Article 0508

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INTRODUCTIONOne of the widely recognized references on processvalidation with regard to sampling and testing plansis the US Food and Drug Administration’s Draft Guid-ance for Industry: Powder Blends and Finished DosageUnits—Stratified In-Process Dosage Unit Sampling andAssessment (1) that is based on the Product Quality Re-search Institute (PQRI)’s Recommendation Report (2).However, it is a non-binding document (i.e., the in-dustry may use any alternative approaches even afterit becomes the official guidance). Another well-knownrelevant reference is the PDA Technical Report No. 25:Blend Uniformity Analysis: Validation and In-Process Test-ing (3). The sampling, testing, and corresponding ac-ceptance criteria limits in validation study will followthese two statistics-based documents. The validationtest results with respect to critical quality attributes(CQAs) require to be statistically evaluated (e.g., esti-mating confidence limits as appropriate, demonstrat-ing the high probability of passing the tests, etc.).

According to Torbeck (4), “… If statistical proce-dures were given in the USP, companies would havelittle incentive to develop better procedures.” His com-ment is now reconfirmed. The industry may not have

a good approach like J.S. Bergum’s method if theUnited States Pharmacopeia (USP) provided somekind of statistical procedures. Bergum is one of theleading professionals who suggested the use of the newstatistical procedures. His methods (5, 6) introducedboth how to establish the validation acceptance crite-ria and how to evaluate the validation test results. Inprotocol development, all the validation practitionersmay follow some recognized documents includingBergum’s in establishing the acceptance criteria lim-its. However some of them may not be confident inusing statistical tools for evaluation of the test results,especially for the multiple stage tests (e.g., content uni-formity and dissolution).

To provide an alternative to such a statistical evalu-ation, this article introduces an approach to using lowerprobability bound distribution charts, constructed ac-cording to Bergum’s methods, for evaluation of con-tent uniformity test results.

USP TEST ACCEPTANCE CRITERIAThe two USP content uniformity tests may be summa-rized in Tables I and II.

Evaluation of ValidationContent Uniformity TestResults Using LowerProbability BoundDistribution ChartsPramote Cholayudth

ABOUT THE AUTHORPramote Cholayudth is a validation consultant to Biolab in Thailand and executive director of Valitech, a well-established GMP and validation service firm to the pharmaceutical industry. He is a guest speaker on process validationto the industry organized by local FDA. He can be contacted by e-mail at [email protected].

For more Author

information,

go to

ivthome.com/bios[

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Table I: Current USP uniformity of dosage units: Test acceptance criteria.

USP Criteria Stage 1: Assay 10 units. Pass if the following criteria are met.

USP Criteria Stage 2: Assay 20 additional units. Pass if, for all 30 units, the following criteria are met.

1) Relative standard deviation (RSD) is not more than 6.0% (n = 10)

2) Not more than c unit(s) is outside 85 – 115% labelclaim (LC) and no unit is outside 75 – 125% LCwhere c = 0 for tablet and 1 for capsule

1) Relative standard deviation (RSD) is not more than 7.8% (n = 30)

2) Not more than c unit(s) is outside 85 – 115% label claim (LC) and no unit is outside 75 – 125% LC where c = 1 fortablet and 3 for capsule

Table II: New USP uniformity of dosageunits: Test acceptance criteria.

USP Criteria Stage 1: Assay 10 units. Pass if the following criteria are met.

USP Criteria Stage 2: Assay 20 additional units. Pass if, for all 30 units, thefollowing criteria are met.

1. 1. 2. Xmin > 0.75M and

Xmax < 1.25M

Where M = reference value, s = standard deviation, 5 content uniformity data mean, Xmin 5 minimum and

Xmax 5 maximum (individual values)

Acceptance Value (AV) = 1 ks < L1, k = 2.4 (n 5 10) and 2.0 (n = 30), Xmin > (1 2 L2* 0.01)M, Xmax < (1 1 L2*0.01)MIf not specified in individual monographs, L1 5 15 and L2 5 25

Table III: New USP uniformity of dosage units: Reference value criteria.

Case Subcase M AV

Target (T) < 101.5 % of label claim (% LC)

98.5 < < 101.5 ks

< 98.5 98.5 98.5 2 1 ks

> 101.5 101.5 2 101.5 1 ks

Target (T) > 101.5 % LC

98.5 < < T ks

< 98.5 98.5 98.5 2 1 ks

> T T 2 T 1 ks

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To help understand the new USP test acceptance cri-teria, a scenario for calculation of acceptance value(AV) is introduced: In a new USP content uniformitytesting, the stage 1 test results (n = 10) are mean = 101.2% of label claim (LC) and standard deviation (SD) =4.15 % LC. The manufacturing target is 102.5 % LC.The acceptance value is (101.2-101.2) + 2.4x4.15 = 9.96(< 15), so the AV limit is met.

PROBABILITY OF PASSING THE CURRENTCONTENT UNIFORMITY TESTAccording to Bergum’s method described in “Use ofthe Bergum Method and MS Excel to Determine theProbability of Passing the USP Content UniformityTest” (7), the probability formulae are illustrated in

Table IV. The formulae in Tables IV, XIV, and XV maybe copied to construct the Microsoft Excel file for com-puting the probability. However, note that the sampleis taken in accordance with sampling plan 1 (one unitfrom each of 30 locations).

PROBABILITY OF PASSING THE NEW CONTENT UNIFORMITY TESTThe article “Using Bergum’s New Method and MS Excelto Determine the Probability of Passing the New ICHUSP 29 Content Uniformity Test” (8), has the formu-lae as illustrated in Table V. The readers may copy theformulae in Tables V, VI, and VII to construct the Mi-crosoft Excel file. Also note that the sample is taken inaccordance with sampling plan 1.

Table IV: MS Excel formula sheet1: Current USP test.

Excel Formula Sheet1

A B C D E F

1 Confidence Level (%) 95 Overall Bound Results

2 Sample Size (n) 30 Tablet Capsule

3 Sample Mean (% LC) 98.00 LB Prob 96.50% LB Prob 99.96%

4 Sample RSD (%) 3.50 Prob1 99.90% Prob1 100.00%

5 UB: Mean (% LC) 99.93 Prob2 96.50% Prob2 99.96%

6 LB: Mean (% LC) 96.07 Prob at UB: Mean

7 UB: SD (% LC) 4.74 Part 1/1 89.08%

8 Part 2/1 100.00%

9 Prob at LB: Mean

10 Part 1/2 84.63%

11 Part 2/2 99.96%

UB: Upper Bound, LB: Lower Bound, UB & LB formulae are as below:B5 =B3+B7*NORMSINV(1-(1-(B1/100)^0.5)/2)/B2^0.5B6 =B3-B7*NORMSINV(1-(1-(B1/100)^0.5)/2)/B2^0.5B7 =B4*(B3/100)*((B2-1)/(CHIINV((B1/100)^0.5,B2-1)))^0.5The cells B1 – B4 are entered with sample data. The numerical results in the other cells, including those in D3 and F3, are generated using the formulae in TablesXIV and XV. The Excel file (as a combination of tables IV, XIV, and XV) can be downloaded from www.pharmtech.com – search “Pramote”.

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Table V: Microsoft Excel formula sheet1: New USP test.

Excel Formula Sheet1Formula Examples

A B C D

1 UB: Mean 99.93 UB: SD 4.74 B1 =C22, D1 =C24

2 Stage 1 (n = 10) Stage 2 (n = 30) —

3 I1 63.19% I1 91.62% See formulae below (B3 & D3)

4 I2 12.93% I2 3.52% B4 =Sheet2!B36, D4 =Sheet2!D36

5 I3 14.73% I3 4.86% B5 =Sheet2!C36, D5 =Sheet2!E36

6 P(S1) 90.85% P(S2) 99.99% B6 =SUM(B3:B5), D6 (See below)

7 Probability 99.99% C7 =MAX(B6,D6)

8 LB: Mean 96.07 UB: SD 4.74 B8 =C23, D8 =C24

9 Stage 1 (n = 10) Stage 2 (n = 30) —

10 I1 4.81% I1 0.24% B10, D10: Follow formulae for B3 & D3

11 I2 0.01% I2 0.00% B11 =Sheet3!B36, D11 =Sheet3!D36

12 I3 64.67% I3 97.74% B12 =Sheet3!C36, D12 =Sheet3!E36

13 P(S1) 69.50% P(S2) 97.90% B13 =SUM(B10:B12), D13 (See below)

14 Probability 97.90% C14 =MAX(B13,D13)

15 Lbound Probability 97.90% C15 =MIN(C7,C14)

16 Sample Data C22 =C20+C24*NORMSINV(1-(1-0.95^0.5)/2)/C19^0.517 Target 100

18 Confidence Level (%) 95 C23 =C20-C24*NORMSINV(1-(1-0.95^0.5)/2)/C19^0.519 Sample Size (n) 30

20 Sample Mean (% LC) 98.00 C24 =(C20*C21/100)*((C19-1)/(CHI-INV(0.95^0.5,C19-1)))^0.521 Sample RSD (%) 3.60

22 Upper Bound: Mean 99.93 Linked to B1 & Sheet2!B2

23 Lower Bound: Mean 96.07 Linked to B8 & Sheet3!B2

24 Upper Bound: SD 4.74 Linked to D1,D8,Sheet2!C2,&Sheet3!C2

B3 =(NORMSDIST((10^0.5)*(100-B1)/D1)-NORMSDIST((10^0.5)*(98.5-B1)/D1))*(1-CHIDIST((10-1)*(15/(2.4*D1))^2,10-1)) = 63.19%(For B10, replace B1 with B8 and D1 with D8)

D3 =(NORMSDIST((30^0.5)*(100-B1)/D1)-NORMSDIST((30^0.5)*(98.5-B1)/D1))*(1-CHIDIST((30-1)*(15/(2*D1))^2,30-1)) = 91.62% (For D10, replace B1 with B8 and D1 with D8)

D6 =MAX(SUM(D3:D5)+((NORMSDIST((123.125-B1)/D1)-NORMSDIST((IF(C17<=101.5,101.5,C17)-24.625-B1)/D1))^30)-1,0) D13 =MAX(SUM(D10:D12)+((NORMSDIST((123.125-B8)/D8)-NORMSDIST((IF(C17<=101.5,101.5,C17)-24.625-B8)/D8))^30)-1,0)

The cells C17 – C21 are entered with sample data information. The numerical results in the other cells, including the probability andLB results in C7, C14, and C15, are generated by the program.

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When sample data (n = 30) associated with samplemean: 98% LC and sample RSD: 3.6% are plotted, thelower probability bound distributions can be con-structed and illustrated in Figures 1 and 2. In these fig-ures, one can imagine how a sample data comprisinga mean and relative standard deviation (RSD) valueswill influence the probability of passing a content uni-formity test. Furthermore, the way in which a largersample size influences the distribution patterns isdemonstrated in Figure 3.

JUSTIFICATION OF USING THE PROBABILITY CHARTSValidation content uniformity test results must be eval-uated for probability of passing the test. The evalua-tion employs Bergum’s methods by using statisticalprograms like SAS or Microsoft Excel. To provide apractical tool as an alternative to such complicatedmethods, the distribution curves for lower probabilitybounds constructed in a high precision scale are intro-duced so that validation practitioners can use them todetermine the probability instead of using the pro-grams. However one must realize that the use of Excelfor validation work requires validation of the spread-sheet itself (e.g., Tables IV, V, VI, and VII).

Table VI: MS Excel formula sheet2: New USP test.

Excel Formula Sheet2Formula Examples

A B C D E

1 Target UB: Mean UB: SD h i

B6 =(NORMSDIST((B4^0.5)*((101.5+A6*D2)-B2)/C2)-NORMSDIST((B4^0.5)*((101.5+(A6-1)*D2)-B2)/C2))*(1-CHIDIST((B4-1)*(15-(A6-0.5)*D2)^2/(2.4*C2)^2,B4-1)) = 5.85%

B35=(NORMSDIST((B4^0.5)*((101.5+A35*D2)-B2)/C2)-NORMSDIST((B4^0.5)*((101.5+(A35-1)*D2)-B2)/C2))*(1-CHIDIST((B4-1)*(15-(A35-0.5)*D2)^2/(2.4*C2)^2,B4-1)) = 0.00%

B36 =SUM(B6:B35) = 12.93%

2 100 99.93 4.74 0.5 1 ➔ 30

3 — Stage 1 Stage 2

4 — 10 30

5 i I2 I3 I2 I36 1 5.85% 0.00% 2.67% 0.00%

7 2 3.58% 0.00% 0.70% 0.00%

8 3 1.95% 0.00% 0.13% 0.00%

9 4 0.94% 0.00% 0.02% 0.00%

10 5 0.40% 0.00% 0.00% 0.00%

11 ➔ 30 6 ➔ 25 ... ➔ ...% ... ➔ ...% ... ➔ ...% ... ➔ ...%

31 26 0.00% 0.49% 0.00% 0.00%

32 27 0.00% 1.13% 0.00% 0.03%

33 28 0.00% 2.28% 0.00% 0.21%

34 29 0.00% 4.08% 0.00% 1.02%

35 30 0.00% 6.47% 0.00% 3.59%

36 Sum 12.93% 14.73% 3.52% 4.86%

The number of intervals (i) 30 with interval width (h) 0.5 is selected to ensure that the integration result,especially when using the higher sigma values, is valid. The stage 2 formula is similar except for n = 30 (B4 ➔ D4) and k = 2.0 (2.4 ➔ 2). The Target (also Mean and Sigma) value is linked from Sheet1 e.g. A2 =Sheet1!B2. And I2 (B36 & D36) and I3 (C36 & E36) are linked to Sheet1 e.g., B4 (of Sheet1) =Sheet2!B36

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Table VII: MS Excel Formula Sheet3: New USP Test.

Excel Formula Sheet3Formula Examples

A B C D E

1 Target LB: Mean UB: SD h i

B6 =(NORMSDIST((B4^0.5)*((101.5+A6*D2)-B2)/C2)-NORMSDIST((B4^0.5)*((101.5+(A6-1)*D2)-B2)/C2))*(1-CHIDIST((B4-1)*(15-(A6-0.5)*D2)^2/(2.4*C2)^2,B4-1)) = 0.01%

B35=(NORMSDIST((B4^0.5)*((101.5+A35*D2)-B2)/C2)-NORMSDIST((B4^0.5)*((101.5+(A35-1)*D2)-B2)/C2))*(1-CHIDIST((B4-1)*(15-(A35-0.5)*D2)^2/(2.4*C2)^2,B4-1)) = 0.00%

B36 =SUM(B6:B35) = 0.01%

2 100 96.07 4.74 0.5 1 ➔ 30

3 — Stage 1 Stage 2

4 — 10 30

5 i I2 I3 I2 I36 1 0.01% 0.00% 0.00% 0.00%

7 2 0.00% 0.00% 0.00% 0.00%

8 3 0.00% 0.00% 0.00% 0.00%

9 4 0.00% 0.00% 0.00% 0.00%

10 5 0.00% 0.00% 0.00% 0.00%

11 ➔ 30 6 ➔ 25 ... ➔ ...% ... ➔ ...% ... ➔ ...% ... ➔ ...%

31 26 0.00% 9.80% 0.00% 22.13%

32 27 0.00% 9.54% 0.00% 16.74%

33 28 0.00% 8.21% 0.00% 9.13%

34 29 0.00% 6.25% 0.00% 3.59%

35 30 0.00% 4.22% 0.00% 1.02%

36 Sum 0.01% 64.67% 0.00% 97.74%

The Target value (also Mean and Sigma) is linked from Sheet1 e.g., A2 =Sheet1!B2. And I2 (B36 & D36) and I3 (C36 & E36) are linked to Sheet1e.g., B11 (of Sheet1) =Sheet3!B36

Figure 1: Operating Characteristic (OC) Curves for USP Content.

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Figure 2: Distribution Curves for Probability of Passing USP Content Uniformity Test (n=30).

Figure 3: Distribution Curves for Probability of Passing USP Content Uniformity Test (n = 70).

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tablet product tested using the current USP contentuniformity test with sample mean = 100.15% LC andRSD = 3.9%, is performed by determining on Figure4 the intersection of the curves for mean = 100.2(rounded up) and RSD = 3.9. The point will indicatethe lower probability bound of approximately 97%.The probability generated using the Excel program is97.46%. The determined value deviates slightly fromthe computed one.

To justify the use of probability charts is to justifysuch deviations, so analysis of the deviation data inTables VIII, IX, and X is carried out. Each numericalvalue of mean and RSD is intended to provide the sec-ond decimal digits with 4, 5, or 6 (e.g., 97.04, 4.25,97.06) so that when the numbers are rounded up, themaximized deviation in the probability determinationresult is challenged. The results are satisfactory sincemost of the deviations are close to or equal to the cal-culated results except for those data sets with meansgreater than the target (> 100% LC) and RSDs with thesecond decimals with 4, 5, or 6 where the maximumbiases (deviation) will occur. In the worst case, themaximum deviation is 5.3% (Table IX) or 4.6% (TableX). Therefore, the use of these types of probability chartsshould be justified.

Figure 4: Determining Probability Using the Probability Charts (n = 30).

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Mean (% LC)

RSD (%)Tablet Capsule

Prob Excel (%) Prob Deter. (%) Deviation (%) Prob Excel (%) Prob Deter. (%) Deviation (%)

97.00 4.20 68.57 69 0.00 96.70 97 0.00

97.04 4.24 67.08 69 1.49 96.26 97 0.44

97.05 4.25 66.70 65 1.92 96.14 95 0.66

97.06 4.26 66.32 65 1.54 96.01 95 0.53

97.10 4.30 64.78 65 0.00 95.48 95 0.00

102.90 4.20 58.04 58 0.00 93.95 94 0.00

102.94 4.24 55.09 58 2.95 92.84 94 1.11

102.95 4.25 54.35 51 3.70 92.54 91 1.62

102.96 4.26 53.61 51 2.96 92.24 91 1.32

103.00 4.30 50.65 51 0.00 90.92 91 0.00

Mean (% LC)

RSD (%)

ProbExcel (%)

ProbDeter. (%)

Deviation(%)

Mean (% LC)

RSD (%)

Prob Excel(%)

Prob Deter.(%)

Deviation(%)

97.00 3.90 79.19 79 0.00 102.90 3.90 65.12 65 0.00

97.04 3.94 77.32 79 1.87 102.94 3.94 60.98 65 4.14

97.05 3.95 76.85 74 2.45 102.95 3.95 59.94 55 5.31

97.06 3.96 76.36 74 1.96 102.96 3.96 58.88 55 4.25

97.10 4.00 74.40 74 0.00 103.00 4.00 54.63 55 0.00

Mean (% LC)

RSD (%)

ProbExcel (%)

ProbDeter. (%)

Deviation(%)

Mean (% LC)

RSD (%)

Prob Excel(%)

Prob Deter.(%)

Deviation(%)

97.00 4.60 73.71 74 0.00 102.90 4.60 59.04 59 0.00

97.04 4.64 72.10 74 1.61 102.94 4.64 55.38 59 3.66

97.05 4.65 71.70 70 2.06 102.95 4.65 54.46 50 4.63

97.06 4.66 71.29 70 1.65 102.96 4.66 53.53 50 3.70

97.10 4.70 69.64 70 0.00 103.00 4.70 49.83 50 0.00

Table VIII: Comparison of Excel and Determination Results, Current CU Test (n=30).

Table IX: Comparison of Excel and Determination Results, New CU Test (n = 30).

Table X: Comparison of Excel and Determination Results, New CU Test (n = 60).

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SAMPLING PLAN 1 AND 2To take a validation sample of the dosage units (e.g.,tablets or capsules) for content uniformity testing, strat-ified sampling plan 1 or 2 is followed. Sampling plan1 will involve taking one unit from each of L locations(e.g., 30 locations). Sampling plan 2 involves takingtwo or more units from each of L locations through-out the tablet compression or encapsulation cycle. Inmultiple stage tests (including content uniformity), itis unavoidable to employ sampling plan 2 since theoverall (stages 1 and 2) test number of dosage unitsper location is more than 1 unit. Examples for sam-pling plan 2, during compression or encapsulationcycle, are illustrated in Table XI.

RECOMMENDATION FOR USE OF PROBABILITY CHARTSFor sampling plan 1 (one unit from each of L loca-tions), the validation practitioners can simply use theprobability charts by using the sample mean and RSD.For sampling plan 2 (two or more units from each ofL locations), a number of different charts are provided.The data are required to be computed for within-loca-tion standard deviation (SE) and between-locationstandard deviation (SM) prior to determination of theprobability on the charts. Examples for computingthese statistics (SE and SM) and determining the prob-ability using sampling plan 2 data are demonstratedin Table XII and Figure 5, respectively. Table XII is pro-vided with content uniformity data in cells B3:K5 andrelated calculation formulae (10).

Table XI: Sampling Plans 1 and 2 with Examples for Plan 2.

Sampling/Testing PlansLocation # (of 20 Locations, L = 20)

1 2 3 4 5 6 ➔ 19 20

Sampling Plan 1 (One Unit from Each Location)

Sampling plan: 1x20 1 1 1 1 1 1 ➔ 1 1

Test plan: 1x20 1 1 1 1 1 1 ➔ 1 1

Take 1 unit from each of 20 locations. Test each unit in order.

Sampling Plan 2 (More than One Unit, e.g., 7 Units, from Each Location)

Sampling plan: 7x20 7 7 7 7 7 7 ➔ 7 7

Take 7 units from each of 20 locations throughout the operation cycle and keep each location sample in separatecontainer.

Stage 1 test plan: 3x20 3 3 3 3 3 3 ➔ 3 3

Test 3 units of each location in order, the test results for 3x20 units require to meet stage 1’s acceptance criteria. Iffailed, proceed to stage 2.

Stage 2 test plan: 4x20 4 4 4 4 4 4 ➔ 4 4

Test 4 remaining units of each location in order, the overall test results for 7x20 units should meet stage 2’s acceptance criteria.

Examples for Stratified Sampling Plan 2: Compression/Encapsulation Cycle *

Tests Sampling Plans (nxL) Testing Plans (nxL)

Content Uniformity 7 units x 20 locationsStage1: 3 units x 20 locations

Stage2: 4 units x 20 locations

Dissolution 5 units x 20 locationsStage1: 2 units x 20 locations

Stage2: 3 units x 20 locations

Degradents 3 units x 20 locationsStage1: 1 unit x 20 locations

Stage2: 2 units x 20 locations

* Modified from Reference (9), n: sample size at each location, L: number of locations

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Upon completing a trial using an Excel formula sheet(using worst cases of numerical values), the deviationwas found to be about 6% at maximum because ofpoor processes, i.e., the mean deviated from the targetvalue with high variability (within-location and be-tween-location), resulting in low probability results.Table XIII provides an example of the worst cases andprobability results data.

CONCLUSIONThe concept of probability charts will help validationpractitioners visualize the integrated views of the lowerprobability bound distributions and understand theeffect of sample mean location and variability (e.g.,RSD, SE, and SM) on the probability of passing theUSP content uniformity test. Acceptability of the prob-ability charts is subject to the chart accuracy. The chartswith accuracy better than those provided in Appendix2 of this article can be developed, but the consequence

Table XII: Evaluation of Data from Sampling Plan 2 (N = nxL = 3x10).

Excel Formula Sheet

A B C D E F G H I J K

1Unit #

Stratified Sampling Location # (Sampling Plan 2: 3 Units x 10 Locations)

2 1 2 3 4 5 6 7 8 9 10

3 1 95.01 93.91 99.37 97.97 94.93 93.83 101.31 98.74 97.87 106.44

4 2 100.93 99.11 103.93 105.8 98.52 105.85 96.48 97.53 103.71 99.18

5 3 102.27 98.96 99.83 97.64 100.27 98.68 97.46 95.83 98.23 96.14

6 SQD 29.85 17.52 12.61 42.67 14.82 73.14 13.04 4.27 21.42 56.01

7 Average (% LC) 99.19* RSD (%) 3.43 N (nxL) 30

8 Degree of freedom (between-location) (L-1) 9

C7 =AVERAGE(B3:K5)G7 =STDEV(B3:K5)/C7, K7 =3*10B6 = DEVSQ(B3:B5)C6,…,K6 – same as B6F8 =10-1, F9 =(3-1)*10F10 =DEVSQ(B3:K5), F11 =SUM(B6:K6)F12 =F10-F11, F13 =(F11/F9)^0.5F14 =(F12/F8)^0.5

9 Degree of freedom (within-location) {(n-1)L} 20

10 Total square deviation 335.56

11 Square deviation (within-location) 285.35

12 Square deviation (between-location) 50.21

13 Standard deviation (within-location) (SE) 3.78*

14 Standard deviation (between-location) (SM) 2.36*

15 Note: SQD: Square Deviation -

16 Probability of Passing the USP CU Test Calculated** Determined

17 Probability (Current Tablet CU Test) 91.17% 90%

18 Probability (Current Capsule CU Test) 99.25% 99%

19 Probability (New CU Test) 91.31% 90%

20 *These data are used for determination of the probability in Figure 5 where rounded numbers are used i.e., 99.19 ➔ 99.2 (C7), 3.78 ➔ 3.8 (F13) & 2.36 ➔ 2.4 (F14). 21

22 **Calculated (in Tables IV & V ) from the upper & lower bounds estimated using ANOVA (11)

23 SE = Square Root of Mean Square Error, SM = Standard Deviation of Location Means

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Table XIII: Comparison of Excel and Determination Results (n = 30).

Comparison of Excel and Determination Results

Mean(% LC)

SE SMCurrent CU Test: Tablets New CU Test

Prob Exc(%)

Prob Det (%) Dev (%) Prob Exc (%) Prob Det (%) Dev (%)

96.54 3.65 2.65 61.44 57 4.44 48.79 43 5.79

97.54 3.75 2.75 72.00 68 4.00 62.70 57 5.70

98.54 3.85 2.85 79.72 77 2.72 74.26 70 4.26

101.55 3.75 2.75 84.07 81 3.07 79.80 75 4.80

102.55 3.65 2.65 76.73 73 3.73 69.38 64 5.38

103.55 3.55 2.55 66.54 62 4.54 56.10 50 6.10*

SE = Square Root of Mean Square Error, SM = Standard Deviation of Location Means, * Maximum

Figure 5: Determining Probability Using Sampling Plan 2 Data (n = 30).

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P R A M O T E C H O L AY U D T H

are that a lot of charts will have to be generated, sinceone chart may be broken down into two or three charts,resulting in complication of their use. Justification ofthe accuracy (i.e., deviation) on practical basis, as de-scribed earlier, should be acceptable. Since the worstcase probability results (low results at 50 to 60% withdeviation of up to 5 or 6%) will occur only to inade-quately controlled and/or developed processes. Theadequately developed processes with proper in-processcontrol will not fall into this case (i.e., the deviationwill be much less than 5%).

REFERENCES1. FDA Center for Drug Evaluation and Research (CDER),

Draft Guidance for Industry: Powder Blends and FinishedDosage Units—Stratified In-Process Dosage Unit Samplingand Assessment, Rockville, MD , October 2003.

2. Product Quality Research Institute (PQRI) Blend Unifor-mity Working Group (BUWG), “The Use of Stratified Sam-pling of Blend and Dosage Units to Demonstrate Ade-quacy of Mix for Powder Blends,”Final Report on BlendUniformity Recommendations, December 20, 2002,www.pqri.org.

3. Parenteral Drug Association, “Blend Uniformity Analy-sis: Validation and In-Process Testing,” PDA Technical Re-port No. 25,1997.

4. Torbeck, L. D., “In Defense of USP Singlet Testing,” Phar-maceutical Technology, Volume 29, Number 2, February2005, www.pharmtech.com.

5. J. S. Bergum, “Constructing Acceptance Limits for Multi-ple Stage Tests,” Drug Development and Industrial Phar-macy, 16 (14), Marcel Dekker, Inc, 1990, pp. 2153-2166.

6. J. S. Bergum and H. Li, “Acceptance Limits for the NewICH USP 29 Content-Uniformity Test,” PharmaceuticalTechnology, October 2007, Vol. 31, No. 10,www.pharmtech.com.

7. Cholayudth, P., “Use of the Bergum Method and MS Excelto Determine the Probability of Passing the USP ContentUniformity Test,” Pharmaceutical Technology, Volume 28,Number 9, September 2004, www.pharmtech.com.

8. Cholayudth, P., “Using Bergum’s New Method and MSExcel to Determine the Probability of Passing the NewICH USP 29 Content Uniformity Test” Journal of Valida-tion Technology, Volume 14, No. 2, February 2008.

9. Pluta, P., “Keep in Step with Confidence; Keep in Stepthrough Benchmarking” Journal of Validation Technology,Volume 12, No. 1, November 2005.

10. Cholayudth, P., “Application of Probability of PassingMultiple Stage Tests in Benchmarking and Validation ofProcesses” Journal of Validation Technology, Volume 13,No. 4, August 2007.

11. Chow, S.C. and Liu, Statistical Design and Analysis in Phar-maceutical Science: Validation, Process Controls, Practicaland Clinical Applications, 3rd ed. New York: Marcel Dekker,Inc. JVT

ARTICLE ACRONYM LISTINGAV Acceptance ValueCQAs Critical Quality AttributesFDA Food and Drug AdministrationICH International Conference on HarmonizationLB Lower BoundLC Label ClaimMS MicrosoftOC Operating CharacteristicPDA Parenteral Drug AssociationPQRI Product Quality Research InstituteRSD Relative Standard DeviationSD Standard Deviation (for a Sample)SE Square Root of Mean Square ErrorSigma Population Standard DeviationSM Standard Deviation of Location MeansUB Upper BoundUSP United States Pharmacopeia

ACKNOWLEDGMENTThis paper is intended to support James Bergum’s meth-ods with regard to probability of passing the currentand new USP Content Uniformity tests. Although theMicrosoft Excel programs were developed from his SASprograms by the author (7, 8), a more practical ap-proach to use the distribution curves for lower proba-bility bounds in place of the Excel programs is intro-duced. Finally, the author is very grateful to thereviewers of this paper for their helpful comments es-pecially regarding the OC curves.

APPENDIX 1 EXCEL FORMULAE

APPENDIX 2 PROBABILITY CHARTSAppendix 2 is available for download at http://www.ivthome.com/jvtspring. Probability charts provided inAppendix 2 are presented in order of sampling plan types and overall sample sizes. The charts for 1 unit x 60locations are also available although it is not practical to do the sampling. The author only wants the readersto have the integrated views on this sampling plan 1.

Table XIV: Tablet formulae: Current USP test.

Tablet formulae are as below:

D3 =MIN(D4,D5)

D4 =MAX((FDIST(10/((0.06^2)*(1+10*(B5/B7)^2)),(1+10*(B5/B7)^2)^2/(1+2*10*(B5/B7)^2),10-1))+((NORMSDIST((115-B5)/B7)-NORMSDIST((85-B5)/B7))^10)-1,(FDIST(30/((0.078^2)*(1+30*(B5/B7)^2)),(1+30*(B5/B7)^2)^2/(1+2*30*(B5/B7)^2),30-1))+((NORMSDIST((115-B5)/B7)-NORMSDIST((85-B5)/B7))^30+COMBIN(30,1)*((NORMSDIST((115-B5)/B7)-NORMSDIST((85-B5)/B7))^29)*(((NORMS-DIST((85-B5)/B7)-NORMSDIST((75-B5)/B7))+(NORMSDIST((125-B5)/B7)-NORMSDIST((115-B5)/B7)))^1))-1,0)

D5 =MAX((FDIST(10/((0.06^2)*(1+10*(B6/B7)^2)),(1+10*(B6/B7)^2)^2/(1+2*10*(B6/B7)^2),10-1))+((NORMSDIST((115-B6)/B7)-NORMSDIST((85-B6)/B7))^10)-1,(FDIST(30/((0.078^2)*(1+30*(B6/B7)^2)),(1+30*(B6/B7)^2)^2/(1+2*30*(B6/B7)^2),30-1))+((NORMSDIST((115-B6)/B7)-NORMSDIST((85-B6)/B7))^30+COMBIN(30,1)*((NORMSDIST((115-B6)/B7)-NORMSDIST((85-B6)/B7))^29)*(((NORMSDIST((85-B6)/B7)-NORMSDIST((75-B6)/B7))+(NORMSDIST((125-B6)/B7)-NORMSDIST((115-B6)/B7)))^1))-1,0)

Table XV: Capsule formulae: Current USP test.Capsule formulae are as below:

F3 =MIN(F4,F5), F4 =MAX(F7,F8,0), F5 =MAX(F10,F11,0)

F7 =(FDIST(10/((0.06^2)*(1+10*(B5/B7)^2)),(1+10*(B5/B7)^2)^2/(1+2*10*(B5/B7)^2),10-1))+((NORMSDIST((115-B5)/B7)-NORMSDIST((85-B5)/B7))^10+COMBIN(10,1)*((NORMSDIST((115-B5)/B7)-NORMSDIST((85-B5)/B7))^9)*(((NORMSDIST((B5-75)/B7)-NORMSDIST((B5-85)/B7))+(NORMSDIST((125-B5)/B7)-NORMSDIST((115-B5)/B7)))^1))-1

F8 =(FDIST(30/((0.078^2)*(1+30*(B5/B7)^2)),(1+30*(B5/B7)^2)^2/(1+2*30*(B5/B7)^2),30-1))+((NORMSDIST((115-B5)/B7)-NORMSDIST((85-B5)/B7))^30+COMBIN(30,1)*((NORMSDIST((115-B5)/B7)-NORMSDIST((85-B5)/B7))^29)*(((NORMSDIST((85-B5)/B7)-NORMSDIST((75-B5)/B7))+(NORMSDIST((125-B5)/B7)-NORMSDIST((115-B5)/B7)))^1)+COMBIN(30,2)*((NORMSDIST((115-B5)/B7)-NORMSDIST((85-B5)/B7))^28)*(((NORMSDIST((85-B5)/B7)-NORMSDIST((75-B5)/B7))+(NORMSDIST((125-B5)/B7)-NORMSDIST((115-B5)/B7)))^2)+COMBIN(30,3)*((NORMS-DIST((115-B5)/B7)-NORMSDIST((85-B5)/B7))^27)*(((NORMSDIST((85-B5)/B7)-NORMSDIST((75-B5)/B7))+(NORMS-DIST((125-B5)/B7)-NORMSDIST((115-B5)/B7)))^3))-1

F10 =(FDIST(10/((0.06^2)*(1+10*(B6/B7)^2)),(1+10*(B6/B7)^2)^2/(1+2*10*(B6/B7)^2),10-1))+((NORMSDIST((115-B6)/B7)-NORMSDIST((85-B6)/B7))^10+COMBIN(10,1)*((NORMSDIST((115-B6)/B7)-NORMSDIST((85-B6)/B7))^9)*(((NORMSDIST((B6-75)/B7)-NORMSDIST((B6-85)/B7))+(NORMSDIST((125-B6)/B7)-NORMSDIST((115-B6)/B7)))^1))-1

F11 =(FDIST(30/((0.078^2)*(1+30*(B6/B7)^2)),(1+30*(B6/B7)^2)^2/(1+2*30*(B6/B7)^2),30-1))+((NORMSDIST((115-B6)/B7)-NORMSDIST((85-B6)/B7))^30+COMBIN(30,1)*((NORMSDIST((115-B6)/B7)-NORMSDIST((85-B6)/B7))^29)*(((NORMSDIST((85-B6)/B7)-NORMSDIST((75-B6)/B7))+(NORMSDIST((125-B6)/B7)-NORMSDIST((115-B6)/B7)))^1)+COMBIN(30,2)*((NORMSDIST((115-B6)/B7)-NORMSDIST((85-B6)/B7))^28)*(((NORMSDIST((85-B6)/B7)-NORMSDIST((75-B6)/B7))+(NORMSDIST((125-B6)/B7)-NORMSDIST((115-B6)/B7)))^2)+COMBIN(30,3)*((NORMS-DIST((115-B6)/B7)-NORMSDIST((85-B6)/B7))^27)*(((NORMSDIST((85-B6)/B7)-NORMSDIST((75-B6)/B7))+(NORMS-DIST((125-B6)/B7)-NORMSDIST((115-B6)/B7)))^3))-1

P E E R R E V I E W E D

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Journal of Validation Technology MAY 2008 ISSUE

ARTICLE:

Evaluation of Validation Content Uniformity Test Results Using Probability Distribution Charts

By: Pramote Cholayudth

APPENDIX 2: PROBABILITY CHARTS

Probability charts provided in the following pages are presented in order of product

types, sampling plan types and overall sample sizes. All the charts are constructed on

95% joint confidence level. The charts for 1 unit x 60 locations are also available

although it is not practical to do the sampling. The author only wants the readers to

have the integrated views on this sampling plan 1. In the new USP test, the

probability charts provided are applicable to the processes with target of not more

than 101.5% label claim (LC). For processes with target > 101.5% LC, please

contact [email protected].

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TABLE OF CONTENTS (CURRENT USP TEST: TABLETS)

� Sampling Plan 1 (1 x 30): Current USP Test (RSD: 2.1 – 4.8%) 4

� Sampling Plan 1 (1 x 60): Current USP Test (RSD: 2.7 – 5.4%) 7

� Sampling Plan 2 (3 x 10): Current USP Test (SE: 2.0 – 4.7, SM: 0.3 – 0.7) 10

� Sampling Plan 2 (3 x 10): Current USP Test (SE: 1.9 – 4.6, SM: 0.8 – 1.2) 13

� Sampling Plan 2 (3 x 10): Current USP Test (SE: 1.9 – 4.6, SM: 1.3 – 1.7) 16

� Sampling Plan 2 (3 x 10): Current USP Test (SE: 1.8 – 4.5, SM: 1.8 – 2.2) 19

� Sampling Plan 2 (3 x 10): Current USP Test (SE: 1.7 – 4.4, SM: 2.3 – 2.6) 22

� Sampling Plan 2 (3 x 10): Current USP Test (SE: 1.6 – 4.3, SM: 2.7 – 2.9) 25

� Sampling Plan 2 (3 x 10): Current USP Test (SE: 1.6 – 4.3, SM: 3.0 – 3.2) 28

� Sampling Plan 2 (3 x 10): Current USP Test (SE: 1.4 – 4.1, SM: 3.3 – 3.5) 31

� Sampling Plan 2 (3 x 10): Current USP Test (SE: 1.0 – 3.7, SM: 3.6 – 3.8) 34

� Sampling Plan 2 (3 x 20): Current USP Test (SE: 2.6 – 5.3, SM: 0.3 – 0.7) 37

� Sampling Plan 2 (3 x 20): Current USP Test (SE: 2.6 – 5.3, SM: 0.8 – 1.2) 40

� Sampling Plan 2 (3 x 20): Current USP Test (SE: 2.5 – 5.2, SM: 1.3 – 1.7) 43

� Sampling Plan 2 (3 x 20): Current USP Test (SE: 2.5 – 5.2, SM: 1.8 – 2.2) 46

� Sampling Plan 2 (3 x 20): Current USP Test (SE: 2.5 – 5.2, SM: 2.3 – 2.6) 49

� Sampling Plan 2 (3 x 20): Current USP Test (SE: 2.5 – 5.2, SM: 2.7 – 2.9) 52

� Sampling Plan 2 (3 x 20): Current USP Test (SE: 2.4 – 5.1, SM: 3.0 – 3.2) 55

� Sampling Plan 2 (3 x 20): Current USP Test (SE: 2.4 – 5.1, SM: 3.3 – 3.5) 58

� Sampling Plan 2 (3 x 20): Current USP Test (SE: 2.4 – 5.1, SM: 3.6 – 3.8) 61

TABLE OF CONTENTS (CURRENT USP TEST: CAPSULES)

� Sampling Plan 1 (1 x 30): Current USP Test (RSD: 2.5 – 5.2%) 5

� Sampling Plan 1 (1 x 60): Current USP Test (RSD: 3.0 – 5.7%) 8

� Sampling Plan 2 (3 x 10): Current USP Test (SE: 2.3 – 5.0, SM: 0.3 – 0.7) 11

� Sampling Plan 2 (3 x 10): Current USP Test (SE: 2.3 – 5.0, SM: 0.8 – 1.2) 14

� Sampling Plan 2 (3 x 10): Current USP Test (SE: 2.3 – 5.0, SM: 1.3 – 1.7) 17

� Sampling Plan 2 (3 x 10): Current USP Test (SE: 2.2 – 4.9, SM: 1.8 – 2.2) 20

� Sampling Plan 2 (3 x 10): Current USP Test (SE: 2.2 – 4.9, SM: 2.3 – 2.6) 23

� Sampling Plan 2 (3 x 10): Current USP Test (SE: 2.1 – 4.8, SM: 2.7 – 2.9) 26

� Sampling Plan 2 (3 x 10): Current USP Test (SE: 2.1 – 4.8, SM: 3.0 – 3.2) 29

� Sampling Plan 2 (3 x 10): Current USP Test (SE: 2.1 – 4.8, SM: 3.3 – 3.5) 32

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� Sampling Plan 2 (3 x 10): Current USP Test (SE: 1.9 – 4.6, SM: 3.6 – 3.8) 35

� Sampling Plan 2 (3 x 20): Current USP Test (SE: 3.1 – 5.8, SM: 0.3 – 0.7) 38

� Sampling Plan 2 (3 x 20): Current USP Test (SE: 3.0 – 5.7, SM: 0.8 – 1.2) 41

� Sampling Plan 2 (3 x 20): Current USP Test (SE: 3.0 – 5.7, SM: 1.3 – 1.7) 44

� Sampling Plan 2 (3 x 20): Current USP Test (SE: 3.0 – 5.7, SM: 1.8 – 2.2) 47

� Sampling Plan 2 (3 x 20): Current USP Test (SE: 3.0 – 5.7, SM: 2.3 – 2.6) 50

� Sampling Plan 2 (3 x 20): Current USP Test (SE: 3.0 – 5.7, SM: 2.7 – 2.9) 53

� Sampling Plan 2 (3 x 20): Current USP Test (SE: 3.0 – 5.7, SM: 3.0 – 3.2) 56

� Sampling Plan 2 (3 x 20): Current USP Test (SE: 2.9 – 5.6, SM: 3.3 – 3.5) 59

� Sampling Plan 2 (3 x 20): Current USP Test (SE: 2.9 – 5.6, SM: 3.6 – 3.8) 62

TABLE OF CONTENTS (NEW USP TEST: TABLETS/CAPSULES)

• Sampling Plan 1 (1 x 30): New USP Test (RSD: 2.0 – 4.7%) 6

• Sampling Plan 1 (1 x 60): New USP Test (RSD: 2.7 – 5.4%) 9

• Sampling Plan 2 (3 x 10): New USP Test (SE: 2.0 – 4.7, SM: 0.3 – 0.7) 12

• Sampling Plan 2 (3 x 10): New USP Test (SE: 1.9 – 4.6, SM: 0.8 – 1.2) 15

• Sampling Plan 2 (3 x 10): New USP Test (SE: 1.9 – 4.6, SM: 1.3 – 1.7) 18

• Sampling Plan 2 (3 x 10): New USP Test (SE: 1.7 – 4.4, SM: 1.8 – 2.2) 21

• Sampling Plan 2 (3 x 10): New USP Test (SE: 1.6 – 4.3, SM: 2.3 – 2.6) 24

• Sampling Plan 2 (3 x 10): New USP Test (SE: 1.4 – 4.1, SM: 2.7 – 2.9) 27

• Sampling Plan 2 (3 x 10): New USP Test (SE: 1.4 – 4.1, SM: 3.0 – 3.2) 30

• Sampling Plan 2 (3 x 10): New USP Test (SE: 1.0 – 3.7, SM: 3.3 – 3.5) 33

• Sampling Plan 2 (3 x 10): New USP Test (SE: 0.7 – 3.4, SM: 3.6 – 3.8) 36

• Sampling Plan 2 (3 x 20): New USP Test (SE: 2.7 – 5.4, SM: 0.3 – 0.7) 39

• Sampling Plan 2 (3 x 20): New USP Test (SE: 2.7 – 5.4, SM: 0.8 – 1.2) 42

• Sampling Plan 2 (3 x 20): New USP Test (SE: 2.6 – 5.3, SM: 1.3 – 1.7) 45

• Sampling Plan 2 (3 x 20): New USP Test (SE: 2.5 – 5.2, SM: 1.8 – 2.2) 48

• Sampling Plan 2 (3 x 20): New USP Test (SE: 2.5 – 5.2, SM: 2.3 – 2.6) 51

• Sampling Plan 2 (3 x 20): New USP Test (SE: 2.4 – 5.1, SM: 2.7 – 2.9) 54

• Sampling Plan 2 (3 x 20): New USP Test (SE: 2.4 – 5.1, SM: 3.0 – 3.2) 57

• Sampling Plan 2 (3 x 20): New USP Test (SE: 2.3 – 5.0, SM: 3.3 – 3.5) 60

• Sampling Plan 2 (3 x 20): New USP Test (SE: 2.3 – 5.0, SM: 3.6 – 3.8) 63

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Sampling Plan 1 (1 x 30): Current USP Test (RSD: 2.1 – 4.8%)

Probability of Passing Current USP Tablet Content Uniformity Test (N = 1x30 = 30, RSD = 2.1-4.7%)

50%

55%

60%

65%

70%

75%

80%

85%

90%

95%

100%

95.0

95.2

95.4

95.6

95.8

96.0

96.2

96.4

96.6

96.8

97.0

97.2

97.4

97.6

97.8

98.0

98.2

98.4

98.6

98.8

99.0

99.2

99.4

99.6

99.8

100.

0

100.

2

100.

4

100.

6

100.

8

101.

0

101.

2

101.

4

101.

6

101.

8

102.

0

102.

2

102.

4

102.

6

102.

8

103.

0

103.

2

103.

4

103.

6

103.

8

104.

0

104.

2

104.

4

104.

6

104.

8

105.

0

CU Sample Mean (% LC)

Pro

bab

ilit

y (%

)

2.1%

2.3%

2.5%

2.7%

2.9%

3.1%

3.3%

3.5%

3.7%

3.9%

4.1%

4.3%

4.5%

4.7%

Probability of Passing Current USP Tablet Content Uniformity Test (N = 1x30 = 30, RSD = 2.2-4.8%)

50%

55%

60%

65%

70%

75%

80%

85%

90%

95%

100%

95.0

95.2

95.4

95.6

95.8

96.0

96.2

96.4

96.6

96.8

97.0

97.2

97.4

97.6

97.8

98.0

98.2

98.4

98.6

98.8

99.0

99.2

99.4

99.6

99.8

100.

0

100.

2

100.

4

100.

6

100.

8

101.

0

101.

2

101.

4

101.

6

101.

8

102.

0

102.

2

102.

4

102.

6

102.

8

103.

0

103.

2

103.

4

103.

6

103.

8

104.

0

104.

2

104.

4

104.

6

104.

8

105.

0

CU Sample Mean (% LC)

Pro

bab

ilit

y (%

)

2.2%

2.4%

2.6%

2.8%

3%

3.2%

3.4%

3.6%

3.8%

4%

4.2%

4.4%

4.6%

4.8%

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Sampling Plan 1 (1 x 30): Current USP Test (RSD: 2.5 – 5.2%)

Probability of Passing Current USP Capsule Content Uniformity Test (N = 1x30 = 30, RSD = 2.5-5.1%)

50%

55%

60%

65%

70%

75%

80%

85%

90%

95%

100%

95.0

95.2

95.4

95.6

95.8

96.0

96.2

96.4

96.6

96.8

97.0

97.2

97.4

97.6

97.8

98.0

98.2

98.4

98.6

98.8

99.0

99.2

99.4

99.6

99.8

100.

0

100.

2

100.

4

100.

6

100.

8

101.

0

101.

2

101.

4

101.

6

101.

8

102.

0

102.

2

102.

4

102.

6

102.

8

103.

0

103.

2

103.

4

103.

6

103.

8

104.

0

104.

2

104.

4

104.

6

104.

8

105.

0

CU Sample Mean (% LC)

Pro

bab

ilit

y (%

)

2.5%

2.7%

2.9%

3.1%

3.3%

3.5%

3.7%

3.9%

4.1%

4.3%

4.5%

4.7%

4.9%

5.1%

Probability of Passing Current USP Capsule Content Uniformity Test (N = 1x30 = 30, RSD = 2.6-5.2%)

50%

55%

60%

65%

70%

75%

80%

85%

90%

95%

100%

95.0

95.2

95.4

95.6

95.8

96.0

96.2

96.4

96.6

96.8

97.0

97.2

97.4

97.6

97.8

98.0

98.2

98.4

98.6

98.8

99.0

99.2

99.4

99.6

99.8

100.

0

100.

2

100.

4

100.

6

100.

8

101.

0

101.

2

101.

4

101.

6

101.

8

102.

0

102.

2

102.

4

102.

6

102.

8

103.

0

103.

2

103.

4

103.

6

103.

8

104.

0

104.

2

104.

4

104.

6

104.

8

105.

0

CU Sample Mean (% LC)

Pro

bab

ilit

y (%

)

2.6%

2.8%

3%

3.2%

3.4%

3.6%

3.8%

4%

4.2%

4.4%

4.6%

4.8%

5%

5.2%

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Sampling Plan 1 (1 x 30): New USP Test (RSD: 2.0 – 4.7%)

Probability of Passing New USP 29 Content Uniformity Test (N = 1x30 = 30, RSD = 2.0-4.6%)

50%

55%

60%

65%

70%

75%

80%

85%

90%

95%

100%

95.0

95.2

95.4

95.6

95.8

96.0

96.2

96.4

96.6

96.8

97.0

97.2

97.4

97.6

97.8

98.0

98.2

98.4

98.6

98.8

99.0

99.2

99.4

99.6

99.8

100.

0

100.

2

100.

4

100.

6

100.

8

101.

0

101.

2

101.

4

101.

6

101.

8

102.

0

102.

2

102.

4

102.

6

102.

8

103.

0

103.

2

103.

4

103.

6

103.

8

104.

0

104.

2

104.

4

104.

6

104.

8

105.

0

CU Sample Mean (% LC)

Pro

bab

ilit

y (%

)

2%

2.2%

2.4%

2.6%

2.8%

3%

3.2%

3.4%

3.6%

3.8%

4%

4.2%

4.4%

4.6%

Probability of Passing New USP 29 Content Uniformity Test (N = 1x30 = 30, RSD = 2.1-4.7%)

50%

55%

60%

65%

70%

75%

80%

85%

90%

95%

100%

95.0

95.2

95.4

95.6

95.8

96.0

96.2

96.4

96.6

96.8

97.0

97.2

97.4

97.6

97.8

98.0

98.2

98.4

98.6

98.8

99.0

99.2

99.4

99.6

99.8

100.

0

100.

2

100.

4

100.

6

100.

8

101.

0

101.

2

101.

4

101.

6

101.

8

102.

0

102.

2

102.

4

102.

6

102.

8

103.

0

103.

2

103.

4

103.

6

103.

8

104.

0

104.

2

104.

4

104.

6

104.

8

105.

0

CU Sample Mean (% LC)

Pro

bab

ilit

y (%

)

2.1%

2.3%

2.5%

2.7%

2.9%

3.1%

3.3%

3.5%

3.7%

3.9%

4.1%

4.3%

4.5%

4.7%

INSTITUTE OF VALIDATION TECHNOLOGY

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Sampling Plan 1 (1 x 60): Current USP Test (RSD: 2.7 – 5.4%)

Probability of Passing Current USP Tablet Content Uniformity Test (N = 1x60 = 60, RSD = 2.7-5.3%)

50%

55%

60%

65%

70%

75%

80%

85%

90%

95%

100%

95.0

95.2

95.4

95.6

95.8

96.0

96.2

96.4

96.6

96.8

97.0

97.2

97.4

97.6

97.8

98.0

98.2

98.4

98.6

98.8

99.0

99.2

99.4

99.6

99.8

100.

0

100.

2

100.

4

100.

6

100.

8

101.

0

101.

2

101.

4

101.

6

101.

8

102.

0

102.

2

102.

4

102.

6

102.

8

103.

0

103.

2

103.

4

103.

6

103.

8

104.

0

104.

2

104.

4

104.

6

104.

8

105.

0

CU Sample Mean (% LC)

Pro

bab

ilit

y (%

)

2.7%

2.9%

3.1%

3.3%

3.5%

3.7%

3.9%

4.1%

4.3%

4.5%

4.7%

4.9%

5.1%

5.3%

Probability of Passing Current USP Tablet Content Uniformity Test (N = 1x60 = 60, RSD = 2.8-5.4%)

50%

55%

60%

65%

70%

75%

80%

85%

90%

95%

100%

95.0

95.2

95.4

95.6

95.8

96.0

96.2

96.4

96.6

96.8

97.0

97.2

97.4

97.6

97.8

98.0

98.2

98.4

98.6

98.8

99.0

99.2

99.4

99.6

99.8

100.

0

100.

2

100.

4

100.

6

100.

8

101.

0

101.

2

101.

4

101.

6

101.

8

102.

0

102.

2

102.

4

102.

6

102.

8

103.

0

103.

2

103.

4

103.

6

103.

8

104.

0

104.

2

104.

4

104.

6

104.

8

105.

0

CU Sample Mean (% LC)

Pro

bab

ilit

y (%

)

2.8%

3%

3.2%

3.4%

3.6%

3.8%

4%

4.2%

4.4%

4.6%

4.8%

5%

5.2%

5.4%

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Sampling Plan 1 (1 x 60): Current USP Test (RSD: 3.0 – 5.7%)

Probability of Passing Current USP Capsule Content Uniformity Test (N = 1x60 = 60, RSD = 3.0-5.6%)

50%

55%

60%

65%

70%

75%

80%

85%

90%

95%

100%

95.0

95.2

95.4

95.6

95.8

96.0

96.2

96.4

96.6

96.8

97.0

97.2

97.4

97.6

97.8

98.0

98.2

98.4

98.6

98.8

99.0

99.2

99.4

99.6

99.8

100.

0

100.

2

100.

4

100.

6

100.

8

101.

0

101.

2

101.

4

101.

6

101.

8

102.

0

102.

2

102.

4

102.

6

102.

8

103.

0

103.

2

103.

4

103.

6

103.

8

104.

0

104.

2

104.

4

104.

6

104.

8

105.

0

CU Sample Mean (% LC)

Pro

bab

ilit

y (%

)

3%

3.2%

3.4%

3.6%

3.8%

4%

4.2%

4.4%

4.6%

4.8%

5%

5.2%

5.4%

5.6%

Probability of Passing Current USP Capsule Content Uniformity Test (N = 1x60 = 60, RSD = 3.1-5.7%)

50%

55%

60%

65%

70%

75%

80%

85%

90%

95%

100%

95.0

95.2

95.4

95.6

95.8

96.0

96.2

96.4

96.6

96.8

97.0

97.2

97.4

97.6

97.8

98.0

98.2

98.4

98.6

98.8

99.0

99.2

99.4

99.6

99.8

100.

0

100.

2

100.

4

100.

6

100.

8

101.

0

101.

2

101.

4

101.

6

101.

8

102.

0

102.

2

102.

4

102.

6

102.

8

103.

0

103.

2

103.

4

103.

6

103.

8

104.

0

104.

2

104.

4

104.

6

104.

8

105.

0

CU Sample Mean (% LC)

Pro

bab

ilit

y (%

)

3.1%

3.3%

3.5%

3.7%

3.9%

4.1%

4.3%

4.5%

4.7%

4.9%

5.1%

5.3%

5.5%

5.7%

INSTITUTE OF VALIDATION TECHNOLOGY

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Sampling Plan 1 (1 x 60): New USP Test (RSD: 2.7 – 5.4%)

Probability of Passing New USP 29 Content Uniformity Test (N = 1x60 = 60, RSD = 2.7-5.3%)

50%

55%

60%

65%

70%

75%

80%

85%

90%

95%

100%

95.0

95.2

95.4

95.6

95.8

96.0

96.2

96.4

96.6

96.8

97.0

97.2

97.4

97.6

97.8

98.0

98.2

98.4

98.6

98.8

99.0

99.2

99.4

99.6

99.8

100.

0

100.

2

100.

4

100.

6

100.

8

101.

0

101.

2

101.

4

101.

6

101.

8

102.

0

102.

2

102.

4

102.

6

102.

8

103.

0

103.

2

103.

4

103.

6

103.

8

104.

0

104.

2

104.

4

104.

6

104.

8

105.

0

CU Sample Mean (% LC)

Pro

bab

ilit

y (%

)

2.7%

2.9%

3.1%

3.3%

3.5%

3.7%

3.9%

4.1%

4.3%

4.5%

4.7%

4.9%

5.1%

5.3%

Probability of Passing New USP 29 Content Uniformity Test (N = 1x60 = 60, RSD = 2.8-5.4%)

50%

55%

60%

65%

70%

75%

80%

85%

90%

95%

100%

95.0

95.2

95.4

95.6

95.8

96.0

96.2

96.4

96.6

96.8

97.0

97.2

97.4

97.6

97.8

98.0

98.2

98.4

98.6

98.8

99.0

99.2

99.4

99.6

99.8

100.

0

100.

2

100.

4

100.

6

100.

8

101.

0

101.

2

101.

4

101.

6

101.

8

102.

0

102.

2

102.

4

102.

6

102.

8

103.

0

103.

2

103.

4

103.

6

103.

8

104.

0

104.

2

104.

4

104.

6

104.

8

105.

0

CU Sample Mean (% LC)

Pro

bab

ilit

y (%

)

2.8%

3%

3.2%

3.4%

3.6%

3.8%

4%

4.2%

4.4%

4.6%

4.8%

5%

5.2%

5.4%

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Sampling Plan 2 (3 x 10): Current USP Test (SE: 2.0 – 4.7, SM: 0.3 – 0.7)

Probability of Passing Current USP Tablet Content Uniformity Test (N = 3x10 = 30, SE = 2.0-4.6, SM = 0.5)

50%

55%

60%

65%

70%

75%

80%

85%

90%

95%

100%

95.0

95.2

95.4

95.6

95.8

96.0

96.2

96.4

96.6

96.8

97.0

97.2

97.4

97.6

97.8

98.0

98.2

98.4

98.6

98.8

99.0

99.2

99.4

99.6

99.8

100.

0

100.

2

100.

4

100.

6

100.

8

101.

0

101.

2

101.

4

101.

6

101.

8

102.

0

102.

2

102.

4

102.

6

102.

8

103.

0

103.

2

103.

4

103.

6

103.

8

104.

0

104.

2

104.

4

104.

6

104.

8

105.

0

CU Sample Mean (% LC)

Pro

bab

ilit

y (%

)

2%

2.2%

2.4%

2.6%

2.8%

3%

3.2%

3.4%

3.6%

3.8%

4%

4.2%

4.4%

4.6%

Probability of Passing Current USP Tablet Content Uniformity Test (N = 3x10 = 30, SE = 2.1-4.7, SM = 0.5)

50%

55%

60%

65%

70%

75%

80%

85%

90%

95%

100%

95.0

95.2

95.4

95.6

95.8

96.0

96.2

96.4

96.6

96.8

97.0

97.2

97.4

97.6

97.8

98.0

98.2

98.4

98.6

98.8

99.0

99.2

99.4

99.6

99.8

100.

0

100.

2

100.

4

100.

6

100.

8

101.

0

101.

2

101.

4

101.

6

101.

8

102.

0

102.

2

102.

4

102.

6

102.

8

103.

0

103.

2

103.

4

103.

6

103.

8

104.

0

104.

2

104.

4

104.

6

104.

8

105.

0

CU Sample Mean (% LC)

Pro

bab

ilit

y (%

)

2.1%

2.3%

2.5%

2.7%

2.9%

3.1%

3.3%

3.5%

3.7%

3.9%

4.1%

4.3%

4.5%

4.7%

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Sampling Plan 2 (3 x 10): Current USP Test (SE: 2.3 – 5.0, SM: 0.3 – 0.7)

Probability of Passing Current USP Capsule Content Uniformity Test (N = 3x10 = 30, SE = 2.3-4.9, SM = 0.5)

50%

55%

60%

65%

70%

75%

80%

85%

90%

95%

100%

95.0

95.2

95.4

95.6

95.8

96.0

96.2

96.4

96.6

96.8

97.0

97.2

97.4

97.6

97.8

98.0

98.2

98.4

98.6

98.8

99.0

99.2

99.4

99.6

99.8

100.

0

100.

2

100.

4

100.

6

100.

8

101.

0

101.

2

101.

4

101.

6

101.

8

102.

0

102.

2

102.

4

102.

6

102.

8

103.

0

103.

2

103.

4

103.

6

103.

8

104.

0

104.

2

104.

4

104.

6

104.

8

105.

0

CU Sample Mean (% LC)

Pro

bab

ilit

y (%

)

2.3%

2.5%

2.7%

2.9%

3.1%

3.3%

3.5%

3.7%

3.9%

4.1%

4.3%

4.5%

4.7%

4.9%

Probability of Passing Current USP Capsule Content Uniformity Test (N = 3x10 = 30, SE = 2.4-5.0, SM = 0.5)

50%

55%

60%

65%

70%

75%

80%

85%

90%

95%

100%

95.0

95.2

95.4

95.6

95.8

96.0

96.2

96.4

96.6

96.8

97.0

97.2

97.4

97.6

97.8

98.0

98.2

98.4

98.6

98.8

99.0

99.2

99.4

99.6

99.8

100.

0

100.

2

100.

4

100.

6

100.

8

101.

0

101.

2

101.

4

101.

6

101.

8

102.

0

102.

2

102.

4

102.

6

102.

8

103.

0

103.

2

103.

4

103.

6

103.

8

104.

0

104.

2

104.

4

104.

6

104.

8

105.

0

CU Sample Mean (% LC)

Pro

bab

ilit

y (%

)

2.4%

2.6%

2.8%

3%

3.2%

3.4%

3.6%

3.8%

4%

4.2%

4.4%

4.6%

4.8%

5%

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Sampling Plan 2 (3 x 10): New USP Test (SE: 2.0 – 4.7, SM: 0.3 – 0.7)

Probability of Passing New USP 29 Content Uniformity Test (N = 3x10 = 30, SE = 2.0-4.6, SM = 0.5)

50%

55%

60%

65%

70%

75%

80%

85%

90%

95%

100%

95.0

95.2

95.4

95.6

95.8

96.0

96.2

96.4

96.6

96.8

97.0

97.2

97.4

97.6

97.8

98.0

98.2

98.4

98.6

98.8

99.0

99.2

99.4

99.6

99.8

100.

0

100.

2

100.

4

100.

6

100.

8

101.

0

101.

2

101.

4

101.

6

101.

8

102.

0

102.

2

102.

4

102.

6

102.

8

103.

0

103.

2

103.

4

103.

6

103.

8

104.

0

104.

2

104.

4

104.

6

104.

8

105.

0

CU Sample Mean (% LC)

Pro

bab

ilit

y (%

)

2%

2.2%

2.4%

2.6%

2.8%

3%

3.2%

3.4%

3.6%

3.8%

4%

4.2%

4.4%

4.6%

Probability of Passing New USP 29 Content Uniformity Test (N = 3x10 = 30, SE = 2.1-4.7, SM = 0.5)

50%

55%

60%

65%

70%

75%

80%

85%

90%

95%

100%

95.0

95.2

95.4

95.6

95.8

96.0

96.2

96.4

96.6

96.8

97.0

97.2

97.4

97.6

97.8

98.0

98.2

98.4

98.6

98.8

99.0

99.2

99.4

99.6

99.8

100.

0

100.

2

100.

4

100.

6

100.

8

101.

0

101.

2

101.

4

101.

6

101.

8

102.

0

102.

2

102.

4

102.

6

102.

8

103.

0

103.

2

103.

4

103.

6

103.

8

104.

0

104.

2

104.

4

104.

6

104.

8

105.

0

CU Sample Mean (% LC)

Pro

bab

ilit

y (%

)

2.1%

2.3%

2.5%

2.7%

2.9%

3.1%

3.3%

3.5%

3.7%

3.9%

4.1%

4.3%

4.5%

4.7%

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Sampling Plan 2 (3 x 10): Current USP Test (SE: 1.9 – 4.6, SM: 0.8 – 1.2)

Probability of Passing Current USP Tablet Content Uniformity Test (N = 3x10 = 30, SE = 1.9-4.5, SM = 1.0)

50%

55%

60%

65%

70%

75%

80%

85%

90%

95%

100%

95.0

95.2

95.4

95.6

95.8

96.0

96.2

96.4

96.6

96.8

97.0

97.2

97.4

97.6

97.8

98.0

98.2

98.4

98.6

98.8

99.0

99.2

99.4

99.6

99.8

100.

0

100.

2

100.

4

100.

6

100.

8

101.

0

101.

2

101.

4

101.

6

101.

8

102.

0

102.

2

102.

4

102.

6

102.

8

103.

0

103.

2

103.

4

103.

6

103.

8

104.

0

104.

2

104.

4

104.

6

104.

8

105.

0

CU Sample Mean (% LC)

Pro

bab

ilit

y (%

)

1.9%

2.1%

2.3%

2.5%

2.7%

2.9%

3.1%

3.3%

3.5%

3.7%

3.9%

4.1%

4.3%

4.5%

Probability of Passing Current USP Tablet Content Uniformity Test (N = 3x10 = 30, SE = 2.0-4.6, SM = 1.0)

50%

55%

60%

65%

70%

75%

80%

85%

90%

95%

100%

95.0

95.2

95.4

95.6

95.8

96.0

96.2

96.4

96.6

96.8

97.0

97.2

97.4

97.6

97.8

98.0

98.2

98.4

98.6

98.8

99.0

99.2

99.4

99.6

99.8

100.

0

100.

2

100.

4

100.

6

100.

8

101.

0

101.

2

101.

4

101.

6

101.

8

102.

0

102.

2

102.

4

102.

6

102.

8

103.

0

103.

2

103.

4

103.

6

103.

8

104.

0

104.

2

104.

4

104.

6

104.

8

105.

0

CU Sample Mean (% LC)

Pro

bab

ilit

y (%

)

2%

2.2%

2.4%

2.6%

2.8%

3%

3.2%

3.4%

3.6%

3.8%

4%

4.2%

4.4%

4.6%

INSTITUTE OF VALIDATION TECHNOLOGY

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Sampling Plan 2 (3 x 10): Current USP Test (SE: 2.3 – 5.0, SM: 0.8 – 1.2)

Probability of Passing Current USP Capsule Content Uniformity Test (N = 3x10 = 30, SE = 2.3-4.9, SM = 1.0)

50%

55%

60%

65%

70%

75%

80%

85%

90%

95%

100%

95.0

95.2

95.4

95.6

95.8

96.0

96.2

96.4

96.6

96.8

97.0

97.2

97.4

97.6

97.8

98.0

98.2

98.4

98.6

98.8

99.0

99.2

99.4

99.6

99.8

100.

0

100.

2

100.

4

100.

6

100.

8

101.

0

101.

2

101.

4

101.

6

101.

8

102.

0

102.

2

102.

4

102.

6

102.

8

103.

0

103.

2

103.

4

103.

6

103.

8

104.

0

104.

2

104.

4

104.

6

104.

8

105.

0

CU Sample Mean (% LC)

Pro

bab

ilit

y (%

)

2.3%

2.5%

2.7%

2.9%

3.1%

3.3%

3.5%

3.7%

3.9%

4.1%

4.3%

4.5%

4.7%

4.9%

Probability of Passing Current USP Capsule Content Uniformity Test (N = 3x10 = 30, SE = 2.4-5.0, SM = 1.0)

50%

55%

60%

65%

70%

75%

80%

85%

90%

95%

100%

95.0

95.2

95.4

95.6

95.8

96.0

96.2

96.4

96.6

96.8

97.0

97.2

97.4

97.6

97.8

98.0

98.2

98.4

98.6

98.8

99.0

99.2

99.4

99.6

99.8

100.

0

100.

2

100.

4

100.

6

100.

8

101.

0

101.

2

101.

4

101.

6

101.

8

102.

0

102.

2

102.

4

102.

6

102.

8

103.

0

103.

2

103.

4

103.

6

103.

8

104.

0

104.

2

104.

4

104.

6

104.

8

105.

0

CU Sample Mean (% LC)

Pro

bab

ilit

y (%

)

2.4%

2.6%

2.8%

3%

3.2%

3.4%

3.6%

3.8%

4%

4.2%

4.4%

4.6%

4.8%

5%

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Sampling Plan 2 (3 x 10): New USP Test (SE: 1.9 – 4.6, SM: 0.8 – 1.2)

Probability of Passing New USP 29 Content Uniformity Test (N = 3x10 = 30, SE = 1.9-4.5, SM = 1.0)

50%

55%

60%

65%

70%

75%

80%

85%

90%

95%

100%

95.0

95.2

95.4

95.6

95.8

96.0

96.2

96.4

96.6

96.8

97.0

97.2

97.4

97.6

97.8

98.0

98.2

98.4

98.6

98.8

99.0

99.2

99.4

99.6

99.8

100.

0

100.

2

100.

4

100.

6

100.

8

101.

0

101.

2

101.

4

101.

6

101.

8

102.

0

102.

2

102.

4

102.

6

102.

8

103.

0

103.

2

103.

4

103.

6

103.

8

104.

0

104.

2

104.

4

104.

6

104.

8

105.

0

CU Sample Mean (% LC)

Pro

bab

ilit

y (%

)

1.9%

2.1%

2.3%

2.5%

2.7%

2.9%

3.1%

3.3%

3.5%

3.7%

3.9%

4.1%

4.3%

4.5%

Probability of Passing New USP 29 Content Uniformity Test (N = 3x10 = 30, SE = 2.0-4.6, SM = 1.0)

50%

55%

60%

65%

70%

75%

80%

85%

90%

95%

100%

95.0

95.2

95.4

95.6

95.8

96.0

96.2

96.4

96.6

96.8

97.0

97.2

97.4

97.6

97.8

98.0

98.2

98.4

98.6

98.8

99.0

99.2

99.4

99.6

99.8

100.

0

100.

2

100.

4

100.

6

100.

8

101.

0

101.

2

101.

4

101.

6

101.

8

102.

0

102.

2

102.

4

102.

6

102.

8

103.

0

103.

2

103.

4

103.

6

103.

8

104.

0

104.

2

104.

4

104.

6

104.

8

105.

0

CU Sample Mean (% LC)

Pro

bab

ilit

y (%

)

2%

2.2%

2.4%

2.6%

2.8%

3%

3.2%

3.4%

3.6%

3.8%

4%

4.2%

4.4%

4.6%

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Sampling Plan 2 (3 x 10): Current USP Test (SE: 1.9 – 4.6, SM: 1.3 – 1.7)

Probability of Passing Current USP Tablet Content Uniformity Test (N = 3x10 = 30, SE = 1.9-4.5, SM = 1.5)

50%

55%

60%

65%

70%

75%

80%

85%

90%

95%

100%

95.0

95.2

95.4

95.6

95.8

96.0

96.2

96.4

96.6

96.8

97.0

97.2

97.4

97.6

97.8

98.0

98.2

98.4

98.6

98.8

99.0

99.2

99.4

99.6

99.8

100.

0

100.

2

100.

4

100.

6

100.

8

101.

0

101.

2

101.

4

101.

6

101.

8

102.

0

102.

2

102.

4

102.

6

102.

8

103.

0

103.

2

103.

4

103.

6

103.

8

104.

0

104.

2

104.

4

104.

6

104.

8

105.

0

CU Sample Mean (% LC)

Pro

bab

ilit

y (%

)

1.9%

2.1%

2.3%

2.5%

2.7%

2.9%

3.1%

3.3%

3.5%

3.7%

3.9%

4.1%

4.3%

4.5%

Probability of Passing Current USP Tablet Content Uniformity Test (N = 3x10 = 30, SE = 2.0-4.6, SM = 1.5)

50%

55%

60%

65%

70%

75%

80%

85%

90%

95%

100%

95.0

95.2

95.4

95.6

95.8

96.0

96.2

96.4

96.6

96.8

97.0

97.2

97.4

97.6

97.8

98.0

98.2

98.4

98.6

98.8

99.0

99.2

99.4

99.6

99.8

100.

0

100.

2

100.

4

100.

6

100.

8

101.

0

101.

2

101.

4

101.

6

101.

8

102.

0

102.

2

102.

4

102.

6

102.

8

103.

0

103.

2

103.

4

103.

6

103.

8

104.

0

104.

2

104.

4

104.

6

104.

8

105.

0

CU Sample Mean (% LC)

Pro

bab

ilit

y (%

)

2%

2.2%

2.4%

2.6%

2.8%

3%

3.2%

3.4%

3.6%

3.8%

4%

4.2%

4.4%

4.6%

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Sampling Plan 2 (3 x 10): Current USP Test (SE: 2.3 – 5.0, SM: 1.3 – 1.7)

Probability of Passing Current USP Capsule Content Uniformity Test (N = 3x10 = 30, SE = 2.3-4.9, SM = 1.5)

50%

55%

60%

65%

70%

75%

80%

85%

90%

95%

100%

95.0

95.2

95.4

95.6

95.8

96.0

96.2

96.4

96.6

96.8

97.0

97.2

97.4

97.6

97.8

98.0

98.2

98.4

98.6

98.8

99.0

99.2

99.4

99.6

99.8

100.

0

100.

2

100.

4

100.

6

100.

8

101.

0

101.

2

101.

4

101.

6

101.

8

102.

0

102.

2

102.

4

102.

6

102.

8

103.

0

103.

2

103.

4

103.

6

103.

8

104.

0

104.

2

104.

4

104.

6

104.

8

105.

0

CU Sample Mean (% LC)

Pro

bab

ilit

y (%

)

2.3%

2.5%

2.7%

2.9%

3.1%

3.3%

3.5%

3.7%

3.9%

4.1%

4.3%

4.5%

4.7%

4.9%

Probability of Passing Current USP Capsule Content Uniformity Test (N = 3x10 = 30, SE = 2.4-5.0, SM = 1.5)

50%

55%

60%

65%

70%

75%

80%

85%

90%

95%

100%

95.0

95.2

95.4

95.6

95.8

96.0

96.2

96.4

96.6

96.8

97.0

97.2

97.4

97.6

97.8

98.0

98.2

98.4

98.6

98.8

99.0

99.2

99.4

99.6

99.8

100.

0

100.

2

100.

4

100.

6

100.

8

101.

0

101.

2

101.

4

101.

6

101.

8

102.

0

102.

2

102.

4

102.

6

102.

8

103.

0

103.

2

103.

4

103.

6

103.

8

104.

0

104.

2

104.

4

104.

6

104.

8

105.

0

CU Sample Mean (% LC)

Pro

bab

ilit

y (%

)

2.4%

2.6%

2.8%

3%

3.2%

3.4%

3.6%

3.8%

4%

4.2%

4.4%

4.6%

4.8%

5%

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Sampling Plan 2 (3 x 10): New USP Test (SE: 1.9 – 4.6, SM: 1.3 – 1.7)

Probability of Passing New USP 29 Content Uniformity Test (N = 3x10 = 30, SE = 1.9-4.5, SM = 1.5)

50%

55%

60%

65%

70%

75%

80%

85%

90%

95%

100%

95.0

95.2

95.4

95.6

95.8

96.0

96.2

96.4

96.6

96.8

97.0

97.2

97.4

97.6

97.8

98.0

98.2

98.4

98.6

98.8

99.0

99.2

99.4

99.6

99.8

100.

0

100.

2

100.

4

100.

6

100.

8

101.

0

101.

2

101.

4

101.

6

101.

8

102.

0

102.

2

102.

4

102.

6

102.

8

103.

0

103.

2

103.

4

103.

6

103.

8

104.

0

104.

2

104.

4

104.

6

104.

8

105.

0

CU Sample Mean (% LC)

Pro

bab

ilit

y (%

)

1.9%

2.1%

2.3%

2.5%

2.7%

2.9%

3.1%

3.3%

3.5%

3.7%

3.9%

4.1%

4.3%

4.5%

Probability of Passing New USP 29 Content Uniformity Test (N = 3x10 = 30, SE = 2.0-4.6, SM = 1.5)

50%

55%

60%

65%

70%

75%

80%

85%

90%

95%

100%

95.0

95.2

95.4

95.6

95.8

96.0

96.2

96.4

96.6

96.8

97.0

97.2

97.4

97.6

97.8

98.0

98.2

98.4

98.6

98.8

99.0

99.2

99.4

99.6

99.8

100.

0

100.

2

100.

4

100.

6

100.

8

101.

0

101.

2

101.

4

101.

6

101.

8

102.

0

102.

2

102.

4

102.

6

102.

8

103.

0

103.

2

103.

4

103.

6

103.

8

104.

0

104.

2

104.

4

104.

6

104.

8

105.

0

CU Sample Mean (% LC)

Pro

bab

ilit

y (%

)

2%

2.2%

2.4%

2.6%

2.8%

3%

3.2%

3.4%

3.6%

3.8%

4%

4.2%

4.4%

4.6%

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Sampling Plan 2 (3 x 10): Current USP Test (SE: 1.8 – 4.5, SM: 1.8 – 2.2)

Probability of Passing Current USP Tablet Content Uniformity Test (N = 3x10 = 30, SE = 1.8-4.4, SM = 2.0)

50%

55%

60%

65%

70%

75%

80%

85%

90%

95%

100%

95.0

95.2

95.4

95.6

95.8

96.0

96.2

96.4

96.6

96.8

97.0

97.2

97.4

97.6

97.8

98.0

98.2

98.4

98.6

98.8

99.0

99.2

99.4

99.6

99.8

100.

0

100.

2

100.

4

100.

6

100.

8

101.

0

101.

2

101.

4

101.

6

101.

8

102.

0

102.

2

102.

4

102.

6

102.

8

103.

0

103.

2

103.

4

103.

6

103.

8

104.

0

104.

2

104.

4

104.

6

104.

8

105.

0

CU Sample Mean (% LC)

Pro

bab

ilit

y (%

)

1.8%

2%

2.2%

2.4%

2.6%

2.8%

3%

3.2%

3.4%

3.6%

3.8%

4%

4.2%

4.4%

Probability of Passing Current USP Tablet Content Uniformity Test (N = 3x10 = 30, SE = 1.9-4.5, SM = 2.0)

50%

55%

60%

65%

70%

75%

80%

85%

90%

95%

100%

95.0

95.2

95.4

95.6

95.8

96.0

96.2

96.4

96.6

96.8

97.0

97.2

97.4

97.6

97.8

98.0

98.2

98.4

98.6

98.8

99.0

99.2

99.4

99.6

99.8

100.

0

100.

2

100.

4

100.

6

100.

8

101.

0

101.

2

101.

4

101.

6

101.

8

102.

0

102.

2

102.

4

102.

6

102.

8

103.

0

103.

2

103.

4

103.

6

103.

8

104.

0

104.

2

104.

4

104.

6

104.

8

105.

0

CU Sample Mean (% LC)

Pro

bab

ilit

y (%

)

1.9%

2.1%

2.3%

2.5%

2.7%

2.9%

3.1%

3.3%

3.5%

3.7%

3.9%

4.1%

4.3%

4.5%

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Sampling Plan 2 (3 x 10): Current USP Test (SE: 2.2 – 4.9, SM: 1.8 – 2.2)

Probability of Passing Current USP Capsule Content Uniformity Test (N = 3x10 = 30, SE = 2.2-4.8, SM = 2.0)

50%

55%

60%

65%

70%

75%

80%

85%

90%

95%

100%

95.0

95.2

95.4

95.6

95.8

96.0

96.2

96.4

96.6

96.8

97.0

97.2

97.4

97.6

97.8

98.0

98.2

98.4

98.6

98.8

99.0

99.2

99.4

99.6

99.8

100.

0

100.

2

100.

4

100.

6

100.

8

101.

0

101.

2

101.

4

101.

6

101.

8

102.

0

102.

2

102.

4

102.

6

102.

8

103.

0

103.

2

103.

4

103.

6

103.

8

104.

0

104.

2

104.

4

104.

6

104.

8

105.

0

CU Sample Mean (% LC)

Pro

bab

ilit

y (%

)

2.2%

2.4%

2.6%

2.8%

3%

3.2%

3.4%

3.6%

3.8%

4%

4.2%

4.4%

4.6%

4.8%

Probability of Passing Current USP Capsule Content Uniformity Test (N = 3x10 = 30, SE = 2.3-4.9, SM = 2.0)

50%

55%

60%

65%

70%

75%

80%

85%

90%

95%

100%

95.0

95.2

95.4

95.6

95.8

96.0

96.2

96.4

96.6

96.8

97.0

97.2

97.4

97.6

97.8

98.0

98.2

98.4

98.6

98.8

99.0

99.2

99.4

99.6

99.8

100.

0

100.

2

100.

4

100.

6

100.

8

101.

0

101.

2

101.

4

101.

6

101.

8

102.

0

102.

2

102.

4

102.

6

102.

8

103.

0

103.

2

103.

4

103.

6

103.

8

104.

0

104.

2

104.

4

104.

6

104.

8

105.

0

CU Sample Mean (% LC)

Pro

bab

ilit

y (%

)

2.3%

2.5%

2.7%

2.9%

3.1%

3.3%

3.5%

3.7%

3.9%

4.1%

4.3%

4.5%

4.7%

4.9%

INSTITUTE OF VALIDATION TECHNOLOGY

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Sampling Plan 2 (3 x 10): New USP Test (SE: 1.7 – 4.4, SM: 1.8 – 2.2)

Probability of Passing New USP 29 Content Uniformity Test (N = 3x10 = 30, SE = 1.7-4.3, SM = 2.0)

50%

55%

60%

65%

70%

75%

80%

85%

90%

95%

100%

95.0

95.2

95.4

95.6

95.8

96.0

96.2

96.4

96.6

96.8

97.0

97.2

97.4

97.6

97.8

98.0

98.2

98.4

98.6

98.8

99.0

99.2

99.4

99.6

99.8

100.

0

100.

2

100.

4

100.

6

100.

8

101.

0

101.

2

101.

4

101.

6

101.

8

102.

0

102.

2

102.

4

102.

6

102.

8

103.

0

103.

2

103.

4

103.

6

103.

8

104.

0

104.

2

104.

4

104.

6

104.

8

105.

0

CU Sample Mean (% LC)

Pro

bab

ilit

y (%

)

1.7%

1.9%

2.1%

2.3%

2.5%

2.7%

2.9%

3.1%

3.3%

3.5%

3.7%

3.9%

4.1%

4.3%

Probability of Passing New USP 29 Content Uniformity Test (N = 3x10 = 30, SE = 1.8-4.4, SM = 2.0)

50%

55%

60%

65%

70%

75%

80%

85%

90%

95%

100%

95.0

95.2

95.4

95.6

95.8

96.0

96.2

96.4

96.6

96.8

97.0

97.2

97.4

97.6

97.8

98.0

98.2

98.4

98.6

98.8

99.0

99.2

99.4

99.6

99.8

100.

0

100.

2

100.

4

100.

6

100.

8

101.

0

101.

2

101.

4

101.

6

101.

8

102.

0

102.

2

102.

4

102.

6

102.

8

103.

0

103.

2

103.

4

103.

6

103.

8

104.

0

104.

2

104.

4

104.

6

104.

8

105.

0

CU Sample Mean (% LC)

Pro

bab

ilit

y (%

)

1.8%

2%

2.2%

2.4%

2.6%

2.8%

3%

3.2%

3.4%

3.6%

3.8%

4%

4.2%

4.4%

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Sampling Plan 2 (3 x 10): Current USP Test (SE: 1.7 – 4.4, SM: 2.3 – 2.6)

Probability of Passing Current USP Tablet Content Uniformity Test (N = 3x10 = 30, SE = 1.7-4.3, SM = 2.5)

50%

55%

60%

65%

70%

75%

80%

85%

90%

95%

100%

95.0

95.2

95.4

95.6

95.8

96.0

96.2

96.4

96.6

96.8

97.0

97.2

97.4

97.6

97.8

98.0

98.2

98.4

98.6

98.8

99.0

99.2

99.4

99.6

99.8

100.

0

100.

2

100.

4

100.

6

100.

8

101.

0

101.

2

101.

4

101.

6

101.

8

102.

0

102.

2

102.

4

102.

6

102.

8

103.

0

103.

2

103.

4

103.

6

103.

8

104.

0

104.

2

104.

4

104.

6

104.

8

105.

0

CU Sample Mean (% LC)

Pro

bab

ilit

y (%

)

1.7%

1.9%

2.1%

2.3%

2.5%

2.7%

2.9%

3.1%

3.3%

3.5%

3.7%

3.9%

4.1%

4.3%

Probability of Passing Current USP Tablet Content Uniformity Test (N = 3x10 = 30, SE = 1.8-4.4, SM = 2.5)

50%

55%

60%

65%

70%

75%

80%

85%

90%

95%

100%

95.0

95.2

95.4

95.6

95.8

96.0

96.2

96.4

96.6

96.8

97.0

97.2

97.4

97.6

97.8

98.0

98.2

98.4

98.6

98.8

99.0

99.2

99.4

99.6

99.8

100.

0

100.

2

100.

4

100.

6

100.

8

101.

0

101.

2

101.

4

101.

6

101.

8

102.

0

102.

2

102.

4

102.

6

102.

8

103.

0

103.

2

103.

4

103.

6

103.

8

104.

0

104.

2

104.

4

104.

6

104.

8

105.

0

CU Sample Mean (% LC)

Pro

bab

ilit

y (%

)

1.8%

2%

2.2%

2.4%

2.6%

2.8%

3%

3.2%

3.4%

3.6%

3.8%

4%

4.2%

4.4%

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Sampling Plan 2 (3 x 10): Current USP Test (SE: 2.2 – 4.9, SM: 2.3 – 2.6)

Probability of Passing Current USP Capsule Content Uniformity Test (N = 3x10 = 30, SE = 2.2-4.8, SM = 2.5)

50%

55%

60%

65%

70%

75%

80%

85%

90%

95%

100%

95.0

95.2

95.4

95.6

95.8

96.0

96.2

96.4

96.6

96.8

97.0

97.2

97.4

97.6

97.8

98.0

98.2

98.4

98.6

98.8

99.0

99.2

99.4

99.6

99.8

100.

0

100.

2

100.

4

100.

6

100.

8

101.

0

101.

2

101.

4

101.

6

101.

8

102.

0

102.

2

102.

4

102.

6

102.

8

103.

0

103.

2

103.

4

103.

6

103.

8

104.

0

104.

2

104.

4

104.

6

104.

8

105.

0

CU Sample Mean (% LC)

Pro

bab

ilit

y (%

)

2.2%

2.4%

2.6%

2.8%

3%

3.2%

3.4%

3.6%

3.8%

4%

4.2%

4.4%

4.6%

4.8%

Probability of Passing Current USP Capsule Content Uniformity Test (N = 3x10 = 30, SE = 2.3-4.9, SM = 2.5)

50%

55%

60%

65%

70%

75%

80%

85%

90%

95%

100%

95.0

95.2

95.4

95.6

95.8

96.0

96.2

96.4

96.6

96.8

97.0

97.2

97.4

97.6

97.8

98.0

98.2

98.4

98.6

98.8

99.0

99.2

99.4

99.6

99.8

100.

0

100.

2

100.

4

100.

6

100.

8

101.

0

101.

2

101.

4

101.

6

101.

8

102.

0

102.

2

102.

4

102.

6

102.

8

103.

0

103.

2

103.

4

103.

6

103.

8

104.

0

104.

2

104.

4

104.

6

104.

8

105.

0

CU Sample Mean (% LC)

Pro

bab

ilit

y (%

)

2.3%

2.5%

2.7%

2.9%

3.1%

3.3%

3.5%

3.7%

3.9%

4.1%

4.3%

4.5%

4.7%

4.9%

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Sampling Plan 2 (3 x 10): New USP Test (SE: 1.6 – 4.3, SM: 2.3 – 2.6)

Probability of Passing New USP 29 Content Uniformity Test (N = 3x10 = 30, SE = 1.6-4.2, SM = 2.5)

50%

55%

60%

65%

70%

75%

80%

85%

90%

95%

100%

95.0

95.2

95.4

95.6

95.8

96.0

96.2

96.4

96.6

96.8

97.0

97.2

97.4

97.6

97.8

98.0

98.2

98.4

98.6

98.8

99.0

99.2

99.4

99.6

99.8

100.

0

100.

2

100.

4

100.

6

100.

8

101.

0

101.

2

101.

4

101.

6

101.

8

102.

0

102.

2

102.

4

102.

6

102.

8

103.

0

103.

2

103.

4

103.

6

103.

8

104.

0

104.

2

104.

4

104.

6

104.

8

105.

0

CU Sample Mean (% LC)

Pro

bab

ilit

y (%

)

1.6%

1.8%

2%

2.2%

2.4%

2.6%

2.8%

3%

3.2%

3.4%

3.6%

3.8%

4%

4.2%

Probability of Passing New USP 29 Content Uniformity Test (N = 3x10 = 30, SE = 1.7-4.3, SM = 2.5)

50%

55%

60%

65%

70%

75%

80%

85%

90%

95%

100%

95.0

95.2

95.4

95.6

95.8

96.0

96.2

96.4

96.6

96.8

97.0

97.2

97.4

97.6

97.8

98.0

98.2

98.4

98.6

98.8

99.0

99.2

99.4

99.6

99.8

100.

0

100.

2

100.

4

100.

6

100.

8

101.

0

101.

2

101.

4

101.

6

101.

8

102.

0

102.

2

102.

4

102.

6

102.

8

103.

0

103.

2

103.

4

103.

6

103.

8

104.

0

104.

2

104.

4

104.

6

104.

8

105.

0

CU Sample Mean (% LC)

Pro

bab

ilit

y (%

)

1.7%

1.9%

2.1%

2.3%

2.5%

2.7%

2.9%

3.1%

3.3%

3.5%

3.7%

3.9%

4.1%

4.3%

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Sampling Plan 2 (3 x 10): Current USP Test (SE: 1.6 – 4.3, SM: 2.7 – 2.9)

Probability of Passing Current USP Tablet Content Uniformity Test (N = 3x10 = 30, SE = 1.6-4.2, SM = 2.8)

50%

55%

60%

65%

70%

75%

80%

85%

90%

95%

100%

95.0

95.2

95.4

95.6

95.8

96.0

96.2

96.4

96.6

96.8

97.0

97.2

97.4

97.6

97.8

98.0

98.2

98.4

98.6

98.8

99.0

99.2

99.4

99.6

99.8

100.

0

100.

2

100.

4

100.

6

100.

8

101.

0

101.

2

101.

4

101.

6

101.

8

102.

0

102.

2

102.

4

102.

6

102.

8

103.

0

103.

2

103.

4

103.

6

103.

8

104.

0

104.

2

104.

4

104.

6

104.

8

105.

0

CU Sample Mean (% LC)

Pro

bab

ilit

y (%

)

1.6%

1.8%

2%

2.2%

2.4%

2.6%

2.8%

3%

3.2%

3.4%

3.6%

3.8%

4%

4.2%

Probability of Passing Current USP Tablet Content Uniformity Test (N = 3x10 = 30, SE = 1.7-4.3, SM = 2.8)

50%

55%

60%

65%

70%

75%

80%

85%

90%

95%

100%

95.0

95.2

95.4

95.6

95.8

96.0

96.2

96.4

96.6

96.8

97.0

97.2

97.4

97.6

97.8

98.0

98.2

98.4

98.6

98.8

99.0

99.2

99.4

99.6

99.8

100.

0

100.

2

100.

4

100.

6

100.

8

101.

0

101.

2

101.

4

101.

6

101.

8

102.

0

102.

2

102.

4

102.

6

102.

8

103.

0

103.

2

103.

4

103.

6

103.

8

104.

0

104.

2

104.

4

104.

6

104.

8

105.

0

CU Sample Mean (% LC)

Pro

bab

ilit

y (%

)

1.7%

1.9%

2.1%

2.3%

2.5%

2.7%

2.9%

3.1%

3.3%

3.5%

3.7%

3.9%

4.1%

4.3%

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Sampling Plan 2 (3 x 10): Current USP Test (SE: 2.1 – 4.8, SM: 2.7 – 2.9)

Probability of Passing Current USP Capsule Content Uniformity Test (N = 3x10 = 30, SE = 2.1-4.7, SM = 2.8)

50%

55%

60%

65%

70%

75%

80%

85%

90%

95%

100%

95.0

95.2

95.4

95.6

95.8

96.0

96.2

96.4

96.6

96.8

97.0

97.2

97.4

97.6

97.8

98.0

98.2

98.4

98.6

98.8

99.0

99.2

99.4

99.6

99.8

100.

0

100.

2

100.

4

100.

6

100.

8

101.

0

101.

2

101.

4

101.

6

101.

8

102.

0

102.

2

102.

4

102.

6

102.

8

103.

0

103.

2

103.

4

103.

6

103.

8

104.

0

104.

2

104.

4

104.

6

104.

8

105.

0

CU Sample Mean (% LC)

Pro

bab

ilit

y (%

)

2.1%

2.3%

2.5%

2.7%

2.9%

3.1%

3.3%

3.5%

3.7%

3.9%

4.1%

4.3%

4.5%

4.7%

Probability of Passing Current USP Capsule Content Uniformity Test (N = 3x10 = 30, SE = 2.2-4.8, SM = 2.8)

50%

55%

60%

65%

70%

75%

80%

85%

90%

95%

100%

95.0

95.2

95.4

95.6

95.8

96.0

96.2

96.4

96.6

96.8

97.0

97.2

97.4

97.6

97.8

98.0

98.2

98.4

98.6

98.8

99.0

99.2

99.4

99.6

99.8

100.

0

100.

2

100.

4

100.

6

100.

8

101.

0

101.

2

101.

4

101.

6

101.

8

102.

0

102.

2

102.

4

102.

6

102.

8

103.

0

103.

2

103.

4

103.

6

103.

8

104.

0

104.

2

104.

4

104.

6

104.

8

105.

0

CU Sample Mean (% LC)

Pro

bab

ilit

y (%

)

2.2%

2.4%

2.6%

2.8%

3%

3.2%

3.4%

3.6%

3.8%

4%

4.2%

4.4%

4.6%

4.8%

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Sampling Plan 2 (3 x 10): New USP Test (SE: 1.4 – 4.1, SM: 2.7 – 2.9)

Probability of Passing New USP 29 Content Uniformity Test (N = 3x10 = 30, SE = 1.4-4.0, SM = 2.8)

50%

55%

60%

65%

70%

75%

80%

85%

90%

95%

100%

95.0

95.2

95.4

95.6

95.8

96.0

96.2

96.4

96.6

96.8

97.0

97.2

97.4

97.6

97.8

98.0

98.2

98.4

98.6

98.8

99.0

99.2

99.4

99.6

99.8

100.

0

100.

2

100.

4

100.

6

100.

8

101.

0

101.

2

101.

4

101.

6

101.

8

102.

0

102.

2

102.

4

102.

6

102.

8

103.

0

103.

2

103.

4

103.

6

103.

8

104.

0

104.

2

104.

4

104.

6

104.

8

105.

0

CU Sample Mean (% LC)

Pro

bab

ilit

y (%

)

1.4%

1.6%

1.8%

2%

2.2%

2.4%

2.6%

2.8%

3%

3.2%

3.4%

3.6%

3.8%

4%

Probability of Passing New USP 29 Content Uniformity Test (N = 3x10 = 30, SE = 1.5-4.1, SM = 2.8)

50%

55%

60%

65%

70%

75%

80%

85%

90%

95%

100%

95.0

95.2

95.4

95.6

95.8

96.0

96.2

96.4

96.6

96.8

97.0

97.2

97.4

97.6

97.8

98.0

98.2

98.4

98.6

98.8

99.0

99.2

99.4

99.6

99.8

100.

0

100.

2

100.

4

100.

6

100.

8

101.

0

101.

2

101.

4

101.

6

101.

8

102.

0

102.

2

102.

4

102.

6

102.

8

103.

0

103.

2

103.

4

103.

6

103.

8

104.

0

104.

2

104.

4

104.

6

104.

8

105.

0

CU Sample Mean (% LC)

Pro

bab

ilit

y (%

)

1.5%

1.7%

1.9%

2.1%

2.3%

2.5%

2.7%

2.9%

3.1%

3.3%

3.5%

3.7%

3.9%

4.1%

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Sampling Plan 2 (3 x 10): Current USP Test (SE: 1.6 – 4.3, SM: 3.0 – 3.2)

Probability of Passing Current USP Tablet Content Uniformity Test (N = 3x10 = 30, SE = 1.6-4.2, SM = 3.1)

50%

55%

60%

65%

70%

75%

80%

85%

90%

95%

100%

95.0

95.2

95.4

95.6

95.8

96.0

96.2

96.4

96.6

96.8

97.0

97.2

97.4

97.6

97.8

98.0

98.2

98.4

98.6

98.8

99.0

99.2

99.4

99.6

99.8

100.

0

100.

2

100.

4

100.

6

100.

8

101.

0

101.

2

101.

4

101.

6

101.

8

102.

0

102.

2

102.

4

102.

6

102.

8

103.

0

103.

2

103.

4

103.

6

103.

8

104.

0

104.

2

104.

4

104.

6

104.

8

105.

0

CU Sample Mean (% LC)

Pro

bab

ilit

y (%

)

1.6%

1.8%

2%

2.2%

2.4%

2.6%

2.8%

3%

3.2%

3.4%

3.6%

3.8%

4%

4.2%

Probability of Passing Current USP Tablet Content Uniformity Test (N = 3x10 = 30, SE = 1.7-4.3, SM = 3.1)

50%

55%

60%

65%

70%

75%

80%

85%

90%

95%

100%

95.0

95.2

95.4

95.6

95.8

96.0

96.2

96.4

96.6

96.8

97.0

97.2

97.4

97.6

97.8

98.0

98.2

98.4

98.6

98.8

99.0

99.2

99.4

99.6

99.8

100.

0

100.

2

100.

4

100.

6

100.

8

101.

0

101.

2

101.

4

101.

6

101.

8

102.

0

102.

2

102.

4

102.

6

102.

8

103.

0

103.

2

103.

4

103.

6

103.

8

104.

0

104.

2

104.

4

104.

6

104.

8

105.

0

CU Sample Mean (% LC)

Pro

bab

ilit

y (%

)

1.7%

1.9%

2.1%

2.3%

2.5%

2.7%

2.9%

3.1%

3.3%

3.5%

3.7%

3.9%

4.1%

4.3%

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Sampling Plan 2 (3 x 10): Current USP Test (SE: 2.1 – 4.8, SM: 3.0 – 3.2)

Probability of Passing Current USP Capsule Content Uniformity Test (N = 3x10 = 30, SE = 2.1-4.7, SM = 3.1)

50%

55%

60%

65%

70%

75%

80%

85%

90%

95%

100%

95.0

95.2

95.4

95.6

95.8

96.0

96.2

96.4

96.6

96.8

97.0

97.2

97.4

97.6

97.8

98.0

98.2

98.4

98.6

98.8

99.0

99.2

99.4

99.6

99.8

100.

0

100.

2

100.

4

100.

6

100.

8

101.

0

101.

2

101.

4

101.

6

101.

8

102.

0

102.

2

102.

4

102.

6

102.

8

103.

0

103.

2

103.

4

103.

6

103.

8

104.

0

104.

2

104.

4

104.

6

104.

8

105.

0

CU Sample Mean (% LC)

Pro

bab

ilit

y (%

)

2.1%

2.3%

2.5%

2.7%

2.9%

3.1%

3.3%

3.5%

3.7%

3.9%

4.1%

4.3%

4.5%

4.7%

Probability of Passing Current USP Capsule Content Uniformity Test (N = 3x10 = 30, SE = 2.2-4.8, SM = 3.1)

50%

55%

60%

65%

70%

75%

80%

85%

90%

95%

100%

95.0

95.2

95.4

95.6

95.8

96.0

96.2

96.4

96.6

96.8

97.0

97.2

97.4

97.6

97.8

98.0

98.2

98.4

98.6

98.8

99.0

99.2

99.4

99.6

99.8

100.

0

100.

2

100.

4

100.

6

100.

8

101.

0

101.

2

101.

4

101.

6

101.

8

102.

0

102.

2

102.

4

102.

6

102.

8

103.

0

103.

2

103.

4

103.

6

103.

8

104.

0

104.

2

104.

4

104.

6

104.

8

105.

0

CU Sample Mean (% LC)

Pro

bab

ilit

y (%

)

2.2%

2.4%

2.6%

2.8%

3%

3.2%

3.4%

3.6%

3.8%

4%

4.2%

4.4%

4.6%

4.8%

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Sampling Plan 2 (3 x 10): New USP Test (SE: 1.4 – 4.1, SM: 3.0 – 3.2)

Probability of Passing New USP 29 Content Uniformity Test (N = 3x10 = 30, SE = 1.4-4.0, SM = 3.1)

50%

55%

60%

65%

70%

75%

80%

85%

90%

95%

100%

95.0

95.2

95.4

95.6

95.8

96.0

96.2

96.4

96.6

96.8

97.0

97.2

97.4

97.6

97.8

98.0

98.2

98.4

98.6

98.8

99.0

99.2

99.4

99.6

99.8

100.

0

100.

2

100.

4

100.

6

100.

8

101.

0

101.

2

101.

4

101.

6

101.

8

102.

0

102.

2

102.

4

102.

6

102.

8

103.

0

103.

2

103.

4

103.

6

103.

8

104.

0

104.

2

104.

4

104.

6

104.

8

105.

0

CU Sample Mean (% LC)

Pro

bab

ilit

y (%

)

1.4%

1.6%

1.8%

2%

2.2%

2.4%

2.6%

2.8%

3%

3.2%

3.4%

3.6%

3.8%

4%

Probability of Passing New USP 29 Content Uniformity Test (N = 3x10 = 30, SE = 1.5-4.1, SM = 3.1)

50%

55%

60%

65%

70%

75%

80%

85%

90%

95%

100%

95.0

95.2

95.4

95.6

95.8

96.0

96.2

96.4

96.6

96.8

97.0

97.2

97.4

97.6

97.8

98.0

98.2

98.4

98.6

98.8

99.0

99.2

99.4

99.6

99.8

100.

0

100.

2

100.

4

100.

6

100.

8

101.

0

101.

2

101.

4

101.

6

101.

8

102.

0

102.

2

102.

4

102.

6

102.

8

103.

0

103.

2

103.

4

103.

6

103.

8

104.

0

104.

2

104.

4

104.

6

104.

8

105.

0

CU Sample Mean (% LC)

Pro

bab

ilit

y (%

)

1.5%

1.7%

1.9%

2.1%

2.3%

2.5%

2.7%

2.9%

3.1%

3.3%

3.5%

3.7%

3.9%

4.1%

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Sampling Plan 2 (3 x 10): Current USP Test (SE: 1.4 – 4.1, SM: 3.3 – 3.5)

Probability of Passing Current USP Tablet Content Uniformity Test (N = 3x10 = 30, SE = 1.4-4.0, SM = 3.4)

50%

55%

60%

65%

70%

75%

80%

85%

90%

95%

100%

95.0

95.2

95.4

95.6

95.8

96.0

96.2

96.4

96.6

96.8

97.0

97.2

97.4

97.6

97.8

98.0

98.2

98.4

98.6

98.8

99.0

99.2

99.4

99.6

99.8

100.

0

100.

2

100.

4

100.

6

100.

8

101.

0

101.

2

101.

4

101.

6

101.

8

102.

0

102.

2

102.

4

102.

6

102.

8

103.

0

103.

2

103.

4

103.

6

103.

8

104.

0

104.

2

104.

4

104.

6

104.

8

105.

0

CU Sample Mean (% LC)

Pro

bab

ilit

y (%

)

1.4%

1.6%

1.8%

2%

2.2%

2.4%

2.6%

2.8%

3%

3.2%

3.4%

3.6%

3.8%

4%

Probability of Passing Current USP Tablet Content Uniformity Test (N = 3x10 = 30, SE = 1.5-4.1, SM = 3.4)

50%

55%

60%

65%

70%

75%

80%

85%

90%

95%

100%

95.0

95.2

95.4

95.6

95.8

96.0

96.2

96.4

96.6

96.8

97.0

97.2

97.4

97.6

97.8

98.0

98.2

98.4

98.6

98.8

99.0

99.2

99.4

99.6

99.8

100.

0

100.

2

100.

4

100.

6

100.

8

101.

0

101.

2

101.

4

101.

6

101.

8

102.

0

102.

2

102.

4

102.

6

102.

8

103.

0

103.

2

103.

4

103.

6

103.

8

104.

0

104.

2

104.

4

104.

6

104.

8

105.

0

CU Sample Mean (% LC)

Pro

bab

ilit

y (%

)

1.5%

1.7%

1.9%

2.1%

2.3%

2.5%

2.7%

2.9%

3.1%

3.3%

3.5%

3.7%

3.9%

4.1%

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Sampling Plan 2 (3 x 10): Current USP Test (SE: 2.1 – 4.8, SM: 3.3 – 3.5)

Probability of Passing Current USP Capsule Content Uniformity Test (N = 3x10 = 30, SE = 2.1-4.7, SM = 3.4)

50%

55%

60%

65%

70%

75%

80%

85%

90%

95%

100%

95.0

95.2

95.4

95.6

95.8

96.0

96.2

96.4

96.6

96.8

97.0

97.2

97.4

97.6

97.8

98.0

98.2

98.4

98.6

98.8

99.0

99.2

99.4

99.6

99.8

100.

0

100.

2

100.

4

100.

6

100.

8

101.

0

101.

2

101.

4

101.

6

101.

8

102.

0

102.

2

102.

4

102.

6

102.

8

103.

0

103.

2

103.

4

103.

6

103.

8

104.

0

104.

2

104.

4

104.

6

104.

8

105.

0

CU Sample Mean (% LC)

Pro

bab

ilit

y (%

)

2.1%

2.3%

2.5%

2.7%

2.9%

3.1%

3.3%

3.5%

3.7%

3.9%

4.1%

4.3%

4.5%

4.7%

Probability of Passing Current USP Capsule Content Uniformity Test (N = 3x10 = 30, SE = 2.2-4.8, SM = 3.4)

50%

55%

60%

65%

70%

75%

80%

85%

90%

95%

100%

95.0

95.2

95.4

95.6

95.8

96.0

96.2

96.4

96.6

96.8

97.0

97.2

97.4

97.6

97.8

98.0

98.2

98.4

98.6

98.8

99.0

99.2

99.4

99.6

99.8

100.

0

100.

2

100.

4

100.

6

100.

8

101.

0

101.

2

101.

4

101.

6

101.

8

102.

0

102.

2

102.

4

102.

6

102.

8

103.

0

103.

2

103.

4

103.

6

103.

8

104.

0

104.

2

104.

4

104.

6

104.

8

105.

0

CU Sample Mean (% LC)

Pro

bab

ilit

y (%

)

2.2%

2.4%

2.6%

2.8%

3%

3.2%

3.4%

3.6%

3.8%

4%

4.2%

4.4%

4.6%

4.8%

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Sampling Plan 2 (3 x 10): New USP Test (SE: 1.0 – 3.7, SM: 3.3 – 3.5)

Probability of Passing New USP 29 Content Uniformity Test (N = 3x10 = 30, SE = 1.0-3.6, SM = 3.4)

50%

55%

60%

65%

70%

75%

80%

85%

90%

95%

100%

95.0

95.2

95.4

95.6

95.8

96.0

96.2

96.4

96.6

96.8

97.0

97.2

97.4

97.6

97.8

98.0

98.2

98.4

98.6

98.8

99.0

99.2

99.4

99.6

99.8

100.

0

100.

2

100.

4

100.

6

100.

8

101.

0

101.

2

101.

4

101.

6

101.

8

102.

0

102.

2

102.

4

102.

6

102.

8

103.

0

103.

2

103.

4

103.

6

103.

8

104.

0

104.

2

104.

4

104.

6

104.

8

105.

0

CU Sample Mean (% LC)

Pro

bab

ilit

y (%

)

1%

1.2%

1.4%

1.6%

1.8%

2%

2.2%

2.4%

2.6%

2.8%

3%

3.2%

3.4%

3.6%

Probability of Passing New USP 29 Content Uniformity Test (N = 3x10 = 30, SE = 1.1-3.7, SM = 3.4)

50%

55%

60%

65%

70%

75%

80%

85%

90%

95%

100%

95.0

95.2

95.4

95.6

95.8

96.0

96.2

96.4

96.6

96.8

97.0

97.2

97.4

97.6

97.8

98.0

98.2

98.4

98.6

98.8

99.0

99.2

99.4

99.6

99.8

100.

0

100.

2

100.

4

100.

6

100.

8

101.

0

101.

2

101.

4

101.

6

101.

8

102.

0

102.

2

102.

4

102.

6

102.

8

103.

0

103.

2

103.

4

103.

6

103.

8

104.

0

104.

2

104.

4

104.

6

104.

8

105.

0

CU Sample Mean (% LC)

Pro

bab

ilit

y (%

)

1.1%

1.3%

1.5%

1.7%

1.9%

2.1%

2.3%

2.5%

2.7%

2.9%

3.1%

3.3%

3.5%

3.7%

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Sampling Plan 2 (3 x 10): Current USP Test (SE: 1.0 – 3.7, SM: 3.6 – 3.8)

Probability of Passing Current USP Tablet Content Uniformity Test (N = 3x10 = 30, SE = 1.0-3.6, SM = 3.7)

50%

55%

60%

65%

70%

75%

80%

85%

90%

95%

100%

95.0

95.2

95.4

95.6

95.8

96.0

96.2

96.4

96.6

96.8

97.0

97.2

97.4

97.6

97.8

98.0

98.2

98.4

98.6

98.8

99.0

99.2

99.4

99.6

99.8

100.

0

100.

2

100.

4

100.

6

100.

8

101.

0

101.

2

101.

4

101.

6

101.

8

102.

0

102.

2

102.

4

102.

6

102.

8

103.

0

103.

2

103.

4

103.

6

103.

8

104.

0

104.

2

104.

4

104.

6

104.

8

105.

0

CU Sample Mean (% LC)

Pro

bab

ilit

y (%

)

1%

1.2%

1.4%

1.6%

1.8%

2%

2.2%

2.4%

2.6%

2.8%

3%

3.2%

3.4%

3.6%

Probability of Passing Current USP Tablet Content Uniformity Test (N = 3x10 = 30, SE = 1.1-3.7, SM = 3.7)

50%

55%

60%

65%

70%

75%

80%

85%

90%

95%

100%

95.0

95.2

95.4

95.6

95.8

96.0

96.2

96.4

96.6

96.8

97.0

97.2

97.4

97.6

97.8

98.0

98.2

98.4

98.6

98.8

99.0

99.2

99.4

99.6

99.8

100.

0

100.

2

100.

4

100.

6

100.

8

101.

0

101.

2

101.

4

101.

6

101.

8

102.

0

102.

2

102.

4

102.

6

102.

8

103.

0

103.

2

103.

4

103.

6

103.

8

104.

0

104.

2

104.

4

104.

6

104.

8

105.

0

CU Sample Mean (% LC)

Pro

bab

ilit

y (%

)

1.1%

1.3%

1.5%

1.7%

1.9%

2.1%

2.3%

2.5%

2.7%

2.9%

3.1%

3.3%

3.5%

3.7%

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Sampling Plan 2 (3 x 10): Current USP Test (SE: 1.9 – 4.6, SM: 3.6 – 3.8)

Probability of Passing Current USP Capsule Content Uniformity Test (N = 3x10 = 30, SE = 1.9-4.5, SM = 3.7)

50%

55%

60%

65%

70%

75%

80%

85%

90%

95%

100%

95.0

95.2

95.4

95.6

95.8

96.0

96.2

96.4

96.6

96.8

97.0

97.2

97.4

97.6

97.8

98.0

98.2

98.4

98.6

98.8

99.0

99.2

99.4

99.6

99.8

100.

0

100.

2

100.

4

100.

6

100.

8

101.

0

101.

2

101.

4

101.

6

101.

8

102.

0

102.

2

102.

4

102.

6

102.

8

103.

0

103.

2

103.

4

103.

6

103.

8

104.

0

104.

2

104.

4

104.

6

104.

8

105.

0

CU Sample Mean (% LC)

Pro

bab

ilit

y (%

)

1.9%

2.1%

2.3%

2.5%

2.7%

2.9%

3.1%

3.3%

3.5%

3.7%

3.9%

4.1%

4.3%

4.5%

Probability of Passing Current USP Capsule Content Uniformity Test (N = 3x10 = 30, SE = 2.0-4.6, SM = 3.7)

50%

55%

60%

65%

70%

75%

80%

85%

90%

95%

100%

95.0

95.2

95.4

95.6

95.8

96.0

96.2

96.4

96.6

96.8

97.0

97.2

97.4

97.6

97.8

98.0

98.2

98.4

98.6

98.8

99.0

99.2

99.4

99.6

99.8

100.

0

100.

2

100.

4

100.

6

100.

8

101.

0

101.

2

101.

4

101.

6

101.

8

102.

0

102.

2

102.

4

102.

6

102.

8

103.

0

103.

2

103.

4

103.

6

103.

8

104.

0

104.

2

104.

4

104.

6

104.

8

105.

0

CU Sample Mean (% LC)

Pro

bab

ilit

y (%

)

2%

2.2%

2.4%

2.6%

2.8%

3%

3.2%

3.4%

3.6%

3.8%

4%

4.2%

4.4%

4.6%

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Sampling Plan 2 (3 x 10): New USP Test (SE: 0.7 – 3.4, SM: 3.6 – 3.8)

Probability of Passing New USP 29 Content Uniformity Test (N = 3x10 = 30, SE = 0.7-3.3, SM = 3.7)

50%

55%

60%

65%

70%

75%

80%

85%

90%

95%

100%

95.0

95.2

95.4

95.6

95.8

96.0

96.2

96.4

96.6

96.8

97.0

97.2

97.4

97.6

97.8

98.0

98.2

98.4

98.6

98.8

99.0

99.2

99.4

99.6

99.8

100.

0

100.

2

100.

4

100.

6

100.

8

101.

0

101.

2

101.

4

101.

6

101.

8

102.

0

102.

2

102.

4

102.

6

102.

8

103.

0

103.

2

103.

4

103.

6

103.

8

104.

0

104.

2

104.

4

104.

6

104.

8

105.

0

CU Sample Mean (% LC)

Pro

bab

ilit

y (%

)

0.7%

0.9%

1.1%

1.3%

1.5%

1.7%

1.9%

2.1%

2.3%

2.5%

2.7%

2.9%

3.1%

3.3%

Probability of Passing New USP 29 Content Uniformity Test (N = 3x10 = 30, SE = 0.8-3.4, SM = 3.7)

50%

55%

60%

65%

70%

75%

80%

85%

90%

95%

100%

95.0

95.2

95.4

95.6

95.8

96.0

96.2

96.4

96.6

96.8