sampling and sampling plan
TRANSCRIPT
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WHO Technical Report Series, No. 929, 2005
WHO guidelines for sampling of pharmaceutical
products and related materials
SAMPLING AND SAMPLING
PLAN
SAMPLING
The process of removing an appropriate number of items from a
population in order to make inferences to the entire population.
Population is the total of all actual or conceivable
items of a certain class under consideration
A sample is a finite number of objects selected
from a population
A random sample is a sample chosen in such a
manner that one object has a good chance of
being selected as another
MATERIALS FOR SAMPLING
Representatives of materials to be sampled are:
Raw materials, Packaging and printed
materials;
Intermediate products/ Bulk products
Final products
INSPECTION
The comparison of certain attributes and
dimensions of a product against specifications
to find out if the product is within the
prescribed limits.
An inspection is, most generally, an
organized examination or formal evaluation
exercise.
INSPECTION
Objectives of an inspection process:
- to conduct physical test
- to conduct periodic examination
- to look for any defects
TYPES
100% Inspection
1. If the acceptable percentage for non-conforming is
zero; expensive
Why sampling inspection is preferred?
100% inspection is tiring and the probability that
the inspector will commit errors is high.
The inspection operation may involve destructive
testing. The cost of 100% inspection is
prohibitive.
A statistical sampling plan well applied may give
better quality assurance than 100% inspection.
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SAMPLING PLAN
A sampling plan is a definite working rule regarding size and
frequency of sample and the basis for acceptance or rejection
Sampling plans can be designed and applied in such a manner as to reduce
the risks to a minimum and over a period of time, give assurance of
quality products
SAMPLING PLAN
In sampling, one must consider the laws of
probability.
Risks of error:
Producer’s risk ( ∞ ) is the probability of
rejecting a good batch
Consumer’s risk ( β ) is the probability of
accepting a bad batch
SAMPLING PLAN
AQL – Acceptance Quality Level
maximum percent defective
- the maximum number of defects per 100
units.
- trivial defects – AQL value is high
- serious defects- AQL value is low
SAMPLING PLAN
The percentage of defects at which a
consumer(buyer) is willing to accept lots as
“good.”
If the supplier’s process average nonconforming is
below the AQL, the consumer will accept all the
shipped lots.
If the supplier’s process average nonconforming is
above the AQL, the consumer will reject all the
shipped lots.
SAMPLING PLAN
It requires that three numbers be specified:
number of items (N) in the lot or batch from which
the sample is drawn
number of items (n) in the random sample drawn
from the lot
acceptance number (c).
Example, if N = 50, n = 5, c = 0
“Take a random sample of 5 from a lot of 50. If the sample contains
more than 0 defects, reject the lot; otherwise, accept the lot
SAMPLING PLAN FOR STARTING MATERIALS
Square root system: n plan uses the formula: n = 1 + √N
1927, AOAC (Assoc of Official Agricultural
Chemists) adopted this as a convenient,
memorizable rule for sample-size determination
Use to determine the number of containers to
inspect
Number of units to inspect, where Ac=0 or for
variables, ave is within the specification
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SAMPLING PLAN FOR STARTING MATERIALS
p-plan
The “p plan” may be used when the material is
uniform;
is received from a recognized source;
and the main purpose is to test for identity.
p = 0.4√N
SAMPLING PLAN
“r plan”
used when the material is suspected to be non-
uniform
and/or is received from a source that is not
well known.
Also used for herbal medicinal products
r = 1.5√N
GOVERNMENT SAMPLING PLAN
It consists of master tables first developed in
1942 by a group of engineers from the Bell
Telephone Laboratories
These tables were further developed and
adopted by the US Department of Defense.
Thus, they are now known as the military
standards
SAMPLING PLAN
Attributes:
MIL-STD-105A - 1950
MIL-STD-105E ANSI Z1.4 – 2008 /ISO 2859/ British Standard BS 6001-1
Variables: MIL-STD-414D ANSI Z1.9 – 2008/ISO 3951/ British Standard BS 6002-1
AT THE START OF THE INSPECTION
To correctly use Z1.4, Identify 5 things:
Inspection Level – lot history
Lot Size
Sample size code letter
Single, Double, or Multiple Sampling
AQL
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Lot Size
Inspection
Level
Code
Letter
(Tbl. I)
INSPECTION LEVELS
General Inspection Levels are usually used for
non destructive inspection
I, II, III
II – for more than 90% of inspections
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Start Normal
Tightened
Reduced
Discontinue
10 of 10
Acc
1 of 1
Rej
2 of 5
Rej
5 of 5
Acc
10 of 10
Rej
Substandard or unknown
quality
Consistent good quality
TIGHTENED INSPECTION
ISO – Tightened inspection is the use of a
sampling plan with an acceptance criterion that
is tighter than that for the corresponding plan
for normal inspection
INSPECTION LEVELS
Special Levels are used where relatively small
sizes are necessary or large sample risks are
taken.
Inspection often is destructive and costly
Inspection is time consuming
;
AQL
Objective Limit
Types of defects
Critical – harm the user, cause the products to be
disapproved
Major – not acceptable my MOST of the consumers
Minor – contains non-conformities but SOME will
still buy
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SAMPLE
TYPES OF DEFECTS
Defect
Class Definition Description AQL
Critical A defect that can compromise product safety, purity, or identity that may be harmful to the consumer.
Incorrect label, carton, insert, foreign tablet, incorrect code
0.01 %
Major A defect that jeopardizes the integrity or function of the package.
Missing band, deformed/cracked closure, no foil, short count/overfill, etc.
0.65%
Minor A defect that does not affect product safety, purity, or identity, or package integrity of function.
Grease on the bottle, double code on the label, flaps not glued on the carton.
4.0%
Critical – 0, Major 2.5%, Minor – 4.0%
EXAMPLE 1: LOT SIZE OF 40,000, AQL OF 2.5, NORMAL AND SINGLE SAMPLING PLAN
200 500 800 8 13 32 80
Level I II III S-1 S-2 S-3 S-4
Sample
size
Ac
number
200 500 800 8 13 32 80
L N P D E G J
SINGLE SAMPLING PLAN
The most common and the easiest plan
Inspect a sample of n pieces
If the number of defects in the samples exceed the
standard, reject, otherwise, accept.
DOUBLE SAMPLING PLANS
1. Take small initial sample
- If # of defectives < lower limit, accept
- If # of defectives > upper limit, reject
- If # of defectives are between limits, take a second
sample
2. Accept or reject a lot based on 2 samples
3. Less inspection than in sampling plan
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MULTIPLE SAMPLING PLANS
Advantage: uses a smaller sample size
Take initial sample
- If # of defectives < lower limit, accept
- If # of defectives > upper limit, reject
- If # of defectives are between limits, re sample
Continue sampling until accept or reject lot based
on all sample data
Sample
number
Sample
size
Cumul-tive n Ac
no.
Re
no.
DOUBLE
1st 50 50 1 4
2nd 50 100 4 5 MULTIPLE
Ist 20 20 - 3
2nd 20 40 0 3
3rd 20 60 1 4
4th 20 80 2 5
5th 20 100 3 6
6th 20 120 4 6
7th 20 140 6 7
DOUBLE SAMPLING PLAN
Disintegration Test
All of the tablets have disintegrated completely
If 1 or 2 tablets fail to disintegrate completely,
repeat test on 12 additional tablets
The requirement is met if 16 of 18 tablets tested
disintegrated
DISSOLUTION TEST
Dissolution Test
S Number Tested Acceptance Criteria
S1 6 Each unit is nlt Q + 5%
S2 6 Average of 12 is equal to or greater
than Q, no unit is less than Q - 15%
S3 12 Average of 24 is equal to or greater
than Q, not more than 2 units are less
than Q-15%, no unit is less than Q -
25%
Sampling Plans:
1. Fourteen drums of muriatic acid were received in the warehouse. Each drum has a capacity of 5L
a. if the shipment has the same batch number in all drums, how many drums should be sampled using square root system and military std tables
b. if the shipment consists of 2 drums with one batch number and 12 drums with another batch number, give the sample sizes using the 2 sampling plans.
2. In acceptance sampling under the ABC standard, single sampling is to be used with inspection level II, for a batch of 10,000 pieces of labels. Give the AQL for normal sampling.
3. True or False? A sample size of 5 units with an AQL of 6.5 can have an acceptance number of 1
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4. The following materials were delivered and received in the warehouse with a status of ready for sampling. Determine the number of samples to be taken (using both sampling plan) include the acceptance and rejection number.
Labels - 3 packs of 12 bundles by 500, another batch of 1 pack of 14 bundles by 500
Bottles, 30 mL cap – 210 shippers x 144
Inserts – 55 packs by 500, 1 pack by 300
Cartons – 100 packs by 250
A batch size of 25 was inspected, 3 defectives
were found during the inspection. The
acceptance limit is 2.5% defectives. Determine
the sample size code letter, sample size,
acceptance number and disposition using the
master table. Give the N if the sample size is 5
using square root system.
Sample
number
Sample
size
Cumulative n Ac
no.
Re
no.
DOUBLE
1st 50 50 1 4
2nd 50 100 4 5 MULTIPLE
Ist 20 20 - 3
2nd 20 40 0 3
3rd 20 60 1 4
4th 20 80 2 5
5th 20 100 3 6
6th 20 120 4 6
7th 20 140 6 7
1. Using a double sampling method, 3 defectives
were found during the first sampling. Give the
disposition
2. Total number of defectives after the 4th
inspection gave 4 defects. On the fifth
sampling, three more defectives were found. Is
the lot acceptable?
PERCENTAGE ACCEPTED
Percentage of lots to be accepted
= 100 - (n) (percent non conforming)
Ex. AQL of 0.40% non conforming with sample
size code letter G
Ans = 87.2% of the lot
Percent non-conforming
= (100 - Percentage of lots to be accepted) / n
1. Batch size using square root for a sample size of 317 bottles from a trusted supplier. Using military sampling plan, what is n? what inspection level to be used?
2. Total labels delivered were 6 packs of 20 bundles by 500, what is n using square root system? With AQL of 1.0, what is the Ac and Re no?
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Amount of Samples for RM: For total weight of sample is less than 100 Kg, the sample should be at least
250 g;
for total weight of drug greater than 100Kg, the sample weigh 125 g
For total weight of drug that is less than 10Kg, sample weight should be 125 g.
2/3 for complete analysis, 1/3 as retention sample
Company X acquired his supplies from Supplier Y, a new supplier. The following were delivered:3 drums, each containing 30 Kg of Chloramphenicol and 12 packs of MCC, 25 kg each pack.