Deviation/Investigations/CAPAs

Follow up activities after EM

After EM activities are completed during manufacturing activities, plates are incubated in appropriate temperatures and appropriate incubation periods. After incubation the results are read and recorded onto EM data sheets. Microorganisms recovered from the EM plates that reach the alert or action levels are identified. Vitek® Microbial Identification System is an example of ID system used in QC labs. Non-viable particulate air results should be printed out on the day of manufacturing and attached onto EM datasheets.

EM excursions higher than or equal to Alert levels are out of specifications (OOS). OOS results should be documented in deviation reports. Deviation reports usually include the site of the excursion, its result(s), microbial ID results, manufacturing department’s response (cleaning activities of the room for example), and the next consecutive sample’s result.

EM excursions higher than or equal to action levels are first documented in deviation reports and are usually escalated to investigations. Investigation reports include the same information mentioned in previous paragraph plus any CAPAs issued and implemented, previous results trends from the same site, and if the deviation had any adverse impact on the product. Three consecutive alert level excursions of a site warrant an escalated investigation.
Three action level excursions will have a major investigation. Recovery of objectionable microorganisms, regardless of the count, will result in action level major investigation. During the time of a major investigation, production may be halted until quality assurance, QC, and manufacturing group can work out CAPAs to the problem. The alert or action level status of a site is resolved if the next consecutive sample’s result are below the alert level. Deviation and investigation reports are usually due 30 business days after they were initiated.

TrackWise Event Tracking System® (SPARTA Systems; Holmdel, NJ) and SAP Quality Notification System® (SAP; Walldorf, Germany) are two commercially available software to document deviation reports, escalating the reports to investigations, and issuing Corrective Action/Preventative Actions. These systems block any batches of products with open deviation or investigations reports to be released to packaging or distribution centers.

Corrective Action/ Preventative Action (CAPA)

CAPAs are assigned to various department heads to be implemented. CAPAs have deadlines in which their owners have to complete the action items. Examples of CAPAs include sanitizing affected sites with secondary sporocidal disinfectant after recovery of objectionable microorganisms by manufacturing department, installing additional High Efficiency Particulate Air (HEPA) filters in a classified room with consistently high level non-viable particulate air counts by maintenance department, and retraining on proper aseptic and gowning techniques to manufacturing operators who consistently fail gowning samples by QC personnel.