About more than 127 Warning Letters given by USFDA are having above observation of 21 CFR 211.192
Let us discuss a few elements of MARCS-CMS 620576 — MARCH 17, 2022
Regulatory Authority said
"You lacked adequate investigations, including insufficient root cause determination and failure to expand investigations to all potentially affected batches."
"This statement that failure to expand the investigation." is also common in almost all the observations.
While reviewing the OOS investigation have you reviewed that study should be extended to all the impacted batches?
For example, your deviation report stated, “when transferring (b)(4) from formulation vessel to the ISO 5 filling space… the ink from the tubing started leeching into the solution.” It also stated, “It seems the ink, or the process by which the ink is applied to tubing changed.”
Although you rejected the sub-batch, the investigation lacked a determination of the root cause.
Note above sentence that even after the batch was rejected, the root cause was not identified properly.
Your investigation also lacked a well-justified scope, including a review of other batches of (b)(4) and other drug products manufactured using the same tubing that may have been adversely affected by this chemical contamination.
The investigation also lacked information relating to the toxicity of this foreign contaminant in parenteral products.
Your response is inadequate because you failed to evaluate the potential of ink leaching into previously manufactured batches of drug products.
You committed to performing a risk assessment to evaluate the change in transfer tubing.
However, you failed to provide your risk assessment in your subsequent responses.
Have you noticed a few things 1. The investigation was not extended to other batches, 2. the investigation lacked a determination of the root cause.3.investigation also lacked a well-justified scope, 4. The investigation also lacked information relating to the toxicity of this foreign contaminant in parenteral products. 5. Failed to evaluate the potential of ink leaching into previously manufactured batches of drug products, 6. Risk Assessment was committed but not provided in the response.
Now your assignment is that check the type of gaps are there in your investigations? If yes then pls review and take necessary actions as per the guidance & procedure.