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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

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Workload

Assumption vs. Reality • During GDUFA negotiations it was

assumed new ANDA submissions would not exceed 700/year.

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5 Prepared by Glen Smith

• 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

cien

cy

Effe

ctiv

enes

s

11 Prepared by Glen Smith

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Chemistry Program Enhancements

Supplement Reduction – Cross-office Teamwork

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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

0

50

100

150

200

250

300 PAS Completed

ONDQA/OTR PAS Complete

OGD SRT PAS complete

0

100

200

300

400

500

600

700

CBE Completed

OPS-IO CBE Complete

OGD SRT CBE complete

16 Prepared by Robert Iser

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Chemistry Program Enhancements

Stability – Preparing for the Change

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

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Chemistry Program Enhancements

Controlled Correspondences

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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Chemistry-Related Controlled Correspondences

25 Prepared by Geoffrey Wu

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

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Chemistry Program Enhancements

Hiring New Chemistry Reviewers

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)

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How the Generic Industry Can Help

Submission Quality

• 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

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