USFDA 483 to Laurus: Lapses in cleaning, documentation.

Observation 3:

Deficiencies in cleaning and maintenance: During walk through auditors observed rust on interior of equipment, residues on cleaned equipment, cleaned transfer hoses not stored and maintained in a way that residual solvents and moisture do not remain in hoses, cleaning tags missing on hoses, outside light could be seen through gaps in the room where product is packed.

Observation 4:

Documentation lapses: Accessories like transfer hoses and portable gauges for process water, gauge pressure, product transfer hoses are not identified and recorded in the BMR (Batch record);

Observation 5:

Lapses in document control: Pages for recording weights are printed by Production personnel and attached as annexure to Batch records; These pages can be used for any purpose as part of batch records; but are not issued, controlled and reconciled in such a way that data and records are complete and all pages are accounted for.

Ensure basic GMPs are followed whether it is intermediate or API operations, as elaborated in ICH Q7A and WHO GMP Guidelines (GMP is applicable from the point Key Starting Material is introduced into the process).

• Cleaning, cleaning validation, cleaning verification of equipment with checkpoints for rust, dirt, residues
• All transfer hoses (and other accessories as well) with identification tag and  identification of cleaning status; cleaned hoses may be stored by hanging from hooks in such a way that all liquid inside the hose drains out
• Facility maintenance; Gaps in room walls, partition panels, ceilings, windows etc cause ingress of outside dust, entry of insects during night time and add to contamination risks. Establish building maintenance procedures and periodic checks, systems to report and correct issues immediately.
• Regulatory expectations on completeness of documentation are going up; ALCOA+ principles demand complete documentation and traceability. Transfer hoses (as well as other equipment and accessories) used during a batch, their usage, cleaning are important aspects which can have an impact on product quality. Record of their identity, usage and traceability to cleaning records are important batch documentation data and are also critical for failure investigations (Note that Observation 1 in the 483 was on inadequate failure investigations).
• Ensure adequate controls in document issuance, usage and reconciliation. Even if annexure sheets are printed from a controlled DMS (Document Management System) software, the document control is complete only when each print of the page is traceable to the purpose for which it was printed, who, when and how many copies were printed, used, discarded and reconciled. Gaps in such controls give room for misuse and potential data integrity issues.

Systems and procedures apart, focus on training the team in Good Manufacturing Practices (GMP), and also on guiding and coaching them to embrace the true essence and intent of GMP.