12 th Annual FDA & the Changing Paradigm for Blood Regulation – 01/16/2009 – Las Vegas, NV – Gilliam B. Conley 1 FDA perspective on “Where are we? Where.

12th Annual FDA & the Changing Paradigm for Blood Regulation – 01/16/2009 – Las Vegas, NV – Gilliam B. Conley 1

FDA perspective on “Where are we?

Where can we go?”

12th Annual FDA & the Changing Paradigm for Blood Regulation16 January 2009 -- Las Vegas, NV

Gilliam B. Conley Director, Division of Inspections & SurveillanceFDA, Center for Biologics Evaluation & Research Office of Compliance & Biologics Quality

http://www.fda.gov/


Introduction

We will discussFDA inspection dataFatalities reported to FDABiological Product Deviation Reports Where (can) should we go?

http://www.fda.gov/


FY-2008 Inspections Conducted

Blood Bank – Level 1 679

Blood Bank – Level 2 316

Blood Bank – Total: ~ 1,000

Source Plasma – Level 1 89

Source Plasma – Level 2 60

Source Plasma – Pre-license/Pre-approval 19

Source Plasma – Total: 165

note: totals may not match because some inspections are for products in multiple categories

http://www.fda.gov/


Top 10 Biologics ObservationsFY-2008 (Oct. ’07 through Sept. ’08)

http://www.fda.gov/


Top 10 Blood & Blood Component ObservationsFY-2008 (Oct. ’07 through Sept. ’08)

Cite ID Count 21 CFR… Text

#1 76 116 606.100(b) Written standard operating procedures including all steps to be followed in the [collection] [processing] [compatibility testing] [storage] [distribution] of blood and blood components for [homologous transfusion] [autologous transfusion] [further manufacturing purposes] are not always [maintained] [followed] [maintained on the premises]. Specifically, ***

#2 98 31 606.100(c) Failure to [perform a thorough investigation] [make a record of the conclusions and follow-up] of [an unexplained discrepancy] [a failure of a lot or unit to meet any of its specifications]. Specifically,***

#3 9225 29 606.171 Failure to submit a biological product deviation report [within 45 days from the date you acquired information suggesting that a reportable event occurred]. Specifically, ***

http://www.fda.gov/


Top 10 Blood & Blood Component Observations FY-2008 (Oct. ’07 through Sept. ’08) - continued

Cite ID Count 21 CFR… Text (abbreviated)

#4 31 26 606.20(b) Personnel…to assure competent performance of their assigned functions, and to ensure that the final product has the safety, purity, potency, identity and effectiveness it purports or is represented to possess.

#5 4425 23 606.60(a) Equipment…to assure that it performs in the manner for which it was designed.

#6 160 19 606.160(a)(1) Records…so as to provide a complete history of work performed.

http://www.fda.gov/


Top 10 Blood & Blood Component Observations FY-2008 (Oct. ’07 through Sept. ’08) - continued

Cite ID Count 21 CFR… Text (abbreviated)

#7 154 17 606.160(a)(1) Records concurrently maintained with the performance of each significant step…

#8 67 16 606.65(e) Use supplies and reagents in a manner consistent with instructions provided by the manufacturer

#9 155 15 606.160(b) Failure to maintain…records

#10 159 10 606.160(a)(1) Records…

http://www.fda.gov/


Inspection Classification – FY-2008

Blood Banks Source Plasma

NAI 743 107

VAI 243 50

OAI 13 1

Note: These numbers represent a snapshot in time from our inspections database. Because of the further routine review following an investigator’s initial recommendation for an OAI inspection decision, the year-end actual numbers are fewer than the 14 reported here.

http://www.fda.gov/


Regulatory Actions – FY-2008

Warning Letters> 1 – Source Plasma> 3 – transfusion services or blood centers

Adverse Determination Letters> 1 – issued under consent decree

covered multiple facility inspections

Find on the web:WL - http://www.fda.gov/foi/warning.htmADL - http://www.fda.gov/ora/frequent/default.htm

http://www.fda.gov/


Adverse ReactionsRegulatory Requirements, Guidance, Reports

Requirement 21 CFR 606.170(a) Requires Records & Investigation

Requirement 21 CFR 606.170(b) Requires reporting to FDA “a complication … confirmed to be fatal … as soon as possible”

Requirement 21 CFR 640.73 – re: Source Plasma Requires reporting “a fatal reaction which, in any way, may be associated with plasmapheresis…”

Guidance http://www.fda.gov/cber/gdlns/bldfatal.htm Sept., 2003 Final Guidance

Reports & FDA contacts

http://www.fda.gov/cber/transfusion.htm 2nd annual report was posted in mid-Nov.

http://www.fda.gov/


Transfusion-related fatalities

Complication FY ’05 FY ’06 FY’ 07 TotalTRALI 29 35 34 98 (55%)HTR (non-ABO) 16 9 2 27 (15%)Microbial Infection 8 7 6 21 (12%)TACO 1 8 5 14 (8%)HTR (ABO) 6 3 3 12 (7%)Anaphylaxis 0 1 2 3 (2%)Other 2 0 0 2 (1%)

Totals: 62 63 52 177

http://www.fda.gov/


Reports of TRALI by implicated Blood Product

http://www.fda.gov/


Hemolytic Transfusion Rx.

http://www.fda.gov/


Microbial Infection by Implicated Organism

Organism FY ’05 FY ’06 FY ’07 Total

Babesia microti 0 2 3 5 (24%)

Staphylococcus aureus 3 0 1 4 (19%)

Escherichia coli 0 3 0 3 (14%)

Serratia marcescens 2 0 0 2 (10%)

Staphylococcus lugdunensis 1 0 0 1 (05%)

Staphylococcus epidermidis 1 0 0 1 (05%)

Eubacterium limosum 1 0 0 1 (05%)

Morganella morganii 0 1 0 1 (05%)

Yersinia enterocolitica 0 1 0 1 (05%)

Streptococcus dysgalactiae 0 0 1 1 (05%)

Klebsiella oxytoca 0 0 1 1 (05%)

Total: 8 7 6 21

http://www.fda.gov/


Biological Product Deviation ReportsRegulatory Requirements, Guidance, Reports

Requirement 21 CFR 600.14

§ 606.171 Report any event … may affect safety, purity, or potency of distributed product

Guidance http://www.fda.gov/cber/gdlns/devbld.htm Oct., 2006 – Final Guidance

Reports & FDA contacts

http://www.fda.gov/cber/biodev/reports.htm 5 years of annual reports are available

http://www.fda.gov/


BPDR for Blood & Blood ComponentsManufacturing System FY-2003 FY-2004 FY-2005 FY-2006 FY-2007

Donor Suitability 32,453 28,952 29,148 29,067 32,280

Post Donation Info 30,331 26,854 27,452 27,427 30,033

Donor Screening 2,030 2,007 1,628 1,548 2,027

Donor Deferral 92 91 68 92 220

QC & Distribution 2,706 3,740 3,934 4,134 4,555

Labeling 2,429 2,415 2,405 2,199 2,309

Laboratory Testing 1,126 1,122 981 1,013 1,163

Routine Testing 1,037 1,027 912 945 1,103

Viral Testing 89 95 69 66 60

Collection 1,133 851 972 718 704

Component Preparation 371 368 407 401 419

Miscellaneous 288 382 525 658 1,400

Total: 40,506 37,830 38,372 38,188 42,830

http://www.fda.gov/


0

5,000

10,000

15,000

20,000

25,000

30,000

35,000

# Reports

FY03 FY04 FY05 FY06 FY07

Reports Received

BPD Reports

PDIDSDDQCLARTVTBCCPMI

Biological Product Deviation Reporting

http://www.fda.gov/


Total BPD Reports

315003200032500330003350034000345003500035500


Reports Received

# R

eport

sBlood Establishments

http://www.fda.gov/


Post Donation Information Reports

150016001700180019002000210022002300Oct

Nov

Dec Jan

Feb

Mar

Apr

May Jun

Jul

Aug

Sep

Reports Received FY07

# R

epor

tsBlood Establishments

http://www.fda.gov/



0100200300400500600700800

Oct

Nov

Dec Jan

Feb

Mar

Apr

May Jun

Jul

Aug Sep


# R

epor

ts

Malaria CJD travel Tattoo/Piercing

Blood Establishments

http://www.fda.gov/


Total BPD Reports

010002000300040005000600070008000


Reports Received

# R

eport

sPlasma Establishments

http://www.fda.gov/



0100200300400500600700800Oct

Nov

Dec Jan

Feb

Mar

Apr

May Jun

Jul

Aug

Sep


# R

epor

tsPlasma Establishments

http://www.fda.gov/



04080120160200240280320360


# R

eport

s

Tattoo Piercing Incarceration

Plasma Establishments

http://www.fda.gov/


Donors who subsequently test positive for viral marker

FY-’05 FY-’06 FY-’07

Lookback; Subsequent

unit confirmed pos (MI-02) – total:

495 608 1,367

HIV (MI-02-02) 92 99 210

HBV (MI-02-03) 50 90 344

HCV (MI-02-04) 333 372 708From FY-2007 annual BPDR summary reportBlood Safety Team (BST) reviewed rising numbers of reportsBST requested additional information from several manufacturersRise appears to be the result of

>Altered reporting patterns after the October, 2006 final Guidance published Biological Product Deviation Reporting for Blood and Plasma Establishments >Rising numbers of collections – especially in Source Plasma centers

BST will continue to monitor these seroconversion rates

http://www.fda.gov/


Where (can) should we go?We will continue to gather informationWe will continue to report information

(web based information, public presentations, …)

We are interested in learning:> How do you use FDA’s posted data?

• Analyze with own data?• Institute quality change?

> Which FDA-posted data is most useful?> What are your success stories?

Please find a way to share with others

http://www.fda.gov/


Questions

Please join in the Q & A session

at the conclusion

of this morning’s session.

http://www.fda.gov/

12 th Annual FDA & the Changing Paradigm for Blood Regulation – 01/16/2009 – Las Vegas, NV – Gilliam B. Conley 1 FDA perspective on “Where are we? Where.

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