In my previous article, I broadly introduced the Six Sigma approach to process excellence, along with some examples of its application and a discussion of its Sigma levels, roadmap, and educational and experience levels (belt colors). If you haven’t read that article, it would be helpful to do so before proceeding with this installment, which will begin a deeper dive into the Six Sigma process — also known as DMAIC, which stands for define, measure, analyze, improve, and control.
The first phase of DMAIC is the Define stage. It compiles the project goals in terms everyone can understand and agree to, and lists deliverables, both for internal and external customers. It is perhaps the most difficult stage, requiring a multidisciplinary approach. It also necessitates a thorough understanding of the process, and that understanding will differ between functional roles in an organization. Though the project definition is the accountability of the Six Sigma team, input should be solicited from:
- Internal roles: These can include quality assurance/control (QA/QC), product development, manufacturing, engineering, environmental health and safety (EHS), regulatory, logistics, sales/marketing/forecasting, training, the Six Sigma team champion, and others. Note that the Six Sigma team members may serve as representatives themselves.
- External roles: Valuable insights may be gleaned from raw material and/or packaging component suppliers, contracted services, brokers, and equipment representatives, among others.
Whether internal or external, additional roles may also be called into play. The Six Sigma team would boil the advice, opinions, and concerns into the project definition.
Attributes of a Project Definition
As mentioned earlier, a thorough understanding of process and opportunities for improvement are fundamental to authoring a workable and achievable definition. We seek high-impact, low-performing processes for improvement, or we seek root causes for processes gone awry. With those in mind, a definition must have these attributes:1
- Project charter: This is the overarching project document. It provides direction and helps guard against scope creep. A good project charter covers the:
- Precise problem statement(s) (e.g., defects, downtime, dissatisfied customers)
- Business impact (productivity, costs, growth opportunities)
- GMP impact (regulatory issues, recalls)
- Goals (short-, intermediate-, and long-term, as appropriate)
- Defined team, including sponsors and champion
The project charter is created once and reviewed or updated with each project.
- List of validated customer’s needs, expectations, and requirements: Simply put, these are:
- What the internal or external customers consider important (the voice of the customer)
- What the business considers important (voice of the business)
- What regulators consider important
- A prioritization of measurable, validated, contributing variables that can reasonably be improved, and the degree to which improvement is expected through the DMAIC process
- A process map highlighting the problem at hand: The suppliers, inputs, process, outputs, and customers (SIPOC) format is often used for this attribute.
- A communication plan: This identifies the functionaries and beneficiaries of the Six Sigma project, and the format and frequency for updates.
- Project plans
- Stage gate review and agreement to move to the Measurement phase
Variables and Sources of Variation
Before moving to examples, let’s take a moment to prioritize them. Often, quite a bit of data is accumulated during a process, typically more than required for a root cause analysis or achievement of specific goals. So how do we separate the critical few variables from the trivial many?
Though a topic unto itself, variables may be prioritized using brainstorming, background materials, formulation reports, equipment/facility maintenance records, interviews, facility layout plans, meteorological data,2 process maps, process observation, fishbone diagrams, cause-and-effect matrices, failure modes and effects analyses (FMEA), and on and on. Through meetings, interviews, formulation criteria, review of data, and statistical techniques, some targeted variables should rise to the top. And through these variables, the DMAIC process is applied.
Six Sigma refers to sources of variation as the 6Ms. Any or all sources may come to into play when targeting manufacturing goals or root cause analyses. The 6Ms are:
- Mother Nature (environment to which the product or facility is exposed)
- Man (human factors)
When authoring a problem statement, consideration should be given to each of the 6Ms. Whether all the 6Ms above are necessary to include is best determined through the collective efforts of the Six Sigma team and associate colleagues. Generally, machines, raw materials, and measurements are most common, but commonality does not invalidate other sources.
One Size Does Not Fit All
Readers of this article come from all segments of the pharmaceutical industry — oral solid dose, topicals, sterile products, biotech, aerosols, and others. Each segment has unique products, processes, equipment, analytical methods, environments, training, etc. The role of the Six Sigma team is to tailor the DMAIC approach to specific goals for each industry.
An Example of a Project Definition
Let’s revisit the first example mentioned in my previous article: A product experiences a change in one or more of its critical variables. This is a high-impact issue with the potential to affect patient safety, regulatory compliance, recalls, expenses, company reputation, and so forth.
In general terms, let’s assemble a definition:
- Project charter: Focusing only on the problem statement of the charter, it might read, “Find the root cause(s) for a downward shift in tablet weight during compression from a target of 100 mg to an average of 85 mg”. Admittedly, this is a straightforward problem statement, and its simplicity is purely intended to exemplify the Define stage. The timeline for this example would be ASAP, since field incident reports and follow-up actions are heavily time-dependent.
- List of validated customer’s needs, expectations, and requirements: In this example, the product specifications are the sole requirements.
- A prioritization of measurable, contributing variables that can reasonably be improved, and the degree to which improvement is expected, through the DMAIC process: This list is assembled through brainstorming and other techniques. Variables typically come from two sources:
- Paper-based systems:In these, all hand-written entries comprise data.For retrospective analyses, these must be converted to spreadsheets or e-data files.Note that equipment and facility maintenance files are considered data.
- Acquired e-data files from process controls and archive/history files.
- A process map highlighting the problem at hand: The SIPOC format is often used for this phase.
- A communication plan: Generally weekly, but in critical cases such as this example, daily or twice-daily communications might be needed.
- Project plans: The Six Sigma team would assemble a documented path forward. The details provided at this step are in keeping with process knowledge and investigation findings.
- Stage gate review and agreement to move to the Measurement phase (per your company’s policies and procedures)
In this article, I’ve tried to emphasize the complexity of the Define stage with a straightforward example of a critical specification failure.Project definitions are multidisciplinary, focused, inclusive, and tailored to a specific goal or set of related goals.Often, the DMAIC process is called into root-cause analyses but also for forward-looking projects, such as process optimization or technology transfer.
A properly educated, mentored Six Sigma team is invaluable to this process.If your company has such a team in place, and if the team is supported and diverse in function, then certainly continuous improvements in the development, manufacturing, and management of pharmaceutical products are already part of your culture.If not, then I hope you’ll consider the formation of such a group, training, Master Black Belt mentorship, and the ensuing career enhancements of forming your own group.
- George, M.L., et al, The Lean Six Sigma Pocket Toolbook, McGraw-Hill, Sept. 2004.
- Sudden changes in outside weather conditions may temporarily overwhelm facility HVAC systems and introduce environmental variability. I use www.wunderground.com/history/ for global, historical weather information, if pertinent.
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, process scale-up, validation (PV and CV), and optimization. He led a Six Sigma deployment that yielded 10 Black Belts and 1 Master Black Belt. His interests include process excellence, lean manufacturing, and championing teams. He may be reached firstname.lastname@example.org, www.linkedin.com/in/stevenzebovitz/, or 215-704-7629.
The author thanks his Six Sigma teacher and mentor, Joseph Ficalora (email@example.com, 973-727-3788) for his critique of this manuscript. Mr. Ficalora is a Lean Six Sigma Master Black Belt and deployment coach. The author also thanks Joseph Owens (firstname.lastname@example.org) for his editorial review of the manuscript.