific Pharmaceutical equivalent requirement or specific.

PowerPoint Presentation:

Identification of Critical Quality Attributes (CQAs) and defining its criticality Summarize the CQAs on the basis of quality attributes identified as a target along with the justification for being CQA QA of DP Target Is it CQA? Justification It should include product and process specific quality attributes Desired quality Based on impact of attribute on QTPP Statement should clearly justify the CQA criticality level scientifically as well as technically. Drug Product CQAs: Physical Attribute, Assay, Content Uniformity, Drug Release/ Dissolution, Degradation Products, etc.

PowerPoint Presentation:

Identification of Critical Material Attributes (CMAs) Physical characterization of Drug Substance Physical, PSD, pH-solubility, Hygroscopisity, MP, Flow, Solid State Form, Polymorphism, etc. Chemical Characterization of Drug Substance pH, pKa , FDS, Stability, etc. Biological Characterization of Drug Substance Partition coefficient, BCS, etc. ………. to identify the CMAs

PowerPoint Presentation:

Initial Risk Assessment for Drug Substance Attributes It involves quality risk evaluation in three levels, LOW, MEDIUM, HIGH based on safety and efficacy linked to scientific knowledge ultimately Drug Product CQAs Drug Substance Attributes A B C D X Low Y Medium Z High Drug Substance Attributes: SSF, PSD, Moisture, Hygroscopisity, RS, Solubility, Flow, Chemical Stability, etc. Drug Product CQAs: Physical Attribute, Assay, Content Uniformity, Drug Release/ Dissolution, Degradation Products, etc.

PowerPoint Presentation:

Justification for Initial Risk Assessment for Drug Substance Attributes Table should provide the impact of drug substance attributes on CQAs and scientific as well as technical justification for the level of risk identified Drug Substance Attributes Drug Product CQAs Justification A,B,C,D, etc. X,Y,Z,etc justification for the level of risk identified

PowerPoint Presentation:

Selection of Excipients (Provide Rationale / Justification) Excipients Compatibility Studies Development of Q&Q formula for initial Formulation Development Important QbD Aspects & Development Flow…

PowerPoint Presentation:

Initial Risk Assessment for Formulation Components Drug Product CQAs Formulation Components E F G H X Low Y Medium Z High It involves quality risk evaluation in three levels, LOW, MEDIUM, HIGH based on safety and efficacy linked to scientific knowledge ultimately Formulation Components: Drug substance PSD, Diluent ratio, Diluent PSD, Disintegration level, Lubricant Level, etc. Drug Product CQAs: Physical Attribute, Assay, Content Uniformity, Drug Release/ Dissolution, Degradation Products, etc.

PowerPoint Presentation:

Justification for Initial Risk Assessment for Formulation Components Table should provide the impact of Formulation components on CQAs and scientific as well as technical justification for the level of risk identified Formulation Components Drug Product CQAs Justification E,F,G,H, etc. X,Y,Z,etc justification for the level of risk identified

PowerPoint Presentation:

Designing Development Strategies Design of Experiments ( DoE ) for Formulation Development (This information includes DOE implementation in Product Development by using commercially available DOE software e.g. Minitab, Design Expert, Stat Graphics, etc.) DOE should be carried out at, two main stages of Product development, To optimize formulation To optimize manufacturing process Formulation Development…

PowerPoint Presentation:

Design of Experiments ( DoE ) for Formulation Development Why DoE ? To find answers of following common questions, What is an optimum formulation? How does the optimum change if changes are made to formulation or process? Which variables is sensitive to the machine or process? For performance consistency , what are the limits for these variables? How one design can effectively troubleshoot the problem? To save Time, To Reduce Cost, To get Reliable Quality. The factors to be studied in a DoE could come from the risk assessment exercise or prior knowledge.

PowerPoint Presentation:

DOE Flow…

PowerPoint Presentation:

Key Elements of Experiments…

PowerPoint Presentation:

Design of Experiments ( DoE ) for Formulation Development DoE to be apply and discuss in brief with respect to Design Steps as follows, Screening DoE : Selection of only vital factors from the factors identified in initial risk assessment. Characterization DoE : Choice of experimental design which gives potential interactions in selected vital factors. Performance of experiments. Statistical analysis of data. Conclusion along with recommendations if any. DoE in terms of factors, levels, response variables, design applied, significance and non significance (p-value)

PowerPoint Presentation:

Design of Experiments ( DoE ) for Formulation Development Three basic principles of statistical experimental designs, Randomization By properly randomizing the experiments, the effects of uncontrollable factors that may be present can be “averaged out”. Blocking It is the blocking arrangement of experimental units into groups (blocks) that are similar to one another. Blocking reduces known but irrelevant sources of variation between groups and thus allows greater precision in the estimation of the source of variation under study. Replication It allows the estimation of the pure experimental error for determining whether observed differences in the data are really statistically different.

PowerPoint Presentation:

Factorial Designs – Identify the vital factors that affect your process or product. Then you can make breakthrough improvements. Response Surface Methods (RSM) – Find the ideal process settings. Achieve optimal performance. Mixture design techniques – Discover the optimal formulation. Combined designs - Combine process variables, mixture components and categoric factors in one design! Design of Experiments ( DoE ) for Formulation Development

PowerPoint Presentation:

Defining Design Space for CQAs, CMAs or Formulation Components Pilot Bioequivalence Studies Update of Initial Risk Assessment for Drug Substance Attributes Update of Initial Risk Assessment for Formulation Components Justify the Levels of Risks changed Well Defined Control Strategy Important QbD Aspects & Development Flow…

PowerPoint Presentation:

Manufacturing Process Development It involves identification of all possible known material attributes and critical process parameters that could impact the performance of the process. Initial Risk Assessment for Manufacturing Process Risk assessment can be done for each unit operation of manufacturing process steps separately depends up on the critical considerations for process optimization. Based on the selected process and CMAs, Initial risk assessment can be done. (Stage of risk assessment is not fixed. Risk assessment is depends on the criticality of manufacturing process steps.)

PowerPoint Presentation:

Drug Product CQAs Manufacturing Process Steps (Each unit operation process step should be cover) I J K L X Low Y Medium Z High Manufacturing Steps: Mixing, Granulation, Lubrication, Compression, Coating, etc. Drug Product CQAs: Physical Attribute, Assay, Content Uniformity, Drug Release/ Dissolution, Degradation Products, etc. Initial Risk Assessment for Manufacturing Process

PowerPoint Presentation:

Justification for Initial Risk Assessment of Manufacturing Process Table should provide the impact of Formulation components on CQAs and scientific as well as technical justification for the level of risk identified Formulation Components Drug Product CQAs Justification E,F,G,H, etc. X,Y,Z,etc justification for the level of risk identified

PowerPoint Presentation:

DOE for Optimization of Manufacturing Process (Each unit step) Defining Design Space for identified CQAs or CPPs Pilot Bioequivalence Study Justify the Levels of Risks changed Well Defined Control Strategy Important QbD Aspects & Development Flow…

PowerPoint Presentation:

Scale-up from Lab to Pilot Scale & then Commercial Scale Pre-exhibit / Exhibit Batch Update of Initial Risk Assessment for Manufacturing Process Pivotal Bioequivalence Control Strategy for Drug Product Container Closure System Development Studies to be supported with Stability Studies Important QbD Aspects & Development Flow…

PowerPoint Presentation:

Formulation Development Report Flow As Per QbD 1.1. Executive Summary 1.2. Analysis of Reference Listed Drug 1.2.1. Clinical 1.2.2. Pharmacokinetics 1.2.3. Drug Release 1.2.4. Physicochemical Characterization 1.2.5. Composition 1.3. Quality Target Product Profile 1.4. Dissolution Method Development & Bioequivalence Studies. 1.4.1. Development Dissolution Method 1.4.2. Pivotal / Pilot Bioequivalence Study 2.1. Components of Drug Product 2.1.1. Drug Substance 2.1.1.1. Physical Properties 2.1.1.2. Chemical Properties 2.1.1.3. Biological Properties 2.1.1.4. Initial Risk Assessment of Drug Substance Attributes

PowerPoint Presentation:

2.1.2. Excipients 2.1.2.1. Excipients Compatibility 2.2. Drug Substance 2.2.1. Formulation Development 2.2.1.1. Initial Risk Assessment of the Formulation Components 2.2.1.2. Drug substance Particle Size Selection For Drug Product 2.2.1.3. Process Selection 2.2.1.4. Formulation Development Studies (#1, #2, #3, etc.) 2.2.1.5. Prototype Formulation 2.2.1.6. Formulation Development Conclusion 2.2.1.7. Updated Risk Assessment for Drug Substance 2.2.1.8. Updated Risk Assessment of the Formulation Components 2.2.2. Overages 2.3. Manufacturing Process Development 2.3.1. Initial Risk Assessment of the Drug Product Manufacturing Process 2.3.2. Each Unit Operation Development (Granulation, Compression, Coating) Formulation Development Report Flow As Per QbD

PowerPoint Presentation:

2.3.3. Scale-up From Lab Scale to Pilot Scale and Commercial Scale 2.3.3.1. Scale-up of Each Process Step (Granulation, Compression, Coating) 2.3.4. Pre-exhibit Batch 2.3.5. Exhibit Batch 2.3.6. Updated Risk Assessment of The Drug Product Mfg. Process 2.4. Container Closure System 2.5. Microbiological Attributes 2.6. Compatibility 2.7. Control Strategy 2.8. Development Conclusion ***~ ~ THE END ~ ~ *** Formulation Development Report Flow As Per QbD

PowerPoint Presentation:

Product Development & Life Cycle

PowerPoint Presentation:

Intelligent Peoples doesn't make MISTAKES… But….. mistakes make peoples INTELLIGENT……………

PowerPoint Presentation:

Thank You… Mr. Nitin M. Kadam [email protected] [email protected] http://nitinkadam.webs.com Questions are welcome….

authorStream Live Help