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Zero Tolerance Criteria Do Not Assure Product Quality

Zero Tolerance Criteria Do Not Assure Product Quality

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Zero Tolerance Criteria Do Not Assure Product Quality

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  1. Zero Tolerance Criteria Do Not Assure Product Quality John R. Murphy, Ph.D. Meeting of the Advisory Committee for Pharmaceutical Science 21 October 2003 ACPS 10/2003

  2. What is a Zero Tolerance criterion? • Is a Zero Tolerance necessary or required? • If not required, is ZT a good thing to have anyway? ACPS 10/2003

  3. A Zero Tolerance criterion as an element of final product testing cannot eliminate nonconforming product. • A Zero Tolerance criterionis not inherently better than any other acceptance criterion, and for DDU testing is probably a poor choice amongst many available alternatives. ACPS 10/2003

  4. What Is a “ZT Criterion”? A Zero Tolerance (ZT) criterion requires that none of the test results can be outside certain fixed limits. ACPS 10/2003

  5. Is a “ZT Criterion” Necessary or Required? • The ZT criterion appears to have been borrowed from the current USP Uniformity of Dosage Units test. • While USP methods are referee methods, batch release tests may be performed using alternate methods. ACPS 10/2003

  6. If not Required, is a ZT Criterion a Good Thing Anyway? Not Necessarily, because: • A Zero Tolerance criterion as an element of final product testing cannot eliminate nonconforming product. • A Zero Tolerance criterionis not inherently better than any other acceptance criterion, and for DDU testing is probably a poor choice amongst many available alternatives. ACPS 10/2003

  7. Zero Tolerance Criterion in the Context of Sampling and Acceptance • Perfection is not achieved even with 100% screening. (Consider Airport Security Screening) • It cannot be guaranteed that batches are free from nonconforming product. • You cannot change the laws of probability. ACPS 10/2003

  8. Example: Sampling and Acceptance Plan is to inspect a random sample of 30 units and to accept the batch if zero nonconforming units are found. About a 10% chance of passing a batch containing as high as 7.5% nonconforming units. Slightly more than a 10% chance of failing a batch containing only 0.4% nonconforming units. ACPS 10/2003

  9. ACPS 10/2003

  10. To summarize: • You cannot eliminate nonconformances, no matter how hard you try, not even with 100% screening. • When you can test only a sample (due to destructive testing), what is observed in the sample does not provide certainty regarding the untested units. • Finding zero nonconforming units in the sample tested does not mean that the batch is free from nonconforming units. Therefore: A Zero Tolerance criterion as an element of final product testing cannot eliminate nonconforming product. ACPS 10/2003

  11. Zero Tolerance Criterion in the Context of Zero Accept criteria for Sampling and Acceptance Plans • A zero accept criterion is only one of several available options – often the least desirable. • Zero accept criteria apply to sampling and acceptance for attributes. • Zero accept criteria remove flexibility and lead to minimalist strategies. ACPS 10/2003

  12. Zero Tolerance Criterion in the Context of Zero Accept criteria for Sampling and Acceptance Plans • A zero accept criterion is only one of several available options – often the least desirable. • Zero accept criteria apply to sampling and acceptance for attributes. • Zero accept criteria removes flexibility and leads to minimalist strategies. ACPS 10/2003

  13. ACPS 10/2003

  14. Zero Tolerance Criterion in the Context of Zero Accept criteria for Sampling and Acceptance Plans • A zero accept criterion is only one of several available options – often the least desirable. • Zero accept criteria apply to sampling and acceptance for attributes. • Zero accept criteria removes flexibility and leads to minimalist strategies. ACPS 10/2003

  15. Sampling and Acceptance for Attributes (yes-no, black-white) .. Attribute can be clearly counted or classified without error. • Where to draw the line. • Risks of misclassification may be high if the measurement process cannot distinguish • Disregards much, if not most, of the useful information. Example: Try to classify beads as black or white in a container where the beads range continuously from dark gray to light gray. ACPS 10/2003

  16. Zero Tolerance Criterion in the Context of Zero Accept criteria for Sampling and Acceptance Plans • A zero accept criterion is only one of several available options – often the least desirable. • Zero accept criteria apply to sampling and acceptance for attributes. • Zero accept criteria removes flexibility and leads to minimalistic strategies. ACPS 10/2003

  17. ACPS 10/2003

  18. Two Important Negative Consequences of Forcing a Minimalistic Strategy • Validation Often want more data than for routine testing. Cannot do without increasing the risk of failing the validation. Can force validation to be little more than a “roll of the dice” • Stability Testing Risk of a “stability failure” increases as the number of tests are performed (even for cases where the characteristic does not actually change over time). ACPS 10/2003

  19. To summarize; In the context of Attribute Sampling: • A Zero Tolerance (zero accept) criterion is only one of several options one might consider when designing a plan. • A yes-no criterion applied to continuous data: • Discards information, retaining only counts or classifications (much less powerful) • Causes argument and uncertainty about the boundary point • Raises the potential for significant misclassification • A Zero Tolerance criterion can force a minimalistic strategy in order to cope with an untenable situation. Therefore: Zero Tolerance for DDU testing is a very poor choice from the available options. ACPS 10/2003

  20. Is a ZT Criterion Required? If not Required, is a ZT Criterion a Good Thing to Use in DDU Testing Anyway? • No - appears to be borrowed from a USP test criterion for uniformity of Dosage Units. • Cannot eliminate nonconforming product. • Poor choice from many alternatives • Major drawbacks that render it inapplicable to DDU testing ACPS 10/2003