Digging for 483 Gold: How to Mine FDA's Inspection Reports

Transcription

1 Digging for 483 Gold: How to Mine FDA's Inspection Reports An FDANews Webinar December 8, 2014 Michael A. Swit, Esq Duane Morris LLP. All Rights Reserved. Duane Morris is a registered service mark of Duane Morris LLP. Duane Morris Firm and Affiliate Offices New York London Singapore Los Angeles Chicago Houston Hanoi Philadelphia San Diego San Francisco Baltimore Boston Washington, D.C. Las Vegas Atlanta Miami Pittsburgh Newark Boca Raton Wilmington Cherry Hill Lake Tahoe Ho Chi Minh City Duane Morris LLP A Delaware limited liability partnership

2 Standard Disclaimers The views expressed here are solely mine and do not reflect those of my firm or any of its clients or FDAnews. As to FDAnews, I am the chairman of its Board of Directors, as it was founded by my late father, but I am not involved in its day-to-day operations. This presentation supports an oral briefing and should not be relied upon solely on its own to support any conclusion of law or fact. These slides and this presentation are intended to provide general educational information and are not intended to convey legal advice. 2

3 What We Will and Won t Cover What We Will Cover: The Data FDA Inspections Statistics Panning the Gold examples of what you can glean from a 483 courtesy of How to Respond to a 483 Not today Conducting an inspection Deep drill down on observations Warning Letters and later enforcement activity 3

4 FDA Inspections FY

5 483s by All FDA Centers/Program Areas 5

6 Digging for Gold 6

7 483sonline.com 7

8 Specific Company A Look at Lilly Caribe 8

9 Other Inspections Lilly 9

10 Subject Aseptic sue_date=&to_issue_date=&company=&region=& author=&q=aseptic&483_search=search 42 hits 10

11 Pick one -- Gilead eports/drug- 2010/archives/2/20/201/ dr.5.gileadscience sinc.pdf?

12 Investigator Gilead s Carla Lundi Who else has she inspected? Let s look &to_issue_date=&company=&region=&author=3423&q=&48 3_search=Search 11 other inspections in the database (Teva Parenterals twice) 12

13 Lundi s Inspections.. 13

14 Observation Who Else Got Did Lundi Cite for Contamination Issues? From the Gilead 483: Let s search Ms. Lundi and contamination 14

15 the result of Lundi and contamination What do these two other 483s say about contamination and Ms. Lundi? Delpharm Tours -- a French sterile drug manufacturer Ebewe Pharma an Austrian sterile drug manufacturer 15

16 Delpharm Tours Different contamination issue, but still sterile processing What about Ebewe 16

17 Ebewe Pharma 17 We now can conclude that Lundi has significant expertise on aseptic manufacturing. Why? Foreign inspections FDA does not send just anyone overseas; typically they are very well-trained and often are Subject Matter experts Eight different aseptic makers Gilead, Delpharm, Ebewe, Teva, Amphastar, Cardinal Health 414 (PET), PrimaPharm, Alliance Medical

18 Other Key Points to Search 18

19 Responding to a

20 Enhanced Enforcement In Action Timely 483 Responses Policy Aug. 11 Federal Register notice Post-inspection 483 responses timing policy published 15 business days Timely Responses FDA will conduct detailed review in deciding any enforcement action If FDA issues a warning letter, letter will address sufficiency of response 20 20

21 Enhanced Enforcement In Action Timely 483 Responses Policy Late responses Response will not be considered by FDA in deciding to take enforcement action such as a warning letter If warning letter issues after a late 483 response, FDA will consider the 483 response in assessing firm s later reply to warning letter Purpose of Warning Letter: ensure seriousness and scope of the violations are understood by top management and that the appropriate resources are allocated to fully correc the violations and prevent their recurrence 21 21

22 Strategies in Replying to a 483 Written response to 483: Show the likelihood of recurrence of the problem/violation is low Show the company is doing all it can reasonably to remedy the situation: specific steps, timetable, monitoring Problems attributable to a specific cause have/will be fixed with permanent remedies Show that senior management understands 22 22

23 Strategies in Replying to 483s Provide specific evidence to minimize public health risk number/scope of product s distribution ability to do stock recall technical assessment If inspection follows product recall, note company was on the ball and caught the problem, as it was supposed to; foreclosing greater risk If did not catch, say what changes are being made to catch sentinel events/data in the future 23

24 Strategies in Replying to 483s Address each observation separately Never agree that an observation is valid: instead, state changes you intend to make Disagreements: Present your argument remember Science wins!! Be responsive, not argumentative Have reviewed by multiple parties Hold time to sleep on it before finalizing Attach copies of changed documents if not done yet, make sure to send later 24 24

25 483/EIR: Inspection Results NAI No action indicated --no objectionable conditions or practices were found during the inspection (or the objectionable conditions found do not justify further regulatory action) VAI - Voluntary action indicated --objectionable conditions or practices were found, but the District is not prepared to take or recommend any administrative or regulatory action OAI Official action indicated --regulatory and/or administrative actions will be recommended 25 25

26 FDA Expectation on Your Response Wants to Hear Your D.R.U.M. expects your response to have these qualities: Direct i.e., address the items directly raised in the 483 or warning letter Related go beyond those to potentially related problems Universal expand to review those issues company-wide Monitoring and Management show that you will stay on top of the issues show that senior management is involved Source: Compliance and Enforcement. Presentation by David K. Elder, Director, FDA Office of Enforcement, at the Orange County Regulatory Affairs (OCRA)/FDA Joint Educational Conference. June 15, Irvine, California. 26

27 Questions? Call, or fax: Michael A. Swit, Esq. Special Counsel, FDA Practice Duane Morris LLP San Diego, California direct: fax: Follow me on: LinkedIn: Twitter: 27

28 About Your Speaker Michael A. Swit, Esq., is a Special Counsel in the San Diego office of the international law firm, Duane Morris, LLP, where he focuses his practice on solving FDA legal challenges faced by highlyregulated pharmaceutical and medical device companies. Before joining Duane Morris in March 2012, Swit served for seven years as a vice president at The Weinberg Group Inc., a preeminent scientific and regulatory consulting firm in the Life Sciences. His expertise includes product development, compliance and enforcement, recalls and crisis management, submissions and related traditional FDA regulatory activities, labeling and advertising, and clinical research efforts for all types of life sciences companies, with a particular emphasis on drugs, biologics and therapeutic biotech products. Mr. Swit has been addressing vital FDA legal and regulatory issues since 1984, both in private practice with McKenna & Cuneo and Heller Ehrman, and as vice president, general counsel and secretary of Par Pharmaceutical, a top public generic and specialty drug firm. He also was, from 1994 to 1998, CEO of FDANews.com, a premier publisher of regulatory newsletters and other specialty information products for FDA-regulated firms. He has taught and written on many topics relating to FDA regulation and associated commercial activities and is a past member of the Food & Drug Law Journal Editorial Board. He earned his A.B., magna cum laude, with high honors in history, at Bowdoin College, and his law degree at Emory University, and is a member of the California Bar and previously was admitted in both Virginia and D.C., but is inactive in those jurisdictions. 28