SOP for Operation and Cleaning of Tablet Disintegration Tester

In short: This is an illustrative example SOP for operating and cleaning a double-basket tablet disintegration tester used for in-process checks. It shows the usual sections and checks. Adapt the details, instrument steps and frequencies to your own instrument manual, validated method and quality system before use.

Background

The disintegration test checks whether tablets or capsules break up within a stated time when moved up and down in a liquid at a set temperature. Disintegration here does not mean the unit or its active ingredient has fully dissolved. The apparatus and method are described in USP general chapter <701> Disintegration and in Ph. Eur. 2.9.1 (Disintegration of tablets and capsules); the Indian Pharmacopoeia carries its own corresponding text. USP, Ph. Eur. and JP texts were evaluated under ICH Q4B Annex 5(R1), which allows them to be used interchangeably for tablets and capsules, but not for tablets and capsules longer than 18 mm that need a different apparatus, nor for delayed-release, gastro-resistant or enteric-coated forms. Product-specific conditions (medium, use of discs) and acceptance criteria must come from the application dossier and the product’s registered specification.

In general terms, the apparatus consists of a basket-rack assembly with six transparent open tubes and a stainless steel mesh at the bottom, a beaker for the immersion fluid, a thermostatic arrangement that holds the fluid at the specified temperature, and a mechanism that raises and lowers the basket at a set rate over a fixed stroke length. In the harmonised text, as printed in the Japanese Pharmacopoeia (JP XVII, general test 6.09, which states that it is harmonised with Ph. Eur. and USP), the beaker is a 1000 mL low-form beaker, the thermostat holds the fluid between 35 and 39 °C, the basket moves at 29 to 32 cycles per minute through 53 to 57 mm, and immediate-release units are tested at 37 ± 2 °C unless the monograph says otherwise.

This template is a Production (IPQC) SOP. Disintegration testing for QC release is covered in a separate post: see SOP for operation and calibration of disintegration tester apparatus.

1. Objective

To lay down a procedure for the operation and cleaning of the tablet disintegration tester.

2. Scope

This SOP applies to the double-basket tablet disintegration tester used in the IPQC area of the manufacturing department at [site name]. Make and model: [e.g. as per equipment list].

3. Responsibility

• Officer / Executive, Production: operates and cleans the tester and fills in the logs.
• Head of Production (or designee): ensures this SOP is implemented effectively.
• Quality Assurance: reviews the logs and approves changes to this SOP.

4. Procedure

4.1 Preliminary checks

• Confirm the instrument is within its calibration due date, is clean, and is suitable for use. Cleanliness is checked immediately before use (21 CFR 211.67(b)(6)).
• Confirm the instrument is connected to a stabilised power supply.
• Fill the beaker with purified water or the medium specified in the product test method. In the original version of this SOP the beaker was filled to approximately 700 mL.
• Change the water in the water bath at the start of each shift and record the change in Annexure I. This frequency is an example in-house criterion; set your own after a risk assessment.

4.2 Operation

The key-by-key menu steps differ between makes and software versions, so follow the manufacturer’s operating manual. The sequence below shows what an operator generally does.

1. Switch the instrument on at the mains switch and wait for the start-up screen.
2. Select or create a program for the product. Enter the sample name, the apparatus type (for example, the standard basket-rack or the one for longer units, as the test method requires), the test time and the media temperature set point. Protect program entry with user-level passwords as defined in your computerised-system procedure.
3. Place one unit in each of the six tubes. Add a disc to each tube only if the product test method specifies or allows it.
4. Lower the basket-rack assembly into the immersion fluid and start the run.
5. When the run ends, lift the basket and observe the units against the acceptance criterion in the product specification. Repeat or investigate according to the specification and the OOS procedure; do not repeat tests without a documented reason.
6. Print or record the results, and attach them to the batch record or IPQC record.
7. Record use of the instrument in the equipment usage log.

4.3 Cleaning

1. After use, switch off the instrument and remove the basket-rack assembly.
2. Rinse the tubes, discs and mesh with potable water to remove product residue, then rinse with purified water.
3. Discard the water from the beaker, clean it and let it dry, or refill it for the next run if the same product is tested.
4. Wipe the outer surfaces of the instrument with a lint-free cloth moistened with purified water.
5. Remove or erase any labels or identification from the previous product, and protect the clean assembly from contamination until it is next used.
6. Record the cleaning in the equipment cleaning and usage log.

4.4 Logs and records

21 CFR 211.182 requires a log of major cleaning, maintenance and use of equipment, in time order, with the date, time, product and lot or batch number. The person who did the cleaning or maintenance and the person who double-checked it date and sign or initial the log (where automated equipment under 211.68 does the cleaning, only the person verifying it signs). 21 CFR 211.67 requires written cleaning procedures covering responsibility, schedule, methods, label removal and protection of clean equipment, and records of cleaning and inspection.

Records and logs must be kept at least 1 year after the expiry date of the respective product batch (EU GMP Part I, Chapter 4, paragraph 4.11, or 5 years after certification by the Qualified Person if longer; 21 CFR 211.180(a)), and longer if local law or the marketing authorisation requires.

4.5 Calibration and maintenance

The tester must be calibrated or verified under a written schedule (21 CFR 211.68(a)). Calibration covers the items in the instrument’s qualification, such as temperature, stroke rate, stroke length and basket dimensions. A calibration interval of six months or one year is a common example in-house criterion, not a regulatory number. Use the interval from your own calibration programme. See also SOP for calibration.

5. Annexure I: Water bath change and usage log (example)

6. Abbreviations

7. Frequently asked questions

Does disintegration mean the tablet has dissolved?

No. The pharmacopoeial definition says disintegration does not imply complete solution of the unit or of its active constituent. Dissolution is a separate test.

Can the same method be used for enteric-coated tablets?

The product’s registered method decides. ICH Q4B Annex 5(R1) does not treat the harmonised disintegration test as interchangeable for delayed-release, gastro-resistant or enteric-coated forms, so follow the specific method in the marketing authorisation or the pharmacopoeial monograph.

Do I need an equipment usage log for this tester?

Yes, for GMP. 21 CFR 211.182 asks for a log of major cleaning, maintenance and use, and EU GMP expects the same kind of traceability.

Related reading

• SOP for operation and calibration of disintegration tester apparatus
• SOP for calibration
• SOP for operation and cleaning of compression machine

References

1. US FDA. 21 CFR 211.67 (Equipment cleaning and maintenance), 21 CFR 211.68 (Automatic, mechanical and electronic equipment), 21 CFR 211.180(a) and 21 CFR 211.182 (Equipment cleaning and use log), ecfr.gov.
2. European Commission. EudraLex Volume 4, Part I, Chapter 4: Documentation (January 2011), paragraph 4.11.
3. ICH Q4B Annex 5(R1): Evaluation and recommendation of pharmacopoeial texts for use in the ICH regions on Disintegration Test general chapter (Step 4, 10 June 2009; R1 dated 27 September 2010), database.ich.org.
4. USP general chapter <701> Disintegration; European Pharmacopoeia 2.9.1 Disintegration of tablets and capsules; Japanese Pharmacopoeia, 17th edition (English version), general test 6.09 Disintegration Test, pmda.go.jp; Indian Pharmacopoeia, apparatus for disintegration test (edition in use at the site).

Revision history (example)