Dissolution investigation

In pharmaceutical quality control, when a product fails the S1 stage of dissolution (like the 78% result in your example), you don’t just blindly move on to testing more units at the S2 stage. The very first action in an Out of Specification (OOS) or atypical result investigation is to

**”Check the product history.”**

Here is exactly what that means and why it is a critical first step:

Why Check the History First?
The primary goal is to figure out if the failing result is a **true manufacturing defect** (something is wrong with the tablet/capsule itself) or a **laboratory error** (something went wrong during the test). Checking the history gives you the context needed to make this decision.

What Specifically Are You Checking ?

* **Previous Batch Performance:**

Have past batches of this exact product routinely passed S1 with high numbers (e.g., 95–100%), or do they usually hover dangerously close to the 90% limit? If previous batches routinely struggle, this failure might be a formulation or manufacturing issue.

* **Historical Trends:**

Is there a gradual downward trend in dissolution results over the last few months? Trend analysis can reveal systemic issues before they become catastrophic failures.

* **Equipment and Lab History:**

You need to check the history of the specific dissolution apparatus (baths, paddles, baskets) used for this test. Have there been recent calibration issues, maintenance work, or similar failures on this specific machine?

* **Analyst History:**

Is the analyst who performed the test new to this specific method? Have they had a higher-than-normal rate of OOS results recently? This isn’t about placing blame, but identifying if retraining on sample preparation or technique is required.

* **Method Robustness:** Is this specific testing method known to be highly variable? Some products have historically “noisy” data where a rogue low result occasionally pops up due to the nature of the chemical method.

### The Next Step
Once you review the history, if you find evidence of an obvious laboratory error (e.g., the analyst used the wrong pH buffer, or the machine wasn’t heating properly), you would typically invalidate the 78% result, document the error, fix the root cause, and repeat the S1 test.
If the history shows no obvious lab errors and the testing environment was perfect, the result is considered valid. **Only then** do you proceed to the **S2 stage**, testing an additional 6 units to see if the batch as a whole can still meet the wider acceptance criteria.