An MD&DI March 1998 Column
Manufacturers can increase the odds of beating the competition to market by developing an SPC program that allows for continual release of product.
In the medical device industry, increased competition and limits on insurance price reimbursement have forced a cost-reduction philosophy in what was once a highly profitable business. Manufacturers now need to retain or improve time to market and quality while keeping costs down. Further, FDA regulatory enforcement issues concerning items such as generic drugs, silicone breast implants, and heart valves have increased FDA scrutiny and tightened regulations.1 Such responses have slowed release to market, which in turn has reduced profits. Medical device firms are now focusing on improving their processes to shorten time to market and improve product quality.
One way to improve a process is to implement a statistical process control program. Typically used in mass production, an SPC program enables a company to continually release a product through the use of control charts rather than inspecting individual lots of a product. As long as a device company maintains meticulously reviewed and signed documentation of its process, and the process is within specification, FDA will allow product release using SPC. This will reduce time to market by eliminating interruptions in production. SPC enables a company to detect trends and defects earlier in production, thereby reducing inspection, rework, and scrap costs. SPC is usually represented by a control chart, which is a simple graph of process information.2 The use of graphs to understand processes, improve efficiencies, and reduce costs began when Walter Shewhart introduced the control chart at Bell Labs in 1924.3
Implementation of an SPC program and its corresponding control charts appears relatively simple. Utilization of control charts as a mechanism for product release, however, requires a bit more. Control charts are data collection tools that require an operator and/or a computer to tabulate the data and plot them accordingly. Strict compliance becomes necessary when manipulating and plotting these data if they are going to be used to release product. In this sense, the use of control charts is no different from the use of any other inspection operation. Regardless of what data are being collected, the chart is a graphical representation of process performance data used to control the manufacture and support the release of a medical device, and hence must be controlled to the same extent as other release documents.3
THE SPC SYSTEM
Prior to initiating an SPC program, all aspects of the process must be planned and documented in an appropriate format. An outline mechanism such as a flowchart would be useful to complete this step. This activity is usually handled by a diversified group from within the organization with knowledge of process, SPC, and good manufacturing practices (GMPs). This group should outline all aspects of the program, from selecting control chart sites to archiving the completed charts. Next, a control charting standard operating procedure (SOP) or company guideline should be developed and approved prior to initiating the program. Either method will ensure that chart development and maintenance are handled consistently.
The purpose of the flowcharting or brainstorming session is not to redevelop SPC. SPC is a commonly used technique, and its use and benefits can be reviewed in many quality assurance journals. The working group should have a basic understanding of SPC and realize that it is developing a system built on using the charts and ensuring control of the ancillary activities that support them. The specifics will vary according to each individual company, but the following are areas that may be addressed as part of maintaining an overall SPC system that can be used for product release:
- Preliminary engineering activities, including process and characteristic selection, chart selection, sampling frequency, subgroup size, and control limit calculations.
- Control chart preparation.
- Documentation of standardized chart templates/SOPs.
- Out-of-control engineering notification and investigation.
- Changing control limits.
- Review and approval process.
- Archiving of data and charts.
- Computerized control charts.
As with any system, responsibilities must be appropriately defined. In nonregulated industries, it is typical to assign sole responsibility for the charts and associated activities to one operator, but SPC use in the medical industry involves several individuals. Operators should be responsible for the charts (e.g., plotting, recognizing out-of-control points, etc.); however, the ancillary activities should be supported by a group that is responsible for process engineering. This group can document its findings and take the appropriate actions to meet GMP regulations.
Before the actual charting is assigned to line operators, the system should be fully functioning. It's a good idea for trained engineers to debug the system prior to transferring any charting activities. Operators should not be given the impression that they have sole ownership of the system. Engineers must be constantly involved to ensure that out-of-control conditions, such as process drift, are promptly and properly addressed.
PRELIMINARY ENGINEERING ACTIVITIES
Many activities need to transpire prior to the initiation of a control chart. The system should be set up to ensure that the activities detailed below are initiated and appropriately documented for each new chart. An appendix to the SOP detailing these steps is a good way to ensure that these activities take place. The appendix can serve as a checklist to guide the user through the required steps for process and characteristic selection, control chart type identification, subgroup size, and sampling frequency determinations, and control limit calculations.
Additionally, the document should provide space to record selection rationales. The completed document should be reviewed and approved by management prior to the initiation of any control chart. Once approved, the document will act as a baseline from which all future chart-specific activities are to be established, and it should be filed for future reference or presentation during an FDA audit (Figure 1). The following sections provide detail of the areas that should be included in the document.
Figure 1. A sample form to track process analysis and control limit change data.
Process and Characteristic Selection. Typically, a manufacturing process comprises several smaller steps. In most instances, it is not appropriate to monitor only the overall process on a control chart. Instead, it's better to focus on the substeps operating within the main process. The engineer responsible for the process usually decides which of these substeps must be monitored to determine control over the overall process. The association between the substeps and the end products adherence to specifications must be appropriately documented. If possible, this association may be supported by a process validation previously performed on the substeps or overall system. More than one chart may be necessary to capture the required information. Deciding which process steps to monitor can be based on several factors (e.g., revalidation, cost savings, or failure investigation), and the rationale behind the decision should be documented. Because organizational changes often occur, the original intent of the charting exercise should be recorded as well.
Chart Selection. The chart selection should be based on the data to be collected. For variables (numerical) data, X bar and R, moving range, and X bar and sigma charts would be used. For attributes (go/no-go, pass/fail) data, use np, p, u, or c charts. (Readers who are unfamiliar with these charts should review an SPC textbook to learn about their use.) The rationale for the selection of the chart should also be documented and approved prior to its implementation. Selection is eased by including a control chart decision tree within the SOP, which will enable a user to select which chart to use as well as ensuring a consistent application of the charts relative to the data being collected.
Sampling Frequency. The frequency of subgroup sampling may prompt a question from an auditing agency. Samples may be taken at different time intervals depending on the process being monitored. For example, a line producing 20 parts per hour would not be sampled as frequently as a line producing 10,000 parts per hour. The practical problem is whether to take large samples at less-frequent intervals or small samples at more-frequent intervals.4 The intervals must be frequent enough to ensure that the potential to detect defects is high. Sample frequency must ensure random sampling; sampling every fifth piece from a continuous process is not random. It is essential that the proper research into appropriate sampling methods be completed before attempting this selection process. It is especially important to ensure that the decision regarding sampling frequency is appropriately supported, documented, and approved.
Subgroup Size. Nothing is more important in terms of setting up a control chart than the careful determination of subgroups.4 Depending on the chart selected, varying subgroup sizes may be necessary. Attribute charts typically require more samples per subgroup size than do variables control charts. Trade-offs may be required when determining subgroup size. Whereas frequent sampling may use small subgroup sizes, infrequent sampling will require large sample sizes. As historical information is obtained on the process, the rationale for subgroup selection becomes less cumbersome. In the chart development stages, however, this selection should be done carefully to ensure that the process does not drift out of control.
Control Limit Calculations. Most quality practitioners have been trained in the calculation of control chart limits. This activity is one of the most fundamental aspects of control charting, yet it is often misapplied. To correctly determine control chart limits, the appropriate statistical data must be obtained from 25 to 30 subgroups. These subgroups must be plotted against the calculated control limits. If any of the plotted subgroup points fall outside the calculated control limits, those limits are artificially inflated or deflated. This condition occurs when limits are calculated using nonrandom biased data in which an assignable cause of the drift was present. The assignable cause must be found and eliminated and new limits must be calculated before another round of subgroups is obtained. The 25 to 30 subgroups must be plotted within the calculated limits before the derived control chart limits can be officially established.
CONTROL CHART PREPARATION
Although the steps mentioned above may appear to involve considerable effort, the work is really no different than that used to create a traditional chart. In the development of traditional charts, the rationales for chart selection, sample sizes, frequencies, and so forth, are required. However, the requirements for documenting and applying them in a consistent manner are not present, which is necessary if the charts are going to be used to support product release. Documenting these activities also provides a development trail for use in future engineering projects and audits.
Prior to actually using an SPC chart, it is a good idea to update the applicable work instruction to reference the actual usage of the chart to ensure that the operator completes the charting process per the requirements of the work instruction. This step should also include an update to the device master record (DMR) for the product or products represented by the chart. The charting activity may also be referenced in the device history record (DHR). Since most medical manufacturing systems are equipped to track DHR activities and work instructions, this step should not be a burden to implement.
At this point, the chart is ready to be employed. Descriptions of the techniques for plotting control charts can be found in standard statistical and quality control reference books. The SOP should provide guidance for handling operator requirements (such as calculating and plotting of points) and contingency activities (such as when samples are not obtained from the process at the required frequencies).
DOCUMENTATION OF STANDARDIZED CHART TEMPLATES/SOPs
A control chart template for all SPC charts should be developed. A basic grid should include required information blocks to ensure consistency among charts. Consistently formatted charts will help workers read the charts from process to process and reduce plotting errors. Consistent chart templates can also serve as official records to lessen the risk of outside agencies questioning compliance. When different charts are used for each process, they are usually applied inconsistently, filled out differently, and stored wherever it may be convenient. The probability that each chart will be completed correctly and in compliance with GMPs is low.
The standard chart template should be referenced in the SOP so it will be recognized as an official document. Large master chart templates can be created that are visible from the manufacturing floor. One company created large charts with dimensions that could be reduced on a photocopying machine to a standard, easy-to-file, 81/2 x 11 document. The SOP should also describe the processes for removing old charts and filing new ones.
OUT-OF-CONTROL ENGINEERING NOTIFICATION AND INVESTIGATION
Out-of-control conditions cause the most consternation among SPC users. Even the most tightly controlled processes exhibit occasional out-of-control conditions.2 These conditions are not all bad, and even processes that are improving will eventually show an out-of-control state, most likely in the form of excessive consecutive points above or below an average. However, these conditions must be addressed in an expeditious and consistent manner, particularly if the chart is being used to make product release decisions.
An out-of-control condition should be handled in a manner similar to that of a noted discrepancy or deviation during routine quality control inspections. Most medical device companies have documented systems in place to handle such discrepancies when they occur. The control charts can use a similar system. The control charting SOP should describe methods for handling out-of-control conditions and include an investigation report template, similar to the discrepancy report noted above, to ensure consistent investigations. The engineer can use the template to document the process investigation and corrective action (Figure 2).
Figure 2. Sample investigational report for an out-of-control condition.
CHANGING CONTROL LIMITS
Occasionally, the calculated control chart limits need to be changedsometimes because of a process improvement. Nonetheless, changing a control chart limit is analogous to changing a specification. Although the control limits are not necessarily represented by the actual release specification limits, they should not be changed without authorization based on the steps outlined in the control document. Again, an attachment to the SOP would serve this purpose. A control limit revision form should be used for every change to a control limit. The form should document the new control chart limits, note the rationale and support for the change, and provide for the proper approval signatures. The completed form should also be filed.
REVIEW AND APPROVAL PROCESS
A completed control chart should be reviewed and signed by the QA engineer, the process engineer, or the area supervisor before filing. It is usually not a good idea to require an operator's signature on the completed chart since more than one operator may be involved and each person's initials are usually signed next to every data entry point they plot. Nonetheless, the SOP should detail whose responsibility it is to review the completed chart, whose signatures are required for product release, and where the chart is to be filed.
ARCHIVING DATA AND CHARTS
&An SPC program requires that many documents be filed and maintained. In addition, the control charts themselves eventually are completed and filed. Since the data captured on the charts are used to release product, it is important to maintain a consistent archiving system. It is best to retain all documents in specific SPC files. These files can be listed numerically or by process description and should contain all information related to the development and maintenance of the chart (or charts) for a specific process. Thus, the information is readily available if any question arises related to the process history. These files should be retained within document control to ensure safekeeping and ease of retrieval.
COMPUTERIZED CONTROL CHARTS
Computers play a big part in modern SPC systems, but users must realize that a computer will not make a system perform well if inaccurate and inconsistent information is input. The old adage "garbage in, garbage out" still applies. It may be best to begin with a manual system of three or four charts. Starting manually will allow time for the system to be debugged and the organization to determine if the merits of the system justify a long-term commitment of computers and software.
The differences between a manual and computerized system will be in the data entry method and the control chart. In most computerized systems, the process information is entered directly into the computer and the chart is automatically created. However, the frequency of sampling, calculation of control limits, determination of subgroup sizes, and many other factors must still be selected manually for the computer program to perform correctly, and these activities still need to be documented. The charts should be printed periodically, formally approved, and properly archived.
For an SPC program to be effective, a thorough training program for both the operators and the process engineers must be initiated and maintained. The operators must understand their involvement in the process and the importance of proper calculations and plotting. The process will flow much more smoothly if the operators are comfortable with what they are doing. The process engineers must be aware of the basic statistical concepts of SPC as well as of the SOP requirements.
SPC training may be conducted inhouse; however, professional societies, consulting companies, and industrial associations also sponsor courses. It is a good idea to break the program into one-hour sessions and to limit groups to fewer than seven people for easier and open discussion. The course instructor must understand the limitations of the group being trained. Some individuals may not have experience in using calculators and plotting graphs. It may be beneficial to begin the operator training with a brushup session in basic mathematics and the use of calculators. To ensure even better results, the type of calculators used should be standardized.
In today's environment of ever-increasing regulation and litigation, proper documentation of product release data is essential. Following the steps outlined in this article will ensure that any organization that maintains an SPC product release system will meet the challenges of this environment. A comprehensive SPC system will benefit the organization by providing historical information related to existing process performance and assisting in the decision-making process involved in bringing current and future product releases to the marketplace.
1. Code of Federal Regulations, 21 CFR 808, 812, 820.
2. Braverman JD, Fundamentals of Statistical Quality Control, Reston, VA, Reston Publishing, 1981.
3. Juran JM, Quality Control Handbook, New York, McGraw-Hill, 1974.
4. Duncan AJ, Quality Control and Industrial Statistics, Homewood, IL, Richard D. Irwin, 1974.
Dan Bracco is director of quality assurance at Cytyc Corp. (Boxborough, MA).
Illustration by Kirk Botero