The Panjab University Pharmaceutical Science Oration 2014: Educating the Next Generation Pharmacist for Industry.
“The dream begins with a teacher who believes in you, who tugs and pushes and leads you to the next plateau, sometimes poking you with a sharp stick called ‘truth’.“
Plato, the Republic
What are the most influential ideas, concepts, and developments introduced by ‘pharmaceutical scientists’ over the last 50 years?
How have these ideas/concepts introduced into practice?
How can we improve?
Visioning the Next Decade: NIPTE-FDA CollaborationAjaz Hussain
NIPTE Seminar at US FDA, 16 March 2016.
QBR as an Organizing Principle for the Proposed NIPTE Center of Excellence for Pharmaceutical Formulations (CEPF)
We are defining the problem too narrowly. Our paradigm of pharmaceutical quality sifted long-ago. We have harmonized on a regulatory methodology for QbD (e.g., ICH Q8). However, with the prevailing ontological gaps (for example as illustrated in the continuing challenges posed with the current FDA’s Inactive Ingredient Database) - How good are the scientific explanations in regulatory submissions? Is quality risk-assessment - metaphysical or an epistemological category?
Good Regulators of Pharmaceuticals (GRP) 22 October 2014Ajaz Hussain
Sharing thoughts on what makes a Good Regulator of Pharmaceuticals with pharmacy students at the Universities of Minnesota and Iowa. A point of emphasis on "we all are regulators" is explained and three areas for learning - (a) Systems and Integrative Thinking, (b) Argumentation and (c) Behavioral Economics described.
I hope you, the viewers, will also find some value in reviewing these slides. If you are a student and have some questions please feel free to drop me a email (a2zpharmsci@msn.com).
CHIR Best Brains Exchange 22 January 2016Ajaz Hussain
Quality of drugs manufactured in emerging economies: Are cost containment strategies heightening the likelihood of substandard drugs in Canada?
What regulatory, policy, and/ or governance changes are needed to address new and increased risks?
How can Canada prevent and reduce health risks that emerge when the pharmaceutical industry adopts globalized production strategies?
On FDA’s Guidance on Pharmaceutical Process Validation (2011)lAjaz Hussain
Connectors between Culture – Metrics – Continued Process Verification in Process Validation?
Confidence is a critical quality attribute. CGMP violations erode confidence and increase nocebo effects. Currently – “breaches in assurance of data integrity” is a global concern. Have exposed the prevailing ‘regulator heterogeneity’. Re-building ‘epistemic trust” is difficult generally; more so with US FDA. Some thoughts on how to ....
Chemometrics, Pharmacometrics and Econometrics Dimensions_of_QualityAjaz Hussain
25 May 2012 Basel, Switzerland. A philosophical exploration - Scientific understanding and risk-based regulatory decisions on Quality by Design. How good are the scientific explanations in regulatory submissions? Scientific explanations yield understanding; quality of explanations differ.What role can Chemometrics, Pharmacometics and Econometrics play? Understanding multidisciplinary (cGMP, CMC, Clin. Pharm., Tox., Clinical, Public Health) perspectives on risk is important. Opportunities; only when the disciplinary divides are bridged. Within the regulatory realm how we set specifications and assess risk have progressed incrementally; at this rate the Vision 2020 may be expected to be visible broadly over time, by 2020?
We are on a journey to make quality medicines affordable to all. In the 21st Century, this journey will be successful to the extent we recognize that quality has to be built-in by design and that it cannot be tested into products, utilize and improve a global Quality Management System (QMS), and implement science based risk assessment in our decision making. Pharmacopoeias are an integral part of this global QMS and have been setting public or market standards for medical products for many centuries. In the 21st Century, Pharmacopoeias can and should be a champion for the practice of quality by design. To do so most effectively it would be useful to recognize how, in the 21st Century, human factors help and hinder optimal development, and correct interpretation, of public or market standards in design, development, control and manufacturing decisions. To explore this aspect in this presentation, cognitive biases – blind spots or alleys – are collected and organized on topics relevant to this workshop: (a) Impurities & Contaminants, (b) Analytical Method Validation, and (c) Public/market standards and Release Testing. How to confront these biases will be discussed. Steps to help in maximally leveraging the Pharmacopoeias on the 21st Century journey will be highlighted.
Visioning the Next Decade: NIPTE-FDA CollaborationAjaz Hussain
NIPTE Seminar at US FDA, 16 March 2016.
QBR as an Organizing Principle for the Proposed NIPTE Center of Excellence for Pharmaceutical Formulations (CEPF)
We are defining the problem too narrowly. Our paradigm of pharmaceutical quality sifted long-ago. We have harmonized on a regulatory methodology for QbD (e.g., ICH Q8). However, with the prevailing ontological gaps (for example as illustrated in the continuing challenges posed with the current FDA’s Inactive Ingredient Database) - How good are the scientific explanations in regulatory submissions? Is quality risk-assessment - metaphysical or an epistemological category?
Good Regulators of Pharmaceuticals (GRP) 22 October 2014Ajaz Hussain
Sharing thoughts on what makes a Good Regulator of Pharmaceuticals with pharmacy students at the Universities of Minnesota and Iowa. A point of emphasis on "we all are regulators" is explained and three areas for learning - (a) Systems and Integrative Thinking, (b) Argumentation and (c) Behavioral Economics described.
I hope you, the viewers, will also find some value in reviewing these slides. If you are a student and have some questions please feel free to drop me a email (a2zpharmsci@msn.com).
CHIR Best Brains Exchange 22 January 2016Ajaz Hussain
Quality of drugs manufactured in emerging economies: Are cost containment strategies heightening the likelihood of substandard drugs in Canada?
What regulatory, policy, and/ or governance changes are needed to address new and increased risks?
How can Canada prevent and reduce health risks that emerge when the pharmaceutical industry adopts globalized production strategies?
On FDA’s Guidance on Pharmaceutical Process Validation (2011)lAjaz Hussain
Connectors between Culture – Metrics – Continued Process Verification in Process Validation?
Confidence is a critical quality attribute. CGMP violations erode confidence and increase nocebo effects. Currently – “breaches in assurance of data integrity” is a global concern. Have exposed the prevailing ‘regulator heterogeneity’. Re-building ‘epistemic trust” is difficult generally; more so with US FDA. Some thoughts on how to ....
Chemometrics, Pharmacometrics and Econometrics Dimensions_of_QualityAjaz Hussain
25 May 2012 Basel, Switzerland. A philosophical exploration - Scientific understanding and risk-based regulatory decisions on Quality by Design. How good are the scientific explanations in regulatory submissions? Scientific explanations yield understanding; quality of explanations differ.What role can Chemometrics, Pharmacometics and Econometrics play? Understanding multidisciplinary (cGMP, CMC, Clin. Pharm., Tox., Clinical, Public Health) perspectives on risk is important. Opportunities; only when the disciplinary divides are bridged. Within the regulatory realm how we set specifications and assess risk have progressed incrementally; at this rate the Vision 2020 may be expected to be visible broadly over time, by 2020?
We are on a journey to make quality medicines affordable to all. In the 21st Century, this journey will be successful to the extent we recognize that quality has to be built-in by design and that it cannot be tested into products, utilize and improve a global Quality Management System (QMS), and implement science based risk assessment in our decision making. Pharmacopoeias are an integral part of this global QMS and have been setting public or market standards for medical products for many centuries. In the 21st Century, Pharmacopoeias can and should be a champion for the practice of quality by design. To do so most effectively it would be useful to recognize how, in the 21st Century, human factors help and hinder optimal development, and correct interpretation, of public or market standards in design, development, control and manufacturing decisions. To explore this aspect in this presentation, cognitive biases – blind spots or alleys – are collected and organized on topics relevant to this workshop: (a) Impurities & Contaminants, (b) Analytical Method Validation, and (c) Public/market standards and Release Testing. How to confront these biases will be discussed. Steps to help in maximally leveraging the Pharmacopoeias on the 21st Century journey will be highlighted.
Pharmaceutical quality decisions are made by multidisciplinary teams (a range of maturity), at different times and in various organizations; understanding of the QbD paradigm and methodology is derived experientially -One Quality Voice is hard to achieve!
Legacy challenges, various ontological assumptions, and weak epistemology curtails knowledge sharing, delays consensus and keeps us trapped in a reactive mode (3rd Order)
The risk of irrational decision making needs to be accounted. ”Cut-paste” or “check-the-box” practices are reminders that we are not achieving an optimal integration or practicing systems thinking.
A reactive approach (3rd Order) to filling the noted gaps poses risk of continued erosion in the confidence the public should have in our assurance of pharmaceutical quality
We need a thoughtful, planned approach to filling these gaps –NIPTE should take on this challenge! Will it?
Behavioral Economics and Managment of Pharmaceutical QbD 25 August 2016Ajaz Hussain
Pharmaceutical knowledge pyramid can be toppled easily!
Serendipitous intersection of Behavioral Economics & CGMP.
Why attention to Behavioral Economics can improve management of QbD work-streams?
How? What (benefits)?
Between regulatory query and response there is Design Space. In that space is our comparability protocol…
Generic non-biological complex drugs DIA CMC Workshop 2017Ajaz Hussain
#DIACMC17
Assigned title for the talk by the organizers:“The need of conducting clinical study for assuring safety and efficacy, as well as a lack of immunogenicity for generic NBCDs”
SUMMARY
Integrated analytical, product and process development to reduce uncertainty in ‘pharmaceutical equivalence’ is the foundation on which confidence in generic drugs rests
Need to leverage the context: RLD “Prescribe-ability” and lot-lot “Switchability” is acceptable
The “sameness” mindset (as opposed to an “equivalence” mindset) poses challenges to evidence ‘synthesis” (not “piece meal” check the box ) in ANDA submissions
Integrated evidence must a priori account for posed/anticipated “legal challenges” intrinsic to the US system
Clinical assessment of Therapeutic Equivalence of generic product intended (i.e., designed) to be equivalent to RLD should only be needed in rare circumstances
When there is a need to provide assurance to non-scientists stakeholders
Currently the FDA’s GADUFA Research and efforts by many in the sector are predominantly focused on developing a “test of bioequivalence”
For most complex products such a test, in and of itself, may be insufficient to ensure therapeutic equivalence over generic product life-cycle
Regulatory Aspects of Continuous Pharmaceutical ManufacturingAjaz Hussain
Digital Pharma Manufacturing RoundtableKronberg, Germany, March 17 2017
A story about manufacturing two products, medicinal product and documented data, and a “little secret”
Part 1: FDA Trends
Background: The little secret – swept under the rug? No more!
Challenge or opportunity: Unprecedented juxtaposition – at the Tipping Point!
Questions: What consideration are needed for building your validation roadmap? Three options: Pathfinder, Standard or Emergency; what will you choose?
Part II: A higher level of confidence in quality assurance : State of Control (stability, capability with statistical confidence)
Case example: Challenges of implementing a roadmap to process capability for some currently commercialized products.
Excipient Knowledge Management Mumbai 12 March 2015 Part 1 & 2Ajaz Hussain
Why attention to excipient knowledge management (specifically their functionality) is critical to mitigating risks (or to leverage opportunities) posed by the rapidly increasing complexity and uncertainty
Note: Knowledge management in the context of ‘intellectual property’ is not the focus of this talk
Totality of Evidence & Theraputic Equivalence 15 October 2016Ajaz Hussain
Put R back in R&D & recognize It is a “complex” product and process!
Invest smartly in analytics, mathematics & statistics, and large sample sizes; and in systems/integrative thinking and data integration
Get to know the RLD – multiple lots; open the door with large sample size
Build capability to justify measured RLD variability is relevant to development of the proposed generic/biosimilar
Exquisite regulatory communication strategy
This is not a ‘complicated process’ for which typical “good practices” will work seamlessly (e.g., typical project management approach); this is a complex process – with multiple interactions and “emergent properties”
Treat it as it is - a complex process and plan; anticipate and address “emergent issues” - in technical, regulatory and legal dimensions; at a certain point be prepared for stakeholder (payers, patient groups,..) communications
The IFPAC Session: Controlling excipient impact during the product lifecycle.
Excipients enable the delivery of actives as a pharmaceutical product. Quality by Design requires that the impact of excipient variability on finished product quality be minimized, or, as paraphrased by Tobyn: - What matters doesn’t vary, and what varies doesn’t matter.
This parallels the current practice of categorizing excipients into critical vs non-critical, the assumption being that the latter do not impact the finished product Critical Quality Attributes. This binary classification of criticality has been criticized as too simple and it is not uncommon to observe excursions in finished product quality correlating with variability of a so-called non-critical excipient. The complexity of the excipients, and the products into which they are formulated, contributes to this uncertainty. For excipients, what varies may not have mattered prior to approval, but may come to matter later in the product lifecycle, especially for continuously manufactured products with real time release.
Excipients, even if fully compliant and manufactured under GMP, represent a reservoir of special cause variability in finished product quality. By definition this can only be addressed via the Control Strategy. Risk management requires continuous multivariate monitoring of finished product and raw materials to maintain quality and model fidelity.
Emerging diagnostic technologies proving the clinical application through g...Lyssa Friedman
Next Generation Sequencing is an exciting new technology for diagnostics companies. But is it right for all products and for all companies? This presentation was delivered via Webinar for a IVD audience for Q1 Productions, March 25, 2014.
Sharpen your Unique Sensing Proclivity: Dissolution is a process in mind and ...Ajaz Hussain
Self-authorship bridging the Academia to Industry (A2I) Gap. The challenge in our systems asking why signifies ignorance. Perhaps until a correction is needed. But after corrective and preventive actions (CAPA) often nothing changes. Errors reoccur and we acquire an “immunity to change.”
Sense of urgency, lessons learned, organizational alignment, team approach, training and an increasing engineering and statistical capability at CDER FDA can be expected to facilitate a move by industry towards continues manufacturing, FDA’s current emphasis on ‘statistical confidence’, Process Validation Guidance 2011, is likely to highlight certain issues (e.g., special causes) within current batch processing; these observation will need to be addressed in an appropriate risk-based manner
Ensuring that pragmatic consideration for specifications & control (intended use) is essential and importance of pragmatic decisions should not be forgotten (e.g., as in case of Design Space Vs. SUPAC), Effective regulatory communication (considering the engineering and statistical emphasis) will be crucial for ensuring regulatory uncertainty is managed in a timely manner,
Systems Engineering of Pharmaceutical Quality by Design 18 December 2017 Alb...Ajaz Hussain
Invitation by Prof. Olivier Lecoq to deliver a lecture at the School of Mines, Albi, France. The topics of interest are connected to the international world of the industrial pharmacy, so the drug development, the product and process quality, the GMP's, the international regulation, the authorities, the industries...
The talk you presented at the "International Rencontres in Pharmaceutical Engineering" in 2004 in Albi, could be an interesting idea to start with if you agree. The keywords being: PAT, FDA, pharmaceutical engineering of the 21st century!
Visiting My Alma mater University of Cincinnati 20 April 2017Ajaz Hussain
On a recent visit to my alma mater, University of Cincinnati, I shared my thoughts in a talk entitled Epistemology and a Medicine Maker: If I Could Send a Message Back in Time? What was the message - build self-confidence based on facts and not fake news by practicing questioning how do I know what I know (epistemology) before choosing the appropriate feeling or emotional response. This practice will help to feel (build emotional state) based on facts. This practice can become your pursuit of (true) happiness. See: Epistemology necessary to break the Procrustean bed: 4+ Order of Consciousness & Pharm. Quality which posted on LinkedIn, March 23, 2016.
Critical Path Initiative Challenges: FDA ACPS Meeting 19 October 2004Ajaz Hussain
Each section within P2 can have an impact on the other P2 sections and similarly other sections of a submission and to CGMP’s By recognizing this as a complex design system that involves multiple attributes, goals, constraints, multidisciplinary design teams (subsystems), different degrees of uncertainty, risk tolerance, etc., we wish to find opportunities to identify robust designs and design space that provides a sound basis for risk assessment and mitigation
One size does not fit all unique study management challenges for diagnostic ...Lyssa Friedman
When partnering with a CRO, diagnostic company needs are different from those of pharmaceutical and device companies. This presentation was delivered at Outsourcing in Clinical Trials West Coast 2015, February 3-4, Burlingame, California.
Study design for laboratory developed tests (LDT) and in vitro diagnostics (IVD) can make or break product and business success. This top-down description of how to pick the right study design was delivered at the 5th Clinical Affairs & Regulatory Approvals For Diagnostics, October 27-29, 2014, in Alexandria, Virginia.
Equivalence Assessment and Maturity of Quality Management SystemsAjaz Hussain
Challenge: As a system or cohort, we can do more to adequately appreciate that “systems” proficiency is a stage in adult development that most struggle to achieve.
High variability in PK can be a characteristic of certain drug products which require different from ordinary strategies and study designs for establishing bioequivalence.
Pharmaceutical quality decisions are made by multidisciplinary teams (a range of maturity), at different times and in various organizations; understanding of the QbD paradigm and methodology is derived experientially -One Quality Voice is hard to achieve!
Legacy challenges, various ontological assumptions, and weak epistemology curtails knowledge sharing, delays consensus and keeps us trapped in a reactive mode (3rd Order)
The risk of irrational decision making needs to be accounted. ”Cut-paste” or “check-the-box” practices are reminders that we are not achieving an optimal integration or practicing systems thinking.
A reactive approach (3rd Order) to filling the noted gaps poses risk of continued erosion in the confidence the public should have in our assurance of pharmaceutical quality
We need a thoughtful, planned approach to filling these gaps –NIPTE should take on this challenge! Will it?
Behavioral Economics and Managment of Pharmaceutical QbD 25 August 2016Ajaz Hussain
Pharmaceutical knowledge pyramid can be toppled easily!
Serendipitous intersection of Behavioral Economics & CGMP.
Why attention to Behavioral Economics can improve management of QbD work-streams?
How? What (benefits)?
Between regulatory query and response there is Design Space. In that space is our comparability protocol…
Generic non-biological complex drugs DIA CMC Workshop 2017Ajaz Hussain
#DIACMC17
Assigned title for the talk by the organizers:“The need of conducting clinical study for assuring safety and efficacy, as well as a lack of immunogenicity for generic NBCDs”
SUMMARY
Integrated analytical, product and process development to reduce uncertainty in ‘pharmaceutical equivalence’ is the foundation on which confidence in generic drugs rests
Need to leverage the context: RLD “Prescribe-ability” and lot-lot “Switchability” is acceptable
The “sameness” mindset (as opposed to an “equivalence” mindset) poses challenges to evidence ‘synthesis” (not “piece meal” check the box ) in ANDA submissions
Integrated evidence must a priori account for posed/anticipated “legal challenges” intrinsic to the US system
Clinical assessment of Therapeutic Equivalence of generic product intended (i.e., designed) to be equivalent to RLD should only be needed in rare circumstances
When there is a need to provide assurance to non-scientists stakeholders
Currently the FDA’s GADUFA Research and efforts by many in the sector are predominantly focused on developing a “test of bioequivalence”
For most complex products such a test, in and of itself, may be insufficient to ensure therapeutic equivalence over generic product life-cycle
Regulatory Aspects of Continuous Pharmaceutical ManufacturingAjaz Hussain
Digital Pharma Manufacturing RoundtableKronberg, Germany, March 17 2017
A story about manufacturing two products, medicinal product and documented data, and a “little secret”
Part 1: FDA Trends
Background: The little secret – swept under the rug? No more!
Challenge or opportunity: Unprecedented juxtaposition – at the Tipping Point!
Questions: What consideration are needed for building your validation roadmap? Three options: Pathfinder, Standard or Emergency; what will you choose?
Part II: A higher level of confidence in quality assurance : State of Control (stability, capability with statistical confidence)
Case example: Challenges of implementing a roadmap to process capability for some currently commercialized products.
Excipient Knowledge Management Mumbai 12 March 2015 Part 1 & 2Ajaz Hussain
Why attention to excipient knowledge management (specifically their functionality) is critical to mitigating risks (or to leverage opportunities) posed by the rapidly increasing complexity and uncertainty
Note: Knowledge management in the context of ‘intellectual property’ is not the focus of this talk
Totality of Evidence & Theraputic Equivalence 15 October 2016Ajaz Hussain
Put R back in R&D & recognize It is a “complex” product and process!
Invest smartly in analytics, mathematics & statistics, and large sample sizes; and in systems/integrative thinking and data integration
Get to know the RLD – multiple lots; open the door with large sample size
Build capability to justify measured RLD variability is relevant to development of the proposed generic/biosimilar
Exquisite regulatory communication strategy
This is not a ‘complicated process’ for which typical “good practices” will work seamlessly (e.g., typical project management approach); this is a complex process – with multiple interactions and “emergent properties”
Treat it as it is - a complex process and plan; anticipate and address “emergent issues” - in technical, regulatory and legal dimensions; at a certain point be prepared for stakeholder (payers, patient groups,..) communications
The IFPAC Session: Controlling excipient impact during the product lifecycle.
Excipients enable the delivery of actives as a pharmaceutical product. Quality by Design requires that the impact of excipient variability on finished product quality be minimized, or, as paraphrased by Tobyn: - What matters doesn’t vary, and what varies doesn’t matter.
This parallels the current practice of categorizing excipients into critical vs non-critical, the assumption being that the latter do not impact the finished product Critical Quality Attributes. This binary classification of criticality has been criticized as too simple and it is not uncommon to observe excursions in finished product quality correlating with variability of a so-called non-critical excipient. The complexity of the excipients, and the products into which they are formulated, contributes to this uncertainty. For excipients, what varies may not have mattered prior to approval, but may come to matter later in the product lifecycle, especially for continuously manufactured products with real time release.
Excipients, even if fully compliant and manufactured under GMP, represent a reservoir of special cause variability in finished product quality. By definition this can only be addressed via the Control Strategy. Risk management requires continuous multivariate monitoring of finished product and raw materials to maintain quality and model fidelity.
Emerging diagnostic technologies proving the clinical application through g...Lyssa Friedman
Next Generation Sequencing is an exciting new technology for diagnostics companies. But is it right for all products and for all companies? This presentation was delivered via Webinar for a IVD audience for Q1 Productions, March 25, 2014.
Sharpen your Unique Sensing Proclivity: Dissolution is a process in mind and ...Ajaz Hussain
Self-authorship bridging the Academia to Industry (A2I) Gap. The challenge in our systems asking why signifies ignorance. Perhaps until a correction is needed. But after corrective and preventive actions (CAPA) often nothing changes. Errors reoccur and we acquire an “immunity to change.”
Sense of urgency, lessons learned, organizational alignment, team approach, training and an increasing engineering and statistical capability at CDER FDA can be expected to facilitate a move by industry towards continues manufacturing, FDA’s current emphasis on ‘statistical confidence’, Process Validation Guidance 2011, is likely to highlight certain issues (e.g., special causes) within current batch processing; these observation will need to be addressed in an appropriate risk-based manner
Ensuring that pragmatic consideration for specifications & control (intended use) is essential and importance of pragmatic decisions should not be forgotten (e.g., as in case of Design Space Vs. SUPAC), Effective regulatory communication (considering the engineering and statistical emphasis) will be crucial for ensuring regulatory uncertainty is managed in a timely manner,
Systems Engineering of Pharmaceutical Quality by Design 18 December 2017 Alb...Ajaz Hussain
Invitation by Prof. Olivier Lecoq to deliver a lecture at the School of Mines, Albi, France. The topics of interest are connected to the international world of the industrial pharmacy, so the drug development, the product and process quality, the GMP's, the international regulation, the authorities, the industries...
The talk you presented at the "International Rencontres in Pharmaceutical Engineering" in 2004 in Albi, could be an interesting idea to start with if you agree. The keywords being: PAT, FDA, pharmaceutical engineering of the 21st century!
Visiting My Alma mater University of Cincinnati 20 April 2017Ajaz Hussain
On a recent visit to my alma mater, University of Cincinnati, I shared my thoughts in a talk entitled Epistemology and a Medicine Maker: If I Could Send a Message Back in Time? What was the message - build self-confidence based on facts and not fake news by practicing questioning how do I know what I know (epistemology) before choosing the appropriate feeling or emotional response. This practice will help to feel (build emotional state) based on facts. This practice can become your pursuit of (true) happiness. See: Epistemology necessary to break the Procrustean bed: 4+ Order of Consciousness & Pharm. Quality which posted on LinkedIn, March 23, 2016.
Critical Path Initiative Challenges: FDA ACPS Meeting 19 October 2004Ajaz Hussain
Each section within P2 can have an impact on the other P2 sections and similarly other sections of a submission and to CGMP’s By recognizing this as a complex design system that involves multiple attributes, goals, constraints, multidisciplinary design teams (subsystems), different degrees of uncertainty, risk tolerance, etc., we wish to find opportunities to identify robust designs and design space that provides a sound basis for risk assessment and mitigation
One size does not fit all unique study management challenges for diagnostic ...Lyssa Friedman
When partnering with a CRO, diagnostic company needs are different from those of pharmaceutical and device companies. This presentation was delivered at Outsourcing in Clinical Trials West Coast 2015, February 3-4, Burlingame, California.
Study design for laboratory developed tests (LDT) and in vitro diagnostics (IVD) can make or break product and business success. This top-down description of how to pick the right study design was delivered at the 5th Clinical Affairs & Regulatory Approvals For Diagnostics, October 27-29, 2014, in Alexandria, Virginia.
Equivalence Assessment and Maturity of Quality Management SystemsAjaz Hussain
Challenge: As a system or cohort, we can do more to adequately appreciate that “systems” proficiency is a stage in adult development that most struggle to achieve.
High variability in PK can be a characteristic of certain drug products which require different from ordinary strategies and study designs for establishing bioequivalence.
Emergency: “No-pain No-gain”
Standard: “Plan Do Check & Act”
Pathfinders: B1: “Don’t Use & Don’t Tell”; no more!
B2: Every vertex can be a Tipping Point
G1: Same and Similar
G2: Synthesis & Analysis
From Roadblocks to Roadmap 2017, with a 2020 VisionAjaz Hussain
In 2015 FDA reorganized OPS to the Office of Pharmaceutical Quality (OPQ) and added an emphasis on One Quality Voice. In 2017 novel pharmaceutical technologies, the aspirational 21st Century Cures Act, and the President-elect Trump’s Administration are juxtaposed to re-shape, perhaps radically so, the Critical Path transformation underway since the beginning of this century. How will the Nation’s life-science research priorities change? What should be the next steps to optimally integrate 21st Century Quality, Cures and the Voice of Patients? What can/should NIPTE do next? Do better? Do more -be the third leg of the stool? This report, From Roadblocks to Roadmap 2017, with 2020 Vision, reviews and reflects on strategic directions emphasized by NIPTE in 2016. It recommends ways to strengthen the Voice of NIPTE to advocate its mission more persuasively and to facilitate its members apply their full potential in the interest of the Nation.
Sharing my learning in dealing with complexity and uncertainty and shed some light on:
(a) Understanding the ‘biosimilar paradox’
(b) Accelerating our “QbD” Journey – focusing on ‘from Generics to Biosimilars’
(c) In preparing this talk, collect my thoughts to help NIPTE consider ways for developing its program on Biosimilars to help the Nation improve assurance of quality with confidence and lower costs
(D) Invite the audience to get to know NIPTE and provide us ways to collaborate with industry
BIOSIMILARS - Regulation and Market Trends Joseph Pategou
Nowadays patients and physicians can have access to three types of drugs: a originators, a generic or a biosimilar.
Those drugs have different regulatory systems that apply in Europe; moreover the biosimilars regulation is evolving and may change. Regulation is an important factor that can give more confidence to patients and healthcare professionals. As a consequence, biosimilaires will grow.
The Survivor community can learn more about the state of the art in new tests available in cancer centres, which pinpoint specific types of tumours that will respond best to treatments.
Discovery of Drug and Introduction to Clinical Trial_Katalyst HLSKatalyst HLS
Introduction to Discovery of Drug and Introduction to Clinical Trials in Pharmaceuticals, Bio-Pharmaceuticals, Medical Devices, Cosmeceuticals and Foods.
Structure-Based Drug Design Facts & Figures InfographicJames Prudhomme
Among 32 pharma and biotech companies surveyed, structure-based drug design is the most prevalent activity with the most players emphasizing the fragment-based variation.
Drug Discovery path
Pharma R & D –overview
Discovery & Development
Preclinical research
Clinical Trial
NDA and FDA Approval
Post marketing data
References
A Leapfrog Need and Opportunity for mAbsAjaz Hussain
Leapfrogging on reforming mAbs policies makes sense, and doing so can be a principled duty of care.
SMART Technology, SMART Professionals, SMART Services, SMART Organization.
SMART Quality by Design Applications Not Submissions in 2024Ajaz Hussain
Many generic pharma companies seeking regulatory approval uncritically follow “past” practices and prior knowledge. Few, if any, correct errors and innovate to improve past expertise and techniques. The idea of SMART "QbD in ANDApplications" (not “submission”) builds on this observation.
Intuitively Moving Institutions Towards Global Regulatory Resilience Ajaz Hussain
From my experience, how can I describe an intuitive and self-organizing social force around "attractors" patients' value to be assured of therapeutic equivalence?
Critical Importance of Pharmaceutical Traceability in the Experience.pdfAjaz Hussain
From a narrow viewpoint, serialization is just a process of printing an identifying number on products and shipping cases.
From a long-term view, the integration of serialization numbering systems with the production line as well as the quality control procedures required to maintain the integrity of the numbers.
Validation 4 for Credible Pharma 4 a Keynote for Valconnect 2023.pdfAjaz Hussain
The notion of Validation 4.0 in the title of this keynote relates to the development and maturity of people and professionals, which I will elaborate on in the context of the ValGenesis experiences [of its users and service providers].
Validation 4.0 in this talk is about internal assurance, self-assurance, and self-authoring policies, plans, and procedures, ideally without the need [to wait] for FDA guidance.
SMART Triaxial Compaction, Social Form 483 and VAI or OAI to an Avenger.pdfAjaz Hussain
Why did the company not design and formulate a tablet that did not “cap”? Why wouldn’t NIH fund my proposal for CAFD? Why did the FDA [discount] Pharmaceutical Development Reports, while in the EU and Japan, is it an essential part of the regulatory review?
Under a hypothetical social inspection scheme, a report submitted in 2010 is imagined as PM 483 in the spirit of FDA Form 483 of “Inspectional Observations.”
What do the noted observations suggest about my professional maturity or state of mind at that event in 2010? What would be an appropriate “feedback” response?
Statistical Thinking and Pharmaceutical Professional Development, a keynote b...Ajaz Hussain
In adulthood, to keep maturing, one must acknowledge the elephant in the room – the emotions we feel. To feel is to experience. Experience complements our scientific training. But do we pay attention to the Integrity of our experience? A tonic for wiser statistical thinking to inform the development of pharmaceuticals and professionals.
An Updating Perspective on BAD I in March Madness 2023.pdfAjaz Hussain
Why does it take decades to acknowledge the obvious? Something to ponder and write about. How do you suggest we keep moving closer to the truth? Can we simultaneously personalize our minds, machines, and medicines to develop continuously? How? I am sharing a slide deck of thoughts to discuss meaning-making and the Federal Food, Drug, and Cosmetic Act (FD&C Act) in the context of the post-truth world, which I collected to populate two invited lectures at the University of Minnesota, College of Pharmacy. The slides I am uploading here are in reverse order, 2nd lecture followed by the first. It is, to begin with, a journey to 2020+ to note that the root cause of BAD-I is I and to pose a challenging premise that beyond the age of majority, few adults continue to develop and mature. What evidence warrants this premise, and why? Then how to develop and mature continuously as an adult and a professional.
Mature Managers and Management of Pharmaceutical Quality and QuantitiesAjaz Hussain
We live in a post-truth world, and we like to think we are good. Are we? Do we not need ALCOA for the integrity of our experience?
Remember: Experience means to feel; how you feel determines what you learn! Honoring my grandmother’s advice, keeping intentions clean, इरादों को साफ रखें to begin to recognize a pattern of interactions between how I feel, what I think to explain why I behaved in a certain way.
Some of my thoughts on SMART Objective negotiations and to be better at SMART Experiencing than SMART Machines. The content describes insights from observing the immaturity of political, regulating, and management systems. Why does “immature” claim “I am mature” when it shouldn't?
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Take a smart “development stance” to prepare for 2022 and beyond, envision your journey to 2030. Spiral high and wide like a migratory bird. Recall, Reflect, Research, Remember, Reset and Rebuild: Recycling necessary but not sufficient.
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Sustain and Build a Quality Culture in Today's RealitiesAjaz Hussain
What is quality, what is culture? Culture, quality, and assurance are just a few of the many abstract words in our lexicon. The meaning we make evolves with our development and maturity. Our education and training are necessary but insufficient for our development and maturity. Learning from experience is essential, and experiential learning is highly variable. Some continue to develop, but at different rates; others do not. In this presentation, I share why and how a connect-the-dots framework was developed and what it offers to individuals and organizations. Building refers to a process by which a source code guides software coding programs for a stand-alone computer or an enterprise-wide system. The context of this presentation is experiential. The content is derived from experiencing the real world via an intentional journey beginning in 2015 across the globe; since 2020, this journey has been searching for the source code to what is good. In my imagination and thought experiments, the building is a process, as in the context of software development. Coding for a stand-alone computer is similar but not interchangeable or automatically substitutable for writing and executing a personal or individualized continuous professional development plan. I speak about quality culture to ease the process of continuous learning, development, and maturity in professionals and management systems. To improve feedback and encourage backpropagation of errors of omission and commission to learn how to prevent mistakes and improve continually, I remind that it is increasingly relevant today to begin asking - how might we assess suitability, capability, and comparability of humans and AI in the context of CGMP compliance and maturity of a pQMS. I implicitly use the lexicon of biosimilars, interchangeable biosimilar products, and automatic generic substitution for brand products to help us make sense of our suitability and capability to know the difference in the maturity stages we call professional and good practitioners to appreciate the differences in the regulatory and social expectation of validation and assurance broadly and specifically as in the validation of computer and pharmaceutical systems.
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Compared to “one factor at a time” experiments, increased experimental efficiency, accounting interactions, multivariate predictive capability, minimization, maximization, optimization, graphical illustration for enhanced communication of complex topics.
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Meaning making measurement maturity and management mokshaAjaz Hussain
Power without wisdom is a recipe for disaster. “Your problem is not technology. The problem is you. You lack the will to change” (The Day the Earth Stood Still (2008). “I think we need to do some very serious soul searching,” Woodcock (2020). Adequate, well-controlled, qualified by training and experience, fairly, responsibly (FD&C Act). “Only at the precipice do we evolve.” Is this our moment? Profiteers learn to be patient. Exploitation & Exploration: Bottom and Toplines, the ambidextrous. Quality is integral; warrant connects quantitative evidence with claims. Cease dependence on inspection via maturity of self, systems, & societies. You can find the way forward [to maturity] in the heart. Sense within to awaken. Dil Se! By heart.
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Educating the Next Generation Pharmacist for Industry. The Panjab University Pharmaceutical Science Oration 2014
1. Educating the Next Generation
Pharmacist for Industry
Ajaz S. Hussain, Ph.D.
Insight, Advice & Solutions LLC
Maryland, USA
Executive Director, the National Institute for
Pharmaceutical Technology & Education
12/12/2014 Ajaz@ajazhussain.com 1
The Panjab University Pharmaceutical Science Oration 2014
3. 12/12/2014 Ajaz@ajazhussain.com 3
“The dream begins with a teacher who believes in you,
who tugs and pushes and leads you to the next
plateau, sometimes poking you with a sharp stick
called ‘truth’.“
Plato, the Republic
4. Pharmacist
• B.Pharm., M. Pharm., Pharm. D., Ph.D.,…
• License to practice,..
• Retail, Hospital, Academia, Industry, Government,…..
• Many permutations and combinations….
• Significant differences
12/12/2014 Ajaz@ajazhussain.com 4
5. Pharmaceutical Scientist
• B.Pharm., M. Pharm., Pharm. D., Ph.D.,…
• Other Disciplines
• Academia, Industry, Government,…
12/12/2014 Ajaz@ajazhussain.com 5
6. Three questions
• What are the most influential ideas, concepts, and developments
introduced by ‘pharmaceutical scientists’ over the last 50 years?
• How have these ideas/concepts introduced into practice?
• How can we improve?
12/12/2014 Ajaz@ajazhussain.com 6
7. FIP Survey (2010), Five Groups &
Coordinators
• Drug Discovery (Prof. Christian Noe)
• Pharmacokinetics and Pharmacodynamics
(Prof. Geoffrey Tucker)
• Formulation Sciences (Prof. Daan Crommelin)
• Drug Regulation (Dr Carl Peck)
• Drug Utilisation (Dr Mario Rocci)
12/12/2014 Ajaz@ajazhussain.com 7
Impact of the Pharmaceutical Sciences
Hendrik de Jong, FIP secrétaire scientifique, Correspondant Européen, Académie Nationale de, Pharmacie
8. Who responded to the survey?
12/12/2014 Ajaz@ajazhussain.com 8
Greg Amidon (USA)
Larry Augsburger (USA)
Klaus Peter Bogeso
(Denmark),
Alasdair Breckenridge (UK),
Douwe Breimer
(Netherlands),
Bill Charman (Australia),
Patrick Couvreur (France),
Daan Crommelin
(Netherlands),
Hendrik De Jong
(Netherlands),
Hartmut Derendorf (USA),
Jürgen Engel (Germany),
Alexander Florence (UK),
Leung Fung (USA)
Johan Gabriellson (Sweden),
Giovanni Gaviraghi (Italy),
Anders Grahnen (Sweden),
Theo Guentert (Switzerland),
Richard Guy (UK),
Hideoyshi Harashima
(Japan),
Mitsuru Hashida (Japan),
Keith Jones (UK),
Bill Jusko (USA),
Thomas Kissel (Germany),
Axel Kleemann (Germany),
Larry Lesko (USA)
Panos Macheras (Greece)
Henri Manasse Jr. (USA),
Kamal K. Midha (Canada),
Peter Milligan (UK),
Klaus Mueller (Switzerland),
Ernst Mutschler (Germany),
Tsuneji Nagai (Japan),
Christian Noe (Austria),
Sandy Pang (Canada),
Carl Peck (USA),
Roberto Pelliciari (Italy),
Malcolm Rowland (UK),
Tomas Salmonson (Sweden),
Shigeki Sasaki (Japan),
Hitoshi Sasaki (Japan),
Walter Schunack (Germany),
Vinod Shah (USA),
Chang-Koo Shim (South
Korea),
Juergen Siepmann (France),
Phil Smith (USA),
Don Stanski (Switzerland),
Kjell Strandberg (Sweden),
Yusuke Tanigawara (Japan),
Henk Timmermann
(Netherlands),
Vladimir Torchilin (USA),
Geoffrey Tucker (UK),
Mitsuru Uchiyama (Japan),
Albert Wertheimer (USA)
9. Drug Discovery
• Molecular drug targets
• Classification of pharmacological receptors including their subtypes for better insight into drug-target interaction of
increasingly complex systems
• Computation in drug design
• Calculation of physical-chemical parameters (QSAR), pharmacophore modelling and high throughput docking
• Molecular Biology – Tools and Drugs
• Biopharmaceuticals, new tools in discovery and development, new imaging techniques, stratification of patients (trials
and therapy)
• Automated screening
• Increased efficiency in hit identification
• Biochemistry, signaling pathways and metabolic networks
• Better mapping of disease biology and design of new drugs with “individualised” therapeutic properties
12/12/2014 Ajaz@ajazhussain.com 9
10. Pharmacokinetics and
Pharmacodynamics
• The linkage of PK and PD in combined models
• Enhanced interpretation of drug response and the design of optimal dosage regimens
• The Clearance concept
• Allowed understanding of the impact of physiological and pathological changes on the elimination of drugs from the body
• Whole Body Physiologically-Based PK modelling
• Improved prediction of human (and animal) PK and drug-drug interactions, and associated variability
• The concepts of Bioavailability / Bioequivalence
• Provided a scientific basis for improved design of oral (and other) drug products and evaluation of the therapeutic equivalence
of innovator and generic products
• Nonlinear Mixed Effect modelling (“Population PK”)
• Improved insight into population variability in response to drugs (both PK and PD) based on sparse data from individuals.
12/12/2014 Ajaz@ajazhussain.com 10
11. Formulation Sciences
• Development and implementation of more and more advanced equipment for the production of
high quality “classical” pharmaceutical formulations
• Computational pharmaceutics
• Improved process design and development (ANN, QbD, PAT...)
• Bioavailability concept
• Translated into the concept of Biowaivers / Biopharmaceutics Classification System (BCS)
• Modified release dosage forms (oral and parenteral delivery)
• Improved PK characteristics of medicines and new relevant excipients
• Drug targeting concept with carrier systems
• Temporal and spatial release of medicines, targeted actions of medicines (efficacy, toxicity...)
• New routes of administration apart from oral and parenteral routes
• Improved bioavailability features for transdermal and pulmonary (systemic) delivery
12/12/2014 Ajaz@ajazhussain.com 11
12. Drug Regulation
• ADME/PK-PD modeling concepts, pharmacometric analyses, and simulation
techniques, leading to:
• Regulatory guidance/ standards for safer, more effective individualized dosing regimens. Facilitated development and
regulatory decisions.
• BioAvailability / BioEquivalence
• Efficient bridging of candidate drug formulations and abbreviated regulatory pathway for generic products
• Pharmacogenomics
• Regulatory acceptance of genetic biomarkers associated with PK-PD variability and disease states
• Risk-benefit evaluation methods
• PKPD, drug metabolism and simulation methods for identification, evaluation and guidance on drug-related Risks
• Formulation optimization / drug delivery systems
• Reduction of regulatory burden via regulatory guidance and evaluation of drug products, including the
Biopharmaceutical Classification System (BCS)
12/12/2014 Ajaz@ajazhussain.com 12
13. Drug Utilisation
• Generic Drug Products
• Effective treatment of diseases at a greatly reduced cost. Strong stimulus for the continual innovation that brings new
drugs to market
• Drug Utilization Reviews
• Maximizing the therapeutic benefit while minimizing adverse effects at the lowest overall cost
• Biotechnology
• New way of treating diseases through complex molecules (vaccines, antibodies, therapeutic proteins, gene therapy)
• Novel Dosage Forms
• Improve patient’s adherence and effectiveness of drug therapy; reduce the frequency of adverse effects
• Personalized Medicine
• Disease are heterogeneous in nature. Highly target approach to the development of drugs based on patient attributes.
In its infancy, will happen – strong societal and scientific forces at play
12/12/2014 Ajaz@ajazhussain.com 13
14. Their conclusions
• Along with scientists from other fields, ‘pharmaceutical scientists’
have contributed significantly to the discovery and development of
new drugs and drug preparations, and to improving the efficacy and
safety of existing drugs and drug preparations.
• In particular, pharmaceutical scientists have been key players in
facilitating the translation of these discoveries and developments
into better healthcare
12/12/2014 Ajaz@ajazhussain.com 14
Impact of the pharmaceutical sciences on health care: A reflection over the past 50 years. Malcolm Rowland, Christian R. Noe, Dennis A. Smith, G. T.
Tucker, Daan J. A. Crommelin, Carl C. Peck, Mario L. Rocci Jr., Luc Besançon and Vinod P. Shah. J.Pharm Sci 2012 Aug 21
15. Formulation Sciences - Drug Utilization -
Drug Regulation
12/12/2014 Ajaz@ajazhussain.com 15
Computational
pharmaceutics
Improved process design
and development (ANN,
QbD, PAT...)
Bioavailability concept
Translated into the concept
of Biowaivers /
Biopharmaceutics
Classification System (BCS)
Generic Drug Products
Effective treatment of diseases at a greatly
reduced cost. Strong stimulus for the
continual innovation that brings new drugs
to market
Drug Utilization Reviews
Maximizing the therapeutic benefit while
minimizing adverse effects at the lowest
overall cost
Biotechnology
New way of treating diseases through
complex molecules (vaccines, antibodies,
therapeutic proteins, gene therapy)
Novel Dosage Forms
Improve patient’s adherence and
effectiveness of drug therapy; reduce the
frequency of adverse effects
ADME/PK-PD modeling
concepts, pharmacometric
analyses, and simulation
techniques, leading to:
Regulatory guidance/ standards for safer,
more effective individualized dosing
regimens. Facilitated development and
regulatory decisions.
BioAvailability /
BioEquivalence
Efficient bridging of candidate drug
formulations and abbreviated regulatory
pathway for generic products
Formulation optimization /
drug delivery systems
Reduction of regulatory burden via
regulatory guidance and evaluation of
drug products, including the
Biopharmaceutical Classification System
(BCS)
16. Next 50 years?
12/12/2014 Ajaz@ajazhussain.com 16
Formulation Sciences - Drug Utilization - Drug Regulation
Don’t limit a child to your own learning, for he was born in another time.
Rabindranath Tagore
17. Providing a healing touch – a higher
standard than ‘do no harm’
• “Work is love made visible” ~
Kahlil Gibran
• “Your task is not to seek for love,
but merely to seek and find all
the barriers within yourself that
you have built against it.”
~Rumi
12/12/2014 Ajaz@ajazhussain.com 17
18. By Design: Intention to act consciously
• In the interest of patients, and to continually improve this ability
• To provide a healing touch – one life at a time, in what we do, and how we
do it.
12/12/2014 Ajaz@ajazhussain.com 18
Consciously
Scientific methodology
Engineering Design
Plan-Do-Check-Act
Subconsciously
Habits (work to get rid of bad ones)
Habits (work to cultivate good one)
Keystone habits (Safety @ Alcoa;
A.L.C.O.A. of data integrity)
The Power of Habit: Why We Do What We Do in Life and Business. Charles Duhigg (2012)
http://www.slideshare.net/a2zpharmsci/pharmaceutical-culture-of-quality
19. “we can be blind to the obvious, and we are also
blind to our blindness.”
Daniel Kahneman, Thinking, Fast and Slow
12/12/2014 Ajaz@ajazhussain.com 19
20. We like to think we're rational human
beings; few examples of our biases
• The way you feel filters the way you interpret the worldAffect heuristic
• People are over-reliant on the first piece of information they hearAnchoring bias
• We tend to listen only to the information that confirms our preconceptionsConfirmation bias
• Failing to recognize your cognitive biases is a bias in itselfBias blind spots
• When you choose something, you tend to feel positive about it, even if the choice has flaws.Choice-supportive bias
• Tendency to see patterns in random eventsClustering illusion
• Overestimate the importance of information that is available to themAvailability heuristic
• Where a word, name or thing you just learned about suddenly appears everywhereFrequency illusion
• The tendency for people to want an immediate payoff rather than a larger gain later on.Hyperbolic discounting:
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http://www.businessinsider.com/cognitive-biases-2014-6?op=1#ixzz3L8GdJOVe
21. The squares marked A and B
12/12/2014 Ajaz@ajazhussain.com 21
http://web.mit.edu/persci/people/adelson/checkershadow_proof.html
Same or
different
shade of
gray?
23. By Design is the foundation of Culture of
Quality
It is hard to foster a Culture of Quality!
also @ FDA
12/12/2014 Ajaz@ajazhussain.com 23
24. Quality & Security
What was the root cause?
• Both pure and applied science have
gradually pushed further and further
the requirements for accuracy and
precision. However, applied science,
particularly in the mass production
of interchangeable parts, is even
more exacting than pure science in
certain matters of accuracy and
precision. Walter A. Shewhart
12/12/2014 Ajaz@ajazhussain.com 24
http://www.cbsnews.com/news/more-malaria-for-liberia-marines/ http://www.slideshare.net/a2zpharmsci/performance-testing-pharmaceutical-quality-2004
(accessed 6 December 2014) (accessed 6 December 2014)
25. Do no harm → Providing a healing touch
First few days @
FDA
• Learning about death of a child; Fentanyl Patch Transfer
when the child slept in a bed used by grandmother
Working hard to
change minds and
policies
• Hitting a brick wall
Last couple of
months @ FDA
• Death of a young lady following a visit to a dentist; again
poor adhesion a contributing factor
Day 1 to Last
couple of months
@ FDA, and
Currently
• Quality impacts one life at a time, and it manifests in what
we do, and how we do it!
12/12/2014 Ajaz@ajazhussain.com 25
http://www.slideshare.net/a2zpharmsci/good-regulators-of-pharmaceuticals-grp-22-october-2014
26. We need to learn how not to create
problems in the first place!
12/12/2014 Ajaz@ajazhussain.com 26
http://www.slideshare.net/a2zpharmsci/performance-testing-pharmaceutical-quality-2004
(accessed 6 December 2014)
27. 12/12/2014 Ajaz@ajazhussain.com 27
In order to conform to in-process blend uniformity test specifications, powder blends
were either enriched with additional drug (fentanyl) or diluted with other
ingredients! FDA response ‘there are no validation studies to assure that there is no
adverse product impact throughout shelf life.
http://www.fda.gov/ohrms/dockets/ac/04/briefing/2004-4080b1_01_manufSciWP.pdf
(accessed 6 December 2014)
28. Practice, Control, Process: Maturity
Initial
• Unpredictable
Managed
• Characterized,
but reactive
Defined
• Characterized;
proactive
Measured &
Controlled
• In control
Optimizing
• Focus on
improvement
12/12/2014 Ajaz@ajazhussain.com 28
Capability Maturity Model Integration; Carnegie Mellon University
A validated process?
29. Maturity Level & Assurance of Quality
Managed Characterized,
but reactive
High risk of
‘Cheating by
Design’
“Trial
Injections”
“Testing in to
Compliance”
Defined Characterized;
proactive
Lower level of
assurance
Stopping &
Correcting
Batch
Rejection
Measured &
Controlled
In control
Quality by
Design
Quality
Assured
Improvement
Opportunities
12/12/2014 Ajaz@ajazhussain.com 29
30. At the individual level, in QC function– how
often does this occur?
attitude
toward
performing the
behavior
Process
validation is
done so quality
is good;
test prone to
error
“Batch failure
means I made
a mistake”
subjective
norm
documentation
not critical;
Compendial
testing
sufficient
Indian
regulators
collect & test
samples – no
issue there!
12/12/2014 Ajaz@ajazhussain.com 30
“Testing into compliance”
In general – low empowerment
is a significant challenge (low
perceived behavioral control);
plus reasons to rationalize….
32. Constraints that keep the system in a
corrective action mode
Compounding standard applied to modern mass production
12/12/2014 Ajaz@ajazhussain.com 32
33. 12/12/2014 Ajaz@ajazhussain.com 33
Rationalization &
Attitude
Pressure &
Incentive
Opportunity –
‘holes in the QMS”
Individual & Team
Blind-Spots
Latent Conditions
Focus of GMP
Remediation – SOP’s
Two products; better than placebo
Healing touch for body and mind
Quality & Confidence
34. Modern, mass production environment
• “The scientific challenges facing pharmaceutical manufacturing go
well beyond the problem of the clinical readout. Despite the slogan
building quality in, most quality assessment today relies on end-
product testing. This is a problem in and of itself. In addition, many
of the tests methods currently being used have severe limitations in
the modern, mass production environment.“
• Woodcock, J. The Concept of Pharmaceutical Quality. American
Pharmaceutical Review. Nov/Dec 2004
12/12/2014 Ajaz@ajazhussain.com 34
35. Measurement System Analysis
• From ‘calibration’ to ‘Gauge R&R’
Particularly for physical
attributes; destructive analysis
• Many (including regulators) have not yet
understood its importance
Gauge R&R well established
but not commonly practiced
• Measurement system in a state of control;
effective CAPA, quality metrics, Culture of Quality
With the move towards
Statistical Process Control
• Demonstrate equivalent in vitro performance;
more exacting criteria
Development of complex
generic products (ER,
Injectable, Inhalation, etc.)
12/12/2014 Ajaz@ajazhussain.com 35
36. Process Validation (2011), Statistical
Confidence, Continued Process Verification…
12/12/2014 Ajaz@ajazhussain.com 36
http://www.slideshare.net/a2zpharmsci/performance-testing-pharmaceutical-quality-2004
(accessed 6 December 2014)
37. Critically important attributes may not be
identified, measured and controlled
• “..the limits on quality attributes are often chosen empirically to
ensure production of batches that resemble the batches tested in the
clinic. However, this approach will only ensure consistent clinical
performance if the relationship between those limits and the clinical
outcome is understood. Without this understanding, the limits could
be overly wide, unnecessarily tight, or completely irrelevant to
clinical performance. Even worse, other, critically important
attributes may not be identified, measured and controlled.”
• Woodcock, J. The Concept of Pharmaceutical Quality. American
Pharmaceutical Review. Nov/Dec 2004
12/12/2014 Ajaz@ajazhussain.com 37
38. 12/12/2014 Ajaz@ajazhussain.com 38
Development
& Application
Commercial
Operations
Pharmacovigilance
Inspections – 483, WL,…
Marketing,….
Manufacturing
Marketing Authorization
Pre-Approval Inspection
Review
Application
Development
“Prone to Process Entropy”
In Control
Continued Process Verification
Effective CAPA
Continual Improvement
“Throw-over the wall”
Knowledge & Technology Transfer
Bio – Exhibit – PQ: Life Cycle
“Satisfy Reviewer Requirements”
First: Define & Satisfy Requirements based
on your expertise; Effective regulatory
communication
First: Define & Satisfy Your Own Requirements
Regulator may not always know what is best for the patients
39. 12/12/2014 Ajaz@ajazhussain.com 39
Novartis-MIT
Center for CM
(2007)
8/12/2008,
11/18/2011,……
FDA WLs
GMP Problems
300 Jobs
Chopped At
Novartis Plant
After Mfg.
Gaffes, Worried
Novartis CEO
Insists 'Quality
Matters’
Novartis CEO -
company plans
to build
commercial-
scale
continuous mfg.
facility by 2015
“This will
change the way
medicine is
made around
the world”
Creating a different mass production
environment: Novartis’s 10 year journey …..
http://www.slideshare.net/a2zpharmsci/eca-continuous-manufactruing-ajaz-hussain
Disclosure: I am an advisor & shareholder @
Why GMP problems occur & difficult to remediate? Will this change anything?
Testable
Hypothesis
(accessed 6 December 2014)
40. From academia
to FDA – to
Industry …
added emphasis
needed on
human behavior
Why do we
regulate?
Pharmaceuticals exhibit market failures that
can have devastating consequences
What do we
regulate? Human behavior
How do we
regulate?
Laws, regulations, policies, review,
inspections, criminal prosecutions,…
Who are the
regulators? All of us, not just the FDA
What is the
foundation for
modern
regulations?
Scientific evidence and compliance with
regulations and ‘Good Practices’
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Attitude
towards the
behavior
Subjective
norm
Perceived
behavioral
control
Intention
Future
Behavior
usually found to predict
behavioral intentions with a
high degree of accuracy
Intentions, in combination
with perceived behavioral
control, can account for a
considerable proportion of
variance in behavior.
Past
Behavior
Ajen, I. The theory of planned behavior. ORGANIZATIONAL
BEHAVIOR AND HUMAN DECISION PROCESSES 50, 179-211
(1991)
Intention to Behavior: Predictably rational or irrational
42. Seek and find all the barriers within yourself
that you have built against it
Consciously asking the right questions in the interest of the patients
Describing the accepted assumptions, and
Pre-defining the level of precision needed in the answers to the
questions we have posed
Keep practicing to make it a habit to consciously ask the right
questions,……
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44. Providing a healing touch – one life at a
time, in what we do, and how we do it
We are scientists, pharmacist, engineers, physicians and managers; trained to be good
practitioners of methodologies developed within our disciplines
We work in teams, to integrate our knowledge and aligning our methodologies, for
developing medicines and the evidence we must provide to satisfy the needs of patients
We recognize that nothing is perfect and there will be some errors in our design, systems,
and procedures, and we may make mistakes in following set procedures
It is normal, easy and rewarding to work within our quality management system, without
fear, to detect, correct and to learn from our mistakes
In doing so we work consciously in the interest of patients, even when no one is looking –
and this describes our Culture of Quality!
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