FMEA: A Risk-Based Approach to Sterility Assurance

Failure Mode and Effects Analysis can help improve the safety of aseptic processing; using written and verbal brainstorming is key

By Craig Alexander, P.E., Monsanto Co.

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Defuse Quality Problems Before They Happen

Editor's Note:

Product recalls, consent decrees, 483s, lost batches. We all know what happens when drug manufacturers lose control of a critical quality parameter, or fail to estimate infrastructure needs. Experts agree that data monitoring, trending and analysis are all that is needed. But that’s often easier said than done. Deciding which data points are the most critical to product safety and quality can be challenging.

Proactive manufacturers prioritize efforts effectively, using various methods and technologies to focus on areas that will yield the greatest return, have the greatest impact on product quality and safety, and optimize process control. The following are case studies in proactivity, approaching the topic from different angles.

  • As you will read below, Monsanto’s veterinary pharmaceuticals division is taking a “worst case” approach to ensure aseptic standards, and applying Failure Mode and Effects Analysis (FMEA) to determine areas of greatest potential vulnerability.


  • Talecris Biotherapeutics,
  • which is also using FMEA, is applying strict quality control methods to every link of its supply chain. On the manufacturing floor, multidisciplinary teams ensure that the right data are being monitored and any blips are identified before they can become issues. In "Proactive QC at Talecris: Leave Nothing to Chance," SVP of manufacturing Mary Kuhn talks about some of the approaches the company is taking.

  • For valuable biotherapeutics, ensuring sufficient power and utilities is critical. In "Maximizing Uptime for Mission-Critical Manufacturing Units," engineer Gary Shamshoian discusses redundancy and other principles guiding Genentech’s approach to maximizing “uptime” for mission critical manufacturing units.


  • New, innovative technology can help minimize risk. But concerns about compliance and validation can often stall efforts to do things differently. "How Early Communication with FDA Sped Up One RMM Implementation" shows how one pharma manufacturing team approached a Rapid Microbial Methods (RMM) implementation project. The technology was adopted to help them ensure the quality of raw materials, material-in-process and finished product. As they note, communicating early and proactively with FDA was critical in implementing the technology and gaining Agency approval for a new drug utilizing the technology.

As these articles show, optimizing quality proactively is not only possible, but is becoming an established practice for more pharmaceutical manufacturing operations. Is yours among them?



    Demonstrating a high degree of sterility assurance is critical to successful aseptic processing. Each process step and each component introduces opportunities for error that can lead to a loss of sterility assurance. The variety of utility systems, lab systems and clean room systems involved in the process further add to the complexity. Proper validation and control of the manufacturing system is crucial since the product may not be suitable for terminal sterilization in its final packaging.

    This article describes a proactive method of improving sterility assurance using a risk-based approach. This initiative focused on the use of Failure Mode and Effects Analysis (FMEA) to identify potential weak points in the sterility management process.

    Gathering Data

    The manufacturing facility described here is still early in its life cycle. Thus far, the sterility program has been solid, with no failures and few questions about the assurance of sterility. Despite this good performance, a proactive approach was taken to identify potential failures in our system. In the spirit of continuous improvement, we thought it was important to leverage our good experiences in sterility management as we sought to improve our existing process.

    Typically, an FMEA would start with a detailed review of historical failure data. This step is important to remove opinion and conjecture from the analysis. However, with limited historical data on loss of sterility assurance, we sought information from process experts to help identify potential areas of concern. The first step was to interview a number of subject-matter experts across our corporation, including personnel in quality assurance, validation, manufacturing and the QC labs.

    Next, our team sought ideas from operations personnel across the site. Groups from each of the aseptic manufacturing areas, the utilities area and microbiology were consulted. Brainstorming sessions with each of these groups across several shifts were organized.

    Our team was concerned that traditional verbal brainstorming might inhibit responses from some individuals who might be uncomfortable in a group. There also was a concern that more dominant individuals would take over the conversation and thus we would miss some good information from quieter personnel. Therefore, our team made use of an alternative brainstorming method called Brainwriting 6-3-5.

    This technique is a written brainstorming tool that refers to having six people each write down three responses to a problem in five minutes. Each participant begins with a worksheet divided into five rows of three columns. A question or problem statement is listed at the top of the page. Each person records three responses to the problem or question within five minutes. Each worksheet is then passed to the left and a new five-minute period begins. Each person reads the first three responses and then writes down three more ideas until the table is full.

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