4. Bulk Holding Time Study Report

8/9/2019 4. Bulk Holding Time Study Report

1/8

CTCBIO INC. Tadalafil Orally Soluble Film 20mg

Confidential document Hold time study

Jul. 29, 2013 page 1/ 8

Hold time study report of

CDFF0213

(Tadalafil Orally Soluble Film 20mg)

Project No. CDFF0213

Document ID PD-PS1-00

Version No. 00

CTCBIO INC.


2/8



Jul. 29, 2013 page 2/ 8

Revision History

Revision No. Date of Revision Details of Revision Revised by

00 July 29, 2013 Initial issue JunGi Kim

Comment

Limit for the waiting period of half-finished products was established for each process.

Investigator Product

research team

Junior

researcher

JunGi Kim (Signature) Date: Jul. 29, 2013

Reviewed by Product

research team

Chief

researcher

SuJun Park (Signature) Date: Jul. 29, 2013

Approved by Product

research team

Senior

researcher

BongSang Lee (Signature) Date: Jul. 29, 2013


3/8



Jul. 29, 2013 page 3/ 8

Contents

1. Summary ............................................................................................................................ 4

2. Purpose ............................................................................................................................... 4

3. Specimen ............................................................................................................................ 4

4. Test Period and Schedule .................................................................................................. 4

5. Test Item ............................................................................................................................. 5

6. Test Methods and Standards ............................................................................................ 5

7. Results ................................................................................................................................ 7

8. Conclusions ........................................................................................................................ 8


4/8



Jul. 29, 2013 page 4/ 8

1. Summary

Establishing the waiting period that is available for half-finished products in each

process of CDFF0213 (Tadalafil Orally Soluble Film 20mg)

2. Purpose

Limit for the waiting period of half-finished products in each process were established

to ensure stability of half-finished products and effective production.

3. Specimen

[Specimen]

- Tadalafil Orally Soluble Film 20mg for lab scale up test

- Lot No.: T002

4. Test Period and Schedule

Test date Process Duration

Jul. 08, 2013Initiation of manufacturing film

solution-

Jul. 10Transfer and coating - Initial film solution

- Initial coating & drying

Jul. 13 - - 3rdday film solution

Jul. 15 - - 5thday film solution

Jul. 17 - - 1stweek coating & drying

Jul. 24 - - 2ndweek coating & drying


5/8



Jul. 29, 2013 page 5/ 8

5. Test Item

Process Test item

Preparation of film solution

1. Content difference between the upper and lower

layers by time and mean weight of the film2.

Increment of impurities by time

3. Microbial limit test by time

(only on 3rdand 5thdays)

Coating & Drying

1. Confirmation of content by time

2. Confirmation of film weight by time

3. Confirmation of loss on drying by time

6. Test Methods and Standards

[Film solution manufacturing process]

(1)Collection of film solution for test

More than 1kg of finished film solution was collected and put in a 1,000-mL

measuring cylinder, covered the opening with plastic wrap and left for maximum 5

days at room temperature (25).

(The initial data of film weight and content test are replaced by those of the initial

sample in the coating & drying process.)

(2)

Sample collection at each time point

For the content test on 3rdand 5thdays, sample was carefully collected on the

corresponding days at 5cm from the surface and approximately 5cm from the bottom

using a pipette. Impurity test and microbial limit test were conducted using the

sample obtained from the upper layer.

(3)Drying the samples

Base films placed on a glass plate was coated with the collected samples and then

dried under the designated conditions for time and temperature. The coating anddrying conditions are as follows.

Coating thickness 460um

Drying temperature 80

Duration of drying 60 min.

(4)Sample analysis

The dried films were evenly sliced and tested for the standard of Tadalafil Orally

Soluble Film 20m and for dosage form uniformity and impurity. Microbial limit test

for the film solution was conducted following the Microbiological examination of


6/8



Jul. 29, 2013 page 6/ 8

nonsterile products: Microbial enumeration tests, USP and the Microbiological

examination of nonsterile products: Tests for specified microorganism, USP .

(5)Standards

Content test

- The content in the initial sample and samples at each time point should be

95-105%.

- The content result at each time point should not be different by more than 2%

compared with the result at the initial time point.

- The content results between the upper and lower layers should not be

different by more than 2% among the samples at each time point.

-

The mean weight difference among 5 sites of the upper and lower layers

should not be more than 3mg among the samples at each time point.

Impurity test

- Impurity test results at each time point should be suitable, and the difference

between the initial and each time point should not be more than 0.1% for

individual unknown impurities and 0.2% for total impurities.

Microbial limit test

-

Microbial limit test results should be suitable at each time point.

[Coating & Drying process]

(1) Preparation of coating solution for test

The manufactured film solution was dried under the condition described below and

the base films were overlapped to the upper and lower surfaces. The packaging

material that was identical to the one described in the manufacture order was used for

packaging and then the samples were left for maximum 2 weeks at room temperature

(25) (packaging performed separately for different time points).

(2) Collection and analysis of samples at each time point

Samples were collected at each time point and tested for the standard of Tadalafil

Orally Soluble Film 20m and for dosage form uniformity and impurity.

(3) Standards

Contents

-

The result of content test at each time point should be 95-105%.


7/8



Jul. 29, 2013 page 7/ 8

- Difference between mean content at each time point and mean content at the

initial time point should not be greater than 2%.

- Difference in mean weight between each time point should not be greater

than 3mg.

Loss on drying

-

Results of loss on drying of samples at each time point, including the initial

sample, should be suitable.

- Difference in the results of loss on drying between the initial and each time

point should not be greater than 3%.

7.

Results

[Film solution manufacturing process]

Process Test itemTime point

Initial 3rdday 5thday

Manufacturing

of film solution

Content (%)

Upper layer 99.94 99.99 99.85

Lower layer 99.76 99.78 99.63

Content difference (%) 0.19 0.21 0.22

Suitability Suitable Suitable Suitable

Mean weight

of film (mg)

Upper layer 120.84 120.24 120.58

Lower layer 120.38 119.74 119.82

Difference in mean weight

(mg)0.10 0.50 0.76


Impurity

Individualknown

impurities

N.D. N.D. N.D.


Total

impuritiesN.D. N.D. N.D.


Microbial limit testNot

detectable

Not

detectable

Not

detectable



8/8



Jul. 29, 2013 page 8/ 8

[Coating & Drying process]

Process Test itemTime point

Initial 1 week 2 weeks

Coating &

Drying

Content (%) 100.15 100.47 100.03


Film weight (mg) 120.48mg 119.10mg 119.92mg


Loss on drying (%) 8.78 8.71 8.86


8. Conclusions

In this hold time study for manufacturing process of film solution and coating &

drying processes, the quality of half-finished products was not significantly reduced

by 5 days after completing the manufacturing process of film solution and by 2 weeks

after completing the coating & drying process.

These results indicate that the quality will be maintained up to the standard for 5 days

after completing the manufacturing process of film solution and for 2 weeks after

completing the coating & drying process. Therefore, the maximum storage time

before proceeding to the next process shall be 5 days and 14 days, respectively, after

the manufacturing process of film solution and after coating & drying process.

The maximum storage time after the coating & drying process refers to the period

until just before the packaging process, and the slitting process shall be completed

within the 14 days of maximum storage time.

4. Bulk Holding Time Study Report

Documents

Transcript of 4. Bulk Holding Time Study Report