Download - NIPTE Roadmap 2017 Discussion @ IFPAC 2017
Ajaz S. Hussain, Ph.D. and Vadim Gurvich, Ph.D.
The National Institute of Pharmaceutical Technology & Education, Inc.
3/3/2017 IFPAC 2017 2
Excipients: IFPAC 2017Chair: Brian Carlin
Background: NIPTE 2016
NIPTE resurgence, passion, and expansion (new members)
Expansion of stakeholders beyond US FDA; while maintaining commitment to FDA collaboration
Reflection on roadblocks and strategies for roadmap 2017
This presentation co-author:
Dr. Vadim Gurvich, Executive Director
3/3/2017 IFPAC 2017 3
Presenter (Ajaz): Declaring my interests
3/3/2017 IFPAC 2017 4
Insight Advice & Solutions LLC
Advisory and Consulting Practice
Complex Generics, Biosimilars & Orphan Drugs
Advisory Boards: Several Companies
When requested:
Systems approach - CGMP Remediation (strategy)
Culture of Pharmaceutical Quality Training
with Emphasis on Data Integrity
President
Share my understanding of challenges
in the assurance of "Pharmaceutical Quality”
Strategic planning and NIPTE advocacy.
Programing and other executive functions.
Legislative recognition: 2006 to 2016FDA leadership, FDA Grants,…..
3/3/2017 IFPAC 2017 5
2006: Federal investments in a major pharmaceutical technology and education initiative led by the Food and Drug Administration in collaboration with university research partners will produce multiple benefits in health care quality and access.2016: FDA may award grants to institutions of higher education and nonprofit organizations for the purpose of studying and recommending improvements to the process of continuous manufacturing of drugs and biological products and similar innovative monitoring and control techniques.
Organizational Maturity, Epistemology and Continuous Improvement Transformation: Biotech “Tipping Point”
3/3/2017 IFPAC 2017 6
Martin VanTrieste, R. Ph. Improving the Quality of Investigations. PIA Meeting – June 21, 2012
3 September 2003
Solid Dosage Form Manufacturing: “Tipping Point” not feasible without an “Angle of Repose”
• Certificate of Analysis • Uncertainty in solid-state material attributes
• Research laboratory measurement systems• Life-cycle stability and reproducibility in QC?
• Fixed equipment and process parameters• Committed in submissions, difficult to change post
approval; why bother finding the real cause?
• Uncertainty in the stability and capability of measurements and manufacturing process• Raises questions on adequacy of sampling and
obstructs risk-based decisions
• Globalization – variable empowerment/oversight• “FDA Approved” and “Validated”; frames the
mindset and provides reasons to rationalization
3/3/2017 IFPAC 2017 7
Repeating deviations and errors & ineffective investigations point to cognitive biases and risk of irrational behaviors
3/3/2017 IFPAC 2017 8
600 days
GXPs & Adult Human Development: The Subjective Dimension [my learning & focus]
An ancient Indian board game: Snakes & Ladder (in the USA: Chutes and
Ladder)
An ancient Indian story: Elephant in the Dark (in
the USA: Six Blind Men & the Elephant)
Integrating: “Orders of Consciousness” (Prof.
Robert Kegan) & “Thinking, Fast and Slow”
(Nobel Laureate Prof. Kahneman)
A journey – “I know it when I see it” to “I can
see clearly now”
3/3/2017 IFPAC 2017 9
Paradigm, Ontology, Epistemology, Methodology, Methods
“Angle of Repose”: Adaptive learning challenges
Solid Oral Dosage Form Manufacturing
At a Tipping Point
• NDA 26038; Orkambi®, Vertex Pharmaceuticals. 25 June 2015
• Post-approval change: NDA 021976 Prezista® , Janssen. 12 April 2016 (Continuous manufacturing with RTRT)
Progress and set-backs
• Several, ….others (new drugs); generics faced OGD push-back
• 2006 MSD/Merck
The Beginning
• 2004-2005 Sanofi-Aventis Comparability Protocol (FDA Approved - Not Implemented)
• (Late 1990’s: Medical Gas; Air Separation Units)
3/3/2017 IFPAC 2017 10
Angle of Repose & Tipping Point From “Don’t use or Don’t tell”* to problem-solving mindset,……
PAT-Continuous Manufacturing – RTRT platforms for rapid
product development, control strategy, and Design Space
• Multiple companies and Schools passionately perusing this opportunity with regulatory encouragement and acknowledgment of its potential for higher level of assurance
• Enforcement of Continued Process Verification (PV 2011) now becoming apparent in the USA; adds an emphasis on statistical confidence and process stability and capability
3/3/2017 IFPAC 2017 11
1
2
3
From: Martin Warman, Kelly Swinney and Justin Pritchard. PAT for In Process Control (IPC) and Real Time Release Testing (RTRT) in Continuous Manufacturing. 7th Pharmaceutical Technology Conference on Continuous Manufacturing, Japan (December 2015)
http://www.fda.gov/ohrms/dockets/ac/02/briefing/3841B1_05_PFIZER.PDF ; FDA Science Board 16 November 2001
Angle of Repose to Tipping Point: Journey needs to now go from extraordinary to normal, easy and rewarding
Technical Learning
• Control strategies (with “new” measurement systems)
• Engineering skills
• Statistics (Chemometrics)
Adaptive Learning
• Culture/Mindset change: reactive to proactive
• Cross-functional collaboration
• Systems thinking, understanding effective QMS, and change management system
3/3/2017 IFPAC 2017 12
Angle of Repose Tipping PointSufficient to achieve?
Law of the Few, the Stickiness Factor and
the Power of Context
Make the journey normal, easy and rewarding
Societal need (e.g., FDASIA) for confidence in [our] assurance of quality
• Confident assurance of quality across a global supply chain; risk ranking
• Recognition that early detection of issues necessary; effective investigations
• Delay insp. = adulteration; explicit assurance of data integrity
Increased appreciation of PAT-QbD-Lifecycle
Approach to Validation needed for effective QMS
• Operational inefficiency and an apparent inability to improve after regulatory approval can have many consequences
• Outsourcing without an objective assessment of QMS effectiveness is not a solution
PAT-Continuous Manufacturing – RTRT
platforms for rapid product development, control
strategy, and Design Space
• Multiple companies and Engineering & Pharmacy Schools, a critical mass (?), passionately perusing this opportunity with regulatory encouragement and acknowledgment of its potential for higher level of assurance
• Enforcement of Continued Process Verification (PV 2011) now becoming apparent in the USA; adds an emphasis on statistical confidence and process stability and capability
3/3/2017 IFPAC 2017 13
Today NIPTE’s mission cannot be clearer and its resolve strongerThe strategic themes identified in 2016 are very relevant to address several roadblocks in the progress of NIPTE
3/3/2017 IFPAC 2017 14
Roadblocks to the “+”
3/3/2017 IFPAC 2017 15
• NIPTE = Integrative + Adaptive + Centralized
• What is NIPTE (centralized)? What it should standardize?
2016 Strategic Themes
1. Team Science2. Centers of Excellence3. Certification of Education & New Prior Knowledge
Roadmap 2017 How to…?
With 2020 Vision?
Roadmap 2017: Road mapping process
3/3/2017 IFPAC 2017 16
Team science, Centers of Excellence & Certification
• NIPTE Roadmap 2017 steps towards becoming the 3rd leg of the stool starting 2020
• [Six ways President Trump can create a tipping point for a renaissance of pharmaceutical manufacturing in the USA ]
-----------------------------------------Currently Outside NIPTE------------------------------------------------------
• USP & C-SOPS Roadmap of Transforming Pharmaceutical Manufacturing from Batch to Continuous (not part of NIPTE; Pro bono advisory support to USP)
------------------------------------------Ajaz’s Advisory & Consulting Practice -----------------------------------
• Note for Disclosure & Transparency: Important elements of my consulting practice:• Making Quality by Design normal easy and rewarding; cheating-by-design not profitable• Advisor CONTINUUS Pharmaceuticals (recipient of $4.4 M Contract with US FDA)
3/3/2017 IFPAC 2017 17
Centralize and standardizeHow to…?
3/3/2017 IFPAC 2017 18
Instill/practice
— Key message to all: You are NIPTE & NIPTE is You
— Support Individualistic/Adaptive Goals and encourage/facilitate/recognize Collaborative/Integrative practices and contributions
— Adopt NCI Team Science Toolkit
Establish Charter, Process, & Leaders
— NIPTE “Think Tanks” to strengthen the Voice of NIPTE
— Senior Faculty led Center that work in their particular areas of interest (e.g., Pediatric Formulation)
— Governing Charter and process for “NIPTE Brand Endorsement”
Develop, Evaluate, Scale-up, & Execute
— Plan/focus on success of Sun-Pharma Program
— NIPTE QbD Education Curricula and Certification
— New Prior Knowledge: New, Generic & Biosimilar applications
Team Science
2020 Vision
NIPTE Certification
Centers of Excellence
3rd leg of the stool?
3/3/2017 IFPAC 2017 19
User fee commitments.
“fire-fighting” to minimize impact of (fewer) failures
New policies, practices & staff
Research priorities
Why NIPTE?
What will NIPTE contribute?
How will NIPTE contribute?
Roadmap 2017
The ‘Third-leg of the stool”?
Push for faster approvals
Pressures to reduce price of medicines
Reduce regulatory burden
Revitalize US manufacturing
Pharmaceutical Technology Research & Education
Needs of the Nation
FDANIPTE: 2020?Macro-
environment
Summary & Next Steps
• NIPTE Roadmap 2017
• NIPTE Advocacy
• Expanding stakeholders and collaborations
• We celebrate successes of pharmaceutical technology!
• You are NIPTE and NIPTE is you!
3/3/2017 IFPAC 2017 20