Chemistry Review Update - Generic Pharmaceutical … · Chemistry Review Update ... •Calculated...
Transcript of Chemistry Review Update - Generic Pharmaceutical … · Chemistry Review Update ... •Calculated...
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Chemistry Review Update Susan Rosencrance, Ph.D.
Deputy Director of Chemistry (Acting) Office of Pharmaceutical Science
GPhA/FDA CMC Workshop June 3-4, 2014
Objectives 1. Workload
2. Chemistry Program Enhancements • Risk-based Quality Assessment – ANDAs • Supplement Reduction – Cross-Office Teamwork • Stability – Preparing for the Change • Controlled Correspondences for Chemistry • Hiring Efforts
3. How the Generic Industry can help • Submission Quality 2
Assumption vs. Reality • During GDUFA negotiations it was
assumed new ANDA submissions would not exceed 700/year.
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• How does Chemistry meet the 10-month review cycle for 90% of ANDAs in Year 5?
• How do we eliminate the backlog within 5 years?
• How can Chemistry enhance the efficiency and effectiveness of the quality assessment (or review)?
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Chemistry Program Enhancements
Risk-based Quality Assessment - ANDAs
‘If we aren’t moving forward, we’re falling behind’
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• Adopting an effective risk management approach enables Chemistry to:
– Increase efficiency by focusing reviewers on the most critical areas
– Allocate review resources based on product risk and patient impact
– Produce more effective and consistent risk-based decisions on generic drug quality
– Strategize and work smart!
ICH Q9 – Quality Risk Management
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Implementation of Risk-based Quality Assessment
August 2013
•Developed an algorithm based on FMECA (Failure Mode, Effects, and Criticality Analysis) for immediate release solid orals
•Calculated an RPN (Risk Priority Number) for each drug product CQA (Critical Quality Attribute) based on severity, probability, and likelihood of detection
•RPN score used to rank overall risk of drug product
October 2013
•Piloted and Tested algorithm on low/medium risk immediate release solid orals
Feb. 2014
•Expanded approach to all immediate release solid orals •Started developing algorithms for other dosage forms
Present
•Undergoing an independent audit to acquire unbiased constructive feedback •A continuous improvement exercise
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Results
Reviewer focused on critical areas associated with product risk; Less time spent on low risk issues; Quality assessment (or review) times decreased;
Better allocation of reviewer resources; Ensures higher risk issues receive the appropriate level of expert scrutiny
Effi
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Effe
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• Receiving an unprecedented number of supplements – Product modernization – Quality improvements – Beneficial for products already on the market
• October 2013 – Strategic Plan – OGD Supplement Review Team – OPS Supplement Review Team (chemists from
OPS-IO, ONDQA, OTR, OBP)
Supplement Reduction
Strategic Plan OGD
Supplement Review Team
• All post-GDUFA Chemistry Supplements
– Prior Approval Supplements (PAS)
– Change Being Effected Supplements (CBE-0 and CBE-30
OPS Supplement Review Team
• All backlog pre-GDUFA Chemistry Supplements
– Prior Approval Supplements (PAS)
– Changes Being Effected Supplements (CBE-0 and CBE-30)
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15 Prepared by Robert Iser
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50
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150
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300 PAS Completed
ONDQA/OTR PAS Complete
OGD SRT PAS complete
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100
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CBE Completed
OPS-IO CBE Complete
OGD SRT CBE complete
Stability Guidance for
ANDAs Published in
Final June 2013
Question& Answer
Guidance Published in
Final May 2014
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Stability Guidances
• CDER Small Business Webinar – November 2013 – An opportunity for small pharmaceutical businesses
(domestic and international) to learn more about the guidances
– Questions addressed in an effort to help ease adoption of the new stability recommendations
• Definition of a month (6 months = 180 days) – resolved inconsistencies between guidances
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Preparations for Change
• Staff Training – April 14th – Training for OGD Filing Reviewers – June 4th – Training for all Chemistry Reviewers
• 2nd Small Business Webinar planned for June – Emphasis on Question & Answer guidance
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Preparations for Change
1. Formal guidances with clear recommendations on stability expectations
2. A formal process for generic drugs that aligns with ICH Q1A-E guidelines
3. Closer harmonization on the stability recommendations for new and generic drugs
4. Global harmonization with other generic programs (Europe, Japan)
5. Overall enhancement in the quality of generic drugs 21
What we Gain - Benefits
Controlled Correspondences • Ever year OGD receives numerous controlled
correspondences
• Controlled correspondences impact many
disciplines/groups: – Regulatory Support Staff - Division of Clinical Review – Chemistry Divisions - Division of Labeling and Program Support – Microbiology Division - Orange Book Staff – Bioequivalence Divisions - Science Staff & Policy Group
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Controlled Correspondences
• Have seen a surge in the number of chemistry-related controlled correspondences since 2013
– Received 65 in the first 4 months of 2014
– Constitutes 16% of all controlled correspondences received by OGD
– In the past (2004-2012), chemistry-related controlled correspondences ranged from 2-8%
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Controlled Correspondences • Now have a centralized, dedicated team to
address chemistry-related controlled correspondences – 2 coordinators – 3 to 6 primary/secondary reviewers – 1 sign-off authority
• Have completed much of the backlog – Presently 90 outstanding chemistry-related controls,
with 90% being those submitted in 2014 – Goal: Steady State by Oct. 2014 (# in = # out)
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How to Better Correspond
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• Be specific, concise, and succinct in your questions; results in a better answer
• Be discipline specific; avoid questions that impact multiple disciplines
• Controlled Correspondence Webpage http://www.fda.gov/aboutfda/centersoffices/officeofmedicalproductsandtobacco/cder/ucm120610.htm
• Stay tuned for a guidance on Controlled Correspondences under GDUFA
Hiring New Chemistry Reviewers • Centralized hiring team that has expanded and
become highly efficient (led by Lane Christensen)
• GDUFA Year 2 Hiring Goal – 140 Chemistry Reviewers (chemists & chemical engineers)
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Hiring New Chemistry Reviewers
• Developed a more systematic approach to interviewing and selecting qualified applicants – Targeted job fairs at professional meetings – Advertisements in professional journals – Outreach of contacts at universities and trade
organizations – Virtual and on-site hiring fairs hosted by FDA – GDUFA hiring website: www.FDA.gov/gdufahiring
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Hiring New Chemistry Reviewers
June 1, 2014
0.00%
10.00%
20.00%
30.00%
40.00%
50.00%
60.00%
70.00%
80.00%
90.00%
100.00%
• 101 chemistry reviewers on board (64% of goal; 101/158 total)
• 125 received official
offers (79%of goal; 125/158 total)
• GDUFA is a commitment akin to a business contract
• For us to do our job efficiently and effectively we need high quality submissions
-’Right the First Time’
• We must strive for a 1 cycle review system and timely approvals
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Submission Quality
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Submission Quality
High Quality Submissions
1 Cycle Reviews
Timely Approvals
‘Right the First Time’ conserves everyone’s
resources!
A Partnership
In order to meet the GDUFA commitments, as well as fulfill our obligation to the American public, its essential
we work together in partnership. 35