An integral part of an effective quality system in a cGMP-compliant pharmaceutical manufacturing operation is a formal self-assessment
process. This is commonly accomplished by performing periodic internal audits of site operations (e.g., quality, manufacturing,
engineering, logistics) and associated systems with potential cGMP impact.
The overall administration of the internal audit program is the responsibility of the quality control unit. The quality control
unit is responsible to assess site operations and associated systems in order to identify the focus, frequency and resources
to support the internal audits as well as to determine the effectiveness of the conducted audits. Audits are typically conducted
according to a predetermined schedule and on a regular basis.
This case study on internal GMP audits is the last of eight in a series put together by the Product Quality Research Institute
Manufacturing Technical Committee (PQRI-MTC) risk-management working group. The series is meant to advance the understanding
and application of the International Conference on Harmonization (ICH) Q9 Quality Risk Management guideline by providing actual
examples of risk-management assessments used by the bio/pharmaceutical industry. The introductory article and first case study,
on defining design space, appeared in the July 2011 issue of Pharmaceutical Technology (1). Subsequent case studies in the series (8 in total) can be viewed online at http://PharmTech.com/pqristudies.
In the current case study, the manufacturing site is a diverse drug-product facility. Ideally, the site would be able to perform
internal audits of all site operations and systems within a given calendar year. Given the breadth and scope of operations
and available support resources, it will be difficult to conduct an internal audit to all operations and systems within that
timeframe. One potential approach to administer an effective internal audit system is to maintain a listing of site operations
that are subject to internal audit and determine audit frequency based upon the criticality of the operation. The site maintains
a list of current operations and also periodically reviews and understands the performance of these operations and associated
systems. As a result, facility management recognizes that there are certain internal systems that could benefit from additional
focus and enhancement. Site management wants to ensure that resources are applied to those operations having the highest potential
for GMP impact and proposes use of quality risk management (QRM) as a tool to effectively apply resources and schedule and
conduct internal audits at their site.
The risk question and assessment method
The risk question developed for the subject case study was: What is the optimal internal audit schedule to ensure that those operations and associated systems with the greatest potential
impact on product quality and, therefore, potentially the patient, are audited on a more frequent interval than those determined
to be less critical?
An internal audit is a diverse activity with more qualitative characteristics than quantitative ones. Therefore, the selected
risk-assessment tool will produce a qualitative description of risk (e.g., high, medium, or low). An additional objective
of the selected tool is to assist in the organization of data as the assessment moves to the next stage of the process. The
developed list of site operations and associated systems ensures identification of the potential risks. As a result, a complex
risk-assessment tool is not required. A simple tool that allows for qualitative analysis and evaluation is sufficient.
The risk methodology selected for the subject case study was: risk ranking and filtering.