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Sampling by Attributes Using the ANSI/ASQ Z1.4-2008 Standard

By Eugenie Webster (Khlebnikova) Nov 24, 2013 12:39 pm PST

Peer Reviewed: Sampling

The views and opinions expressed in this paper are those of the individual author and should not be attributed to any company
with which the author is now or has been employed or affiliated.

Abstract
This paper discusses the application of American National Standards Institute (ANSI)/American Society for Quality (ASQ) Z1.4-
2008: Sampling Procedures and Tables for Inspection by Attributes. It provides simple instructions on how to correctly select
the sampling plan based on the population size and the acceptable risk. In addition, this paper provides a general overview of
statistics behind the development of sampling plans. The intent of this paper is to present a quick refresher on sampling by
attributes using the ANSI/ASQ Z1.4 2008 standard and to educate a reader on the common mistakes users make during the
use of this standard.

Introduction
Attribute sampling plans are often used to inspect the effectiveness of the product/process and to determine the rate of
compliance with established criteria. It is a common pharmaceutical industry practice to employ American National Standards
Institute (ANSI)/American Society for Quality (ASQ) Z1.4-2008: Sampling Procedures and Tables for Inspection by Attributes
for inspection of product/process defects. ANSI/ASQ Z1.4-2008: Sampling Procedures and Tables for Inspection by Attributes
is an acceptance sampling system that provides tightened, normal, and reduced plans to be applied for attributes inspection
for percent nonconforming or nonconformities per 100 units. The use of sampling tables provides a quicker way of selecting
the sampling plan instead of developing a sampling plan using complex statistics. The standard provides instructions on how it
is supposed to be applied; however, it is often misinterpreted. The common mistakes include, but not are limited to, the
selection of incorrect sampling size, selection of incorrect acceptance criteria, or attribute plan used for variable data, etc.
Therefore, it is very important to properly interpret the standard and apply the inspection rules as they are prescribed. Incorrect
application can result in regulatory observations.

The Importance of Sampling

Sampling is a regulatory requirement in the pharmaceutical industry. The current good manufacturing practice (cGMP)
requires sampling plans to be defined as well as samples to be representative of the population and based on appropriate
statistical criteria. For instance, as per Code of Federal Regulations Title (CFR) 21 Part 211.165(d), Acceptance criteria for
the sampling and testing conducted by the quality control unit shall be adequate to assure that batches of drug products meet
each appropriate specification and appropriate statistical quality control criteria as a condition for their approval and release.
The statistical quality control criteria shall include appropriate acceptance levels and/or appropriate rejection levels.

Acceptance inspection is performed at many stages in the pharmaceutical process, from testing raw materials to the final
packaging stage. Acceptance testing is necessary since 100% inspection is not practical and would be very costly. In
acceptance testing by attributes, a sample is randomly taken and inspected against established specifications (allowable
number of defects). If the number of defects exceeds the allowable number of defects, then the entire lot is rejected.

ANSI/ASQ Z1.4-2008 Sampling For Attributes

ANSI/ASQ Z1.4-2008: Sampling Procedures and Tables for Inspection by Attributes is one of the most frequently used plans
by many pharmaceutical companies as well as other industries. It is recognized by the US Food and Drug Administration and
Health Canada. The standard provides various inspection plans without getting into complex statistics.

The standard is intended for inspection of final product, components and raw materials, materials in process, and data and
records.

Acceptance sampling procedures became popular during World War II. Sampling plans, such as MIL-STD-105, were
developed by Harold F. Dodge and others and became frequently used as standards. MIL-STD-105 was a United States
defense standard that provided procedures and tables for sampling by attributes (pass or fail characteristic). The standard was
cancelled in 1995 but the content was adopted by ANSI/ASQ Z1.4-2008: Sampling Procedures and Tables for Inspection by
Attributes.

The Z1.4 provides acceptance sampling tables based on the acceptable quality level (AQL) designation that is generally
specified in the company standard operating procedure (SOP). Different AQLs may be designated for different types of defects
(critical, major, and minor). AQL is defined as the maximum percent defective (or the maximum number of defects per
hundred units) that, for purposes of sampling inspection, can be considered satisfactory as a process average.

Inspection Level
The inspection level determines how the lot size and the sample size are related. The standard divides inspection levels into
two main categories: special inspection levels (S-1, S-2, S-3, and S-4) and general inspection levels (I, II, III). According to the
standard, inspection Level II should be used unless otherwise specified. The sampling acceptance criteria discrimination
increases from special levels to general levels with Level III having the greatest discrimination. Special levels shall be used
when relatively small sample sizes are required and large sampling risks can be tolerated.

Inspection Rules
Provisions for each sampling plan include normal, tightened, or reduced inspection. Normal inspection should always be
conducted at the start of inspection. When normal inspection is applied, tightened inspection can be implemented when two
out of five or fewer consecutive lots failed normal inspection. When tightened inspection is applied, normal inspection can be
implemented when five consecutive lots pass the tightened inspection. The reduced inspection can be used conditionally
when the normal inspection passes for more than two consecutive lots. Inspection can be discontinued when 10 consecutive
lots remain on tightened inspection. The switching rule diagram is provided below.

Figure 1: Switching Inspection Rules.

Sampling Plan Types
Three types of sampling plans are provided: single, double, or multiple. Figure 2 outlines the differences of each plan.

Figure 2: Types of Sampling Plans.

Single Sampling Plan Double Sampling Plan Multiple Sampling Plan

This plan is based on accepting or
rejecting the lot on one sample only.
These plans combine single sample
plans. With double sampling plans,
there are three different conclusions:
accept the lot, reject the lot, and
resample the lot. If the lot is
resampled, the results are combined
with the first sample. A new
Accept/Reject level number is
determined with the second sampling.
At the end of the second sample the
lot is then either accepted or rejected.
Similar to double sampling, there
be many sampling sequences to
determine whether to accept or r
the lot. Although complicated, ini
they may utilize smaller sample s
to accept the lot. However, if ther
rejects, then multiple sampling pl
become very complicated.

Inspection Procedure
The general procedure (Figure 3) in designing the sampling plan is the following.

Figure 3: Inspection Procedure.

Table I: Table I Sample Size Letter Codes

Special Inspection Levels General Inspection Levels

Lot or Batch Size S-1 S-2 S-3 S-4 I II

2 to 8 A A A A A A

9 to 15 A A A A A B

16 to 25 A A B B B C

26 to 50 A B B C C D

51 to 90 B B C C C E

91 to 150 B B C D D F

151 to 280 B C D E E G
 281 to 500

B C D E F H

501 to 1200 C C E F G J

1201 to 3200 C D E G H K

3201 to 10000 C D F G J L

10001 to 35000 C D F H K M

35001 to 150000 D E G J L N

150001 to 500000 D E G J M P

500001 to over D E H K N Q

Table II: Table II Single Sampling Plans for Tightened Inspection

Note: Use ? first sampling plan below arrow. If sample size equals or exceeds lot or batch size, do 100% inspection.

Ac = Acceptance Number

Re = Rejection Number

Caution: Note, the sampling plan consists of a sample size and acceptance criteria at particular AQL. It is common to select
one or another; however, this application of the sampling procedure is incorrect. The correct use of these tables is discussed
further.

Application of a Single Sampling Plan for Packaging Defects

An example of the application of ANSI sampling is the inspection of packaging defects. The packaging defects can be
classified into three major categories: critical, major, and minor. Defect categories are divided based on criticality to product
quality attributes. Each defect category is assigned a different AQL level. Table III provides a list of typical tablet packaging
defect classifications.

Table III: Defect Classification.

Defect Definition Description AQL

Class

Critical A defect that can compromise product Incorrect label, carton, insert, foreign 0.01 %
safety, purity, or identity that may be harmful tablet, incorrect code
to the consumer.

Major A defect that jeopardizes the integrity or Missing band, deformed/cracked closure, 0.65%
function of the package. no foil, short count/overfill, etc.

Minor A defect that does not affect product safety, Grease on the bottle, double code on the 4.0%
purity, or identity, or package integrity of label, flaps not glued on the carton.
function.

For each defect category, defects are also classified into different types. For instance, if inspecting a bottle for tablet count,
closure, seal, label and carton defects, these defects are not added together since they are results of different packaging
processes. Instead, these defects are added based on the product attribute (tablet count, closure, etc.).

The inspection procedure should include the sampling plan with inspection level, type, and accept/reject criteria. For instance,
if the expected packaging lot size is 36,000 bottles, it would be impossible to test all 36,000 bottles, so a representative
sampling size should be selected. To determine an inspection sample size, ANSI/ASQ Z1.4-2008 Sampling by Attributes Plan,
General Inspection II, Tightened Plan can be used. A lot of 36,000 bottles corresponds to letter N (General Inspection Level II)
(see Table I. A sample size from Table II (Table II-B, Single Sampling Plans for Tightened Inspection) is selected. Letter N
corresponds to sample size of 500. If AQL level desired is specified as 0.010%, it means that 2000 samples need to be
inspected and all 2000 samples should have no defects to pass a lot. For AQL 0.65%, 500 samples require inspection failing a
lot if six defects are found. For AQL 4%, only 315 samples require inspection failing a lot if 19 defects are found.

Statistics Behind Sampling Plans

Sampling by attributes is based on binomial distribution. The performance of sampling plan is given by the operating
characteristic (OC) curve. The OC curve shows the probability, Pa, that a submitted lot will be accepted for any given fraction
defective p. To construct an OC curve, one needs to know the sample size (n) and the number of defects (c) one is willing to
accept. For example, with n=100, if c=2, p would equal to 2/100=0.02. Therefore, to compute probabilities for c below and
above 2, to bracket 0.02, Pa versus p is plotted.

Since the sample with up to c defects is accepted, the cumulative binomial distribution is used to compute the probability of
acceptance, P.
The Excel function BINOMDIST(c, n, p, TRUE) can be used, where c = number of defects, n = sample size, p = probability of
defect occurring, and TRUE is for cumulative distribution. Figure 4 shows how BINOMDIST function is used.

Figure 4: Calculating Binomial Distributing Using Excel.

Figure 5 shows the OC constructed by plotting Pa vs. p.

Figure 5: OC Curve Constructed Using Excel.

As shown in Figure 5, the probability of accepting a lot containing 2% defectives is 68% (i.e., out of 100 lots, it is expected to
accept 68 and reject 32 when the sample size is 100 and the acceptance number is two).

Figure 6: OC Curve for n=100.

OC Curve for n=100

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Figure 7 demonstrates that if n is increased while c is constant, we obtain a lower acceptance level with increasing n. As n
increases, we approach 100% sampling. As shown in Figure 7, the probability of accepting a lot containing 2% defectives is
68% for n=100, 24% for n=200, 1% for n=400, and 0% for n=800 at c=2.

Figure 7: OC Curve for n=100, 200, 400, and 800 with c=2.

OC Curve for n=100, 200, 400, and 800 with c=2

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Warning
Since the regulatory requirements are very strict when it comes to defects that are related to safety, purity, etc., it is a common
misconception that the sample inspected must not contain any non-conformance units for the lot to be accepted.

For example, as shown in Figure 8, the OC curves show that lots that are 2% defective will be accepted 90% of the time
inspecting five samples, 82% of the time inspecting 10 samples, 67% of the time inspecting 20 samples, and 13% of the time
inspecting 100 sample. With more samples we test, the probability of accepting a lot with defects decreases. Thus if we claim
that we accept zero defects and test a very small sample, in this case five samples, there is a high probability that we are
accepting defects in the lot without being able to detect them.

Figure 8: Operating Characteristic Curve.

Summary
In summary, correct statistical sampling is required by the pharmaceutical industry regulations. Understanding of ANSI
sampling by attributes and correct application will help to avoid sampling mistakes and potential observations.

Acronym Listing
AQL Average Quality Limit
ANSI American National Standard Institute
ASQ American Society for Quality
FDA US Food and Drug Administration
GMP Good Manufacturing Practice

General References
ASQ, ANSI/ASQ Z1.4-2008: Sampling Procedures and Tables for Inspection by Attributes, 2008.

Code of Federal Regulations, Title 21, Food and Drugs (Government Printing Office, Washington, DC), Part 211.

K. Stephens, The Handbook of Applied Acceptance Sampling: Plans, Procedures, and Principles, ASQ Quality Press, 2001.

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