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The sixth in a series of eight case studies from the Product Quality Research Institute focuses on packaging line GMP optimization.
Packaging represents a critical manufacturing operation requiring strong GMPs and quality oversight to ensure sustained and robust compliance. Historically, inadequate packaging practices have been a meaningful ongoing contributor to product recall actions industry-wide. A strong understanding of the compliance risks associated with product packaging is a necessary and important component of a good quality system.
This case study on packaging line GMP optimization is the sixth 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 PharmTech.com/PQRIstudies.
In this case study, the authoring firm has enjoyed satisfactory compliance performance across their international packaging operations. Nonetheless, recognizing the criticality that packaging plays in ongoing quality assurance, the firm engaged in a risk-assessment of a number of established packaging lines at several key packaging sites worldwide. The goal of the assessment was to further enhance the quality assurance of existing packaging operations and practices.
The risk question and risk-assessment method
The risk question developed for the subject case study is: What processes, procedures, and/or events during the packaging of a product create an unacceptable risk, real or perceived, to the quality of that product as received by our customers?
The project team assigned to this initiative sought to find a method that was inductive, systematic, and comprehensive, with the understanding that the risk factors for this application were generally well defined and quantitative. The risk tool selected to perform the analysis was: functional failures and effects analysis (FFEA). This tool represents a hybrid of failure modes and effects analysis, or FMEA, and uses a risk matrix instead of a risk priority number (RPN). FFEA is a systematic, function-based method for examining the effects of functional failures on system performance.
In this case study, a team of subject-matter experts conducted the analysis by identifying and assessing the effects on a system associated with individual functional failures. To apply risk-based, decision-making concepts to the FFEA, the team also identified the frequency of each functional failure and the severity of the potential effect (outcome) and compared each to predetermined risk-acceptance criteria. The team suggested corrective actions when required by the risk-acceptance criteria or when the team identified opportunities for improvement.
The risk analysis
The assessment effort required that potential product defects from any given packaging operation be defined and graded for severity, frequency, and on the ability of the operation and/or an operator to detect the defect. Tables I and II summarize the definitions and categories applied for severity and frequency. Defect detection was categorized and graded on a 0-to-4 scale to reflect a detection capability of "none" (unable to detect) to "always" detect.
Table I: Sample severity categories.
A team of packaging subject-matter experts, and local site packaging engineers familiar with the subject packaging lines under assessment, worked to collect relevant data about the packaging line. All operations involved with the line function (e.g., equipment, procedures) were listed and all corresponding potential failures were then listed. For each potential failure, the team worked to understand its potential impact on packaging operations and then worked to assign a severity category. Following severity classification, the team reviewed the dominant causes relevant to the defined potential failure and assigned each a frequency category.
For each potential failure, all safeguards (e.g., detection capabilities) were reviewed and a detection capability was assigned. For determinations of severity, frequency, and detection, all relevant data was taken into consideration, to include maintenance and operation logs, batch records, deviation investigations, customer complaint records, and so forth.
Table II: Sample frequency categories.
In the FFEA model, the calculated frequency (F) is combined with the ability to detect (D) and then plotted against severity (S) as follows:
The resulting work output from this assessment was recorded in tabular form. Table III shows an excerpt of the resulting work product.
Table III: Resulting work product (sample).
Using the collected tabular information, a risk matrix was assembled (see Figure 1). In Figure 1, items A through D from Table III are noted to reflect their calculated frequency. The risk matrix helps to visually prioritize the results from the risk analysis. In this case study, item "A" would get immediate action to eliminate or reduce the risk. Items "B" and "D" would be evaluated and actions would be taken if practical and appropriate to reduce or eliminate risk. No actions would be required for item "C".
Figure 1: Risk matrix.
In this case study, risk is reduced by introducing a structured and standardized approach to understand and determine the potential likelihood of system or operator failures and the probability of any resulting defect impacting the final product and end-user. Potential risks which are above a predefined threshold, taking into account severity and frequency of occurrence (the later of which is modified to account for the probability of on-line detection), are considered for elimination or mitigation.
Risk documentation and communication
The risk analysis for the subject case was reviewed by an oversight committee to confirm findings and support risk-mitigation activities. Learnings from the assessment were shared with the firm's other operations that used similar packaging equipment and/or packaging practices. In addition, learnings from the full set of packaging-line risk assessments were captured for consideration in future packaging line design and equipment procurement efforts.
As part of the firm's auditing activities, the corporate group responsible for periodic site audits received copies of the risk conclusions and action plans to confirm that corrective actions were deployed effectively. The risk-assessment summaries were maintained at the local site packaging departments for use in future troubleshooting exercises involving deviation investigations or product complaint evaluations.
Ted Frank is with Merck & Co; Stephen Brooks, Kristin Murray,* and Steve Reich are with Pfizer; Ed Sanchez is with Johnson & Johnson; Brian Hasselbalch is with the FDA Center for Drug Evaluation and Research; Kwame Obeng is with Bristol Myers Squibb; and Richard Creekmore is with AstraZeneca.
*To whom all correspondence should be addressed, at firstname.lastname@example.org