CHALLENGES & OPPORTUNITIES OF ICHQ8 (PHARMACEUTICAL DEVELOPMENT) AN INDUSTRY PERSPECTIVE
|
|
- Katrina Blankenship
- 6 years ago
- Views:
Transcription
1 CHALLENGES & OPPORTUNITIES OF ICHQ8 (PHARMACEUTICAL DEVELOPMENT) AN INDUSTRY PERSPECTIVE Paul Stott, PhD Head of US Product Development AstraZeneca ICH Quality Guidelines Workshop BioKorea 2007 Sept 13-14
2 Overview ICH vision Background Principles and concepts developed by EFPIA PAT Topic Group Fictitious example EFPIA Mock P2 AstraZeneca example from the FDA CMC Pilot Program Cost Savings from AZ QbD examples to date Conclusions
3 The Vision of ICHQ8 (and 9 & 10) Pharmaceutical and Manufacturing Sciences leading to continuous product and process improvement A transparent, science and risk based approach to: product development and dossier submission, review, approval and post-approval changes Manufacturers empowered to effect continual improvement throughout the product life-cycle and supply chain More efficient and effective Regulatory oversight
4 Present Position Lots of check box guidelines in West Specifications set based on batch data Q6A Large numbers of post approval submissions, Timescales different between regions causing difficulties for a global supply chain Lack of clear understanding of some terms: critical quality attributes Regulatory Agreement Design Space etc.
5 The Way Forward? ICH - Q8, Pharmaceutical Development (Step 5) - Q8 (R) (Step 1) - Q9, Quality Risk Management (QRM) (Step 5) - Q10, Quality Systems (Step 2) FDA - Pharmaceutical cgmps for the 21 st Century A Risk Based Approach - Quality Systems Approach to Pharmaceutical Current Good Manufacturing Practice Regulations - PAT A Framework for Innovative Pharmaceutical Development, Manufacturing and Quality Assurance
6 ICH Q8: Pharmaceutical Development Design Space Definition The multidimensional combination and interaction of input variables (e.g., material attributes) and process parameters that have been demonstrated to provide assurance of quality Regulatory Approach Working within the design space is not considered as a change Procedure Design space is proposed by the applicant and is subject to regulatory assessment and approval.
7 Structured Approach to Development & Flow In Dossier Target Product Profile Product/ Prior Process Knowledge Dev. Product/ Process Design Space Control Strategy Regulatory Flexibility Definition of Product Intended Use and predefinition of Quality targets (wrt clinical relevance, efficacy and safety) Summary of Prior Scientific Knowledge (drug substance, excipients; similar formulations and processes). Initial Risk Assessment Overview of Quality by Design key actions and decisions taken to develop New Scientific Knowledge, e.g. DoE, PAT, Risk Assessment and Control Summary of Scientific Understanding of Product and Process. Justification and description of Multi-dimensional Space that assures Quality (interrelation-ships and boundaries of Clinical Relevance). Definition of Control Strategy based on Design Space leading to Control of Quality and Quality Risk Mgmt. (Process Robustness) Proposal of Regulatory Flexibility based on Product and Process Scientific Knowledge and Quality Risk Mgmt. (Materials,Site Scale etc) taken from the EFPIA PAT Topic Group
8 Case Study #1 Examplain Mock P2 Submission: fictitious product developed by the EFPIA PAT Topic Group to illustrate the concepts of QbD
9 Examplain Tablets Brief Description Examplain an immediate release solid dosage form Tablet of 200 mg compression weight containing 20 mg drug substance Biopharmaceutics Class I (highly soluble, highly permeable) Conventional, wet granulated tablet formulation Some potential for degradation (hydrolysis) - fluid-bed drying is a critical step Drug substance properties Low bulk density potential issues with content uniformity crystalline, single stable polymorph Primary amine salt
10 Process Development Drying Curves Drying experiments at 1 kg scale Using wet granulate with water content of 18±0.5% (as is routinely produced by the granulation process) Fluid bed drier inlet temperature and air flow were varied Stopped when the water content was in the range % Water content of the granules, and their particle size distribution were monitored on-line Confirmed at larger scale On monitoring system scale independent
11 Process Development Degradation and generation of fines Degradation Fines Inlet temperature Inlet temperature Air flow Air flow Red = does not meet quality requirements 1 kg scale
12 Process Development Combination of Failure Modes Degradation and fines Inlet temperature Air flow
13 Process Development Drying Process Trajectories (1 kg Scale) 18.5% 17.5% 1 2 % 3 H 2 O % 1.5% Drying time
14 Design Space for Fluid Bed Drying Summary Design Space comprises: Critical Process Parameters Inlet temperature Air flow Drying Time Quality Attributes Degradation Disintegration Uniformity of Content Multivariate process parameters represented by process trajectories for water content Change of scale understood Areas of failure found in this case Clear control strategy
15 Design Space for Drying Graphical Description 18.5% 17.5% % H 2 O Regions of uncertainty Known edge of failure due to fines Known edge of failure due to degradation Trajectories describing the boundaries of the design space where product quality is assured 2.0% 1.5% Drying time
16 Based on: Regulatory Flexibility Mechanistic process understanding Consequent application of Risk Management Development and implementation of Design Space for each unit operation e.g. Fluid bed drying Derivation of the critical to control attributes Regulatory flexibility is proposed for the following topics: Process validation Scale and equipment change Site changes Real time release
17 Case Study #2 An example of an AstraZeneca Development using the Principles of ICHQ8 from the FDA CMC Pilot Program
18 QbD approach Quality Risk Management used throughout to direct and focus development work and review the impact of increased knowledge and understanding IVIVC study Testing of the highest risk product and process variables in vivo and development of a clinically relevant dissolution test (underpins proposed Design Space) Multivariate experiments use of PAT tools to measure in-process product attributes, and suitable data analysis tools to determine the most relevant raw materials and process variables linked to Primary Product Attributes and Secondary Product Attributes The Product Design Space Knowledge and understanding used with risk-based approach to propose regulatory flexibility Used to assure patient safety and efficacy (clinical quality) - not linked to physical quality or manufacturability The Product Control Strategy Used to assure clinical and physical quality Managed by internal change control procedures
19 Drug Substance Properties (part of initial prior knowledge) Amount dissolved in 250 ml (mg) 1000 Molecular Weight: 475 pka: dibasic displays high permeability dissolved in 250 ml (mg) >300mg ph BCS Class II Poor compression properties Yield pressure (slow) MPa Yield pressure (fast) MPa Strain rate sensitivity % Cpd X Ideal 21.7 ~ ~140 <15
20 Initial High Level Risks for the Drug Product Initial Quality Risk Assessment: 1. Impact of product / process variables on in vivo performance (BCS Class II) 2. Compression properties leading to poor physical quality
21 Clinical Quality Risk Assessment 120 (FMEA) Risk Product Number Used to choose the highest risk tablet variants (incorporating both product and process variables) to be included in an IVIVC study 0 Changes in Increased level Decreased Impeded Variability in Insufficient Wet mass - Excessive Incorrect Excessive Increased Variability in API particle of binder level of wetting due to filler level or mixing = poor over- water added or granule milling blend time - compression coating size/properties disintegrant Mg Stearate properties blend granulation holding the wet parameters h'phobic coat force thickness variability uniformity mass for too of mg stearate long - around decrease in granules disintegrant performance Potential Failure Mode Table 1 Highest risk failure modes with the potential to impact in vivo performance Manufacture of Tablet Variants A to D Tested in vivo and in vitro Failure mode Changes in drug substance (vandetanib) particle size Failure to control granulation end-point; overgranulation, Increased level of binder in the formulation Decreased level of disintegrant in the formulation. Dissolution retardation mechanism Impact of drug substance surface area on rate of dissolution Impact of granule density and porosity on the rate of ingress of water Impact of slowed tablet disintegration rate on subsequent drug dissolution
22 In Vitro In Vivo Correlation? Equivalent in vivo performance Couldn't develop an IVIVC as highest risk variants (with different in vitro profiles) shown to perform the same as an oral solution in vivo Clinically relevant dissolution test developed that could be used to test future variants in vitro % Dissolution Variant A (Standard tablet) Variant B (Larger particle size) Variant C (Process variant) Variant D (Formulation variant) Time (minutes) Boundary of clinical quality based on dissolution profile of Tablet Variant D Broad applicability based on different mechanisms of dissolution retardation investigated
23 Output of clinical evaluation of product & process variables The studies provide a tool to define the boundaries of the Design Space based on in vivo performance (safety & efficacy) An understanding that there s a low probability of originally perceived high risk changes impacting in vivo PK An increased detectability as the dissolution method has been shown to be a suitable surrogate for in vivo performance (in conjunction with Assay and Uniformity of Dosage Unit) Product dissolution limits using this method will be based on the profile from Variant D, not on process capability The dissolution method can be used to evaluate other product and process variables in the establishment of the Design Space Future changes such as site, scale, equipment, method of manufacture can be qualified using this dissolution method and limit
24 Process Evaluation studies Impact of extremes of the manufacturing process on dissolution performance: % Dissolved Variant D 20 Variant C Time (minutes) Also no impact on Assay or UoDU
25 Output from Process Evaluation Studies 1. Clinically relevant dissolution test used in conjunction with Assay and UoDU tests to demonstrate that remaining material and process variables have no impact on in vivo PK 2. Detailed understanding of the most relevant parameters wrt product physical quality Risk Product Number Changes in API particle size/properties Increased level of binder Decreased level of disintegrant Increased wetting due to Mg Stearate variability Variability in filler level or properties Insufficient mixing = poor blend uniformity Wet mass - Excessive water over-granulation added or holding the wet mass for too long Potential Failure Mode Incorrect granule Excessive blend milling time - h'phobic parameters coat of mg stearate around granules Increased compression force Variability in coating thickness
26 Demonstrated multivariate cause and effect relationships for product physical quality Impeller Speed =1200 rpm B: Mesh Size Tabs/punch to picking: A: Water Quantity Process parameters Granule attributes Tablet attributes Impeller Speed = 900 rpm Water quantity GSA Hardness B: Mesh Size Wtd Capping: Comil screen size Comil impeller speed % fines fraction Capping MgSt addition method A: Water Quantity Pre-compression Press speed 850 um sieve fraction Picking
27 Using Product Knowledge to Develop the Design Space Primary Attributes (Clinical Quality Design Space) Secondary Attributes (Physical Quality Control Strategy) Dissolution Assay Uniformity of Dosage Units (surrogates for in vivo exposure as demonstrated) These attributes directly impact on patient safety and efficacy These will be key elements of the proposed Design Space Appearance Picking Capping Hardness Do not impact on patient safety and efficacy and as such will not constitute a boundary of the Design Space We will use our in depth manufacturing knowledge to control these & share with the Regulatory Agencies (in the dossier) for information
28 The Drug Product Design Space: Is a combination of Input Boundaries and Primary Attributes boundaries: The Input Boundaries were defined to ensure: a) Low probability* of failure against Primary Attributes throughout the shelf-life of the product b) Low risk* of diminishing the clinical relevance of the clinical quality test methods (especially dissolution) * Assessed using experimentation and prior knowledge The Primary Attribute boundaries were defined to ensure in vivo performance Input Boundaries Constraints on: Drug substance particle size Formulation Process Type Primary Product Attributes (Outputs) Constraints on: Assay Uniformity of Dosage Units Dissolution Ensure correct and consistent dosing to patient Ensures appropriate in vivo performance. No constraints on: Site Scale Equipment and Process Parameters Low probability + High detectability = low risk within Design Space
29 Proposed Regulatory Flexibility The Design Space had no constraints on: Process parameters Equipment type Site of manufacture Scale of Manufacture any change to the above will be qualified by the dissolution method (in conjunction with Assay and UoDU) and managed by internal change control processes Process type (wet gran) and pack were fixed to ensure the clinical relevance of dissolution test and negate the need for further stability studies when working within the Design Space All backed by a sound scientific and risk-based understanding of the impact of product and process variables on the Primary (linked to clinical quality) and Secondary (linked to physical quality) attributes This has the potential to offer Operations real flexibility and will facilitate continual improvement
30 Case Study Conclusions The two case studies demonstrate a systematic approach to establish Design Space Design Space will be different for each product Two very different examples presented One based on process parameters one on product attributes Risk Management has been used to direct each stage of the development process Highly desirable to have boundaries linked to safety and efficacy Writing the Dossier will be a challenge - there is not one way
31 Have AstraZeneca s investment in QbD and Control Strategies been worth the effort? YES! A few examples to illustrate the internal value.
32 Raw Materials polymer quality In-house specs Released (%) RFT = 55 % Year Root Cause: new polymer batches changing release rate Steps: use chemometrics to understand critical polymer properties & implement simple evaluation tools for QC Operations Result: Right First Time increased from 55 % to 93 % (2006) Continuous Improvement: towards 100% RFT
33 In-process control with ACDRA (ACcelerated Dissolution Rate Analysis) > analyses and tests performed since 1993! Losec Losec MUPS Nexium Seloken ZOC
34 Improved quality Losec capsules Fraction of rejected batches based on ACDRA results: 1995: 3.8 % (of 369 batches) 1996: 6.5 % ( 540 ) 1997: 3.8 % ( 639 ) 1998: 0.7 % ( 592 ) 1999: 0.5 % ( 411 ) 2000: 0.0 % ( 521 ) 2001: 0.0 % ( 508 ) 2002: 0.0 % ( 447 ) Why? Improved processes due to feedback to the operators
35 Savings Losec capsules Dissolution tests moved from Q-lab to IPC-lab (ACDRA) Less Q-analyses: kusd ( ) Reduced lead time: 86 kusd (2002)
36 Faster trouble shooting PRODUCT PROBLEM ROOT CAUSE SAVINGS Losec caps (1996) Slow drug release Variation in approved raw material batches MUSD Nexium caps (2000) Poor acid resistance EC solution not homogeneous batches MUSD Nexium tabl (2002) Poor acid resistance Fluid bed coater malfunction batches MUSD Savings thanks to immediate detection of problem by the ACDRA system
37 At-line application NIR for content and moisture Replace IPC-lab HPLC and KF analysis with at-line NIR API content and moisture in granules Benefits (samples not sent to QC-lab): Cost savings: Analysis (ca 0.5 MUSD pa) Cut lead time: ~4 days (ca 0.1 MUSD pa)
38 Challenges & Opportunities of ICHQ8 Challenges: Linking product and process variables to in vivo performance Every QbD development will be different Changing skill requirements (process engineers, biopharmaceutics etc.) Need to demonstrate long term financial & quality benefits to gain senior management buy-in Inherent conservatism of the Pharma Industry Opportunities: enables us to focus on those aspects which have the greatest potential to affect the patient facilitates continuous improvement in the manufacturing process provides flexibility of the supply chain and so ensures an efficient & reliable supply of high quality product Significant efficiency gains & financial savings are possible e.g. reduced batch failures and reduced lead times
39 Acknowledgements Chris Potter (& the EFPIA PAT Topic Group) Ryan Gibb Paul Dickinson Linda Billett Christer Karlsson Staffan Folestad Arne Torstensson and many other colleagues at AZ
PAT and Quality by Design exemplified in a Mock P2 submission for examplain tablets. Part 1: Concept and Principles Part 2: Mock P2 Submission
PAT and Quality by Design exemplified in a Mock P2 submission for examplain tablets Part 1: Concept and Principles Part 2: Mock P2 Submission 1 Part 1 Concept and Principles Introduction Rationale Concept
More informationManufacturing Technology Committee Risk Management Working Group Risk Management Case Studies. Case No. RMWG-07. Space
Manufacturing Technology Committee Risk Management Working Group Risk Management Case Studies Case Study Title: Defining Process Design Space Case No. RMWG-07 GMP System Impacted: Introduction / Background
More informationApplication of Quality by Design (QbD) in product development. James E. Polli September 16, 2015
Application of Quality by Design (QbD) in product development James E. Polli jpolli@rx.umaryland.edu September 16, 2015 Pharmaceutical Equivalence Same active ingredient(s) Same dosage form Same route
More informationRegulatory Assessment
Implementation of ICH Q8, Q9, Q10 Regulatory Assessment International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use Presentation Overview Goal
More informationHow to Identify Critical Quality Attributes and Critical Process Parameters
How to Identify Critical Quality Attributes and Critical Process Parameters Jennifer Maguire, Ph.D. Daniel Peng, Ph.D. Office of Process and Facility (OPF) OPQ/CDER/FDA FDA/PQRI 2 nd Conference North Bethesda,
More informationQuality by Design (QbD)
Evaluating the Critical Quality attributes & Critical Process Parameters-A Case Study-Tablets GMP International Workshop February 20/21, 2008 Mumbai, India Mukund Yelvigi Director, Therapeutic Area Management,
More informationDissolution and clinically relevant specifications: linking clinical performance to dissolution
Dissolution and clinically relevant specifications: linking clinical performance to dissolution Talia Flanagan, Dave Holt, Paul Dickinson, Paul Stott. FDA/PQRI Conference on Evolving Product Quality 16-17
More informationThe use of surrogates for dissolution testing for Immediate Release (IR) formulations, when is it feasible?
The use of surrogates for dissolution testing for Immediate Release (IR) formulations, when is it feasible? Limin Zhang (Bristol-Myers Squibb Company) Andre Hermans (Merck & Co., Inc.) 2017 M-CERSI Workshop
More informationControl Strategy. Implementation of ICH Q8, Q9, Q10
Implementation of ICH Q8, Q9, Q10 Control Strategy International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use Introduction Structure of this session
More informationStage 3 - Process Validation: Measuring what matters
Stage 3 - Process Validation: Measuring what matters Trevor Schoerie - PharmOut A quote. The company that fails is the company that comes to us and says Just tell us what to do and we will do it. The company
More informationApplied Process Understanding in Drug Product Development
Applied Process Understanding in Drug Product Development A combined pharmaceutical science, materials science and chemical process engineering approach 17 October, Heidelberg, Germany ir Sander van den
More informationPAT in Action: A Lifecycle Approach to Applied Process Understanding to set meaningful process and product specifications October, Heidelberg, Germany
PAT in Action: A Lifecycle Approach to Applied Process Understanding to set meaningful process and product specifications October, Heidelberg, Germany ir Sander van den Ban, CEng The Unpredictability of
More informationThe role and future of dissolution testing in a QBD product development framework
The role and future of dissolution testing in a QBD product development framework Paul Dickinson, AstraZeneca, Alderley Park, Cheshire Senior Clinical Pharmacology Scientist paul.dickinson@astrazeneca.com
More informationScientific and Regulatory challenges in Quality by Design (QbD) submissions
Health Santé Canada Canada Scientific and Regulatory challenges in Quality by Design (QbD) submissions Krishnan R. Tirunellai, Ph. D. Bureau of Pharmaceutical Sciences TPD, Health Canada CVG, October 2007
More informationImpact factor: 3.958/ICV: 4.10 ISSN:
Impact factor: 3.958/ICV: 4.10 ISSN: 0976-7908 312 Pharma Science Monitor 9(2),Apr-Jun 2018 PHARMA SCIENCE MONITOR AN INTERNATIONAL JOURNAL OF PHARMACEUTICAL SCIENCES Journal home page: http://www.pharmasm.com
More informationQbD implementation in Generic Industry: Overview and Case-Study
QbD implementation in Generic Industry: Overview and Case-Study Inna Ben-Anat, QbD Strategy Leader, Teva Pharmaceuticals IFPAC JAN 2013 R&D Three Core Components of QbD and Generic Industry: How Do They
More informationTHE NEW QUALITY PARADIGM OPPORTUNITIES AND EXPECTATIONS IN ICH Q8 Q9 Q10 Q11 DR. FRITZ ERNI
THE NEW QUALITY PARADIGM IN ICH Q8 Q9 Q10 Q11 OPPORTUNITIES AND EXPECTATIONS DR. FRITZ ERNI FRITZ@ERNI.NET THE NEW PARADIGM OR QUALITY BY DESIGN Why do we need it! Some background Information The impact
More informationImplementation of PAT for Real Time Release Testing. Mark Smith Process Analytical Sciences Group Pfizer, Cork
Implementation of PAT for Real Time Release Testing Mark Smith Process Analytical Sciences Group Pfizer, Cork PAT at Pfizer A key enabler for transformational strategies and new quality paradigms 9 Delivering
More informationBiowaiver Approaches for Solid Oral Dosage Forms in New Drug Applications Poonam R. Delvadia, Ph.D. Division of Biopharmaceutics\ONDP\OPQ\CDER\FDA
Biowaiver Approaches for Solid Oral Dosage Forms in New Drug Applications Poonam R. Delvadia, Ph.D. Division of Biopharmaceutics\ONDP\OPQ\CDER\FDA PQRI BTC Webinar December 06, 2018 DISCLAIMER The presentation
More informationOutline CLINICALLY RELEVANT SPECIFICATIONS. ISPE Process Validation Conference September 2017 Bethesda, MD
CLINICALLY RELEVANT SPECIFICATIONS Patrick J Marroum Ph.D. Senior Director and ACOS Senior Research Fellow Department of Clinical Pharmacology and Pharmacometrics Abbvie Pharmaceuticals Outline CMC variables
More informationPredictability & Performance Through the Product Lifecycle Thought Provoking Perspectives
Quality by Design & Clinical Relevance: Moving Forward Predictability & Performance Through the Product Lifecycle Thought Provoking Perspectives Roger Nosal 1 & Ravi Shanker 2 1 Vice President & Head Global
More informationImplementing Quality by Design Principles and Concepts to Drug Delivery and Formulation Development. S Betterman 15Apr2015
Implementing Quality by Design Principles and Concepts to Drug Delivery and Formulation Development S Betterman 15Apr2015 Agenda Background Implementation Strategy Infrastructure Building Project Application
More informationConducting Successful pre-ind Meetings to Reach FDA Concurrence for Sound 505(b)(2) Development
Conducting Successful pre-ind Meetings to Reach FDA Concurrence for Sound 505(b)(2) Development 2015 AAPS Annual Meeting and Exposition October 28, 2015 Kimberly Raines, Ph.D. Lead Pharmacologist Quality
More informationInspection. Implementation of ICH Q8, Q9, Q10
Implementation of ICH Q8, Q9, Q10 International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use Outline Aim of - as a key part of the regulatory
More informationQuality by Design, Revolution or Evolution? Wim Oostra
Quality by Design, Revolution or Evolution? Wim Oostra 1993 1998 2007 2009 2013 And many more.. Content Introduction A bit of history Examples A New product Legacy product Today? The triggers The goal
More informationQ8 Pharmaceutical Development
Q8 Pharmaceutical Development For questions regarding this draft document contact (CDER) Ajaz Hussain at 301-594-2847 or (CBER) Christopher Joneckis at 301-435-5681. This draft guidance, when finalized,
More informationFormulation Development
Quality by Design and Formulation Development WF Busch Senior Application Development Specialist Dow Chemical Company IPEC Americas, Quality by Design Committee 5 May 2010 Disclaimer The views and opinions
More informationCurrent Industry Practices in Manufacturing Process Validation. Russ Somma PhD
Russ Somma PhD The objectives for validation are: Demonstrate control over the process and finished product. Demonstrate that the process will consistently produce product which meets all specifications
More informationEvolution of Quality Assessments Recent Trends in FDA Queries. Mike Saleh, Pfizer Inc.
Evolution of Quality Assessments Recent Trends in FDA Queries Mike Saleh, Pfizer Inc. Outline 1. Background 2. Assessment of Information Requests from Recent NDAs 3. Distribution of queries (by focus area)
More informationFuture of Question-based Review and Regulatory Submissions
Future of Question-based Review and Regulatory Submissions Robert Iser Associate Director for Policy Development (Acting) Office of Pharmaceutical Science / CDER / FDA FDA/PQRI Conference on Evolving Product
More informationBiowaivers: BCS and IVIVC
Workshop in Celebration of 25 th Anniversary of the School of Pharmacy School of Pharmacy Faculty of Medicine The Chinese University of Hong Kong Biopharmaceutics of Modified Release Products and Challenging
More informationSUPAC IR/MR Update. Glenn Van Buskirk, Ph.D. PQRI Lead Author April 2013
SUPAC IR/MR Update Glenn Van Buskirk, Ph.D. PQRI Lead Author April 2013 Why do it? SUPAC IR/MR Update Oral solid dosage forms continue to be the most significant class of drug product submissions to FDA
More informationSakura Bloom Tablets P2 Mock
Sakura Bloom Tablets P2 Mock Mock P2 English version Sakura Bloom Tablets Disclaimer This mock provides an example of the contents to be included in CTD 2.3.P.2 Pharmaceutical Development section for a
More informationContent PART I: ANDA Roadmap PART II: Understanding of CPPs & CQAs PART III: Scale-Up and Technology Transfer PART IV: Process Validation & Sampling 2
EMA, FDA- ANDA Readiness -OSD Generics Solution Post Formulation Development Horch Guo, May. 2016, Changzhou, China Hongxing.guo@yahoo.com Content PART I: ANDA Roadmap PART II: Understanding of CPPs &
More informationA Comprehensive Review on Quality by Design (QbD) in Pharmaceuticals
Review Article Hardik Patel* 1, Shraddha Parmar 1, Bhavna Patel 1 1 Post Graduate Department of Pharmaceutical Sciences, Sardar Patel University, Vallabh Vidyanagar, Gujarat, India. *Corresponding author
More informationContinuous Manufacturing: An Industry View
Novartis Pharmaceuticals Continuous Manufacturing: An Industry View Diane Zezza Novartis Pharmaceuticals FDA/PQRI Conference on Advancing Product Quality March 22, 2017 Where are we today? Continuous Manufacturing
More informationICH Q9 An Industry Perspective: Ensuring Quality to Patients in a Risk-Based Regulatory Environment
ICH Q9 An Industry Perspective: Ensuring Quality to Patients in a Risk-Based Regulatory Environment Thomas Schultz, Ph.D. Director, Regulatory Sciences Johnson & Johnson September 12, 2007 Presentation
More informationThe Role of Quality Risk Management in New Drug Development and Manufacturing
The Role of Quality Risk Management in New Drug Development and Manufacturing CASSS CMC Strategy Forum Bethesda, MD July 27, 2009 Terrance Ocheltree, RPh, PhD Pharmaceutical Assessment Lead (Acting) Office
More information2nd FDA/PQRI Conference on Advancing Product Quality
2nd FDA/PQRI Conference on Advancing Product Quality Generic Pharma Perspective on the Identification of Critical Quality Attributes and Critical Process Parameters Bruce D. Johnson, Ph.D. Vice President
More informationProcess Drift: When Do We Detect it? Richard L. Friedman Director, DMPQ CDER/Office of Compliance PQRI Process Drift Workshop December 1, 2010
Process Drift: When Do We Detect it? Richard L. Friedman Director, DMPQ CDER/Office of Compliance PQRI Process Drift Workshop December 1, 2010 Overview Goal of Manufacturing Central Question: Why is process
More informationContinuous Manufacturing
Continuous Manufacturing Continuous ing in the Industry Continuous processing has been adopted by the majority of process industries for the manufacturing of fluids (i.e. liquids and gasses) and solids
More informationImplementation of QBD for Analytical Methods - Session Introduction -
Implementation of QBD for Analytical Methods - Session Introduction - Sonja Sekulic January 24, 2014 Quality by Design (QbD) A Systematic Approach ICH Q8(R2) Product Profile Define quality target product
More informationWHO DRAFT PHARMACEUTICAL DEVELOPMENT FOR MULTISOURCE (GENERIC) PHARMACEUTICAL PRODUCTS
23 April 2008 Quality Assurance Programme Quality Assurance and Safety: Medicines (QSM) Department of Medicines Policy and Standards (PSM) World Health Organization CH-1211 Geneva 27 Switzerland WHO DRAFT
More informationNIRS, PAT, RTR testing EU experience and regulatory perspective
NIRS, PAT, RTR testing EU experience and regulatory perspective Heidelberg, Germany October 2013 European Compliance Academy (ECA) Overview of the presentation General considerations Cases submitted in
More informationBMS Experience with the FDA-EMA QbD/PAT Joint Pilot Ambarish K. Singh, PhD Director, Global Regulatory Sciences-CMC Bristol-Myers Squibb Company
BMS Experience with the FDA-EMA QbD/PAT Joint Pilot Ambarish K. Singh, PhD Director, Global Regulatory Sciences-CMC Bristol-Myers Squibb Company FDA/PQRI Conference on Evolving Product Quality September
More informationQuality Implementation Working Group on Q8, Q9 and Q10 Questions & Answers
INTERNATIONAL CONFERENCE ON HARMONISATION OF TECHNICAL REQUIREMENTS FOR REGISTRATION OF PHARMACEUTICALS FOR HUMAN USE Quality Implementation Working Group on Q8, Q9 and Q10 & Current version dated June
More informationStrategic Implantation of PAT : FDA Perspective
Strategic Implantation of PAT : FDA Perspective Moheb M. Nasr, Ph.D. CDER, FDA MOHEB.NASR@FDA.HHS.GOV IFPAC 2008 Strategic Implantation of PAT Baltimore, MD January 27, 2008 Outline The Desired State -
More informationCOMMON DEFICIENCIES IN FINISHED PHARMACEUTICAL PRODUCT (FPP) DOSSIERS
COMMON DEFICIENCIES IN FINISHED PHARMACEUTICAL PRODUCT (FPP) DOSSIERS Additional guidance for manufacturers This note identifies the most common quality related deficiencies in recently assessed dossiers
More informationINTER CHANGEABILITY and EQUIVALENCE. Where we are and what we still have to determine!
INTER CHANGEABILITY and EQUIVALENCE Where we are and what we still have to determine! Acknowledgement Joint presentation UNICEF/MSF/ICRC Cecile Mace Jean Michel Caudron Birgit Schmauser What do we mean
More informationMeeting Solid Dose Formulation Challenges
Streamlining (Fast Tracking) Solid Dosage Form Development Tony Carpanzano, B.S., R. Ph. Director, Research & Development Streamlining (Fast Tracking) Solid Dosage Form Development Meeting Solid Dose Formulation
More informationQuality by Design Considerations for Analytical Procedures and Process Control
Quality by Design Considerations for Analytical Procedures and Process Control Moheb M. Nasr, Ph.D. ONDQA/CDER/FDA IFPAC 2009 Baltimore, MD January 26, 2009 1 Outline Background on FDA Initiatives and
More informationA Framework and Case Study for Implementing the New Process Validation Guidance
A Framework and Case Study for Implementing the New Process Validation Guidance Presented By Bikash Chatterjee President and Chief Technology Officer Pharmatech Associates Agenda Introduction Comparing
More informationApproach, Information needed and criteria- suggested by the members of the IQ dissolution WG
Framework for setting Clinically relevant Dissolution Specification (CRS) Approach, Information needed and criteria- suggested by the members of the IQ dissolution WG Andreas Abend Merck Research Labs
More informationBetter wet granulation: development, scale-up and manufacture
Better wet granulation: development, scale-up and manufacture By Tim Freeman, Freeman Technology Wet granulation is a common unit operation in the pharmaceutical industry yet accurate endpoint detection
More informationPHARMACEUTICAL PRINCIPLES OF SOLID DOSAGE FORMS
PHARMACEUTICAL PRINCIPLES OF SOLID DOSAGE FORMS J. T. Carstensen, Ph.D. Professor of Pharmacy University of Wisconsin Madison, Wisconsin TECHNOMIC ^PUBLISHING CO.. INC J 1.ANCASTER BASET, TABLE OF CONTENTS
More informationBalancing the time, cost and risk of drug development. Christina Gustafsson, PhD Pharm, Formulation Scientist at Pharmaceutical Development, APL
Balancing the time, cost and risk of drug development Christina Gustafsson, PhD Pharm, Formulation Scientist at Pharmaceutical Development, APL Communicating vessels Risk Time Cost Communicating vessels
More informationClinically Relevant Specifications (CRS): A Regulatory Perspective
Clinically Relevant Specifications (CRS): A Regulatory Perspective Richard (Rik) Lostritto, Ph.D. Acting Deputy Director for Science & Policy and Acting Biopharmaceutics Lead, Office of New Drug Quality
More informationAgilent TRS100 Raman. Quantitative Pharmaceutical Analysis System
Agilent TRS100 Raman Quantitative Pharmaceutical Analysis System Agilent TRS100 Raman Streamlined Quality Control Fast Test hundreds of intact tablets or capsules in minutes Simple Quantify active pharmaceutical
More informationBCS, Biowaivers and Dissolution Test Methodologies
BCS, Biowaivers and Dissolution Test Methodologies Vinod P. Shah, Ph.D., FAAPS, FFIP Pharmaceutical Consultant, (Formerly with US FDA) North Potomac, MD., USA Disso Europe 2016 Romania Advances and Applications
More informationQuality by Design for ANDAs: An Example for Immediate-Release Dosage Forms
Quality by Design for ANDAs: An Example for Immediate-Release Dosage Forms Introduction to the Example This is an example pharmaceutical development report illustrating how ANDA applicants can move toward
More informationReview Article Review on Quality by Designing for Metered Dose Inhaler Product Development Santosh R. Thorat * 1, Sarika M.
Scholars Academic Journal of Pharmacy (SAJP) Sch. Acad. J. Pharm., 2015; 4(6): 324-330 Scholars Academic and Scientific Publisher (An International Publisher for Academic and Scientific Resources) www.saspublisher.com
More informationGuidance for Industry
Guidance for Industry Q8, Q9, and Q10 Questions and Answers U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) Center for Biologics
More informationPHARMACEUTICAL MANUFACTURING
PHARMACEUTICAL MANUFACTURING WHAT IS PHARMACEUTICAL MANUFACTURING IT IS THE PROCESS OF INDUSTRIAL SCALE SYNTHESIS OF PHARMACEUTICAL DRUG BY PHARMACEUTICAL COMPANIES. THE PROCESS CAN BE BROKEN DOWN INTO
More informationPLANKSTADT EXPERTS TAKING CARE
CordenPharma PLANKSTADT EXPERTS TAKING CARE Our History 1977 - Start of Packaging activities (ICI Pharma) 1980 - Start of Formulation activities (ICI Pharma) 1995 - First Pre-approval Inspection by FDA
More informationICH guideline Q12 on technical and regulatory considerations for pharmaceutical product lifecycle management - Annexes
1 2 3 14 December 2017 EMA/CHMP/ICH/831751/2017 Committee for Medicinal Products for Human Use 4 5 6 7 ICH guideline Q12 on technical and regulatory considerations for pharmaceutical product lifecycle
More informationPAT for the On-line Characterization of Continuous Manufacturing Systems
PAT for the On-line Characterization of Continuous Manufacturing Systems Thomas O Connor, Ph.D. Office of Pharmaceutical Science FDA/PQRI Conference: Innovation in Manufacturing and Regulatory Assessment
More informationDECISION TREE #1: ESTABLISHING ACCEPTANCE CRITERION FOR A SPECIFIED IMPURITY IN A NEW DRUG SUBSTANCE
DECISION TREE #1: ESTABLISHING ACCEPTANCE CRITERION FOR A SPECIFIED IMPURITY IN A NEW DRUG SUBSTANCE Determine impurity level in relevant batches 1 Determine mean + upper confidence limit for the impurity
More informationQuality Issues for Clinical Trial Materials: The Chemistry, Manufacturing and Controls (CMC) Review
Quality Issues for Clinical Trial Materials: The Chemistry, Manufacturing and Controls (CMC) Review Presented by Erika E. Englund, Ph.D. Slides courtesy of Dorota Matecka, Ph.D. Office of Pharmaceutical
More informationBiowaivers and Harmonization Guidelines for Class I and 3 Drugs: Biowaiver Case Studies
Biowaivers and Harmonization Guidelines for Class I and 3 Drugs: Biowaiver Case Studies Barbara M. Davit, Merck & Co., Inc. 3 rd FDA/PQRI Conference on Advancing Product Quality March 22, 2017 Disclaimer
More informationICH Q8/Q8(R)
Pharmaceutical Quality for the 21 st Century Temple University May 06, 2008 Joseph Famulare, Deputy Director FDA CDER Office of Compliance CDER Office of Compliance and the Critical Path Initiative Since
More informationFull Length Original Research Paper
Copyright 2015 By IYPF All rights reserved Open Access Contents Int. J. Drug Dev. & Res. January - March 2015 Vol. 7 Issue 1 ISSN 0975-9344 www.ijddr.in A Review on quality by design approach (QBD) for
More informationQuality by Design Specifications for Solid Oral Dosage Forms: Multivariate Product and Process Monitoring for Managing Drug Quality Attributes
Quality by Design Specifications for Solid Oral Dosage Forms: Multivariate Product and Process Monitoring for Managing Drug Quality Attributes by the Specification Design and Lifecycle Management Working
More informationUS FDAs Perspective on Product Quality and Bioequivalence
US FDAs Perspective on Product Quality and Bioequivalence Vinod P. Shah, Ph. D. Pharmaceutical Consultant (Formerly with US FDA) Scientific Principles in Dissolution Methodology and Drug Testing Society
More informationTablet formulation design spaces for direct compression and roller compaction. QbD in Pharmaceutical Development: processes
QbD in Pharmaceutical Development: Tablet formulation design spaces for direct compression and roller compaction processes Morten Allesø, PhD (MSc Pharm) Pharmaceutical scientist ISPE Nordic PAT CoP, June
More informationUSP s Perspective on Drug Product Performance Test
USP s Perspective on Drug Product Performance Test Course Overview 1. The concept of in vitro dissolution Definition and application 2. Compendial dissolution/ drug release testing 3. Method development
More informationTECHNICAL AND REGULATORY CONSIDERATIONS FOR PHARMACEUTICAL PRODUCT LIFECYCLE MANAGEMENT Q12
INTERNATIONAL CONCIL FOR HARMONISATION OF TECHNICAL REQUIREMENTS FOR PHARMACEUTICALS FOR HUMAN USE TECHNICAL AND REGULATORY CONSIDERATIONS FOR PHARMACEUTICAL PRODUCT LIFECYCLE MANAGEMENT Q12 ANNEX Draft
More informationShort review on Quality by design: A new Era of Pharmaceutical drug development
International Journal of Drug Development & Research July-September 2012 Vol. 4 Issue 3 ISSN 0975-9344 Available online http://www.ijddr.in Covered in Official Product of Elsevier, The Netherlands SJR
More informationRecent FDA Guidance For Industry; BCS Class 1 and 3 August 2015
Recent FDA Guidance For Industry; BCS Class 1 and 3 August 2015 Bryan Crist Scientific Affairs Manager, Agilent Technologies, Dissolution Systems Dissolution Exchange WebEx Bryan.crist@agilent.com August,
More informationStreamlined Manufacture of Modified Release Matrix Tablets via Direct Compression. Katie Hewlett, Dow Gus LaBella, Colorcon
Streamlined Manufacture of Modified Release Matrix Tablets via Direct Compression Katie Hewlett, Dow Gus LaBella, Colorcon Controlled Release Alliance Unique Together Leading polymer expertise Quality
More informationSTABILITY TESTING OF NEW DRUG SUBSTANCES AND PRODUCTS
INTERNATIONAL CONFERENCE ON HARMONISATION OF TECHNICAL REQUIREMENTS FOR REGISTRATION OF PHARMACEUTICALS FOR HUMAN USE ICH HARMONISED TRIPARTITE GUIDELINE STABILITY TESTING OF NEW DRUG SUBSTANCES AND PRODUCTS
More informationQUALITY OF PROLONGED RELEASE ORAL SOLID DOSAGE FORMS
QUALITY OF PROLONGED RELEASE ORAL SOLID DOSAGE FORMS Guideline Title Quality of Prolonged Release Oral Solid Dosage Forms Legislative basis Directive 75/318/EEC as amended Date of first adoption October
More informationIndustry Perspective on Manufacturing in Early Development
Industry Perspective on Manufacturing in Early Development IQ Workshop, Feb 4-5, 2014, Washington, D.C. Eric Schmitt AbbVie IQ Drug Product Manufacturing Working Group August 2012 issue of Pharmaceutical
More informationMicrocrystalline Cellulose, Colloidal Silicon Dioxide, Sodium Starch Glycolate, Sodium Stearyl Fumarate
Microcrystalline Cellulose, Colloidal Silicon Dioxide, Sodium Starch Glycolate, Sodium Stearyl Fumarate Ready-to-Use High Functionality Excipient Composite Offering Advantages for Total Cost Savings Superior
More informationReflection paper on the dissolution specification for generic solid oral immediate release products with systemic action
10 August 2017 EMA/CHMP/CVMP/QWP/336031/2017 Committee for Medicinal Products for Human use (CHMP) Committee for Medicinal Products for Veterinary use (CVMP) Quality Working Party (QWP) Reflection paper
More informationReal-Time Prediction of Polymer-Coated Multiparticulate Dissolution using Process Analytical Technology
Real-Time Prediction of Polymer-Coated Multiparticulate Dissolution using Process Analytical Technology Authors: Piyush Patel A, Edward Godek B, Chris O Callaghan C, Dr. Ian Jones D A Colorcon, PA, USA
More informationFederal Institute for Drugs and Medical Devices ICH-Leitlinie Q 8 - Pharmaceutical Development die regulatorische Perspektive
ICH-Leitlinie Q 8 - Pharmaceutical Development die regulatorische Perspektive Dr. Susanne Keitel Swiss Association for Quality Olten, 28. Juni 2006 1 Overview of the Presentation ICH Q 8: background and
More informationProviding insight into pharmaceutical formulations
Providing insight into pharmaceutical formulations Dr Steve Ward-Smith Pharmaceutical Industry The average cost of developing a drug is reported to be approx $500 million, but up to 70% of new chemical
More informationAsian Journal of Pharmaceutical Research and Development
Available online on 15.04.2019 at http://ajprd.com Asian Journal of Pharmaceutical Research and Development Open Access to Pharmaceutical and Medical Research 2013-18, publisher and licensee AJPRD, This
More informationStability Report. Stability profile of. BIWG 98 SE tablets 40 mg SR of 133. This stability report comprises 133 pages.
Stability Report Stability profile of BIWG 98 SE tablets 40 mg Number SR 2001-01-04-01 Date Page 00. 00. 0000 1 of 133 Responsible Company Successful Pharma KG Biberach This stability report comprises
More informationIndustry Perspective on Lifecycle Management
Industry Perspective on Lifecycle Management and Post-Approval Building Changes the Best title here Focus on Quality by Design FDA/PQRI Conference on Evolving Product Quality Sep. 16-17, 2014 Michael Kimball
More informationOral Dosage Formulation Development
Oral Dosage Formulation Development Achieving faster formulation of solid oral dosage forms for FIH supplies Dr. Colin Lorimer - published April 29, 2011 The pharmaceutical industry is increasingly looking
More informationPROCESS VALIDATION ANSM 2015 FDA 2011
PROCESS VALIDATION ANSM 2015 FDA 2011 PBE-Expert Inc CANADA Training Company Agreement CPMT #0059104 Qualified Consultant At the measure 2 of the Levier Program PBE, Training Company Agreement CPMT #0059104
More informationCMC Workshop At September 2009 OutSourcing Conference
CMC Workshop At September 2009 OutSourcing Conference Problem Statement A biotech has just in licensed a Phase 2a clinical oncology candidate that has been given fast track status on September 15, 2009
More informationWhite Paper. Approaches for Establishing Clinically Relevant Dissolution Specifications for Immediate Release Solid Oral Dosage Forms
The AAPS Journal, Vol. 19, No. 6, November 2017 ( # 2017) DOI: 10.1208/s12248-017-0117-1 White Paper Approaches for Establishing Clinically Relevant Dissolution Specifications for Immediate Release Solid
More informationInt. J. Pharm. Sci. Rev. Res., 34(1), September October 2015; Article No. 23, Pages: Process Validation of Tablet Dosage Form in Industries
Review Article Process Validation of Tablet Dosage Form in Industries Ram Mohan S.R, N. Vishal Gupta* Pharmaceutical Quality Assurance group, Dept of Pharmaceutics, JSS University, Sri ShivarathreeshwaraNagara,
More informationScientific and Regulatory Considerations for Continuous Manufacturing Implementation for Drug Product
Scientific and Regulatory Considerations for Continuous Manufacturing Implementation for Drug Product Arwa El Hagrasy, Ph.D. Quality Assessment Lead (Acting) Office of Process and Facilities OPQ/FDA PQRI
More informationApplication of PAT for Tablet Analysis. Case examples from Novartis Lorenz Liesum, Lead PAT Hamburg, 19 th of April 2013
Application of PAT for Tablet Analysis Case examples from Novartis Lorenz Liesum, Lead PAT Hamburg, 19 th of April 2013 Agenda PAT@Novartis Organization Business Drivers and Cases NIR Spectroscopy for
More informationQuestion-based Review: A New Quality Assessment System for Generic Drugs
Question-based Review: A New Quality Assessment System for Generic Drugs Lawrence X. Yu, Ph. D. Director for Science Office of Generic Drugs Food and Drug Administration IFPAC Annual Meeting, Jan. 25-28,
More informationQuality by Design and Expertise: Accelerating time to market of complex oral solid dosage forms
CPhI Worldwide 2017 October 24 th -v 26 th, 2017 Frankfurt Quality by Design and Expertise: Accelerating time to market of complex oral solid dosage forms Lucile KOWALSKI - NPI Project Manager Guy VERGNAULT
More information