By Steven Zebovitz, R.Ph., Ch.E.
The readers of this occasional column on the basics of Six Sigma applied in the pharma space are likely aware that we’re at our final step in our Six Sigma DMAIC roadmap, that of Control. As we progressed along our path to improving a manufacturing or business process, we’ve reviewed the first four steps of defining acronym DMAIC as:
- Define: This entails forming a problem statement and forming a Six Sigma team to address that statement. The problem statement is in keeping with the project charter, inclusive of the customer’s needs, the magnitude of improvement (business and GMP impacts), the goals, the scope, and the time frame in which to achieve that improvement.1 We discussed the composition of the Six Sigma team encompassing internal and external beneficiaries, who formed the key stakeholders. Lastly, we discussed a prioritization of contributing variables and a process map defining the suppliers, inputs, process, outputs, and customers (SIPOC).
- Measure: This phase assembles the process data, which should have been collected in an unbiased fashion while being consistent with the project definition. It must be random, representative, reliable (e.g., same units of measure), holistic to the entire process (i.e., following the SIPOC format), accurate, and precise.2 We also discussed continuous and discrete inputs, and that discrete inputs are further divided into counts, binary, and categorical subsets. This data will be used in the Analyze phase of DMAIC.3
- Analyze: Raw data is converted into understandings about the process. We hope to separate the important few inputs from the trivial many. The reader is cautioned that data might fall nicely into correlations, but that correlations are not causations and proper (possibly stage wise) designs of experiments are needed to nail down the principle components.
- Improve: Now that we know the important inputs to a process, we can estimate the direction those inputs may be adjusted to achieve the goals of the project definition. We assembled likely solutions and selected the best among those solutions, we reported our estimates in the value stream map, we tested our adjustments on the pilot scale, we conducted full-scale runs, and we implemented the solution into commercial manufacturing.4 All the while, the concerns of our internal and external clients are held in the highest regard, particularly those of our regulatory and quality team members as well as the voice of the customer.
The Control Phase
Now that we’ve tested our improvements on the commercial scale and we’ve quantified our expected successes moving forward, we seek to sustain those improvements. Sustaining those improvements occurs according to a control plan. As always, there are a number of steps to formalize the process, starting with your regulatory and quality groups to assure that GMP needs are met. Without their buy-in, we cannot implement these changes into commercial manufacture.
The steps to transition commercial manufacturing to a new level of control plan are:5
- Establish methods and documentation for managing the changes at full scale. The plan should be realistic with the expectation of mistakes, mindful of those executing the launch, and sensitive to kinks observed or reported. It should include procedures, training, control documents, and visual and automated controls.
- Launch the implementation with support from project management.
- Manage the benefits using training, procedural modifications, preapproved specification modifications, modifications to material flow or suite layout, process controls, and error proofing.
- Monitor the implementation via process control plans with active involvement by the Six Sigma team. Key and secondary metrics should be tracked within process and between batches, or at regular, ongoing intervals throughout. Ideally, the data will be collected into a form for convenient analysis.
- Develop process controls and hand-off controls.
- Audit the benefits comparing metrics before and after the implementation. Reporting of key metrics and realization of benefits may occur at 6- and 12-month intervals.
- Complete the project, including “post mortems,” control gate review and approval, and celebrate the hard and successful work of the team.
A Word On Training
Your workforce is the single most important factor in sustaining your hard-won accomplishments. The control plan will likely change their procedures, culture, and habits. The Six Sigma team must train those involved with the control plan on the following:6
- Goals of the control plan.
- Benefits of the control plan in hard numbers with transparency and integrity.
- Implementation schedule and milestones.
- Requirements of the control plan.
- Duties for each employee group including specifics such as: Inputs, outputs, specifications, measurement techniques, control methods, sample sizes and frequencies, and reaction plan.
- Differences the workforce will experience from the current operation.
- New responsibilities and new habits to be put in place.
- Ways of gauging the success or failure of the control plan in vocabulary consistent with job functions.
As a consequence of improved efficiencies, a workforce reduction might be a likely result. Alternatively, companies might plan for expanding capacity rather than workforce reductions. This author sincerely recommends that companies offer generous severances, including retraining. I would suggest that training also include the benefits offered to the displaced workforce as a method of implementing a successful control plan to the remaining functionaries. Without this training, the workforce is not incentivized to succeed.
Monitoring The Six Sigma Process After Launch
The monitoring of the improvements is a mix of art and science and should be built into the control plan. Some improvements, such as yield improvements, are obvious. Others, such as reduction in variation, are less apparent and require analytics after the fact. Input from the quality and financial functions is necessary for the successful adjudication and quantification of improvements.
For this discussion of monitoring, I draw broadly from Breyfogle.7 Often used by this reference is the term “wise.” Breyfogle reminds us that process controls must be engineered with the process and the human operators in mind. The following techniques might be used alone or in combination during the Control phase:
- Target control charts: These include difference, target, ZmR, three-way control charts.
- Moving averages: These include Shewhart, cumulative sum (CUSUM), moving average, and exponentially weighted. Note that the exponentially weighted averages smooth out the effect of noise to better focus on the process.8
- Pre-control charts: The initial data of a process run is assessed prior to beginning a full run. This setup phase is qualified using a color scheme such as green for output within the central half of the tolerance range, yellow if within the tolerance range, and red if it falls beyond the tolerances. Subsequent actions on the part of the operators are dependent on these colors. Setups fall within categories such as classical, two-stage, modified, etc.9
Summarizing the Entire Process
We’ve come a long way in this Six Sigma overview. We’ve defined our problem, measured key variables, analyzed the data with a focus on root causes and principle components, forwarded ideas for improvement and validated them at small scale, and finally, launched full-scale improvement(s). Now, our former business or manufacturing process has become more efficient, less prone to variation or lag times, and is sustainable in a convenient fashion by those actually performing the tasks. Along the way, the Six Sigma team gained education and experience, and through their attentiveness and enthusiasm, “enrolled” others to the cause.
For those with Six Sigma credentials, I hope this series was a good refresher. For those without their Six Sigma belts, I hope you and your organization will see the benefit and will enable training in quality Six Sigma courses. Most importantly, I hope you’ll be instrumental in enhancing the quality and efficiencies of your processes.
- Zebovitz, S., “A Working Introduction to Six Sigma for Pharmaceutical Manufacturers”, Pharmaceutical Online, August 23, 2016, http://www.pharmaceuticalonline.com/doc/a-working-introduction-to-six-sigma-for-pharmaceutical-manufacturers-0001
- Zebovitz, S., “Taking The First Step In Six Sigma: An Overview Of The “Define” Stage”, Pharmaceutical Online, October 4, 2016, www.pharmaceuticalonline.com/doc/taking-the-first-step-in-six-sigma-an-overview-of-the-define-stage-0001
- Zebovitz, S., “Keys To Success In Six Sigma’s ‘Measure’ Stage”, Pharmaceutical Online, November 9, 2016, http://www.pharmaceuticalonline.com/doc/keys-to-success-in-six-sigma-s-measure-stage-0001
- Zebovitz, S., “7 Steps To Navigate Six Sigma's "Improve" Phase”, Pharmaceutical Online, February 17, 2017, https://www.pharmaceuticalonline.com/doc/proven-steps-to-navigate-six-sigma-s-improve-phase-0001
- George, M.L., et al, The Lean Six Sigma Pocket Tool Kit, The McGraw-Hill Companies, USA (2005), p. 17-19.
- Compiled, in part, with assistance from J. Ficalora, President, Sigma Process Improvements, LLC, May 2017.
- Breyfogle, F. W., Implementing Six Sigma, Part V, John Wiley and Sons (1999).
- Ibid, p. 536.
- Ibid, p. 548-550.
The author thanks his Six Sigma teacher and mentor, Joseph Ficalora (firstname.lastname@example.org, 973-727-3788), for his critique of this manuscript. Mr. Ficalora is a Lean Six Sigma Master Black Belt and deployment coach.
About the Author:
Steven Zebovitz, R.Ph., Ch.E., has three decades of pharmaceutical engineering and manufacturing experience in oral solid dose. Much of his experience is in engineering and manufacturing support, including leadership positions in technology transfer, technical services, process scale-up, validation (PV and CV), optimization, and implementation of data-based quality systems. He led a Six Sigma deployment that yielded 10 Black Belts and one Master Black Belt. His interests include process excellence, lean manufacturing, and championing teams. He may be reached at email@example.com, www.linkedin.com/in/stevenzebovitz/, or 215-704-7629.