19.08.2014 |

LOGFILE No. 04/2014 - Key to success in a world of failures

Investigation: A Key to Success in a World of Failures

by Thomas Peither, Maas & Peither AG, GMP Publishing, Germany

Life is full of risks and we all know that failures happen every day not only in every drug-manufacturing department.

The question is not how many failures happen but how to avoid the same failures in the future. One of the key success procedures is the investigation process in a pharmaceutical company.

Important GMP regulations force an investigation process, thus every company has already implemented a procedure to do so. However, does this really have an impact on the recurrence of failures in the future? Are the investigations conducted in a productive way?

This article provides some recommendations for improving investigations with the final goal that recurrence of the same mistakes is eliminated or reduced.

Effective science-based investigations lead to error prevention, operational excellence and 
patient safety. And it is an industry challenge to apply appropriate scientific rigor to investigations. As a GMP fundamental approach the investigation reports must be well documented. This seems to be an easy task. Nevertheless, I recommend taking a close look at your company’s recent investigation reports. Do you really understand the report? Is it written in a clear, precise way and without uncertainty?

I am sure you have already noticed the risks of an investigation report:

  • Inaccurate product impact
  • Inaccurate root cause assessment
  • Incorrect or insufficient corrective actions or preventive actions

This happens, because the process is inadequately implemented, trained or followed. The goal should be to write the best investigations ever leading to a significant reduction of cost and effort.

Implementing an effective investigation procedure will have the following benefits:

  • Assurance of product quality
  • Assurance of product supply
  • Significant reduction of errors

This has been common practice in a lot of industry branches. The only way to reduce errors is to recognize them and to work on a preventive action program.

“A robust investigation program is the most efficient and effective way to run a business.”[i]

The U.S. FDA also realized that an effective CAPA system is critical[ii]. Important elements are:

  • Written program that defines the CAPA system and its interactions with other systems
  • Well qualified staff which understands the technology and failure modes
  • Involvement of the right subject matter experts in each evaluation
  • Meaningful metrics that provide an early warning system
  • Evaluation of the effectiveness of the change
  • Monitoring process for progress of change, and closing out once effectiveness is confirmed

The FDA also observes the following findings that are related to investigations:

  • Complaints are not substantively investigated
  • Scope of investigations: Isolated issue or recurring?
  • Appropriate expertise to investigate/diagnose/correct the failure
  • Addressing failures at contracted sites (CMO, contract lab)
  • Root cause identification and correction
  • Effectiveness checks
  • Resources to make lasting correction

Key factors for success

But there are some factors and questions leading to better investigations:

  • Are the right people and expertise at the evaluation/discussion table?
  • Is the appropriate data complete and is it being reviewed?
  • Is the root cause or are the causes identified?
  • Is there someone with a holistic view?
  • Is each aberrant event reviewed and are corrective measure(s) made?
  • Is there a collective perspective?

One of the most crucial points of the list above - also from my industry & consulting experience - is the first one. Just imagine that the right people are not at the table. How would it be possible to support that all of the appropriate data is reviewed? Which in turn questions the validity of the assessment and identification of the cause/s. And finally, are you sure to implement and execute the appropriate corrective measures?

Try checking the following: Have the following necessary subject matter experts been involved in an investigation?[iii]:

  • Shop floor operations
  • Engineering
  • IT staff
  • Maintenance
  • Laboratory analyst
  • First line supervisor
  • Team leader
  • Manager/director
  • Senior Vice President / Vice President
  • President/CFO/COO/CEO

Points to consider in investigations

Improvement of investigations is a long-term goal. You should consider the following points if it comes to investigations (excerpt):

Organize investigation teams

  • Identify qualified team members with expertise (impacted area)
  • Identify if partners, contract manufacture or supplier should be involved
  • Hold investigation team kick-off

Develop and brief investigation plan

  • Use 6Ms (Six Sigma) approach
  • Identify information to understand event scope
  • Check if impacted products are on drug shortage list
  • Draft investigation timetable
  • Develop plan to determine root cause

Execute Investigations

  • Determine product/patient impact
  • Determine root cause by selecting most appropriate for type of root cause analysis tool for the investigation
  • Gather data
  • Analyse data
  • Validate root cause with data

Evaluate HA[iv] notification

  • Determine if the event under investigations impacts products in the market
  • Determine product quality impact
  • Determine if there is partner, CMO or supplier notification
  • Complete internal documentation on HA notification evaluation

Draft CAPA recommendation

  • Ensure action strategy is evidence based
  • Ensure effected sites/functions impacted review and agree to CAPA
  • Apply CAPA across sites if applicable
  • · 

 

Drafting investigation report

  • Collect and review investigation data
  • Draft, edit and revise the investigation report
  • Draft quality management brief slide check
  • · 

Working with the Quality Management

  • Schedule, at a minimum, weekly informal updates with the quality management
  • Coordinate with the investigation sponsor to ensure they are receiving timely investigation updates
  • Conform best means to update quality management outside of meetings

Summary

Redesigning the investigation process is well worth the effort when it does not support the decrease of failures and investigations in a company. To change the common practice in the organization and use the investigations as a source of knowledge and improvements takes time. This transition is more than a quality topic. It should be part of a change process of quality management and should be supported by experienced and trained change experts. The implementation of an improvement oriented investigation process is a necessary step to a long-lasting improvement of quality in the pharmaceutical industry. It does not ensure to reach the goal but it is an absolutely necessary step.

Organizations that put in place meaningful failure investigations and processes for investigations will not only strengthen their business base but achieve sustainable improvements in their productivity and product quality.


[i] Martin VanTrieste, PDA/FDA Improving Investigations Workshop, Washington DC, 2013

[ii] Rick Friedmann, Associate Director, Office of Manufacturing and Product Quality, Office of Compliance, PDA/FDA Improving Investigations Workshop, Washington DC, 2013

[iii] Thomas Arista, Field Investigator, National Expert Pharmaceutical/Biotechnology, ORA, PDA/FDA Improving Investigations Workshop, Washington DC, 2013

[iv] HA = Health Authority

Author:

Thomas Peither
Peither & Consultants GmbH
Maas & Peither AG, GMP Publishing

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