Acceptable Quality Level (AQL) SOP for Tablets and Capsules

In short: AQL inspection is a statistical sampling check of visual defects in bulk tablets or capsules before packing. This example SOP shows how to choose containers, draw a sample, classify defects as critical, major or minor, apply acceptance limits and handle failures. All sample sizes and limits shown are example in-house criteria, to be adapted under your own quality system.

Objective

To define a procedure for Acceptable Quality Level (AQL) sampling and visual inspection of bulk tablets and capsules before bulk approval.

Scope

This example SOP applies to bulk approval of manufactured core tablets, coated tablets and capsules at a manufacturing site, at the semi-finished stage and before primary packing. The same approach can be used at other stages (compression, encapsulation, coating, packing) when the site’s quality system calls for it.

Responsibility

• Production officer: submits the completed and signed batch manufacturing record (BMR) to QA, performs 100% visual inspection where required, and reports visual abnormalities.
• QA officer (authorised designee): selects containers, draws the sample, inspects it, records the result and decides on release of the bulk.
• Head of QA: ensures compliance with the SOP and reviews repeated failures.

Background: what AQL means

AQL is the largest percentage of defective units that is still treated as acceptable as a long-run process average. A sampling plan states the sample size and the number of defects that leads to acceptance (the acceptance number) or rejection (the rejection number). Attribute inspection simply classifies each unit as defective or not, or counts defects per unit.

The widely used standard for this is ISO 2859-1 (sampling procedures for inspection by attributes, lot-by-lot, indexed by AQL), with the US equivalent ANSI/ASQ Z1.4. These are paid standards, so their tables are not reproduced here. The method works as follows:

1. Choose an inspection level. General level II is the usual default; levels I and III give less or more discrimination, and special levels S-1 to S-4 are used for small samples.
2. Find the sample size code letter from the lot size and the inspection level.
3. Read the sample size and the acceptance and rejection numbers for the chosen AQL (a separate AQL can be set for each defect class).
4. Normal, tightened and reduced inspection are switched according to the recent history of lots.

Use your licensed copy of the standard for the real tables. The sample sizes in this SOP are the site’s own simplified example plan.

Under US GMP, 21 CFR 211.165(d) expects acceptance criteria for sampling and testing to be adequate to assure batches meet specification and appropriate statistical quality control criteria, which include appropriate acceptance and/or rejection levels. A documented AQL plan is one way to show this for visual attributes.

Definitions

Procedure

1. When AQL is applied

1. AQL checks are done at the semi-finished stage for commercial batches of tablets and capsules.
2. For process validation batches, perform 100% visual inspection and record it in the batch record. Separate the rejects and classify them as critical, major or minor.
3. If the visual inspection trend in validation is satisfactory, the validation report may recommend AQL sampling for commercial batches.
4. AQL is carried out only for products on the approved AQL product list. Products with a poor defect history stay on 100% visual inspection.

2. Selecting containers

1. The production officer submits the completed, signed BMR to QA and informs QA that the bulk is ready for AQL.
2. QA checks product name, batch number, manufacturing date and expiry date and selects the containers.
3. The number of containers to sample, per part lot for coated tablets or per batch for capsules and uncoated tablets, is set as follows (example in-house criterion):
   • Up to 10 containers: sample all of them.
   • More than 10 containers (n): sample the first 5 and last 5 fully, then for the remaining (n minus 10) containers sample the square root of that number plus 1. Round any fractional result up.
4. For coated tablets coated in several lots, treat each lot’s size as the batch size.

3. Drawing and inspecting the sample

1. Take an equal quantity from each selected container into a labelled polyethylene bag. Where the sample is fixed by count, divide the required count by the number of containers (for example 1,250 units over 9 containers is about 139 per container) and form a composite sample. Sampling by weight can use the average weight, or count by hand.
2. For coated tablets made in several part lots, draw the sample for each part lot separately (for example 800 tablets per part lot, or 160 tablets from each of 5 containers).
3. Inspect each unit on the inspection trolley in the inspection cubicle. For tablets, check both sides.
4. Production’s 100% inspection and QA’s AQL inspection should be done under the same conditions, in the same area and with the same type of trolley.
5. The sample size follows the site’s table, which is based on general inspection level II. As an example in-house criterion that goes beyond that table, the sample is doubled for batches above 10,00,000 units compared with batches of 5,00,001 to 10,00,000 units.

4. Acceptance criteria

Example in-house criteria (percent defective allowed, by class):

Limit A is tied to a larger sample taken from containers as above. Limit B is a simpler plan in which 25 units are taken from each of 4 random locations in each container, and 100 units per container are pooled for evaluation. Choose one plan, justify it in the SOP and apply it consistently.

5. Defect classification

Broken tablets are classed as a major defect in the example below, and 100% inspection is carried out before loading bulk into the packing hopper.

Core tablets

Coated tablets

Capsules

Each site should keep a defect atlas with pictures and written definitions for each defect, approved by QA.

6. Decision and follow-up

1. Pass: the production officer weighs the bulk, records reconciliation and yield in the BMR, and releases the bulk to the next stage. The inspected good units are added to the last container of good units. Tie the sample bags immediately after sampling.
2. Fail: QA places the part lot or batch on hold, asks production to carry out 100% inspection, and raises an event to find the root cause (see handling of incidents and deviations). After 100% inspection, AQL is repeated and the bulk proceeds on its result.
3. Repeated failure: if 3 consecutive batches fail, investigate and stop further manufacture of the product until the cause is understood (example in-house criterion).
4. Complaints: if market complaints for visual defects recur and the investigation supports it, discontinue AQL for that product and revert to 100% inspection.
5. Restarting AQL: AQL for a product restarts only after the CAPA is implemented (see CAPA step by step).
6. Any abnormality, such as an unusually high rejection percentage for one defect, triggers an investigation and corrective and preventive action.
7. QA enters the result in the AQL record for core tablets, coated tablets or capsules and returns the BMR to production for final yield and reconciliation. The finished sample goes to QC with a test requisition. QA checks yield and the requisition, signs the BMR and releases the bulk in the ERP.
8. Issue the AQL record with each BMR. See also good documentation practices for BMR and BPR.

Records and retention

AQL inspection records form part of the batch record. Keep them at least 1 year after the expiry date of the respective product batch (EU GMP Part I Chapter 4 §4.11, or 5 years after QP certification if longer; 21 CFR 211.180(a)), or longer where local law or the marketing authorisation requires.

Annexures

1. AQL record for core tablets
2. AQL record for coated tablets
3. AQL record for capsules
4. Flow chart of the bulk approval procedure
5. AQL product list

Abbreviations

Frequently asked questions

Does AQL mean a batch is allowed to contain defects?

AQL describes the defect rate that the sampling plan is built to accept most of the time. It is a sampling tool, not permission to pack known defects. Critical defects should be kept as close to zero as possible, and any defects found are removed.

Is AQL sampling required by GMP?

GMP expects statistically sound acceptance criteria where sampling is used (see 21 CFR 211.165(d)) but does not prescribe AQL specifically. The plan is a site decision that should be justified and validated.

Can I use the example limits as they are?

No. The limits and sample sizes here are example in-house criteria. Set yours by risk assessment, product history and the standard you adopt.

References

1. ISO 2859-1:1999, Sampling procedures for inspection by attributes, Part 1: Sampling schemes indexed by acceptance quality limit (AQL) for lot-by-lot inspection (with later amendment).
2. US FDA. 21 CFR 211.165(d), Testing and release for distribution; 21 CFR 211.180(a), General requirements for records.
3. European Commission. EudraLex Volume 4, EU GMP Part I Chapter 4 Documentation, §4.11.