Capability studies

It is recommended at this stage of the text that the reader unfamiliar with the basic concepts of variation and process capability refer to Appendix I for an introductory treatise on statistics, and Appendix II for a discussion of process capability studies. 

A capability study is a statistical tool which measures the variations within a manufacturing process. Samples of the product are taken, measured and the variation is compared with a tolerance. This comparison is used to establish how capable the process is in producing the product. Process capability is attributable to a combination of the variability in all of the inputs. Machine capability is calculated when the rest of the inputs are fixed. This means that the process capability is not the same as machine capability. A capability study can be carried out on any of the inputs by fixing all the others. All processes can be described by Figure 1, where the distribution curve for a process shows the variability due to its particular elements. 

There are five occasions when capability studies should be carried out, these are ... 

The aim is to have a process where the product variability is sulRciently small so that all the products produced are within tolerance. Since variation can never be eliminated, the control of variation is the key to product quality and capability studies give us one tool to achieve this. 

The way of measuring capability is to carry out a capability study and calculate a capability index. There are two commonly used process capability indices, Cp and Cpk. In both cases, it is assumed the data is adequately represented by the Normal distribution (see Appendix I). 

Process design results in the design output, following which the process has to be constructed or installed, personnel trained capability studies conducted, and process verification performed. It will therefore be necessary to generate several other procedures dealing with each of these topics. 

Process development trials, process capability studies, and analyses... 

Process capability study report Measurement systems analysis report... 

Depending on the nature of the work you may require space models, prototypes, process capability studies, or samples of work as evidence of their capability. You may also make a preliminary visit to each potential bidder but would not send out an evaluation team until the qualification stage. 

Process capability studies are studies conducted to obtain information about the inherent variation present in processes that are under statistical control, in order to reduce the spread of variation to less than the tolerances specified in the product specification. 

Preliminary process capability studies are those based on measurements collected from one operating run to establish that the process is in statistical control and hence no special causes are present. Studies of unpredictable processes and the determination of associated capability indices have little value. Preliminary studies should show acceptable results for special characteristics before production approval can be given. These studies and associated indices only apply to the measurement of variables and not to attributes (see below). 

Customer complaints Warranty claims Failure analysis reports Process capability studies Service reports Concessions Change requests Subcontractor assessments Performance analysis Deviations and waivers Contract change records Quality cost data External Quality Audit records... 

Perform tablet hlling machine capability study and demonstrate statistical control. 

Conclusions regarding whether the process is centered at the target and is meeting the specifications can be drawn from the process capability study. When Cp = Cpk, the process is centered. When Cp has a value of 1.0 or greater, the process is capable of producing products meeting specifications otherwise, it is not capable. 

Process demonstration or process capability studies are usually started in this important second stage of the pilot program. Such capability studies consist of process ranging, process characterization, and process optimization as a prerequisite to the more formal validation program that follows later in the piloting sequence. 

In summary, process capability studies start in the development laboratories and/or during product and process development, and continue in well-defined stages until the process is validated in the pilot plant and/or pharmaceutical production. 

Evaluation of cleaning procedures themselves—Many companies prefer to perform a prevalidation study (often referred to as a process capability study or engineering run ) to verify that the cleaning procedure is satisfactory prior to the actual validation runs. This is an excellent opportunity to determine if the cleaning procedures are adequately written. On some occasions, cleaning procedures are not detailed enough and may not provide enough information about, for example, the extent of disassembly of the equipment. If left to interpretation, there is the possibility that different operators may interpret the instructions differ-... 

In Annex 15, the scope was limited to drug products only (omitting APIs), and references to process capability studies (that had not really been given... 

In terms of validation of such a model, a measure of internal consistency is available in the form of the q1 value. However, the ultimate test of a model is its ability to predict activities for newly reported compounds. While the model can do well at predicting variation within its own dataspace, when confronted with unquantified regions not represented in the original dataset, such as those encountered with bulky 8 3-substituted analogues, the model is unreliable. In order to provide full predictive capability, studies in progress address the synthesis of additional top-face or P-oriented analogues that will be bioassayed and added to the model having the correct conformational and chirality hypotheses. 

Build a scorecard for each critical process using data from capability studies (see Process Capability, Technique 37), past experience, manufacturing data, and estimates from similar processes. You can then use this data to predict the overall performance of each of the critical processes and subprocesses. 

As mentioned earlier, as part of a process capability study, an assessment of variability is conducted. 

Process development (process qualification) or process capability studies are normally started in this important stage II of the scale-up sequence. The scope of stage-II process development consists essentially of product optimization and process characterization studies. Product Optimization ... 

However, cause-and-effect relationships in these situations are obscured by rampant variability and multiple mysterious causes. The approach is passive. Classical observational tools for industry usually include sampling plans, control charts, and process capability studies. In addition, Branning has found two of the most useful observational tools for validation and PAT are process flow charts and fishbone diagrams, which help define the process and identify the potential sources of variability. These observational tools need to be used on a routine basis to collect background data for validation and PAT. 

Designed experiments are a key tool for performing this specification translation process and helping to establish such controls. However, designed experiments are not the only tool required to accomplish this task. We will also explore other tools, such as tolerance analysis, robust design, capability studies, and Failure Modes and Effects Analysis (FMEA), to see how to combine these tools into an effective system for vahdation. 

This requires performing capability studies and life testing on the different critical inputs. For hot bar temperature, a temperature transducer was installed to continuously record the temperature. The temperature range over several extended runs varied 6°F up and down from the set point. The range of 12°F is based on continuous measurement of the temperature giving thousands of readings and should conservatively contain... 

Note that c ss does not depend on tp and mt but does depend on hb and dt- Adjusting HB and DT affects the variation. Adjusting P and MT affects the average but not the variation. The capability study in Figure 5 was performed by entering the targets and standard deviations of the input variables from Table 8 into the equation for the average from the response surface study and the previous equation for the standard deviation. 

Designed experiments play a key role in items 3 and 4. They also identify worst-case conditions for OQ testing and result in an understanding that allows more complex control plans to be established. However, designed experiments are not enough. They must be carefully coordinated with other tools like FMEA, mistake proofing, customer research tools, measurement system analysis, capability studies, acceptance... 

The membrane composition should be such that the membrane should be stable and at the same time should have reasonable solute extraction capability. Studies by a number of researchers [10, 45, 58] reveal that the initial extraction rate increases wich increase in surfactant concentration. This is due to the fact chat addition of more surfactant lowers the surface tension and results in smaller droplet size of the W/O emulsion, which gives a larger mass transfer area and thus more efficient solute extraction. With low surfactant concentration, it was observed in certain cases that after large contact times, the external phase solute concentration shghtly increases. Lee and Chan [10] observed that a large amount of surfactant increases the viscosity of the membrane phase and lowers the diffusivity of the solute through the membrane thereby decreasing solute extraction rate. Hence the surfactant concentration cannot be increased indefinitely and there exists an optimum value beyond which if it is increased, the extraction rate may be adversely affected. Chaudhuri and Pyle [58] found that for extraction of lactic acid with Span 80 as surfactant, with 1-2% ot the surfactant concentration, the external phase lactic acid concentration increased after about 3-4 min contact time. Lee and Chan [10] found this optimum value to be 6%. 

The machine must be in statistical control as per capability study. 

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