Avoiding Noncompliance
Lori F. Hirsch
Managing Counsel
July 10, 2013
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• Our vision is to make a difference in the lives of people
globally through our innovative medicines, vaccines,
biologic therapies, consumer health, and animal
products
– >70 manufacturing sites in our internal network.
– Also utilize external manufacturing sites to manufacture APIs,
finished product and packaging.
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Some General Statistics
• More than 100 Regulatory inspections annually of Merck
Manufacturing sites covering:
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Pharmaceuticals
Vaccines
Biologic Therapies
Consumer Health Products
Animal Health Products
Including, without limitiation, FDA, EMA, MHRA, PMDA,
TGA, Health Canada and WHO
• As required, file Field Alert Reports
• As required, file Biologic Product Deviation Reports
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Working at a Pharmaceutical Company
as In-house GMP Counsel!
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Typical Work of
In-house GMP Counsel
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Member of the Global Quality Leadership Team
Member of the Manufacturing Division Compliance Committee
Review of Regulatory Responses to 483s and other Regulatory Agencies’
inspection observations
Member of Fact Finding/Recall Committee
Review of Regulatory notifications to ensure compliance with the
regulations, including Field Alert Reports and Biologic Product Deviation
Reports
Review of Quality Agreements with third parties
Serve as internal consultant on interpreting cGMPs
Perform Regulatory surveillance, such as reviewing Warning Letters,
Regulatory actions, etc, for applicability.
Work with outside counsel on an as needed basis
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The Role of
In-house GMP Counsel
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Help clients understand the “c” in cGMPs.
Know the business – become an expert not only in the law but in the manufacturing
and testing processes as well as the Quality Systems.
– The more you know about the processes, the more effective you are as a lawyer
and the more credible you are with the clients.
Help ensure that the right people, processes and systems are in place to ensure
compliance.
If an issue arises,
– Ensure the use of critical logic (including Risk Based Methodology)
– Help sites drive to root cause
– Ensure that there are both preventative and corrective actions which are
sustainable.
• Has the issue been addressed holistically?
Consider not only tactical fixes but systemic actions needed
Partner and Communicate with your clients, early and often!
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What is needed to ensure
compliance?
Permanent
Inspection
Readiness
Strong Systems
Good Processes
Right People
Strong Compliance Culture
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Quality Culture
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Every person is a Quality Leader!
“Safe to speak up” environment.
Make problems visible and solve them once.
Bottom Up rather than Top Down Quality
Institutionalization of a culture/attitude in which all
employees, regardless of level or function, have
ownership and accountability for Quality and
Compliance.
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Right people
• Must have the right people in the right jobs.
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Do they have the skills to be successful?
Do they have the appropriate background?
Are they trained?
Are people accountable for their actions?
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Processes
• Must have appropriate processes
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Are your processes written?
Are your processes well understood?
Are personnel adequately trained in the processes?
Can your employees explain them in their own words?
Are the processes repeatable and robust?
Do they lend themselves to Right First Time?
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Systems
• Robust systems and Quality oversight must be in place
to ensure long-term success and sustainability.
– Do you have a system in place to find, detect and correct any
issues?
– Do you have an effective and comprehensive audit program (at
sites as well as divisionly)?
– Do you have an effective and comprehensive CAPA system?
– Do you have appropriate checks and balances built into your
system.
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Permanent Inspection Readiness
Permanent
Inspection Readiness
Strong Systems
Good Processes
Right People
Strong Compliance Culture
Key Takeaways:
1. Issues will happen, but what distinguishes a company is how
quickly and comprehensively it reacts to those issues.
2. A company must have a culture that learns from mistakes, and
takes steps to correct an issue and prevent it from recurring.
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What will be the result of
your next inspection?
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What Can You Expect During
an Inspection..…
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Document requests
– Annual Reviews, Investigation and Change Request Lists, BPDRs/Field
Alerts, Sterility Investigations, Environmental Monitoring Results,
Customer Complaints.
– Detailed review of deviations and corresponding investigations and
CAPAs.
Tours of Processing Areas
Interviews with personnel at all levels of the organization (operators through
senior managers)
– Emphasis on bottom-up vs. top-down approach to problem solving.
– Consistent information must be presented.
Review of corrective actions from previous inspection
– Verify implementation was done as committed.
– Data/information to show that actions have prevented recurrence.
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What Investigators Will Expect
– Well maintained/well kept facilities - first impressions
matter!
– Employees know SOPs and core responsibilities, and can
explain them
– Personnel Adhere to GMPs & Procedures
– Strong Quality Systems are in place
– CAPAs are implemented and measured to ensure
effectiveness (problems are solved once)
– Site has self awareness of problems & shortcomings
– Quality Culture is engrained and part of the fabric of the site.
– Documentation of planned future actions (“intentions”)
• E.g., Project Plans, CAPAs, etc.
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Inspection Musts
Ensure that the
RIGHT PEOPLE
discuss the
RIGHT INFORMATION
at the
RIGHT TIME
in the RIGHT WAY!
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What Investigators Will Not Tolerate
• Delays in retrieving documents or the need to
request documents repeatedly
• Incomplete documentation
• Inaccurate information
• Interviewees who do not respond to the questions
asked.
• Being given different answers to the same
question.
• Lack of knowledge
• Lack of transparency
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Key Points to Remember
A good inspection outcome is a function of:
– Training, Competence, Preparation and Confidence of
Personnel
– Detailed knowledge of past commitment actions and status
– Knowledge of current inspection trends
– Effective documentation and clarity
– Effective interactions and communications with Inspectors
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Responding to Inspection
Observations
• Respond within the 15 working day period.
• Responses are the Company’s opportunity to
demonstrate that the Company has corrected or will
correct any deficiencies and that appropriate systems
exist to prevent recurrence.
• Ensure that the responses are well-written, factually
correct and complete, logical and explains the corrective
and preventative actions to be taken
– Responses should respond to the specific observations as well
as describe systemic actions, as appropriate.
– Site is responsible for the responses and commitments.
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How will your manufacturing site be
rated after the inspection?
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Avoiding a Crisis
problems
detected
scrutiny
from more
players
more
problems
detected
problems
not
addressed
increased
scrutiny/
publicity
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Common elements of failure
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Inadequate follow-up
Repeat violations (e.g., ineffective CAPAs)
Local not system wide corrections
Failures to find, detect and correct
Corporate Culture Issues
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Ineffectiveness of Quality organization
Lack of checks and balances
Management Failures
Complacency/Arrogance
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Quality Lessons
• Deficiencies occur/ mistakes happen
• Key is to have systems in place that
– Provide for strict accountability/ checks and
balances
– Investigate root causes
– Assure complete and systemic correction
– Document and validate changes
• Ensure truthfulness in all responses
• Live up to all commitments made to an
Agency.
• Apply “Lessons Learned” across the
organization.
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Questions?
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