Question based Review (QbR) – Impact on Deficiency (ies) · Question based Review (QbR) –...
Transcript of Question based Review (QbR) – Impact on Deficiency (ies) · Question based Review (QbR) –...
IPA CONVENTION 2015
Question based Review (QbR) – Impact on Deficiency (ies)
Presentation by
Zoher T. Sihorwala, M. Pharm.06 June, 2015
Mumbai
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Disclaimer
The views and opinions expressed in the following PowerPoint slides areThe views and opinions expressed in the following PowerPoint slides are
those of the individual presenter and should not be attributed to my
employer or its directors, officers, employees, or affiliates, or any
organization with which the presenter is affiliated.
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Definition(s)
QuestionNoun a sentence worded or expressed so as to elicit information
a matter requiring resolution or discussion
Verb ask (someone) questions, especially in an official context
ReviewVerb write a critical appraisal of (a book, play, film, etc.) for publication in
a newspaper or magazine
assess (something) formally with the intention of instituting change if necessary
Deficiency a lack or shortagey g
Quality the standard of something as measured against other things of a similar kind; the degree of excellence of something
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QbD and its evolution
Why QbD in Pharma – Dr. Janet Woodcock, the then Director of CDER at US FDA
Science based understanding of the product and process to make the
product which meets its predefined quality attributesproduct, which meets its predefined quality attributes.
Being science based, QbD is diametrically opposite to current
industry practice Better understanding of underlying science onindustry practice. Better understanding of underlying science on
product development and process to make the product – makes risk
based compliance possible.
21st Century Initiative
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QbD and its evolution
Absence of QbD
Quality complaints/market recalls
Increased number of supplementary filings to address process improvementsimprovements
Product actually approved to product actually on the market due to continuous working on process
Compliance issues – keeping agency/industry constantly on the toes…
Patients deprived of timely availability of medicines
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Current regulatory scenario
A maximallyA maximally efficient, agile, flexible
pharmaceutical manufacturing sector that
reliably produces high quality drug productsquality drug products
without extensive oversight –
Dr. Janet Woodcock
QbR is a new quality assessment system that focuses on critical
pharmaceutical quality attributes. It transforming ANDA CMC review into a modern, science and risk ,based pharmaceutical quality
assessment system –Dr. Lawrence Yu
Source: Moheb Nasr, 2006 7
QbR – How progressed
Sep 2004 – FDA CGMP initiative and initiation of QbR
J 2005 QbR i d i l d f dJan 2005 – QbR questions and review template drafted
Aug 2005 – QbR White Paper posted on FDA website
Jan 2006 – Model QbR-Quality Overall Summary (QOS) for IR tablet published
M 2006 M d l QbR QOS f ER l bli h dMar 2006 – Model QbR-QOS for ER capsule published
Sep 2006 – First QbR ANDA approval
Jan 2007 – Full implementation of QbR evaluation
May 2010 – 100% ANDAs submitted with QbR-QOS, with few exceptions
Source: www.diahome.org; Question based Review for ANDAs, Chi-wan Chen, Ph.D.; May 2011 8
Purpose and Objective of QbR
Purpose
To transform OGD’s CMC review into a modern, science and risk-based pharmaceutical quality assessment that incorporates and implements the concepts and principles of the 21st Century Initiative
To enable effective allocation of limited review Resources
To assure product quality through design and performance-based specifications
To facilitate continuous improvement and reduce CMC supplements through risk assessment
To enhance the quality of reviews through standardized review questionsTo enhance the quality of reviews through standardized review questions
To reduce CMC review time when applicants submit a quality overall summary that addresses the QbR
Source: www.diahome.org; Question based Review for ANDAs, Chi-wan Chen, Ph.D.; May 2011 9
Purpose and Objective of QbR
Objective
Q ti id iQuestions guide reviewers
A consistent and comprehensive evaluation of the application
Assess critical formulation and manufacturing process variables as well ssess c t ca o u at o a d a u actu g p ocess a ab es as e
as control strategies
Questions guide industryQ g y
Issues we generally consider critical
Direct industry toward quality by design
Prepare high quality QOS
Source: Lawrence Wu. Ph.D., IFPAC Annual Meeting, January 2009,, Baltimore 10
QbR - Past versus Present
No PDR
A S
Assess QbD
Assess Spec.Reviewer
Assess Spec.
Summary
Assess Spec. Performance
Summary QbD
Reviewer
Summary
Body of Data
Summary QbD
Body of DataSponsor
Sponsor
Traditional QbR
Source: Lawrence Wu. Ph.D., IFPAC Annual Meeting, January 2009,, Baltimore 11
QbR - Model
Clear communication
Use of similar language
Common quality standards through QbD mind set
Aligned risk management approachesAligned risk management approaches
Choices made reasonably justified
Transparency enhanced in the applicant’s thinking process
Source: Future of Question-based Review and Regulatory Submissions, Robert Iser, FDA/PQRI Conference, September 2014 12
QbR – Advantage
For the reviewers
Team based quality assessment
Risk based decisions
Effective quality assessment
Guides reviewers for consistent and comprehensive quality evaluation
Includes level of risk associated with design and manufacture of the product
Provides consistency among the submissions
Leads to more focussed and efficient review
Source: Future of Question-based Review and Regulatory Submissions, Robert Iser, FDA/PQRI Conference, September 2014 13
QbR – Advantage
For the applicants
Clear communications with stakeholders
Effective quality assessment
Common quality standards
Standardizes submission expectations
Provides clear expectations
Provides an opportunity to address critical questions about the product’s
design, failure risk and manufacturing controls from both a performance and
patient usability perspective
Use as an internal communication tool (e.g., regulatory affairs with
development etc )development etc….. )
Source: Future of Question-based Review and Regulatory Submissions, Robert Iser, FDA/PQRI Conference, September 2014 14
Future – A synergistic working
FDA can
P id T & Cl E t ti T l t b d kiProvide Transparency & Clear Expectations - Template based working
Industry cany
Provide High Quality Submissions
Source: Future of Question-based Review and Regulatory Submissions, Robert Iser, FDA/PQRI Conference, September 2014 15
Future – Simplify through QbR
Simplicity defined through QbR – Potential question(s) that needs
answer(s)answer(s)….
Volunteer discussions – Pre-ANDA and in the ANDA – FDA finds what it is
looking for – Question(s) (Deficiency) culminates into Clarification….
Facilitate FDA on reduce review cycle – Single cycle
QbD in the submission leading to reduced supplementary filingsQbD in the submission leading to reduced supplementary filings….
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Trend of Deficiency (ies) – A recent industry example
Product DevelopmentDrug Substance Related
12.2
Manufacturing ProcessAnalytical Method Validation
Labelling Product Specification (CQA)
AdministrativeProduct Development
7.18.0
8.89.4
9.9
BioequivalenceSpecification Tightening
Container ClosureDossier Writing ErrorsSerilization / Process
Manufacturing Process
3 74.0
4.36.36.56.5
Regulatory InadequacyInactive Ingredient
Electronic SubmissionsClassification of Impurities
StabiltyDissolution Specifications
0 91.71.7
2.63.1
3.43.7
0.02.0
4.06.0
8.010.0
12.0
Regulatory Inadequacy 0.9
14.0
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Impact on deficiency(ies) through QbR
Product DevelopmentDrug Substance Related
12.2
Manufacturing ProcessAnalytical Method Validation
Labelling Product Specification (CQA)
AdministrativeProduct Development
7.18.0
8.89.4
9.9
BioequivalenceSpecification Tightening
Container ClosureDossier Writing ErrorsSerilization / Process
Manufacturing Process
3 74.0
4.36.36.56.5
Regulatory InadequacyInactive Ingredient
Electronic SubmissionsClassification of Impurities
StabiltyDissolution Specifications
0 91.71.7
2.63.1
3.43.7
0.02.0
4.06.0
8.010.0
12.0
Regulatory Inadequacy 0.9
14.0
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Beyond QbR – Future of Regulatory Submissions
How to “package” the development history and control strategy?What is the control strategy what are the established conditions or “regulatoryWhat is the control strategy, what are the established conditions or regulatory
commitments”?
How can we better present knowledge gained (not just data available) inHow can we better present knowledge gained (not just data available) in
Annual Reports and Supplements over product and submission lifecycle?
H b i i k f ll Q li AHow best to communicate risks for overall Quality Assessment
(API/DP/Mfg./Site)?
Source: Future of Question-based Review and Regulatory Submissions, Robert Iser, FDA/PQRI Conference, September 2014 19
Summary
QbR helps facilitate critical review and speedy product approvals of
SAFE EFFICACIOUS QUALITY and AFFORDABLESAFE, EFFICACIOUS, QUALITY and AFFORDABLE
Medicines for Human Use
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