We are discussing Water System since last three articles about Water System. Today we shall discuss the three case studies and we shall get 15 learnings from those.
Inadequate Water System Design and Controls
1. The firm uses water from its water system as a component to manufacture the drug products, however, firm lack validation studies for it's water system.
2. The firm has not demonstrated that it can effectively design, control, maintain, and monitor the system, so it consistently produces pharmaceutical grade water that, at a minimum, meets the USP monograph for (b)(4) water and appropriate microbial limits.
It means 1. Water system not validated, 2 Water do no meet the USP specification, 3. neither comply with the appropriate microbial limits.
In response to this letter, authority requested for following:
3. A comprehensive, independent assessment of the water system design, control, and maintenance.
4. A thorough remediation plan to install and operate a suitable water system. Include a robust ongoing control, maintenance, and monitoring program to ensure the remediated system design consistently produces water adhering to (b)(4) Water, USP monograph specifications and appropriate microbial limits.
5. Ensure that firm's total microbial count limit for water is appropriate in view of the intended use of the products produced by your firm.
3. Your firm’s quality control unit failed to exercise its responsibility to ensure drug products manufactured are in compliance with CGMP and meet established specifications for identity, strength, quality, and purity (21 CFR 211.22).
1. The firm failed to have adequate procedures and personnel with the CGMP responsibilities and authority for oversight of the manufacture of your OTC drug products.
2.Firm could not provide procedures for investigations, corrective actions and preventive actions (CAPAs), change controls, recalls, qualification of suppliers, equipment cleaning, and water system monitoring.
3. Likewise, the firm releases components for use in manufacturing without identity testing and releases completed lots without appropriate release testing.
1. The firm uses (b)(4) Water as a component to manufacture the drug products that are released for distribution to U.S. consumers.
2. The firm did not establish that the (b)(4) Water system they use to manufacture the drug product is adequately designed, controlled, maintained, and monitored to ensure that it consistently produces water suitable for its intended use.
3. (b)(4) water must be suitable for its intended use and routinely tested to ensure ongoing conformance with appropriate chemical and microbiological attributes.
In response to this letter, provide the following:
4. A procedure for the water system monitoring that specifies routine microbial testing of water to ensure its acceptability for use in each batch of drug products produced by the firm.
5. The current action/alert limits for total counts and objectionable organisms used for your (b)(4) water system.
6. Ensure that the total count limits for firm's (b)(4) water are appropriately stringent in view of the intended use of each of the products produced by the firm.
7.The procedure governing the program for ongoing control, maintenance, and monitoring that ensures the remediated system consistently produces water that meets (b)(4) water, USP monograph specifications and appropriate microbial limits.
Summarise the learnings and audit on your site whether these non-compliances are there on your site.
Fill the gaps.