Corrective and Preventive Action By Superlative BioSciences Corporation October 13, 2007

What is CAPA? Corrective and Preventative Action (CAPA) is a system of quality procedures required to eliminate the causes of an existing nonconformity and to prevent recurrence of nonconforming product, processes, and other quality problems.

Regulatory Guidance “Corrective and Preventive Action,” Quality System Regulation (QSR), 21 CFR Part 820, Medical Devices, Subpart J, Sec. 100, Became effective on June 1, 1997, Replacing the 1978 GMP for Medical Devices. http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm?CFRPart=820 “Overview of the Quality System Regulation for Medical Devices,” Kimberly Trautman – Food and Drug Administration, USA and Chair, Study Group 3, June 29, 1999. http://www.fda.gov/cdrh/reuse/events/cdrom-9.ppt “QSIT Corrective & Preventive Actions,” Quality System Inspection Techniques (QSIT) Guide, August 1999. http://www.fda.gov/ora/inspect_ref/igs/qsit/qsitguide.pdf “Establishment and Maintenance of a Quality Program.” Human Cells, Tissues, And Cellular And Tissue-Based Products (HCT/P's), 21 CFR Part 1271 Subpart D, Current Good Tissue Practice (cGTP), Sec. 160, May 25, 2004. Revised as of April 1, 2006, http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=1271

Terminology Nonconforming Material or Process (Discrepancy) - Any material or process that does not meet its required specifications or documented procedure. Correction – Refers to repair, rework, or adjustment and relates to the disposition of an existing nonconformity. Corrective Action - To identify and eliminate the causes of existing nonconforming product and other quality problems. Preventive Action - To identify and eliminate the causes of potential nonconforming product and other quality problems.

Seven Quality Subsystems

Components Of Corrective And Preventive Action (CAPA) Collect and analyze data to identify nonconforming product and other quality problems Investigate cause Identify and implement corrective and preventive action Verify or validate effectiveness

Components Of Corrective And Preventive Action (CAPA) Communicate information about quality problems, changes made, outcomes, and trends to those persons directly responsible and to the staff in general Forward information for management review Work with staff and management to produce continuous quality improvement

Quality Data Sources

CAPA Case Studies Weak CA, Weak PA (Common) Weak CA, Strong PA (Unusual) Strong CA, Weak or Unlinked PA (Common) Strong PA Linked to a Strong CA (Ideal)

Case Study No. 1 The company develops biopharmaceuticals The company has a CAPA program A review of existing internal and external audits reveal that: nonconformities are documented corrections are proposed (a temporary or permanent change, repair, rework, or scrap) corrections made are timely but the same nonconformities seem to reoccur over and over again customers are complaining

The current investigation indicates that: nonconformities are not adequately categorized and trended the root causes of existing nonconformities are not adequately investigated or addressed preventive actions are not sufficient to eliminate the reoccurrence of the nonconformity discrepancy and CAPA procedures are not well-written or difficult to follow the forms utilized don’t follow the flow of the procedure the forms do not provide enough space for more than a brief entry verbal decisions are not written down responsible people are assigned but a timelines for the follow-ups is not given or is vague

The Solution Revise all Quality Assurance Procedures to emphasize CAPA and to link discrepancy reporting and disposition to preventive action Initiate a trending and root cause analysis program Present these programs to management and to the staff Revise the nonconformity, CA, and PA forms Conduct formal CAPA training Reinforce CAPA awareness in verbal communications Provide a “Quality Update” at the company’s monthly staff meeting

The Results Easier to follow quality procedures More user-friendly forms A better understanding of processes obtained through root cause analysis More proactive thinking vs. reactive thinking Fewer nonconformities Less scrap and rework Fewer customer complaints

Pre-CAPA Post-CAPA Post-CAPA

Thank you