Common Problems with Blood Submissions

1. Common Problems with Blood Submissions Michael Gorman, BA, MT(ASCP)SBB Consumer Safety Officer, CBER, OBRR, DBA September 16, 2009

2. Outline • Presentation Goal • SOPs • Quality Control (QC) • Product Label • Apheresis Informed Consent Content • Comparability Protocol (CP) • Computer Assisted Self Interviews (CASI) Donor Questionnaire • Summary

3. Presentation Goal: Reduction In Submission Problems • Check submissions are complete before sending • Review content to ensure compliance with • Applicable regulations • Recommendations • Review checklists, when applicable • Complete submissions will minimize approval process delays

4. SOPs [21 CFR 606.100(b)] • Applicable SOPs and/or supporting documents not submitted - examples: • Quality Control (QC) • Equipment maintenance • Manufacturers’ instructions or operator manuals

5. SOPs (cont.) • SOPs not applicable to the submission are submitted - examples: • Collection of Apheresis, Red Blood Cells submission also includes SOPs pertaining to Platelets, Pheresis collection • Infectious Disease Testing SOPs

6. SOPs (cont.) • Process steps or information missing - examples: • Acceptance criteria for product QC • Steps for documenting results and interpretations • Steps for entering data into the computer • Donor deferral criteria for red blood cell and plasma loss

7. SOPs (cont.) • Failure Investigation steps missing • When to initiate a failure investigation (failure investigation SOPs) • Methods for investigating and/or correcting failures • Management of products that do not meet minimum manufacturing specifications including QC failures • Role of the quality unit not addressed

8. SOPs (cont.) • SOPs not consistent with manufacturers’ instructions or operator manuals -examples: • Order of steps changed • Steps omitted • Wording changed which changes the manufacturer's intended meaning

9. SOPs (cont.) • SOPs are not consistent with CFR requirements - example: • 21 CFR 606.160(d): Manufacturing record retention timeframes changed in the CFR in 2008 from 5 years to 10 years

10. SOPs (cont.) • SOP not consistent with a firm’s other SOPs or forms – examples: • Acceptance criteria in SOP and QC form do not agree • Form names different in SOPs

11. Monthly Quality Control (QC) Forms Do Not Include All Information • Facility • 21 CFR 211.194(a)(1) • Device manufacturer and type • 21 CFR 211.194(a)(2) • Sample identification • 21 CFR 606.140(c) • Sample collection date • 21 CFR 211.194(a)(1) • Date of testing • 21 CFR 606.160 (a)(1) • Interpretation of results • 21 CFR 606.160 (a)(1)

12. Monthly Quality Control (QC) Forms Do Not Include All Information (cont.) • Yield • 21 CFR 211.186(b)(7) • Acceptable criteria • 21 CFR 211.165(d) • Initials • 21 CFR 606.160 (a)(1) • Evidence of review • 21 CFR 211.194(a)(8) • Records of calculations • 21 CFR 211.194 (a)(5)

13. QC Information Not included or Inadequate Examples • Data not submitted • Two consecutive months of QC data not submitted when applicable • Summary of validation data • Insufficient QC sample size • Refer to FDA Guidance documents

14. QC: Apheresis Data Not Included Examples • Monthly Apheresis, Red Blood Cells QC • Data for fifty units per site submitted but data for both single and double units, when applicable • Data for all collection types including single, double and triple units, when applicable

15. Product Label Submissions • Labels submitted for products not currently licensed by FDA • Labels submitted for products currently licensed by FDA for which a firm does not presently hold a license and is not requesting licensure • FDA only approves labels for a firm’s licensed products

16. Apheresis Informed Consent Content • All possible adverse effects listed in each devices’ Operator Manual not included • Exculpatory language inappropriately included in the consent form

17. Comparability Protocol (CP) • Original CP (PAS) submissions often do not include: • Validation protocols with data summary • Validation performance/acceptance criteria • Description of actions to be taken if acceptable validation results are not achieved • Description of implementation • Proposal to change reporting category (e.g., from PAS to CBE30)

18. Comparability Protocol (CP)(cont.) • Subsequent submissions (e.g., CBE30) often do not include: • References to previously approved CP STNs • SOPs or QC criteria that were part of the original CP were revised but not submitted

19. Computer Assisted Self Interview (CASI) Donor Questionnaire • Not included in submissions: • SOPs • Print screens – none submitted or not all applicable screens submitted • Copy of donor health history questionnaire • Validation protocol • List of interfaces with other medical devices (software, instruments)

20. CASI (cont.) • Not included in submissions: • Software manufacturer’s name • Program name • Version or release number • Information indicating CASI software is 510(k) cleared by FDA [i.e., 510(k) number] • Information indicating wireless functionality is 510(k) cleared by FDA, when applicable (e.g., information from the software manufacturer)

21. Summary • Not an all-inclusive list • Incomplete submissions can delay reviews and approvals