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?

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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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Thank youThank you

Acknowledgments

Ananya Sen, Drug Regulatory Affairs, Wockhardt Limited, India

Ajaz S. Hussain, Ph.D., Insight Advice and Solution LLC, USA

Ali M. Afnan, Ph.D.; Step Change Pharma Inc., USA

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g

Kaushik Desai, M. Pharm., Hon. General Secretary, IPA - India