To ensure FDA readiness, companies must develop a plan to ensure that they are in compliance during inspections, and reduce the likelihood of receiving warning letters.

1. Preparing Your
War Room
Darshan Kulkarni

2. Situation
• FDA presents a 482 and wants to inspect your
investigational drug pharmacy. What are your immediate
concerns?
Who do you
notify?
Why the IDS
pharmacy?

3. • We shall not be getting into:
• The Anatomy of a response
• Legal advice
What is not the goal of this
Presentation?

4. Latest Areas of Enforcement
Activities

5. Who has been targeted?
• Sponsors
• Sites
• CROs
• IRBs

6. Overall Comments (IRBs)
●Inadequate
documentation
Failure to follow
own written
procedures
Inappropriate
use of expedited
procedures
Failure to
appropriately
weigh risks and
benefits

7. Overall Comments (CROs)
• Failure to adequately monitor investigations
• Failure to ensure that study being performed according to
protocol

8. Overall Comments (Sponsors)
Failure to:
adequately
monitor
adequately ensure
that protocol is
followed
adequately warn
other investigators
of new
observations
appropriately
choose
investigators

9. Overall Comments (Sites)
●Failure to timely
report AEs
Failure to protect
the rights, safety
and welfare of
subjects
Failure to obtain
IRB approval for
changes
Failure to
maintain case
histories
Failure to
adequately
dispose of drug.
Failure to
supervise
Failure to follow
protocol

10. Types of Enforcement Activities

11. Civil & criminal Liability/ Park Doctrine
Permanent Debarment of Firms or persons
Temporary Debarment of Firms or persons
Disqualification/ Restriction of Clinical Investigators
Corporate Integrity Agreements
Delayed or no further approval of sponsor applications
Injunction
Warning Letter: Issued by district director/HQ official
Untitled Letter
483: Issued by Investigator at site
Types of Enforcement in Clinical Trials

12. Responding to an inspection

13. Scenario
• You engaged a regulatory lawyer to conduct an audit of
your IDS pharmacy.
Why a lawyer?
FDA asks to see
audit results. Do
you have any
concerns?
You deny the FDA
access. What do
they do?

14. FDA is at the Door
Do I want to
take an
aggressive
posture?
They can enter
What am I going to tell my investors?
What people will I allow them to
interview?
What information am I going to allow
them to have?
External
Factors
Internal
Factors
Respond
What am I going to tell my employees?
YesNoThey cannot enter
Planning for an Enforcement Action

15. Why allow the inspection?
• FDA is doing its job. Its mandate is to be:
"responsible for protecting the public health by assuring
the safety, efficacy, and security of human and
veterinary drugs, biological products, medical devices,
our nation’s food supply, cosmetics, and products that
emit radiation, and by regulating the
manufacture, marketing, and distribution of
tobacco products."

16. Why allow the inspection? cont.
• If the FDA is satisfied regarding compliance, the company
will be subject to inspections of:
• ordinary intensity
• ordinary frequency
• unlikely to be escalated to other enforcement mechanisms (e.g.
Warning letters etc.)

17. Why allow the inspection?
Delaying the inevitable: They will come back.
When they come back, it will not be "pretty"
You may inadvertently escalate a routine inspection into more.
Whatever you want to hide, they may already know it or will often find
out.
You want to be a good corporate citizen.
You want to lower potential fines.

18. Why allow the inspection? cont.
If you are not compliant you setup an adverserial relationship
which may mean:
Fewer
approvals
More
stringent
audits
Enhanced
compliance
measures
Enhanced
response
from the
FDA

19. Why not allow the inspection?
What they see, hear, touch, and/or
record constitutes evidence.
You may inadvertently waive
privileges?
You are exposing yourself to
potential liability and lawsuits.

20. 4 separate teams
POC Inspection Team
Agency
Response
Team
Media
Response
Team

21. Pre- Inspection Planning

22. What information are you going to
provide access to?
Privileged
information
• Will you waive
privilege?
• Can you partially
waive privilege in
your state?
Access to
confidential
information
• Trade secrets?
Financial
Information
Internal audit
records

23. Pre-Inspection planning
Creation of SOPs
Training
Audits
Choose the response team
Establish clear lines of communication

24. Decisions and Discussions
Identify all non essential personnel.
• Should non essential personnel go home?
Will operations continue as normal?
• Will you cease operations for the day?
Who should be present at the inspection table?
Roles of people in the team.
For site/ CROs:
• Should the Sponsor/CRO rep be present (?)

25. Tone Setting Decisions
Will you let auditors in on presentation of the 482?
Will you record the meeting?
Will your lawyer be present?
Will you send people home?

26. Identification
Formulate email/ communication
to go to entire team.
Identify Point of Contact Identify Inspections Team
Official Leader
Official spokesman for team.
Official Attorney
Official Scribe (consider having 2)
Individuals present in war room
Individuals present in audit room

27. Company Communication/ Email
Keep it short and succinct.
• Agency is here
• Scope (if known)
• Cooperate, but does not require volunteering
information.
• Reminder to insist that company lawyer must
be present for all interviews (escalates)
• Other essential information.

28. Points of contact (POC)
There should
be multiple
POCs (3-4 at
least)
First person
to know that
the agency is
here. Assembling
Inspection
Team.
Informing
Sponsor (if
required)
Informing the
site that agency
is present.
Dismissing non
essential
personnel
Assembling war
room
Responsible
for:

29. Response Team
All individuals who must be
available to coordinate response
May include:
Leader
Spokesperson
Lawyer(s)
Principal Investigator(s)
Office Manager
Scribe(s)
Regulatory person(s)
Sponsor representative (?)
CRO representative (?)

30. Leader
• Consults with all stake holders
• Makes final decision and decides official company position
• Communicates through the spokes person.
• Determines direction/ tone/ scope of response.

31. Lawyer
Be present at discussions with
individuals.
Advises the Leader
Determines:
• Does the FDA have the right to ask for the
information?
• Does it impact other on-going litigation?
• Does it impact other prospective litigation?
• Are you waiving privilege(s)?
Should be someone you
trust
Should be someone who
understands your business
Should be someone who
understands how you do
business.

32. Scribe(s)
Expectations:
Should be more than 1 person.
Records everything the audit team does
Takes copious notes
Summarizes notes at the end of each day and at
the end of the audit.
Available to explain notes at time of response.

33. Spokesperson
Expectations
Responds to general questions.
Should be aware of the general actions of the facility.
Should know who specifically to reach out to for area
specific questions.
May/may not be the leader/ lawyer/ owner/
manager.

34. Inspection

35. Agency at the door
Never leave the auditors alone;
Record everything;
Be cordial;
Do not volunteer information;
Only talk if you know.

36. Entry
Expectations:
• Check IDs
• Record entry
• Get business cards
• Contact POC
• Escort them to the audit room

37. POC's actions
Assemble response team.
Informing site that agency is present.
Dismiss non essential individuals
Assemble war room

38. Spokesperson
Identifies themselves to the audit team.
Determines the reason/scope of the audit. (not for/cause?)
Asks audit team to sign any confidentiality agreements etc.
Responds to general questions.
Consults with leader
Negotiates expectations with audit team.

39. What should you likely not include?
• Statements that anger the FDA by:
Abuse audit team
Assert lack of credibility of audit team
Assert lack of technical knowledge of
audit team
Assert lack of competence by the
FDA

40. Post Inspection

41. Post Inspection Reactions
Inspection team
turns over to the
Response team
Smaller
companies:
• Regulatory
Response Team
• Leader
• Legal ((May
become defacto
spokesperson)
• Scribe
• Regulatory (May
become defacto
spokesperson)
• Quality
Larger
Companies
• Regulatory
Response Team
• Media Response
Team

42. FAQs

43. Q. Can I fire the whistleblower?
No. There are specific whistle-blower laws that protect
whistle-blowers. You need to talk to an attorney who can help
you determine how to work with whistleblowers.

44. If the matter is escalating (litigation etc), your business is
stopped or you need to retain counsel, see if your site has
specific insurance covering such expenses?
Q. How can I mitigate financial
expenses?

45. Q. How do I show a good faith effort to
comply?
○Appropriate SOPsTrainingRetraining
Clear
communication with
agency
Self auditsSelf reporting
external auditors
Monitors
Making
commitmentsKeeping
commitments
Terminate
relationships with
violative contractors

46. Should I self report?
• Depends

47. What shouldn't I do?
Commit in haste
Over-commit and under deliver
Commit without assessing impact on operations.

48. Why shouldn't I only use internal
resources?
●You may be a
witness
You may be able to
use attorney client
privilege
You may not have
the specialized
requisite skill
You may be able to
gain credibility by
using a 3rd party.
You may be able to
leverage your 3rd
party's good
relations with the
agency

49. When do you need outside help?
●FDA has expressed the
following concerns
about employees:
• Competence
• Motivation
• Integrity
Discussions of fraud
Discussions of criminal
actions
Presence of significant
findings
Gut feeling of an
escalationYou want to be
proactive.
Responding to the
enforcement action
• Legal/ Regulatory/ Clinical
experience
Addressing the
enforcement issues:
• Technical/ Legal / Regulatory

50. When should I get outside advice?
If you don't have the internal capability to handle it --
Immediately!!!

51. Standard Disclaimers
• This presentation supports an oral briefing and should not
be relied upon solely on its own to support any conclusion
of law or fact.
• This presentation, and the materials included herewith, are
provided for general educational purposes and should not
be construed as legal advice.

52. End of Presentation
Preparing Your War Room

53. Questions?
• Call or e-mail:
•
•
•
• Follow me on:
• LinkedIn:
•
• Twitter:
•
•
Darshan Kulkarni

54. About Your Speaker
Dr. Kulkarni is the Principal Attorney at the Kulkarni Law Firm and
works with a variety of life science companies and their service
providers. Of particular interest, he advises CROs, sites and sponsors
with a variety of services including aggressive and compliant:
• Clinical Trial agreements
• Responses to titled and untitled letters from various governmental.
He has worked as a pharmacist for more than 10 years and is currently
Visiting Professor at the Univ. of the Sciences where he teaches and
develops courses including one on Promotion of Biomedical Products.
He has lectured in engineering, medical, and law schools all over the
country and was voted in the Top 20 of the Top 100 most influential
Social media participants in the annual #pharma100 poll.
Dr. Kulkarni also serves on the Editorial Advisory Board for FDANews
and currently serves as the Chair of the American Bar Association’s
Interest group.
Most recently, Dr. Kulkarni has written several articles, and chapters for
textbooks including the chapter on clinical trials for HCCA’s Research
compliance manual.