INSIGHT BRIEF
Is Your Deviation
Investigation System
Effective and Compliant?
Answer these six questions and find out.
Mike Levitt, Senior Director – Quality Systems
Consulting at Quintiles
Introduction
Deviations, the occurrence of a non-routine event during the manufacture of
pharmaceuticals and biopharmaceuticals, are a fact of life. Equipment
malfunctions, errors by personnel, power interruptions and many other types of
unplanned events can impact normal production operations. Good manufacturing
practices require that each of these events be catalogued and investigated properly
to determine impact to the product, root cause of the event and appropriate
measures to correct or prevent the issue from recurring.
Table of Contents
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Introduction 01
6 Questions to Affirm Compliance 03
Conclusion
05
Deviation Investigation System Effectiveness Checklist 05
About the Author
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Regulatory auditors from around the world recognize the importance of this component of the
quality system. As such, they review deviation histories and individual investigations regularly to
determine if the manufacturing systems are functioning in a proper state of control, and that the
product being released is meeting the filed specifications for safety, purity, strength, quality and
efficacy. It is the responsibility of management to provide adequate resources and training to ensure
that this component of the quality system is effective.
Answering the six questions posed in this paper affirmatively will allow those responsible to validate
that the deviation investigation system is effective and compliant.
1.Can your operations people recognize non-routine events as deviations?
An effective deviation/investigation process begins with knowing when a deviation from
normal processing occurs and taking the initiative to report the event regardless of cause. All
line personnel must be trained fully on expected and required activities. Further, a climate that
encourages reporting of the unexpected including self-committed errors must be developed,
maintained and rewarded. Self-reporting of errors is the strongest indicator that a positive culture
exists and supports the effectiveness of the system. Finally, confirmation that every operational
procedure and training session provides direction on identifying and reporting deviations
strengthens the process.
2.Do your operations personnel know how to report the deviation and determine the
immediate impact?
When a deviation is identified, there must be a clearly defined procedure for describing the event,
determining the significance of the occurrence, establishing the scope of product affected and
completing this assessment in a prescribed window to ensure timely action to restrict product
which may be compromised.
3.Are there sufficient resources to investigate and review these deviations in a timely manner?
Because the investigation may alter the scope or impact of the deviation, most organizations
establish a deadline for completing the investigation, usually 30 to 45 days. Regulatory authorities
consider this critical to ensure that there are no unrecognized problems that may affect product
already in distribution. Utilizing an appropriate metric, a rolling three-month average for example,
each organization must staff their investigation group with sufficient resources to complete
their investigations within the time window while allowing sufficient time for management
review and approval within the established time fence. Management must also establish the
appropriate priorities so reviews are completed within these limits. If a significant backlog beyond
the established process limits exists, it should be managed as a separate compliance issue and
should be treated as an urgent compliance gap.
Answering these six questions will help determine whether
your deviation investigation system is effective and compliant.
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4.Are the investigators capable of performing an effective, well written investigation that
provides an accurate historical record and, if possible, identifies the root cause?
Achieving consistency and appropriate levels of comprehensiveness between investigators
and reviewers is a challenge in every organization. Differences in education, experience and
investigative skills contribute to variability in the quality of and efficiency of the effort. These
issues are compounded in large global organizations with multiple sites.
Investigators must have the ability to think critically, understand the technical issues, have the
capability to find and collect all the relevant data, lead problem solving exercises if needed,
ensure that the investigation covers the appropriate scope and depth and draft a document which
conveys the essence of the investigation to someone unfamiliar with the issue.
A common set of guiding principles for the investigator and their reviewers is essential. The
process will be even stronger if these guidelines provide a process for measuring effectiveness
of individual investigators and each site. There must, however, be some flexibility to account
for what may be unique or different between the sites (e.g., sterile processing, API (active
pharmaceutical ingredient) manufacture, and biopharmaceuticals, among others).
5.When root cause is identified and a corrective or preventive action is proposed, is there
sufficient focus, resources and management commitment to implement the action in a timely
fashion?
All participants in this quality system must remember that there are always two key objectives.
First, there must be assurance that all product affected by the deviation is deemed safe and
effective for release and distribution. The second key objective must be the prevention of a
recurrence of the deviation. This may require efforts and investments of varying degrees that can
delay the completion of a permanent fix. In these cases, some type of interim controls must be
implemented to minimize the possibility of a recurrence.
Maintaining a prioritized list of corrective and preventive actions including interim controls can
monitor this remediation effort effectively. This list of actions should include reasonably detailed
timelines and personnel responsible and must be reviewed with management at regular intervals.
Slippage of timelines should be an early warning of inadequate resources or insufficient focus.
Appropriate trending can monitor effectiveness of the corrective/preventive actions.
6.Has the organization identified the most prevalent events and initiated a process to track and
trend these issues?
Continuous improvement is a basic tenet of an effective quality system. Without an appropriate
mechanism to monitor the impact of corrections or preventive actions made following deviations,
organizations are likely to be burdened with documenting and investigating the same issues
repeatedly. This loop diverts resources into a maintenance mode required to release product
rather than improving processes, cycle times and efficiency.
Implementing a tracking and trending process which identifies repetitive events (e.g., operator
error, equipment failure or document errors), tracks their frequency and trends the impact of
corrective or preventive actions, will allow management to evaluate the effectiveness of the
system and use it for maximum quality and business impact.
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Conclusion and Checklist
Making the deviation/investigation process an effective tool in a company’s journey of continuous
improvement, and sustainable compliance is driven by both the positive impact it can have on
business metrics and assuring the consistent manufacture of quality product.
Deviation Investigation System Effectiveness Checklist
Can your operations people recognize non-routine events as deviations?
>> All line personnel are fully trained on expected and required activities
>> The site’s culture encourages reporting of the unexpected
>> Operational procedures and training provides direction on identifying and reporting
deviations
Do your operations personnel know how to report the deviation and determine the
immediate impact?
>> Procedure in place for impact assessment
Are there sufficient resources to investigate and review these deviations in a timely manner?
>> Metrics in place to monitor timely closure of investigations
>> Staffing is regularly evaluated based on review of workloads
>> Reviewers have established time limits for review completion
>> Backlog is identified and managed as a separate initiative
Are the investigators capable of performing an effective, well written investigation that
provides an accurate historical record and, if possible, identifies the root cause?
>> A guideline is established for all investigators
>> Reviewers evaluating the quality of the investigation use the same criteria
When root cause is identified and a corrective or preventive action is proposed, is there
sufficient focus, resources and management commitment to implement the action in a
timely fashion?
>> Root cause is routinely identified
>> Corrective/Preventive actions (CAPAs) are properly resourced with timelines and
accountability established
>> Management routinely reviews progress on CAPA action items
Has the organization identified the most prevalent events and initiated a process to track
and trend these issues?
>> Deviation history is evaluated and common deviation events identified
>> Procedures are in place for tracking and trending of common events
>> Management conducts regular reviews to evaluate effectiveness of CAPAs
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About the Author
Mike Levitt
Senior Director – Quality Systems, Consulting at Quintiles
What he does: Works with clients in the pharmaceutical, medical device, biologic and biotechnology
industries to develop quality assurance and regulatory strategies for compliance with regulations.
Expertise: Leads project teams to assist clients with Quality Systems and operations improvements,
FDA inspection preparedness training and client assistance to respond to FDA enforcement actions.
Project examples: Managed large-scale project to respond to drug manufacturer’s Warning Letter
issues. Developed plan to bring idled process for an important sedative on drug shortage list back
into successful production. Led project with major diagnostics manufacturer to transform quality
culture and achieve sustainable compliance.
Experience: Veteran operations senior executive with more than 30 years in the industry with
companies like Eli Lilly, Solvay and entrepreneurial biotech operations. Also completed successful
start-up and qualification of major vaccines facility, achieving first-pass zero-483 inspection by FDA.
Education: B.S. Pharmacy, RPh, 1975 – University of Buffalo
Contact Us:
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Email: consulting@quintiles.com
Copyright © 2013 Quintiles. 14.15.18-052013