Embed Size (px)
Citation preview
BEIJING BRUSSELS CHICAGO DALLAS FRANKFURT GENEVA HONG KONG LONDON LOS ANGELES NEW YORK PALO ALTO SAN FRANCISCO SHANGHAI SINGAPORE SYDNEY TOKYO WASHINGTON, D.C.
Preparing for and Managing an FDA Inspection
Greer Lautrup
Washington, DC [email protected]
May 29, 2014
What Do These Have in Common?
Big game
Major performance
Critical exam
To excel, you must . . .
PREPARE And
PRACTICE
Why It Matters
FDA Enforcement Trends
Dietary Supplement Inspections
• 585 in FY 13; 142 in Q1 14
FDA Form 483
• Issued in 65% of DS inspections
Warning Letters
• 70 in FY13
Compliance
• 34% of inspections classified OAI
Perfecting GMP Compliance – A 10-Step Program
1. Read the DS GMPs and Preamble
2. Keep informed of 483s and Warning Letters
3. Consult FDA pharma guidance or industry guidance
4. Conduct baseline audit
5. Develop workplan to address gaps using a risk-based approach
6. Consider targeted use of consultants
7. Practice for an FDA inspection
8. Manage the FDA inspection
9. Submit strong 483 responses
10. Institute process for continued improvement to drive sustainable compliance
The Basics of Inspection Preparation
• Start now!
• Two key elements
1. Facility, processes, systems
2. Inspection management
• Preparation
• Logistics
• SME Readiness
• Baseline audit and/or mock inspection
6
Pre-Inspection Checklist
Prepare inspection notification list
Identify key participants (e.g., scribes, runners)
Collect documents likely to be requested
Conduct walk-throughs of facility
Ensure computer systems are available and work
Practice, Practice, Practice
7
Key Participants
• Inspection coordinator/host
• Backroom coordinator/strategist
• Document retriever
• Subject Matter Experts (SMEs)
• Scribes
• Runners
Investigator Arrival
• Receptionist notifies Inspection Coordinator/Host
– Coordinator arranges for notification of relevant individuals
• Most senior person meets with investigators
• Prepare conference room
– No confidential information should be in the room
9
General Practices
• Give the investigator your full attention
– Don’t focus on your computer, smart phone, Blackberry, etc.
• Turn off cell phones
• Do not engage in side conversations with colleagues in presence of investigator
• Do not conduct business discussions around the investigator
10
Opening Meeting/Presentation
• SHORT presentation sets tone for inspection
• Includes key information such as:
– Corporate structure
– Organizational charts (site, Quality unit)
– Facility diagram
– List of products
– Business hours and shifts
– Improvements/facility changes since prior inspection
11
Facility Tour
• ALWAYS be ready
• Have tour route planned, but be flexible
• Scribes/runners should accompany investigators
12
•DO have goggles, gowns,
keys, etc. available
•DO clarify document
requests
•DO have SMEs available
to answer questions
•Do NOT let investigators
wander off on their own
•Do NOT “linger,” but also
do NOT “rush”
investigators
Responding to Document Requests
• Investigators may request dozens of documents per day
• Keep track of requests and respond promptly – harder than it seems!
– Investigators who are forced to wait for documents may become bored, frustrated and/or angry
– Delays suggest inefficiency and/or incompetence and can extend the inspection
• “Refusals”
• Documents must be complete and accurate and address the investigator’s request
13
Document Flow
• Scribe documents request from investigator and submits to back room (electronically or via paper)
• Back room assigns number and time of request
• Back room works with SMEs to locate documents or otherwise respond to the request
• SME and back room coordinator review document for GDPs, completeness, accuracy, responsiveness
14
Document Flow (cont.)
• Documents should be stamped
• Document should be placed in folder indicating requests to which it is responsive
• Runner takes document to front room and hands to the host, NOT the investigator
• Back room keeps duplicate copy of every requested document
15
Memorializing the Inspection
• Scribes must:
– Shadow investigators and capture all comments, questions and answers
– Keep track of requests
– Find a new scribe if they become the SME
– Not leave the room to get documents
– Check their list of document requests against the back room’s list at the end of each day
16
Providing Documents
• Runners must:
– Clearly announce their presence to the host in the inspection room
– Check in with the host(s) and scribe frequently, including during facility tour
– Record the document requested and the date and time requested (if not submitted electronically)
– Provide documents directly to the host, not to the investigator
17
Interacting with Investigators
• ALWAYS be truthful and accurate
• Provide direct answers
• Do not guess if you do not know the correct answer
– Ask clarifying questions if needed
– Speak to the procedure and state facts
• Do not volunteer information not requested (e.g., opinions, experiences at prior companies)
If you don’t know the
answer, as an SME, it’s
your job to find the answer
18
Interacting with Investigators
• Answer the question asked
– Keep investigator focused on what he/she wants to cover
• Wait for the next question
– “Silence is golden”
• Do not take unrequested documents into the room
• Remember: this is your site
19
Interacting with Investigators
• The investigator asks you whether you have an SOP addressing control of quarantined goods. Your initial response should be*:
Yes. Yes. Would
you like to see it?
20
Yes, but it doesn’t cover
how we handle rejected material.
*Assumes all responses are
factually accurate
Interacting with Investigators
• Avoid empathizing with the investigators about issues they raise. For example, if the investigator says: “I’m not satisfied with your MMRs,” a good response would be:
I agree. Our MMRs ARE terrible.
I understand your concerns. We’ll certainly review
our MMRs to see if they can be improved.
21
Interacting with Investigators
• If the investigator asks “Why do you store staged materials next to quarantined materials?” a good response would be*:
The warehouse
is always too
full which is
why we have to
do this.
22
It’s a temporary
situation due to
construction. The
quarantine area is
usually roped off. I’ll
address this right
away.
That’s a
good
question.
*Assumes all responses are factually
accurate
Management Involvement
• Management should be available to:
– Speak with the investigator when needed
– Appear promptly
– Work on document requests in the back room, including locating and reviewing documents
– Explain certain documents to the investigators
An FDA inspection must be
the site’s top priority
23
Daily Wrap Up
• At the end of each day, host should review the following with investigators:
Outstanding document
requests
When site expects to fill the
requests
Any concerns
Area(s) the investigator will
cover the next day
• After the investigator leaves, inspection team should review:
What investigators covered
and issues raised
Scribe notes to ensure
investigator’s questions
and requests are being
addressed
Schedule for following day
24
Homework
• Scribe and back room personnel should compare notes to ensure all document requests are captured and being filled
• Outstanding documents should be provided to the investigator the following morning
• Correct any issues identified by the investigator that can be addressed during the inspection
• Consider short presentation for major issues
25
Closing Meeting
• Review 483
– Ask for clarification as necessary
– Do not admit fault
– Agree that each observation will be addressed
– If an observation is factually incorrect, request it be corrected prior to the investigator’s departure
• If no 483, note investigator’s comments/suggestions
26
Baseline Audit/Mock Inspection
• Identify key areas of regulatory risk
– May uncover previously unknown issues
– Provides time for remediation of identified issues
• Allows site to test inspection logistics
• Allows SMEs to “practice”
• Key considerations
– Attorney-client privilege
– Auditor experience
– Written report
Responding to a 483
• 15 business days to respond in writing
• Ensure response fully addresses the observation
– Facts and science
– Avoid opinions, beliefs, hopes, dreams and aspirations
• Most items should have CAPAs
– Firm commitment dates
– Relevant attachments
• Keep language neutral
• Consider legal review
Questions?
Greer O. Lautrup
Sidley Austin LLP
(202) 736-8117
