We had discussed about 10 mistakes one should avoid in Water System to avoid getting Warning Letters. This is part 2 with other 13 mistakes to be avoided:
Following non-compliances found which caused warning letter;
1.The firm failed to adequately validate the manufacturing process and water system used in the manufacture of the hand sanitizer and antibacterial hand soap drug products.
2.The batch records included unvalidated in-process adjustments, such as adding (b)(4) as-needed if the density of the antibacterial hand soap was low.
3.The firm did not demonstrate that the manufacturing processes were controlled to consistently yield a drug product of uniform character and quality.
4. The firm has not validated the water system, does not maintain procedures, and did not provide specifications upon request by investigators.
5.The firm lacks an ongoing program for monitoring process control to ensure stable manufacturing operations and consistent drug quality.
1. The firm's purified water system used to manufacture drug products was not designed and maintained appropriately for its intended use.
2. Firm's water system included a dead leg and was not continuously circulating, which could foster the development of biofilms. When the water was not in use, it sat stagnant in the system except when the (b)(4) points-of-use (POUs) were opened.
3. In firm's response, firm discussed the current controls in place for the water system and the use of testing data from their “validation report.” Firm also indicate they employ the use of (b)(4) during production on a (b)(4) basis. Firm commit to increase the testing frequency to include each batch of water produced for OTC drug products and to (b)(4).
4.Firm's response was found to be inadequate by authority. Firm failed to describe how the water system maintenance, cleaning process, seasonal variations, and other actual conditions of use were considered during the “validation” efforts and to provide adequate justification for the sampling frequency. Your response also fails to address that you do not perform (b)(4) testing on the (b)(4) that firm use during production.
5.Microbiological methods used for determining the quality of purified water and finished drug products were deficient.
1. The firm failed to adequately design, validate, and control the water system to ensure that it was suitable for producing water used in the formulation of the drug products.
2. Firm lacked water system validation, chemical and microbiological limits for component water, and routine monitoring for chemical and microbiological quality. Inadequate control and monitoring of the water system pose a potential risk for the presence of objectionable microbiological contamination in the drug products.
3.Pharmaceutical water must meet the Purified Water USP monograph, be suitable for its intended use, and routinely tested to ensure ongoing conformance with appropriate chemical and microbiological attributes. This was not complied by the firm.