Cleaning Validation Protocol for Encapsulation Machine

Your Company's Logo ) Company's Name

ABC Pharmaceutical Company

CLEANING VALIDATION PROTOCOL

Equipment Name

Issued on

Protocol Number

Date

CLVS-000

Location

Encapsulation Area

Room No. 000

Equipment Capsule-filling machine

Model Make and model

Manufacturer Company, Country

20.8.1 Cleaning Validation Protocol for Encapsulation Machine (Type A)

20.8.1.1 Objective

The objective of this protocol is to demonstrate that the cleaning procedure No. ABC-001 will successfully and consistently reduce the level of residues to a predetermined level of acceptability, so as to prevent contamination (product or cleaning process related) from adversely affecting the safety and quality of the next product manufactured.

20.8.1.2 Scope

This protocol will cover pre- and postcleaning of the capsule-filling machine type A for the capsule products (Figure 20.8.1.1). In the grouping matrix, products are divided into various groups based on their a. Water solubility b. Therapeutic dosage

FIGURE 20.8.1.1

Capsulation machine type A.

FIGURE 20.8.1.1

Capsulation machine type A.

c. Toxicity d. Batch size

From each group, one worst-case product is considered for cleaning validation. The following capsule products are encapsulated using this machine:

• Indomethacin 25 mg capsule

• Tetracycline 250 mg capsule

• Oxytetracycline 250 mg capsule

• Doxicycline 100 mg capsule

• Fluoxetine 20 mg capsule

• Azythromycin capsule

The worst-case products among the above-mentioned products are as shown in Table 20.8.1.1.

20.8.1.3 Responsibility

The following personnel are responsible for the execution of this protocol:

Validation officer/productionluf officer/QA inspector/QC chemist/machine operator. For details, please refer to Attachment II.

TABLE 20.8.1.1

Worst-Case Products of Capsulation Machine

TABLE 20.8.1.1

Worst-Case Products of Capsulation Machine

Products

Reason for Selecting as Worst Case

Oxyteracycline 250 mg

Three ingredients that are insoluble in water:

Aerosil 200 (7)

Magnesium stearate (7)

Talc fine (7)

Fluoxetine 20 mg

Minimum therapeutic dose (20 mg)

Oxytetracycline 250 mg

LD50 680 mg/kg oral rat

Indomethacin 25 mg

Largest batch size (1,000,000)

20.8.1.4 Description of the Cleaning Process

Capsule-filling machine ABC encapsulator will be cleaned manually as per SOP No.

ABC-001.

4.1 Label the machine "UNDER CLEANING" as per SOP No. ABC-002

4.2 Open the machine door

4.3 Remove the powder and empty capsules from the hoppers

4.4 Clean the inside of the machine removing powder and capsules by means of vacuum

4.5 Dismantle the powder hopper, capsule hopper, plastic pipe, powder receiver, sigments, and filling nozzle and keep them on a trolley

4.6 Wash these parts with water and dry them with compressed air

4.7 Clean the inside of the machine, outside doors of the machine, sorting machine, and check master with a clean wet towel

4.8 Open the dust collector, remove the powder from inside, and wash the powder receiver with water

4.9 Clean the dust collector from outside and the hoses with a wet towel free from dust

4.10 Assemble the machine if required as per SOP No. ABC-003

4.11 Label the machine "CLEAN"

4.12 Make entries in the cleaning, maintenance, and usage logbooks as per SOP No. ABC-004.

20.8.1.5 Description of the Sampling Process

20.8.1.5.1 Sampling Technique

The swab sampling technique is used to take samples from the capsule-filling machine.

20.8.1.5.2 Sampling Precautions

Before taking the sample, wear the following:

i. Gloves ii. Face mask

20.8.1.5.3 Procedure for Sampling

Samples of the internal surfaces are taken by moistening the swab (ready-made sterile cotton swab) with a suitable solvent (DlW/alcohol-water-alcohol). Sample a 25-cm2 area (see Figures 20.8.1.2 through 20.8.1.5) and place the swab in a test tube containing 10 mL of solvent (suitable solvent). Swab samples from each part of the capsule-filling machine are collected as per Table 20.8.1.2.

20.8.1.5.4 Handling of Samples i. After collecting swab samples for MAC, they are kept in the refrigerator.

ii. Swabs samples for the HPLC analysis collected at the time of manufacturing analysis should be completed within 24 h from the time of collection.

iii. HPLC samples should be kept at room temperature for at least 2 h before testing.

TABLE 20.8.1.2

Surface Swabs Sampling Description

TABLE 20.8.1.2

Surface Swabs Sampling Description

Description

Sample Location

Sample ID

Reference

Capsule-filling machine

Disc top surface

S1

Figure 20.8.1.2

Disc right surface

S2

Disc bottom surface

S3

Capsule channel-1

S4

Figure 20.8.1.3

Capsule channel-2

S5

Capsule channel-3

S6

Capsule channel-4

S7

Capsule channel-5

S8

Capsule channel-6

S9

Capsule hopper left

S10

Figure 20.8.1.4

Capsule hopper center

S11

Capsule hopper right

S12

Capsule tray left

S13

Figure 20.8.1.5

Capsule tray center

S14

Capsule tray right

S15

Filling nozzle-1

S16

Filling nozzle-2

S17

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FIGURE 20.8.1.2

Capsule machine disc and capsule hopper.

FIGURE 20.8.1.3

Capsule channels.

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Your Company's Name

FIGURE 20.8.1.4

Capsule hopper.

S13

S14

Capsule tray.

Your Company's L

Your Company's L

Your Company's N

Your Company's N

20.8.1.6 Test Functions a. Visual inspection: Inspection of the capsule-filling machine is performed visually, at the end of the cleaning procedure.

b. Maximum allowable carryover: The test for MAC of the final rinse/swab is performed as per the HPLC method suitable for each product residue.

Notes:

• Analysis will be carried out by pooling the 10 mL swab extraction for specific

• The validated HPLC test method is used for the determination of chemical c. Bio-burden test: The test for bio-burden is performed as per STM No. MC-0001 by the Microbiology section.

d. Swab recovery challenge test: The recovery challenge test should be performed of the swab sample as per the PDA Guideline.

20.8.1.7 Verification of Documents i. Verify the capsule-filling machine cleaning procedure.

ii. Verify the capsule-filling machine cleaning logbook records.

iii. Verify the cleaning operators and analyst training records (refer to Attachment V).

20.8.1.8 Documentation i. All analyses results are recorded in the analysis logbook.

ii. Printouts and chromatograms are attached to the validation report and a copy of that is also attached to the analytical logbook.

iii. All analyses and data should be verified by the second analyst.

iv. Cleaning validation officer will check all training records.

v. The final report for cleaning validation is prepared by the validation assurance officer.

20.8.1.9 Acceptance Criteria a. Visual inspection: The visible internal equipment surfaces and all critical and difficult-to-clean parts are optically free from visible residues.

b. Maximum allowable carryover: The active ingredient calculated (Z) is either equal to or less than the MAC.

analysis.

residues.

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MAC _ TDx BS x SF MAC _ LDD , where MAC is the maximum allowable carryover, TD is a single therapeutic dose, BS is the batch size of the next product to be manufactured in the same equipment, SF* is the safety factor (0.001), and LDD is the largest daily dose of the next product to be manufactured in the same equipment.

The calculated value is the maximum amount of active ingredient of worst-case product that is allowed to be carried over to the next batch. Calculation:

Y _ X x surface area, where Y is the active ingredient on the corresponding equipment part, X is the active ingredient recovered from 25 cm2 by swab from the corresponding equipment part, and surface area is the area of corresponding equipment parts A-O.

Z _ Y1 + Y2 + Y3 + Y4 + Y5 + Y6 + Y7 + Y8 + Y9 + Y10 + Y11 + Y12 + Y13 + Y14 + Y15, where Z is the total active ingredient recovered from the machine, Y1 is the active ingredient recovered from part S1, Y2 is the active ingredient recovered from part S2, Y3 is the active ingredient recovered from part S3, Y4 is the active ingredient recovered from part S4, Y5 is the active ingredient recovered from part S5, Y6 is the active ingredient recovered from part S6, Y7 is the active ingredient recovered from part S7, Y8 is the active ingredient recovered from part S8, Y9 is the active ingredient recovered from part S9, Y10 is the active ingredient recovered from part S10, Y11 is the active ingredient recovered from part S11, Y12 is the active ingredient recovered from part S12, Y13 is the active ingredient recovered from part S13, Y14 is the active ingredient recovered from part S14, and Y15 is the active ingredient recovered from part S15.

Acceptance criteria:

c. Bio-burden: The bio-burden should not be more than 33 cfu/25 cm2 for the swabs.

d. Swab recovery challenge test: The swab recovery challenge test should be 70% of the known concentration of standard spiked.

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20.8.1.10 List of Attachments

Attachment I Attachment II Attachment III Attachment IV Attachment V Attachment VI

Description of equipment and product Cleaning/testing responsibilities Sampling and testing plan Calculations for surface swabs Training record verification Swabs analysis results

Attachment VII Swab sampling recovery challenge test results

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