Transcript Continuous Flow Mfg Skip-Lot Sampling
Continuous Flow Mfg Skip-Lot Sampling
Domenick Amato Frank Gomez Lynn Torbeck
21 CFR 210.3
210.3(20) “Acceptance Criteria means the product specifications and acceptance/rejection criteria, such as acceptable quality level and unacceptable quality level with an associated sampling plan …” 210.3(21) Representative samples
21 CFR 211.84
Requirements: 1. Representative samples 2. Number of containers to sample 3. Amount of material to be taken 4. Variability – Process average 5. Confidence levels 6. Past quality history
Continuous Flow Mfg
How to define a continuous process? Types of processes?
How to define a “lot” or “batch” in a continuous flow process?
Assumption of homogeneity of product?
Assumptions about defects?
Types of Sampling Plans
Variables Plans: • ANSI/ASQ Z1.9
Attribute Plans • ANSI/ASQ Z1.4
• ISO 2859
Sampling Plans Defined
Population of units, lots or batches AQL: Acceptable Quality Limit LQ: Unacceptable Quality Limit Sample size Accept number Reject number
Risk Management
“Producer’s Risk” The probability that a good lot is rejected by the customer. (Type I error or alpha) “Consumer’s Risk” The probability that a bad lot is accepted by the customer. (Type II error or beta) Levels not fixed but common values are 5% and 10%.
Assumptions for Sampling
Representative samples • Beginning, middle and end • Top, middle and bottom • Every 30 minutes or 100 units • Random Sampling – (difficult) Defects must be randomly distributed !
Sample inspection is 100%
Reduced Testing
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4.
Smaller sample size. Using General Inspection Level I in place of Level II or III in Z1.4.
Not inspecting all characteristics on the CoA or listed in the USP.
Can use reduced testing in Z1.4.
Use the switching rules in Z1.4.
Skip-Lot Sampling
Not all lots are tested.
Only a fraction of lots are inspected.
Goal is to save money or time and still achieve quality products.
Types of Skip-Lot Sampling
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Test every “n th ” lot, not random.
Test “i” lots, if all pass go to a fraction, “f”, of future lots. Select i and f in advance. Lots selected at random. ASQ S1, i and f are determined from the data collected. Lots are selected at random using dice.
Assumptions for Skip-Lot
Supplier and customer agree on a plan. Good communications.
Faith and trust in an honest supplier. Good relations.
Proven history of quality with a stable and continuous process.
Clear criteria for action plan.
Discussion Topics
Compendial requirements Regulatory expectations Current state, pro/con/concerns Desired state for excipients Fraud, counterfeiting, adulteration Processes “Out of control.” Changes without notification
References
NIST http://www.itl.nist.gov/div898/handbook/pmc/section2/pmc22.htm
http://www.itl.nist.gov/div898/handbook/pmc/section2/pmc27.htm
http://www.itl.nist.gov/div898/handbook/pmc/section2/pmc23.htm
ASQ (1996). ANSI/ASQ S1, “Attribute Skip-Lot Sampling Program.” Schilling, E. (1982). Acceptance Sampling in Quality Control, New York, NY: Marcel Dekker, pp 443-451 Juran, J. and Godfrey, A. (1999). Juran’s Quality Handbook, Fifth Edition, pp 46 31, 46-32, New York: McGraw Hill.