1. Problem Management Scenario # 2 September 17,2005

2. Scenario # 2 Weekly EM (static readings, at rest) in one of the facility’s BSCs is outside the acceptable range. Weekly EM (static readings, at rest) in one of the facility’s BSCs is outside the acceptable range. What do you do? What do you do?

3. General Investigational Approach Determine the severity of the excursion. Determine the severity of the excursion. Evaluate recent trending data. Evaluate recent trending data. Initiate investigation: limited or full Initiate investigation: limited or full Identify products processed in BSC. Identify products processed in BSC. Review sterility results for affected products. Review sterility results for affected products. Based on investigation results, evaluate potential impact on products, patients & operations. Based on investigation results, evaluate potential impact on products, patients & operations.

4. What should be done if… Alert level is exceeded for either the particle counts or the viable air sample. Alert level is exceeded for either the particle counts or the viable air sample.

5. Alert Level Exceeded: Investigation Limited investigation to include: Limited investigation to include: Inspect cleanliness of BSC and adjacent areas Inspect cleanliness of BSC and adjacent areas Review BSC equipment log (maintenance & cleaning records, calibration date) Review BSC equipment log (maintenance & cleaning records, calibration date) Review EM trending data for the BSC Review EM trending data for the BSC Review sampling device PM & calibration Review sampling device PM & calibration Identification of organism (if viable air sample in question) Identification of organism (if viable air sample in question)

6. Alert Level Exceeded: Follow-Up Document the investigation and any corrective/preventative actions. Document the investigation and any corrective/preventative actions. If problems identified, possible actions include: If problems identified, possible actions include: BSC Service to verify proper operation – remove from service if fails BSC Service to verify proper operation – remove from service if fails Revision of BSC cleaning procedure Revision of BSC cleaning procedure Increased monitoring frequency and sites Increased monitoring frequency and sites Staff retraining Staff retraining

7. Alert Level Exceeded: Follow-Up Ensure product document includes a cross-reference of the investigation document. Ensure product document includes a cross-reference of the investigation document. Affected Products: Investigation should determine if stored products are suitable for use. Affected Products: Investigation should determine if stored products are suitable for use. Product recall unlikely unless BSC malfunction identified. Product recall unlikely unless BSC malfunction identified.

8. What should be done if… Action level is exceeded for either the particle counts or the viable air sample. Action level is exceeded for either the particle counts or the viable air sample.

9. Action Level Exceeded: Investigation Limited or full investigation depending on product, processing, trending data, size of excursion Limited or full investigation depending on product, processing, trending data, size of excursion Same as for Alert Level Investigation Same as for Alert Level Investigation Possible additional actions include: Possible additional actions include: Verify proper operation of BSC, sampling device Verify proper operation of BSC, sampling device Remove hood from service if excursion serious or BSC fails verification Remove hood from service if excursion serious or BSC fails verification Thoroughly clean & sanitize BSC Thoroughly clean & sanitize BSC Increase monitoring frequency and sites Increase monitoring frequency and sites Evaluate EM trending for adjacent areas Evaluate EM trending for adjacent areas

10. Action Level Exceeded: Follow-Up Same as for the Alert Limit Scenario. Same as for the Alert Limit Scenario. Follow Deviation Reporting SOP to notify appropriate medical/ reporting groups Follow Deviation Reporting SOP to notify appropriate medical/ reporting groups May consider product ‘recall’ based on conclusions of investigation (e.g. organisms identified, nature of BSC malfunction). May consider product ‘recall’ based on conclusions of investigation (e.g. organisms identified, nature of BSC malfunction). Immediately notify FDA district office if recall intended. Immediately notify FDA district office if recall intended.