Continuous Flow Mfg Skip-Lot Sampling. Domenick Amato Frank Gomez Lynn Torbeck. 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 …”
Continuous Flow MfgSkip-Lot Sampling
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
Number of containers to sample
Amount of material to be taken
Variability – Process average
Past quality history
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?
Population of units, lots or batches
AQL: Acceptable Quality Limit
LQ: Unacceptable Quality Limit
“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%.
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%
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.
Not all lots are tested.
Only a fraction of lots are inspected.
Goal is to save money or time and still achieve quality products.
Test every “nth” 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.
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.
Current state, pro/con/concerns
Desired state for excipients
Fraud, counterfeiting, adulteration
Processes “Out of control.”
Changes without notification
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.