Avoiding the small tests may mislead you to not identify the actual material. You may rely on the supplier and skip the testing. But what if the material is found to fail to meet the standard of Identity, purity, strength & other attributes?
The above observation was given due to the following gaps;
The firm failed to test incoming active pharmaceutical ingredients (e.g., camphor and menthol) and other components (e.g., deionized (DI) water) used to manufacture over-the-counter drug products to determine their identity, purity, strength, and other appropriate quality attributes.
For active pharmaceutical ingredients (API), The firm relied solely on certificates of analysis (COA) from suppliers where the firm has not established their reliability.
In addition, you have not shown that your water system can consistently produce water suitable for drug manufacturing, and, at a minimum, meets the USP monograph for purified water and appropriate microbial limits.
The firm has not shown that DI water is suitable for aqueous-based dosage form drug product manufacturing, and, at a minimum, meets the USP purified water monograph and appropriate microbial limits.
Further, the firm lacked sufficient testing of the DI water system.
Inadequate water system design is a repeat observation from the 2016 FDA inspection.
The firm has no record of testing water for Total Organic Carbon (TOC).
In the response, the firm stated, "All products produced since March 2020, have passed micro testing ensuring there are no TOC issues." The firm committed to purchasing a TOC meter but failed to provide a timeline for the purchase and validation of the equipment.
Further, the vendor stated in the TOC meter proposal provided by the firm's response that, based on the current design of the system, TOC will most likely not meet the specification and that a recirculation pump must be added to keep the TOC low.
But this response lacked details on whether the firm will establish appropriate TOC specifications and ensure that firm's water system is adequately designed to meet those specifications.
Since March 2020, the firm failed to monitor the conductivity of the water used as a component in your drug products.
The firm also failed to establish a specification for conductivity.
The firm's response failed to address the lack of a conductivity specification.
Furthermore, the firm’s water system point-of-use ports yielded elevated bioburden counts of 1.3 x 106 and 2.3 x 104 total plate count (TPC)/ml for water used as a component in the drug products.
The firm's action limit was (b)(4) TPC/ml. The firm's associated investigations did not adequately determine potential root cause(s) to fully investigate product impact.
The firm's response did not address bioburden failures that lacked adequate investigation. Also, in multiple instances, the pH of water system Line (b)(4) was out of specification with results ranging between 3.59 and 4.73.
The firm's pH specification was (b)(4). In the response, firm stated that batches manufactured during this period were reviewed and there was no evidence that batches were affected. However, the firm did not provide data to substantiate this claim.
Without routine water monitoring of an appropriately designed system, firm cannot ensure that its water meets minimum microbiological and chemical standards suitable for the manufacture of the drug products.
Review the system whether these gaps are there on your site or not.