Acceptance Quality

Limits and Visual

PDA: A Global
Inspection
Association
Robert Miller, Pfizer Inc.
Pfizer Global Quality, Visual Inspection
rob.miller@pfizer.com
 Objective/Agenda

Understand the use of acceptance sampling along with

visual inspection to reduce risk

Introduction
Requirements
AQL defined, OC curves, UQL defined
Lot Size and Common mistakes
Current Topics and Usage of AQLs
Final Thoughts

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 Introduction
Acceptance Sampling uses statistical sampling to determine
whether to accept or reject a production lot of material.
Brief History
100% Inspection was (is) too costly
Became common during WWII, Mil-Std-105
Allowed buyers to make decision to accept or reject
Same principle for incoming materials for aseptic processing
100% Inspection Sampling after 100% inspection provides a final
Quality Control evaluation, tests the effectiveness of the 100%
inspection and may reveal special cause situations.

Sample Inspect Apply decision rule Accept or Reject

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 Requirements/Sources
21CFR211.22 Responsibilities of quality
control unit
approve or reject all componentsdrug products
identity, strength, quality, and purity
21CFR820.250 Statistical Techniques
(a) Where appropriate, each manufacturer shall establish and maintain
procedures for identifying valid statistical techniques required for establishing,
controlling, and verifying the acceptability of process capability and product
characteristics.
(b) Sampling plans, when used, shall be written and based on a valid statistical
rationale. Each manufacturer shall establish and maintain procedures to
ensure that sampling methods are adequate for their intended use and to
ensure that when changes occur the sampling plans are reviewed. These
activities shall be documented.

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 Uses
Sampling for incoming material release.
Tailgate sample, random sample*
*A sampling method in which all members of a group
(population or universe) have an equal and independent
chance of being selected.

Part of the 100% visual inspection process

of finished goods.

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 AQL Defined
Acceptance Quality Limit
The AQL is the quality level that is the worst tolerable
process average when a continuing series of lots is
submitted for acceptance sampling*

* ANSI/ASQ Z1.4 R2013

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 AQL Defined
0.65% AQL Quality Statement
If you sample 800 and use the acceptance criteria of
accept on 10, reject on 11, you have ~95% probability of
accepting the batch if it contains 0.65% defects or less

95%
Probability
of
Accepting

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 What determines the plan?
Specifications
Required quality level
Destructive/non-destructive testing
Customer Expectations
Regulatory/Compendial Requirements
Acceptance Sampling Plan
ANSI Plans
Binomial Distribution
Evaluation of Risk (95% probability of accepting?)

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 Acceptance Sampling Plans
The purpose of an acceptance sampling plan is to make
accept/reject or pass/fail decisions without evaluating all
units.
Reject/Fail Hold, reinspect, reprocess.
Accept/Pass Release.

Plans are defined by two parameters:

N=800 (sample size)
A=10 (accept number)
This is an ANSI/ASQ plan for a 0.65% AQL
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 What do the numbers mean?
Related to the binomial distribution.
It provides the probability of finding a number of units
(Accept Number) in a sample (N) when the population
has a percentage defects (AQL).

Single Sampling Plan n=800 A=10.

Statistically significant (95%) chance of accepting a
batch with 0.65% defects.
Routinely (95% of the time) chance of accepting a
batch with 0.65% defects.
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 Operation Characteristics Curve - OC
Curve - n=800 A=10.

This is a
probability
curve.

The probability
of accepting
goes down as
the defect rate
goes up.

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 Important Points on the Curve
n=800 A=10.
AQL Point
95% Probability

Acceptance
Quality
Limit

UQL Point
5% Probability of
Acceptance (95%
Probability of
rejection)

Unacceptance
Quality
Limit

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 AQL vs. UQL
Acceptance Quality Limit Represents the
percentage of defects routinely accepted.

Unacceptable Quality Limit Represents the

percentage of defects routinely rejected.
Also referred to as RQL, LTPD or LQ
Commonly 90% or 95% probability of rejection.

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 Protection that the plan provides
Sampling 800
and accepting
the batch with 10 95%+
units.
Routinely (95%
of the time)
accepts batches
that are <=0.77%
defective. >=2.1%
Routinely (95% <=0.77%
of the time)
rejects batches
that are >=2.1%
defective Note: AQL of 0.77% is true 95% value, if you use the ANSI/ASQ plan with a
Defect rate of 0.65% you would have a 98% probability of acceptance.
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 Selecting Plans
ANSI/ASQ Z1.4 0.65% Plans

*Wayne Taylor

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 Lot Size Influence
Lot size has very little to no influence on sampling plans.

A common
misperception
Because of standard
tables

1. Select Lot Size

2.

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 Lot Size Influence
1. Select Lot Size.

2. Sample size is
related to lot size.

3. Read Accept/Reject
Criteria.

XX WRONG XX

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 Lot Size Influence

These are
Not valid

Down Arrow Note is commonly overlooked.

Minimum sample size is necessary to achieve lower AQL
levels.
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Statistical Inference from Sampling
What can we learn from
Two samples of 800 units?

Defect Rate
1 in 800
Pass an AQL of 0.65%
Fail an AQL of 0.015%
We can infer from these samples
The same information.

Defect Rate
1 in 800
Pass an AQL of 0.65%
Fail an AQL of 0.015%
The quantity in the population
Is irrelevant to what we can infer
From the sample. 19
 Recommendations
Understand the OC curves and protection
they provide for both AQL and UQL.

Realize an AQL of 0.65% means routinely

accepting lots with 6500 ppm defect rate.

Understand the sample size is unrelated to

population size (in most situations).

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 Topics: Recommended Levels

General Industry Ranges

Critical Acceptance drives the sample size. For example
to achieve a 0.015% AQL, you must sample 800.

*Proposed USP <1790>

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 Topics: USP 790
Sampling at Batch Release (After 100% Manufacturing
Inspection)
Sample and inspect the batch using ANSI/ASQ Z1.4 (or
ISO 2859-1). General Inspection Level II, single sampling
plans for normal inspection with and AQL of 0.65%.
Alternate sampling plans with equivalent or better
protection are acceptable. NMT the specified number of
units contains visible particulates.

Note the prerequisite.

Note the minimum.

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 Thoughts
This should not be considered a target.
Comprehensive particle reduction is still regulatory
expectation.
The pre-requisite (after 100% inspection) contains a vast
amount of work.
Doesnt preclude the necessary particle
characterizations and elimination.
Opinion: Extrinsic and Atypical particles

95%
Probability of
Accepting

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 Topics: Uses of tightened AQL.

When Batches fail defect

alert limits. Accept
Reject
Indication of special
cause variation from
filling/freeze dry.
Inspection is not
necessarily deficient,
but may want a
sampling plan that
reduces risk.

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 Topics: Uses of tightened AQL.

When Initial AQL fails.

Accept
Indication that overall Reject
lot quality is not
acceptable.
Indication that
inspection was not
effective.
Re-inspect with
another tightened
AQL.

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 Review
Acceptance Sampling is a method to evaluate quality
(and measure inspection effectiveness).
If you are failing your acceptance criteria, your quality is worse
than the AQL.
Quality must be established in the overall process, not by relying
on culling defects.
Understand the % defects that are routinely accepted
and routinely rejected by your sampling plans.
Evaluate capabilities vs. AQL levels for suppliers and
finished goods.

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Questions?

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