Quality Control and Industrial Regulation - CHMG.751 Class 5

1. Industrial Regulation and Quality CHMG 751 Manhattan College Fall 2012 Class 5

2. Agenda • Review Heparin Case Study No. 6 • Quality Control • Inspection, Test and Measurement • Review Homework • Next Week

3. Homework Assignment No. 6 Heparin Study Part II • What were the main takeaways? • Training • Documentation Systems • Change Control • Quality Audit • Quality Risk Management • Did you agree or disagree? Why? • How would you improve the author(s) points? • Are there alternative rationales? • How can you broaden or expand the case study?

4. Quality Control • What is Quality Control? • Definition of Control • Feedback Loop Model • Product versus Process specifications

5. Quality Control • What is Quality Control? • Quality Control: Measures the quality aspects of the product with in the process or by laboratory analysis As opposed to • Quality Assurance: focuses on ensuring the quality systems are in place, addresses deviations, investigations, audits, improvement plans

6. Quality Control • Definition of Control • Process to consistently meet standards. • Involves observing actual performance comparing it with some standard and then taking action if the observed performance is significantly different form the standard Similar to process control loop

7. Quality Control • Definition of Control • Choose the control subject • Establish Measurement • Establish Standards of Performance • Measure Actual Performance • Compare Actual to Standard • Take Action on the difference

8. Quality Control • Establish measurement • What gets measured in quality control? Remember the Product QFD? Specifications!!!

9. Quality Control • Establish measurement • Unit of Measure • Product Feature • Measurement Scale capability • Ratio: weight, length, (example, fill volume in a bottle, particle size distribution) • Interval: time measurement (example dissolution time of a tablet) • Ordinal: ranking order (example customer preference on soft drink taste) • Nominal (categorical) example, black vs. white • Standards exist such as USP, ANSI, ASTM • Sometime firms need to create standard • Sensor • Method or instrument that can carry out the evaluation and state the findings in terms of the unit of measure

10. Quality Control • Establish measurement • Principles of Developing Effective Measurements for Quality • Define the purpose and use of the measurement • Customer related measurements • Easy to collect • Participation in the development • Measurements as close to the activities being measured • Leading vs. lagging indicators • Define plans for data collection, storage, analytics and presentation • KISS! • Periodic evaluations • Ensure resources and training are delivered and managed

11. Quality Control • Establish standards of performance • Criteria for standards • Legitimate • Customer focused: external and internal (downstream) • Measurable • Understandable • In alignment with high goals of the organization (mission and vision of the firm, market positioning, quality management objectives and goals, regulatory based standards) • Equitable and fair to all groups/individuals

12. Quality Control • Establish standards of performance • Examples of Standards • Less than 2% defects per batch of product • Chemical assay of the active ingredient will be from 95-102%. • Expiry of the product will be a minimum of 2 years • Process yield will be from 94-100%

13. Quality Control • Measure Actual Performance • Where? • Typically laboratories are provided samples from • Plant Floor (manufacturing) • Warehouse • Market/Distribution Chain • Auto mated equipment • Evaluate samples • Chemical Composition Analysis (milligrams of active ingredient in a tablet) • Microbiological (number of microorganisms (CFU) • Physical or Dimensional (color, particle size, bottle size, etc.) • Qualitative evaluation (smell such as in fragrances, )

14. Quality Control • Compare to Standards • Direct comparison of actual measurement to some range • Product Assay is 85% compared to a range of 95-102% • Assay does not meet the standard • Statistical Significance • Variability seen in the process may provide different results but the product may still be okay • May need to take several measurements to obtain more accurate picture • Economic Significance • Does the difference impact the profitability of the operation? • Is there a regulatory standard which we cannot change?

15. Quality Control • Take Action on the Difference • Accept product: difference is within acceptable range • Reject product: difference is beyond acceptable range • In closing the feedback loop, quality improvement actions • Eliminate sporadic sources of deficiency (short term) • Example: personnel training or SOP clarification • Eliminate chronic sourced of deficiency (long term) • Example: six sigma project to eliminate variability • Continuous process regulation to minimize variation • Example: implement automated control loop on process parameters linked to the product characteristics

16. Quality Control • Product versus Process specifications • If we measure the process does it control the product? • Possibly but the real answer is found thru the QFD • Without understanding how the process affects the product specifications, it is difficult to control in manufacturing More later when we discuss Process Monitoring and Control

17. Inspection, Test and Measurement • Terminology • Inspection Planning • Classification System • Inspection accuracy • Measurement Errors: Bias, Repeatability, Reproducibility • How much Inspection is necessary? • Theory on Sampling • Statistical theory on Population distribution • Concept of Acceptance Sampling • Sampling Risk • Sampling Plan • AQL levels

18. Inspection, Test and Measurement • Terminology • Inspection • Typically static situation • Conformance to a standard • Test • Static or dynamic situations • Typically more complex items • Sample • Representation of the total population • Typically << batch size or production volume • Used to inspect or test the product

19. Inspection, Test and Measurement • Inspection Planning • Defining the inspection process • How will it be done • Sample size, number, location • Manual, automatic, instrumentation • Where: • Manufacturing location • General lab • Special requirements or equipment • When: • Timing • Frequency • Process implications (sequential steps or sample is time sensitive)

20. Inspection, Test and Measurement • Classification System • Classification Schema • Product Specifications • List of defects • Sometimes the same but sometime not • For example glass bottle surface has a specification of smooth with +/- microns but defects can be holes, hills, scratches • They not behave similarly • For example again the glass bottle has an outer diameter but • Two defects can occur, oversize and undersize • Seriousness • Critical • Major • Minor

21. Inspection, Test and Measurement • Inspection Accuracy • Depends upon • Completeness of inspection planning • Bias and precision of the instruments used • Level of human error: technique, inadvertent, conscious, communication) • Findings • Inspection accuracy decrease as defects decrease • Inspection accuracy increases with repeated inspections • Inspection accuracy decrease with increased product complexity

22. Inspection, Test and Measurement • Measurement Errors • Variation in a process have two sources • Variation of the process making the product • Variation of the measurement systems • Bias: difference between the observed average and the reference value • Repeatability: variation due to measurement gages and equipment • Reproducibility: variation due to appraisers who use the gage/equipment • Linearity: difference in the bias values through out the expected range of the gage • Stability: (drift) the total variation in the measurement obtained with the measurement systems • Reducing and controlling measurement errors • Calibration • Training • Discovery of root causes of variation and eliminate them • Multiple measurements and statistical methodology

23. Inspection, Test and Measurement • How much Inspection is necessary? • Varies from none to 100% • Decision on what to inspect • Incoming supplies • Work in progress • Finished product • Decision on how much and when to inspect • Prior knowledge available • Quality history • Process Capability • Measurement System capability • Process itself • Homogeneity of the lot/batch • Allowable degree of risk • Inspection Economics • Inspection costs money • Inline, Online or Offline • Loss of available product when destructive required (example sterile testing in pharmaceuticals)

24. Inspection, Test and Measurement • Theory on Sampling • Basic statistical theory on Population distribution • Concept of Acceptance Sampling • Sampling Risk • Sampling Plan • Attribute, Variable • Single, Double and Multiple

25. Inspection, Test and Measurement • Theory on Sampling • Concept of Acceptance Sampling • Sample = % of the total population from 0 – 100% but typically 1-20% depending on risk • Process of evaluating a portion of the product for the purpose of accepting or rejecting of the lot • Advantages • Smaller inspection staff • Less damage to the product • Lot is disposed in shorter cycle time • Focus on quality defects as the drivers for the decision • Proper design of sampling plan • When it is used • Cost of Inspection is high relative to damage cost of passing a defective product • 100% inspection is too costly or high rate of errors • Inspection is destructive • What does it do • Absolute values are replaced with a statistical approach • Specifies a accept/reject decision on each lot with specified risk

26. Inspection, Test and Measurement • Theory on Sampling • Concept of Acceptance Sampling • What does it do • Absolute values are replaced with a statistical approach • Specifies a accept/reject decision on each lot with specified risk • The decision is based upon a defined quality specification • What it does not do • Provide judgment on whether or not rejected product is fit for use

27. Inspection, Test and Measurement • Theory on Sampling • Sampling Risk • Sampling nor 100% inspection guarantees that every defective item in a lot will be found. • Sampling does involve risk that the sample will not adequately reflect conditions of the lot • Two kinds of sampling risks • Good lots can be rejected (producer’s risk) • Type I error: Alpha risk • Bad lots can be accepted (consumer’s risk) • Type II error: Beta risk • Operating Characteristic Curve • Quality Indexes • Acceptable Quality Level (AQL) • Limiting Quality Level (IQL)

28. Inspection, Test and Measurement • Theory on Sampling • Sampling Plan • Two Types of Sampling Plans • Attribute Plan: random sample is taken from the lot and is classified as acceptable or not • Variable Plan: sample is taken and measurement of a specified quality characteristic is made on each unit. These measurements are then summarized into a simple statistic (e.g. sample average). This value is compared to the allowable value defined in the plan • Another Way of looking at Sampling Plans • Single: one sample is drawn randomly. If the number of defects is <= to the acceptance number, the lot is accepted. • Double; sequential pair of samplings (if first fails, pull a second) • Multiple; sequential set of samplings of small numbers are taken, keep sampling until a decision is made to accept or reject

29. Inspection, Test and Measurement • Theory on Sampling • ANSI/ASQ Z1.4 • Attributes sampling system. • Uses the AQL quality index • Uses tables based upon batch size • Methodology • Lot Size and Type of Inspection Level • Generates Code Letter • Take the code letter and select the correct AQL • Generates a sample size and accept/reject levels

30. Next Week • Homework Assignment No. 7 • Problem 19.6 • Problem 19.8 • Problem 19.15

31. Next Week • Processing Monitoring and Control • Validation • Quality Improvement Techniques • Business Process Reengineering • Reliability Engineering • Total Quality Management • Introduction to Lean Six Sigma