HCT/P Compliance HCT/P Compliance UpdateUpdate

5th Annual FDA and the Changing 5th Annual FDA and the Changing Paradigm for HCT/P RegulationParadigm for HCT/P Regulation

Las Vegas, NV, January 28, 2009Las Vegas, NV, January 28, 2009Mary Malarkey, Director, OCBQ, Mary Malarkey, Director, OCBQ,

CBERCBER

SummarySummary

Inspections by the numbersInspections by the numbers Inspectional ObservationsInspectional Observations Regulatory citationsRegulatory citations HCT/P casesHCT/P cases HCT/P Deviation ReportsHCT/P Deviation Reports RecallsRecalls

InspectionsInspections

FY08 HCT/P FY08 HCT/P Inspections AccomplishedInspections AccomplishedType of HCT/P Type of HCT/P establishmentestablishment

# # Inspections Inspections

AccomplisheAccomplishedd

Hours/Hours/

InspectionInspection

Reproductive tissuesReproductive tissues 158158 42.442.4

Cord blood stem cellsCord blood stem cells

Peripheral blood stem Peripheral blood stem cellscells

1919 31.731.7

All other HCT/Ps All other HCT/Ps

(e.g. (e.g. musculoskeletal, musculoskeletal, ocular, recovery, ocular, recovery, distributors)distributors)

213213 34.434.4

TotalTotal 383*383* 37.537.5*Sum of individual inspections do not equal total due to some inspections that were conducted for products in multiple categories

FY08 HCT/P FY08 HCT/P Inspection ClassificationsInspection Classifications

Type of HCT/P Type of HCT/P establishmentestablishment

NAINAI VAIVAI OAIOAI

Reproductive tissuesReproductive tissues 106106 4040 1010

Cord blood stem cellsCord blood stem cells

Peripheral blood stem Peripheral blood stem cellscells

1515 44 00

All other HCT/Ps All other HCT/Ps

(e.g. (e.g. musculoskeletal, musculoskeletal, ocular, recovery, ocular, recovery, distributors)distributors)

164164 4646 11

TotalTotal 285285 9090 1111

FDA Form 483FDA Form 483

““This document lists observations made by the This document lists observations made by the FDA representative(s) during the inspection of FDA representative(s) during the inspection of your facility. They are inspectional observations, your facility. They are inspectional observations, and do not represent a final agency and do not represent a final agency determination regarding your compliance. If you determination regarding your compliance. If you have an objection regarding an observation, or have an objection regarding an observation, or have implemented, or plan to implement, have implemented, or plan to implement, corrective action in response to an observation, corrective action in response to an observation, you may discuss the objection or action with the you may discuss the objection or action with the FDA representative(s) during the inspection or FDA representative(s) during the inspection or submit this information to FDA at the address submit this information to FDA at the address above….”above….”

OAI/VAI/NAI?OAI/VAI/NAI?

OAI – Official Action Indicated – OAI – Official Action Indicated – objectionable conditions found that objectionable conditions found that warrant actionwarrant action

VAI – Voluntary Action Indicated – VAI – Voluntary Action Indicated – objectionable conditions found but do objectionable conditions found but do not meet the threshold for regulatory not meet the threshold for regulatory actionaction

NAI – No Action Indicated – no NAI – No Action Indicated – no objectionable conditions found objectionable conditions found (generally no FDA-483)(generally no FDA-483)

http://www.fda.gov/ora/inspect_ref/fmdhttp://www.fda.gov/ora/inspect_ref/fmd/fmd86.htm/fmd86.htm

FY08 HCT/P FY08 HCT/P Inspection ResultsInspection Results

Approx. 30% of HCT/P inspections Approx. 30% of HCT/P inspections resulted in issuance of Form FDA-resulted in issuance of Form FDA-483s; 483s;

Consistent with FY07 and FY06. Consistent with FY07 and FY06.

Inspectional Inspectional Observations:Observations:

Storage and DistributionStorage and Distribution Failure to store HCT/Ps at appropriate Failure to store HCT/Ps at appropriate

temperatures; establish acceptable temperature temperatures; establish acceptable temperature limits; and/or maintain and record storage limits; and/or maintain and record storage temperatures 21 CFR 1271.260 (b) and (e)temperatures 21 CFR 1271.260 (b) and (e)– Storage room temperatures are not recordedStorage room temperatures are not recorded– Freezer did not have a functioning recording Freezer did not have a functioning recording

device and was not equipped with an alarm. device and was not equipped with an alarm. The freezer temperature is not recorded or The freezer temperature is not recorded or monitored after normal operating hoursmonitored after normal operating hours

– Temperature monitoring logs not reviewed Temperature monitoring logs not reviewed prior to removal/transfer of grafts as required prior to removal/transfer of grafts as required in the SOPin the SOP

Inspectional Inspectional Observations:Observations:

ProcessorsProcessors Failure to maintain facility in good state of Failure to maintain facility in good state of

repair 21 CFR 1271.190(a)repair 21 CFR 1271.190(a)– Several processing rooms have damage to the Several processing rooms have damage to the

walls – areas of damage show exposed dry wall walls – areas of damage show exposed dry wall below the level of the paper layerbelow the level of the paper layer

Failure to maintain documentation of Failure to maintain documentation of equipment maintenance, cleaning, equipment maintenance, cleaning, sanitization and calibration 21 CFR 1271. sanitization and calibration 21 CFR 1271. 200(e)200(e)– Cleaning of equipment was not documented. Cleaning of equipment was not documented.

There were no records of cleaning from 1/2006 – There were no records of cleaning from 1/2006 – 3/20083/2008

Inspectional Inspectional Observations:Observations:Processors - 2Processors - 2

Failure to process HCT/Ps in a way that Failure to process HCT/Ps in a way that does not increase the risk of does not increase the risk of introduction, transmission or spread of introduction, transmission or spread of communicable disease 21 CFR communicable disease 21 CFR 1271.220(a)1271.220(a)– There were five occurrences where There were five occurrences where

containers holding tissue from two different containers holding tissue from two different donors were opened at the same time in the donors were opened at the same time in the processing hood. (Note – a cross processing hood. (Note – a cross contamination event had been documented)contamination event had been documented)

Inspectional Inspectional Observations:Observations:Donor TestingDonor Testing

Failure to perform testing for Failure to perform testing for communicable disease agents communicable disease agents according to the manufacturer’s according to the manufacturer’s instructions 21 CFR 1271.80(c)instructions 21 CFR 1271.80(c)– Cadaveric samples tested by NAT Cadaveric samples tested by NAT

assay were routinely tested using a assay were routinely tested using a 1:5 dilution. The package insert 1:5 dilution. The package insert instructs that cadaveric donors be instructs that cadaveric donors be tested “neat.”tested “neat.”

Regulatory ActionsRegulatory Actions

Regulatory ActionsRegulatory Actions

Regulatory Actions IssuedRegulatory Actions Issued– 1 Warning Letter (repro)1 Warning Letter (repro)– 1 Untitled Letter (repro)1 Untitled Letter (repro)– 1 Untitled Letter –website/stem cell 1 Untitled Letter –website/stem cell

treatment – part of our internet treatment – part of our internet surveillance surveillance

FY08 HCT/P Regulatory FY08 HCT/P Regulatory Actions: Deviations Actions: Deviations CitedCited Failure to test specimens from anonymous or Failure to test specimens from anonymous or

directed reproductive donors using appropriate directed reproductive donors using appropriate FDA-licensed, approved, or cleared donor FDA-licensed, approved, or cleared donor screening testsscreening tests, in accordance with the , in accordance with the

manufacturer's instructionsmanufacturer's instructions 21 CFR 1271.80(c).21 CFR 1271.80(c). Failure to screen an anonymous or directed Failure to screen an anonymous or directed

reproductive donor of cells or tissue by reproductive donor of cells or tissue by reviewing the donor's relevant medical records reviewing the donor's relevant medical records for risk factors for, and clinical evidence of, for risk factors for, and clinical evidence of, relevant communicable disease agents and relevant communicable disease agents and diseases 21 CFR 1271.75(a). diseases 21 CFR 1271.75(a).

Regulatory Actions - 2Regulatory Actions - 2

Failure to establish and maintain procedures for all steps that are performed in testing, screening, determining donor eligibility, and complying with all other requirements of Subpart C "Donor Eligibility" in 21 CFR Part 1271. "Establish and maintain" means define, document, and implement; then follow, review, and as needed, revise on an ongoing basis [21 CFR 1271.47(a)]. – The firm's standard operating procedures did not address

all steps required for donor screening and determining donor eligibility, including, but not limited to: (1) donor screening for risk factors for, or clinical evidence of relevant communicable disease agents and diseases; and (2) the criteria used to determine donor eligibility and ineligibility.

HCT/P CasesHCT/P Cases

The DeMarco Case and The DeMarco Case and BeyondBeyond

BTS UpdateBTS Update

DeMarco*DeMarco*

In September 2006, Charlene DeMarco, In September 2006, Charlene DeMarco, a former doctor of osteopathy and her a former doctor of osteopathy and her co-conspirator Elizabeth Lerner, a.k.a. co-conspirator Elizabeth Lerner, a.k.a. “Elizabeth Cooperman,” were convicted “Elizabeth Cooperman,” were convicted of all charges contained in an 11-count of all charges contained in an 11-count federal indictment: one count of federal indictment: one count of conspiracy to commit mail and wire conspiracy to commit mail and wire fraud, three counts of mail fraud, six fraud, three counts of mail fraud, six counts of wire fraud and one count of counts of wire fraud and one count of money laundering.money laundering.

*From FDA News Release , December 19, 2007

DeMarco (cont…)DeMarco (cont…)

““Evidence showed that from October Evidence showed that from October 2002 until November 2004, DeMarco 2002 until November 2004, DeMarco and Lerner agreed to defraud and Lerner agreed to defraud amyotrophic lateral sclerosis (ALS)* amyotrophic lateral sclerosis (ALS)* patients and their families by claiming patients and their families by claiming they could treat ALS patients with stem they could treat ALS patients with stem cell therapy, when they knew they cell therapy, when they knew they could not. The defendants falsely told could not. The defendants falsely told the patients and their families that the patients and their families that DeMarco had previously received FDA DeMarco had previously received FDA approval to treat ALS.”approval to treat ALS.”

*commonly called Lou Gehrig’s disease

DeMarco (cont…)DeMarco (cont…)

In September 2007, Charlene DeMarco, In September 2007, Charlene DeMarco, was sentenced to 57 months in prison, was sentenced to 57 months in prison, ordered to pay $32,190 in restitution to ordered to pay $32,190 in restitution to victims and a criminal fine of $7500.victims and a criminal fine of $7500.

In December 2007, Elizabeth Lerner In December 2007, Elizabeth Lerner was sentenced to 33 months in prison, was sentenced to 33 months in prison, ordered to pay $35,390 in restitution to ordered to pay $35,390 in restitution to victims and a criminal fine of $7500.victims and a criminal fine of $7500.

The Other Side of the The Other Side of the CoinCoin

The National Marrow Donor Program– Public program, relies on unrelated allogeneic Public program, relies on unrelated allogeneic

donorsdonors– Hematopoietic stem cells obtained from Hematopoietic stem cells obtained from

peripheral blood or cord blood are available to peripheral blood or cord blood are available to any patientany patient

– Registry of potential peripheral blood stem Registry of potential peripheral blood stem cell donorscell donors

– Registry of cord blood unitsRegistry of cord blood units– Searchable to match donor or unit to recipient Searchable to match donor or unit to recipient

for hematopoietic reconstitution in patients for hematopoietic reconstitution in patients with hematological malignancies with hematological malignancies

– ““Draft Guidance for Industry: Minimally Draft Guidance for Industry: Minimally Manipulated, Unrelated, Allogeneic Manipulated, Unrelated, Allogeneic Placental/Umbilical Cord Blood Intended for Placental/Umbilical Cord Blood Intended for Hematopoietic Reconstitution in Patients with Hematopoietic Reconstitution in Patients with Hematological Malignancies,” issued 1/16/07 Hematological Malignancies,” issued 1/16/07

Private Banking: Wave of Private Banking: Wave of Future?Future?

Autologous – you pay to bank for Autologous – you pay to bank for future, future, possible possible needneed– Cord blood – potential use for Cord blood – potential use for

siblings too; also baby teethsiblings too; also baby teeth– Adult stem cells – different sources Adult stem cells – different sources

advertisedadvertised

Questioning the Allure of Putting Cells in the Bank By ANDREW POLLACK

Published: January 29, 2008

                                   

FDA RegulationsFDA Regulations

Establishments that collect, process Establishments that collect, process and store (the bank) and potentially and store (the bank) and potentially distribute, are manufacturing distribute, are manufacturing HCT/Ps and, as the use is HCT/Ps and, as the use is autologous and/or 1autologous and/or 1stst and 2 and 2ndnd degree family related allogeneic, degree family related allogeneic, are regulated under section 361 of are regulated under section 361 of the Public Health Service Act and the Public Health Service Act and 21 CFR part 1271. 21 CFR part 1271.

ConcernConcern Maintenance of proper conditions during long-Maintenance of proper conditions during long-

term storageterm storage Banks promote that these HCT/Ps Banks promote that these HCT/Ps willwill cure or cure or

mitigate diseases (e.g. Parkinson’s Disease), and mitigate diseases (e.g. Parkinson’s Disease), and these claims are unproventhese claims are unproven

The manufacturer’s objective intent is one of the The manufacturer’s objective intent is one of the factors taken into account in determining the factors taken into account in determining the level of regulation of HCT/Pslevel of regulation of HCT/Ps

Such promotion might result in a determination Such promotion might result in a determination that the HCT/P be regulated as a biological that the HCT/P be regulated as a biological product under section 351 of the PHSAproduct under section 351 of the PHSA

A biological product must be distributed under an A biological product must be distributed under an FDA-monitored IND, or the manufacturer must FDA-monitored IND, or the manufacturer must prove to FDA that the product is safe and prove to FDA that the product is safe and effective, and be licensed effective, and be licensed

Biomedical Tissue Services Biomedical Tissue Services (BTS)(BTS)

Order to Cease and Retain Order to Cease and Retain HCT/PsHCT/Ps

Immediately cease manufacturing operations Immediately cease manufacturing operations and retain HCT/Ps.and retain HCT/Ps.

To BTS and its CEO and Executive Director, To BTS and its CEO and Executive Director, Michael Mastromarino, D.D.S.Michael Mastromarino, D.D.S.

After initially focusing efforts on assessing After initially focusing efforts on assessing the safety of distributed tissue and the safety of distributed tissue and facilitating recalls, FDA determined that the facilitating recalls, FDA determined that the violations uncovered at BTS, because of their violations uncovered at BTS, because of their serious nature, constitute a danger to health serious nature, constitute a danger to health and took this unprecedented actionand took this unprecedented action

Order to Cease Manufacturing and to Retain Order to Cease Manufacturing and to Retain HCT/Ps issued January 31, 2006HCT/Ps issued January 31, 2006

www.fda.gov/cber/compl/bts013106.htmwww.fda.gov/cber/compl/bts013106.htm

BTS OrderBTS Order

Despite records maintaining otherwise:Despite records maintaining otherwise:– The firm inadequately screened donors for risk The firm inadequately screened donors for risk

factors for, or clinical evidence of, relevant factors for, or clinical evidence of, relevant communicable disease agents and diseases;communicable disease agents and diseases;

– FDA found numerous instances where death FDA found numerous instances where death certificates maintained in BTS’ files were at certificates maintained in BTS’ files were at variance with the death certificates FDA obtained variance with the death certificates FDA obtained from the state where the death occurred:from the state where the death occurred:

Cause, place, and time of death, and the Cause, place, and time of death, and the identity of next of kin.identity of next of kin.

FDA continued to work with other federal, FDA continued to work with other federal, state and local authoritiesstate and local authorities

CDC: MMWR CDC: MMWR Brief Report May 26, Brief Report May 26,

20062006 ““Investigation into Recalled Human Tissue Investigation into Recalled Human Tissue

for Transplantation---United States, 2005--for Transplantation---United States, 2005--2006.”2006.”

Approximately 25,000 BTS-recovered tissue Approximately 25,000 BTS-recovered tissue products distributed to all 50 states and products distributed to all 50 states and internationallyinternationally

FDA and CDC continue to investigate reports FDA and CDC continue to investigate reports of BTS recipients who have undergone of BTS recipients who have undergone screening and tested positive for one of the screening and tested positive for one of the four tested diseasesfour tested diseases

Some positive results would be expected in Some positive results would be expected in any U.S. population tested (prevalence data any U.S. population tested (prevalence data provided)provided)

MMWR cont..MMWR cont..

Relationship between implanted Relationship between implanted BTS tissue and positive test BTS tissue and positive test results reported to FDA and CDC results reported to FDA and CDC is difficult to ascertain because of is difficult to ascertain because of inaccurate BTS donor records inaccurate BTS donor records and, in some cases, the absence and, in some cases, the absence of properly linked donor samples.of properly linked donor samples.

BTS UpdateBTS Update

In March 2008, Michael Mastromarino pleaded guilty In March 2008, Michael Mastromarino pleaded guilty in Brooklyn Supreme Court to body stealing, forgery, in Brooklyn Supreme Court to body stealing, forgery, grand larceny and enterprise corruption and was grand larceny and enterprise corruption and was sentenced to 18 to 54 years. He is serving a sentenced to 18 to 54 years. He is serving a concurrent sentence of 25 to 58 years after pleading concurrent sentence of 25 to 58 years after pleading guilty to similar changes in Philadelphia.guilty to similar changes in Philadelphia.

Co-defendant Lee Cruceta pleaded guilty to Co-defendant Lee Cruceta pleaded guilty to conspiracy, taking part in a corrupt organization, conspiracy, taking part in a corrupt organization, abuse of a corpse and 244 counts each of theft and abuse of a corpse and 244 counts each of theft and forgery in Philadelphia and also has pleaded guilty to forgery in Philadelphia and also has pleaded guilty to related charges in Brooklyn and negotiated pleas to related charges in Brooklyn and negotiated pleas to serve concurrent sentences of 6½ to 20 years. serve concurrent sentences of 6½ to 20 years.

Co-defendant Chris Aldorasi was found guilty of Co-defendant Chris Aldorasi was found guilty of enterprise corruption and other criminal counts in enterprise corruption and other criminal counts in Brooklyn and sentenced to 9 to 27 years.Brooklyn and sentenced to 9 to 27 years.

BTS Update - 2BTS Update - 2

Co-defendant Joseph Nicelli has yet to stand Co-defendant Joseph Nicelli has yet to stand trial in Brooklyntrial in Brooklyn

On December 12, 2008, Jason Gano, a former On December 12, 2008, Jason Gano, a former funeral director in Rochester, NY, was found funeral director in Rochester, NY, was found guilty of 17 counts each of opening graves, guilty of 17 counts each of opening graves, body stealing, and unlawful dissection, as well body stealing, and unlawful dissection, as well as one count of scheming to defraud. He faces as one count of scheming to defraud. He faces up to 20 years in prison when he is sentenced.up to 20 years in prison when he is sentenced.

Six others are expected to stand trial in Six others are expected to stand trial in RochesterRochester

FDA will continue to work cooperatively with FDA will continue to work cooperatively with other Federal, State and local authoritiesother Federal, State and local authorities

HCT/P Deviation HCT/P Deviation ReportingReporting

FY06FY06 FY07FY07 FY08FY08

ReportableReportable 144144 153153 223223

Electronic Electronic ReportsReports

100 100

(69%)(69%)118 118

(77%)(77%)164 164

(74%)(74%)

Non-Non-ReportableReportable 7676 4848 6363

Total ReportsTotal Reports 220220 201201 286286

ProductProductFY0FY066

FY0FY077

FY0FY088

Peripheral Blood Stem Peripheral Blood Stem CellsCells 7171 9898 109109

Cornea/ScleraCornea/Sclera 5151 3535 4444

SkinSkin 66 66 2727

MusculoskeletalMusculoskeletal 2121 1414 2626

Somatic CellsSomatic Cells 00 11 1919

Donor LeukocytesDonor Leukocytes 66 1010 1212

Cord Blood Stem CellsCord Blood Stem Cells 22 44 44

HCT/P Deviation ReportsHCT/P Deviation ReportsProducts InvolvedProducts Involved

HCT/P Deviations ReportedHCT/P Deviations ReportedReportable HCT/P Reportable HCT/P DeviationsDeviations

FY 05FY 05 FY 06FY 06 FY 07FY 07 FY FY 0808

Donor EligibilityDonor Eligibility 88 3232 2424 3737

Donor ScreeningDonor Screening   00 1212 88 1717

Donor TestingDonor Testing 00 3333 5454 5454

Environmental ControlEnvironmental Control 00 11 22 00

Supplies and ReagentsSupplies and Reagents   00 33 66 11

RecoveryRecovery   00 22 88 88

ProcessingProcessing   00 1414 1717 6868

Labeling ControlLabeling Control 11 22 11 22

StorageStorage   00 11 00 00

Receipt, Pre-Dist., Dist.Receipt, Pre-Dist., Dist. 44 4343 3232 3636

TotalTotal 1313 143143 152152 223223

Non-ReportableNon-Reportable 1515 7777 4848 6363

HCT/P Deviation Reports HCT/P Deviation Reports Non-Reportable EventsNon-Reportable Events

No products were distributedNo products were distributed Not associated with disease transmission or Not associated with disease transmission or

contaminationcontamination Not related to core GTPNot related to core GTP Product released under urgent medical needProduct released under urgent medical need Product not subject to HCT/P deviation Product not subject to HCT/P deviation

reportingreporting– Reproductive tissueReproductive tissue– Unrelated Allogeneic Stem CellsUnrelated Allogeneic Stem Cells

Reporting establishment is not an HCT/P Reporting establishment is not an HCT/P manufacturermanufacturer

HCT/P Deviation Reports HCT/P Deviation Reports Non-Reportable EventsNon-Reportable Events

Positive pre-implant culture is in Positive pre-implant culture is in general not reportable as a deviationgeneral not reportable as a deviation– Unless a complaint results in an Unless a complaint results in an

investigation that reveals a departure investigation that reveals a departure from GTPs orfrom GTPs or

– If the recipient had an adverse reaction If the recipient had an adverse reaction then might be reported as an adverse then might be reported as an adverse reaction not HCT/P deviationreaction not HCT/P deviation

  HCT/P Deviation HCT/P Deviation CodeCode

Cellular Cellular HCT/PHCT/P

Tissue Tissue HCT/PHCT/P TotalTotal

Donor EligibilityDonor Eligibility 44 3333 3737 16.6%16.6%

Donor ScreeningDonor Screening 22 1515 1717 7.6%7.6%

Donor TestingDonor Testing 4242 1212 5454 24.2%24.2%

Environmental ControlEnvironmental Control 00 00 00 0.0%0.0%

Supplies and ReagentsSupplies and Reagents 11 00 11 0.4%0.4%

RecoveryRecovery 88 00 88 3.6%3.6%

Processing and Processing and Processing ControlsProcessing Controls 5050 1818 6868 30.5%30.5%

Labeling ControlsLabeling Controls 00 22 22 0.9%0.9%

StorageStorage 00 00 00 0.0%0.0%

Receipt, Pre-Distribution, Receipt, Pre-Distribution, Shipment & DistributionShipment & Distribution 3333 33 3636 16.1%16.1%

TotalTotal 140140 8383 223223 100%100%

HCT/P Deviation Reporting FY08

Tissue HCT/P ReportsTissue HCT/P Reports

Donor Eligibility – 33 reportsDonor Eligibility – 33 reports– Donor accepted when risk factors, clinical Donor accepted when risk factors, clinical

evidence or physical evidence identified – evidence or physical evidence identified – 1818

– Donor accepted when reactive for relevant Donor accepted when reactive for relevant communicable disease – 4communicable disease – 4

– Donor incorrectly evaluated for plasma Donor incorrectly evaluated for plasma dilution – 10dilution – 10

– Donor testing not performed or Donor testing not performed or documented - 1documented - 1

Tissue HCT/P Reports - Tissue HCT/P Reports - 22

Processing and process controls – 18Processing and process controls – 18– HCT/P contaminated, potentially HCT/P contaminated, potentially

contaminated or cross contaminated – 17contaminated or cross contaminated – 17– In-process controls inadequate – 1In-process controls inadequate – 1

Microorganisms involved:Microorganisms involved:– Bacillus, Candida, Clostridium, Bacillus, Candida, Clostridium,

Enterobacter, Group D Enterococcus, Enterobacter, Group D Enterococcus, Staphylococcus, ProteusStaphylococcus, Proteus

Tissue HCT/P Reports - Tissue HCT/P Reports - 33 Donor Screening – 15Donor Screening – 15

– Donor screening not performed or Donor screening not performed or documented – 1documented – 1

– Donor screening (medical history Donor screening (medical history interview) performed incorrectly interview) performed incorrectly (incomplete or inaccurate) – 13(incomplete or inaccurate) – 13

– Donor screening (medical record Donor screening (medical record review) performed incorrectly review) performed incorrectly (incomplete or inaccurate) - 1(incomplete or inaccurate) - 1

Cellular HCT/P ReportsCellular HCT/P Reports

Donor testing – 42Donor testing – 42– Inappropriate test or test lab used; Inappropriate test or test lab used;

Required test not FDA licensed, Required test not FDA licensed, approved or cleared – 41approved or cleared – 41 Six of the above represent HIV/HCV NAT Six of the above represent HIV/HCV NAT

performed on pooled instead of performed on pooled instead of individual samplesindividual samples

– Specimen tested was collected from Specimen tested was collected from a PBSC donor more than 30 days a PBSC donor more than 30 days before recovery - 1before recovery - 1

Cellular HCT/P Reports - Cellular HCT/P Reports - 22 Processing and process controls – 50Processing and process controls – 50

– HCT/P contaminated, potentially HCT/P contaminated, potentially contaminated or cross contaminated during contaminated or cross contaminated during processing – 47processing – 47

One event related to syringe integrityOne event related to syringe integrity– In process controls not followed – 3In process controls not followed – 3

Microorganisms involved:Microorganisms involved:– Diphtheroids, Enterobacter, Group D Diphtheroids, Enterobacter, Group D

Enterococcus, Klebsiella, Micrococcus, Enterococcus, Klebsiella, Micrococcus, Peptostreptococcus, Propionibacterium, Peptostreptococcus, Propionibacterium, StaphylococcusStaphylococcus, , Stenotrophomonas, Stenotrophomonas, StreptococcusStreptococcus

Cellular HCT/P Reports - Cellular HCT/P Reports - 33 Distribution – 33Distribution – 33

– Contaminated or potentially contaminated Contaminated or potentially contaminated HCT/P – 32HCT/P – 32

– Distribution without sign off by a Distribution without sign off by a responsible person – 1responsible person – 1

Microorganisms involved:Microorganisms involved:– Bacillus, Cladosporium, Corynebacterium, Bacillus, Cladosporium, Corynebacterium,

Lactobacillus, Penicillium, Lactobacillus, Penicillium, Propionibacterium, StaphylococcusPropionibacterium, Staphylococcus

Classified RecallsClassified RecallsFY 2007FY 2007

HCT/PHCT/P

RecallsRecallsCBER Total CBER Total

Recalls Recalls

(all (all products)products)

FY 07 Class IFY 07 Class I 77 77

FY 07 Class FY 07 Class IIII

1515 10411041

FY 07 Class FY 07 Class IIIIII

00 381381

Classified RecallsClassified RecallsFY 2008*FY 2008*

HCT/PHCT/P

RecallsRecallsCBER Total CBER Total

Recalls Recalls

(all (all products)products)

FY 08 Class IFY 08 Class I 33 44

FY 08 Class FY 08 Class IIII

1111 950950

FY 08 Class FY 08 Class IIIIII

77 345345

*- This table does not include 3 “mixed class” recalls

FY 2008 Class I FY 2008 Class I HCT/P RecallsHCT/P Recalls

Donors met all DE requirements using Donors met all DE requirements using diagnosticdiagnostic HBsAg and HBcAb tests. HBsAg and HBcAb tests. Re-testing of donors using FDA Re-testing of donors using FDA licensed donor screening tests licensed donor screening tests revealed three donors reactive revealed three donors reactive (confirmed positive) for HBsAg(confirmed positive) for HBsAg– 2 recalls2 recalls

Clostridium perfringens Clostridium perfringens infection in infection in recipient.recipient.

HCT/P RecallsHCT/P Recalls

0

5

10

15

20

25

30

35

40

45

FY00 FY01 FY02 FY03 FY04 FY05 FY06 FY07 FY08

Class I

Class II

Class III

Vision for CBERVision for CBERINNOVATIVE TECHNOLOGY INNOVATIVE TECHNOLOGY ADVANCING PUBLIC HEALTHADVANCING PUBLIC HEALTH

CBER uses sound science and regulatory CBER uses sound science and regulatory expertise to:expertise to:

Protect and improve public and individual Protect and improve public and individual health in the US and, where feasible, globally health in the US and, where feasible, globally

Facilitate development, approval and access Facilitate development, approval and access to safe and effective products and to safe and effective products and promising new technologies promising new technologies

Strengthen CBER as a preeminentStrengthen CBER as a preeminent regulatory organization for biologicsregulatory organization for biologics

We’re Here to Help You!We’re Here to Help You!WWW.FDA.GOV/CBER WWW.FDA.GOV/CBER

Email CBER:Email CBER:–Manufacturers: Manufacturers: matt@cber.fda.govmatt@cber.fda.gov

–Consumers, health Consumers, health carecare

–octma@cber.fda.govoctma@cber.fda.gov Phone:Phone:

–+1-301-827-1800+1-301-827-1800