Applying Continuous Improvement (CI) Manufacturing - - BioPharm International


Applying Continuous Improvement (CI) Manufacturing

BioPharm International

Control charting also helps track and evaluate process performance over time. This is particularly useful after process improvements have been made to ensure the changes have a beneficial effect. For example, changes were recently made to the timing of batch record reviews. The review of manufacturing batch records now takes place in the plant, usually on the day they are completed. Before, the documents were reviewed in an office several days after they were completed. The improved process has reduced the time between document completion by manufacturing and the subsequent review by an independent lot review group and quality assurance (QA). One anticipated benefit of this change was reduction in the number of deviations generated per batch by having QA input available at the plant as batches are being processed. As control charts were already being used to monitor the process, the effects of this change in procedure were quickly evaluated. Changing the timing of the document reviews resulted in a reduction in the mean number of deviations generated per batch (Figure 1).

The successful use of this technique has led to the introduction of control charts to track the performance of other processes. For example, the number of process alarms generated during manufacturing is now monitored using this tool.

Figure 2. Drill blanks have been mistake-proofed by attaching the correct size tubing for which the blanks are intended to be used. This helps to ensure that the correct size blank is used for the appropriate size tubing.
2. Error PreventionThe second principle of the CI philosophy is preventing errors — not just applying corrective actions once they have occurred. This has been achieved using a technique called failure mode effect analysis (FMEA). FMEA is a risk-based prioritization tool that helps to identify known or potential failure modes within a process or system.2 FMEA has been successfully used for one of Lonza's fermentation harvest systems. The technique helped identify and prioritize areas requiring CI focus, engineering investment in the plant, additional operator training, and opportunities for standard operating procedure improvement. A secondary benefit of using FMEA is that the team (consisting of representatives from fermentation, engineering, and pilot and QA compliance) has enhanced its understanding of the harvest system. The team felt that the knowledge they gained would be useful to them in their normal roles.

3. Structured Problem SolvingThe third continuous improvement principle promoted at Lonza is using structured problem solving to help identify root causes of problems more rapidly. Cause and effect analysis has been used to structure problem solving by graphically displaying all possible causes of a problem. Brainstorming sessions are held with members of the relevant teams to generate the list of potential causes. It is essential to involve the people working on the system or process as they possess the best knowledge of likely causes of the problem. It is also useful to include an "outsider" at these sessions because of their ability to ask "obvious" questions that people with in-depth process knowledge frequently overlook. Once a cause-and-effect diagram has been generated, all the possible causes of a problem are investigated. Potential causes are only discounted if factual evidence can be found to back-up that decision. This helps remove subjectivity from investigations. Previously, individuals often presented their opinions as facts, leading to unsubstantiated conclusions being drawn about the actual root cause of a problem.

As well as a more rapid determination of root causes, this technique is also a useful method of documenting an investigation. This helps with the closure of associated manufacturing deviations as it provides clear evidence that an event has been fully investigated. The tool is now a standard problem solving and investigative method in manufacturing.

Figure 3. Instrument port blanking plugs used in fermenter vessels have been color coded to ensure that the correct plugs are used and that the plugs are correctly aligned.
4. Eliminating Root CausesOnce root causes of problems have been identified, it is essential that actions are taken to ensure that they cannot recur. Root cause elimination is the fourth CI principle used at Lonza. Root cause elimination is achieved by using mistake-proofing techniques that have already proved successful in the automotive and aerospace industries.2 Mistake-proofing allows systems and procedures to be designed or modified to help avoid the opportunity for error.

For example, the root cause of a pump tubing split at Lonza was attributed to the incorrect setting of pump roller gaps. Gap measuring devices (blank drill bits) are now being used to ensure that pump rollers are set to the correct operating distance. These gap measuring devices were developed so that it is obvious which size tubing should be used (Figure 2). This has helped reduce opportunities for the wrong operating distance to be used when pumps are set up.

The mistake-proofing technique has also been successfully used to ensure that the instrument port blanking plugs used in fermenter vessels are correctly positioned and aligned prior to commencing a manufacturing batch (Figure 3). Now that the mistake-proofing system is in place, it is obvious to operators, at a glance, if a plug is correctly oriented.

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