FABB - 2013
HOT TOPICS
Current Issues in Blood Banking
Ron Jackson
Director, Compliance Branch
FDA FLORIDA DISTRICT
June 7, 2013

• Published in Federal Register
– “Revisions to Labeling Regulations for Blood and Blood
Components, including Source Plasma”
– 77 FR 7, January 3, 2012
• Became effective July 2, 2012
• Codified in Title 21 of the Code of Federal
Regulations - April 2012 edition
• Affects the following regs:
– 21 CFR 606.121
– 21 CFR 606.122
– 21 CFR 640.70
– 21 CFR 640.74

• April 2012 CFR contains both the old and new regs
• Labeling regs were updated to be consistent with current practices
• Changed the reg citation for certain requirements. For example:
– Recovered plasma label requirements previously in 21
CFR 606.121(e)(5), are now in 21 CFR 606.121(e)(4)
– Source Plasma labeling regs. previously in 21 CFR
640.70, were moved to 21 CFR 606.121

• Unique Facility Identifier (UFI)
– 21 CFR 606.121(c)(2)
– Discussed on page 77 FR 11 of the Federal Register
– UFI now required to be on labels of blood intended for transfusion
– Blood establishments need to track where unit was collected.
The UFI can be:
• The FDA registration number
• The ISBT facility code
• Some other designation that will identify specific location where product was collected
• Incorporated into donation number and use a validated computer or other recordkeeping system to identify where unit was collected
– Not applicable to Source Plasma; FDA is aware the approved labels have sufficient information

• Autologous Unit Labeling
– 21 CFR 606.121(i)
– Previously all auto units were labeled with “For Autologous Use
Only”
– Now acceptable auto units that can be crossed over into allogeneic inventory are labeled as “Autologous Donor”
– Unacceptable auto units that cannot be crossed over are labeled as “For Autologous Use Only”
– Note: AABB standards will only include “For Autologous Use
Only” statement because they discourage crossover
– “For Autologous Use Only” can be on all auto units, but these units cannot be crossed over

• Circular of Information
– Changed name from “Instruction Circular” to “Circular of
Information”
– 21 CFR 606.122(m)(3)
– Removed requirement to administer thawed FFP or PF24 within 6 hours
– States circular must have instructions when to begin administering FFP and PF24 after thawing
– Current circular states FFP and PF24 must be administered within 24 hours after thawing
– Eliminates requirement for 21 CFR 640.120 variance to store thawed FFP and PF24 for up to 24 hours before administering
– Note: Circular states 5-day Thawed Plasma is unlicensed;
CBER will not approve variances for this product

• 77 FR 11 (21 CFR 606.121(b) –
– Original labels may be altered to accurately the identify contents of the unit, e.g., after irradiation, washing, etc.
– This includes reprinting a new full-face label, but blood establishments must be able to re-create all other original information and it must be done with a validated process
• 77 FR 12 (21 CFR 606.121(c)(11) –
– Source Plasma donors are tested for syphilis every 4 months; it is a donor test (vs. a test on the donation)
– Confirmed that it is not required to put negative syphilis results on each Source Plasma unit
– But if syphilis test is reactive, the unit associated with the positive test and all subsequent units from that donor must include positive syphilis test result (until test is negative)

• 77 FR 13 (21 CFR 606.121(c)(11) -
– It is acceptable for Source Plasma units to have negative infectious disease test results on label before testing has been completed
– It is acceptable for these units to be shipped to quarantined storage, including to an independent off-site storage facility
– The storage facilities must be under the control of the
Source Plasma firm; this includes those owned by or under contract to the Source Plasma firm
– If unit is pre-labeled with negative test result but is later found to be positive when testing is completed, the unit must be relabeled; the negative result must be obliterated and replaced with the positive result

• Source Plasma labeling regs were removed from 640.70 and are now included in 606.121
• Blood establishments must be able to determine from label where each unit was collected
• “For Autologous Use Only” can be on the labels of all auto units if they will not be crossed over
• Variances are no longer needed to store thawed FFP and PF24 for up to 24 hours before administering
• Full-face labels on modified products can be re-created using a validated process
• Source Plasma units can be pre-labeled with negative infectious disease test results before testing is completed and shipped to storage facilities under firm’s control; positive units must be relabeled
• Source Plasma units must be labeled with positive syphilis test results (index unit and subsequent units until test is negative)

Federal Register – 77 FR 7, January 3, 2012
• Title 21 CFR – April 2012
– 21 CFR 606.121
– 21 CFR 606.122
– 21 CFR 640.70
– 21 CFR 640.74
• CBER - Blood and Plasma Branch CSOs
– 301-827-3543

• Plasma Frozen Within 24 Hours After
Phlebotomy (PF24)
• Plasma Frozen Within 24 Hours After
Phlebotomy Held At Room Temperature
Up To 24 Hours After Phlebotomy
(PF24RT24)

• Fenwal ALYX
• Fenwal Amicus
• TerumoBCT Trima Accel

• Must be stored at 1 – 6C within 8 hours of collection and prepared and frozen within
24 hours after phlebotomy.
• Indicated for replacement of non-labile clotting factors. This product is not equivalent to Fresh Frozen Plasma.

• Can be stored at room temperature for up to 24 hour after collection. Product must be prepared and frozen within 24 hours after phlebotomy.
• Indicated for replacement of non-labile clotting factors. This product is not equivalent to Fresh
Frozen Plasma.

21 CFR 606.122 Circular of information.
A circular of information must be available for distribution if the product is intended for transfusion.

The December 2009 version of the AABB
COI may be modified by the following FDA accepted statement: http://www.aabb.org/resources/bct/Pages/aabb_coi.aspx

This may either be glued or stapled into the current December
2009 edition

• Whole Blood
– PF24 has been a licensable product for > 20 years
– PF24RT24 has NOT been cleared or approved to be manufactured from Whole
Blood

• Centrifugated platelets aggregate irreversibly if subjected to rough agitation
• The procedures should describe a “Rest
Period” for 10 minutes to an hour prior to resuspension.

21 CFR 640.25 [Platelets] General requirements.
(a) Storage.
Immediately after resuspension,
Platelets shall be placed in storage at the selected temperature range. If stored at 20 to 24 deg. C, a continuous gentle agitation of the platelet concentrate shall be maintained …


• Trima Accel


CaridianBCT Guide to Platelet and Plasma Collections 2001


• Fenwal Amicus

Implementation of an Acceptable
Abbreviated Donor History
Questionnaire (aDHQ) and
Accompanying Materials for Use in
Screening Frequent Donors of Blood and Blood Components

• Two previous donations using the full-length
Donor History Questionnaire (DHQ), one within last 6 months
• Includes deferral of less than 6 months duration, if within 6 months of “successful donation.” (usable component, not a factor)
• Deferrals greater than 6 months disqualify approval for use of aDHQ must start over

• SOP should state actions to be taken if:
– a. Incorrect questionnaire administered
– b. Questionnaire is incomplete
– c. Ensure that donor unit quarantined until eligibility issued are resolved.
• If unit distributed, BDPR required
• Investigation required
• New questions – both full-length DHQ and aDHQ for 1 year from date added.

• Administered on day of donation
• Donor must meet the defined criteria for
“Frequent donor” AND
• blood collection facility has a system in place to determine appropriateness

• Written Procedure (SOP)
• May be Self-Administered with f/u review by trained donor historian
• May be administered by donor historian
• Donor may be deferred prior to completion of entire questionnaire, if specified in SOP
• Encourage donor to ask questions

)
• Must read Donor Education Materials prior to completing questionnaire
• Must be given Medication Deferral List and
• List of BSE countries to be used
• Alternatively, one or all lists can be prominently displayed at donation site for donors’ use while donors complete aDHQ

Timeframe
01/2012 to 12/2012
Approx. # of Inspections in Database
1,038
Approx. # of Observations in Database
343

Blood GMP’s
– 43% relate to Written SOPs
– 27% cite records deficiencies
– 22% pertain to performance failures
– 4% identify training and/or personnel issues
– 4% specify equipment calibration issues

21 CFR
606.100(b)
606.160(a)(1)
606.100(c)
606.160(b)
606.20(b)
606.60(b)
606.65(e)
606.171
Count
- 147
- 70
- 46
- 22
- 15
- 15
- 15
- 13

Cited in 147 inspections
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, ***

Cited in 46 inspections
Failure to [ perform a thorough investigation ]
[make a record of the conclusions and followup] of [an explained discrepancy] [a failure of a lot or unit to meet any of its specifications].
Specifically, ***

Cited in 29 inspections
Records fail to [identify the person performing the work] [include dates of the various entries] [show test results] [include interpretation of the results]
[show the expiration date assigned to specific products] [ be as detailed as necessary ] so as to provide a complete history of the work performed.
Specifically, ***

:
Cited in 28 inspections
Records are not concurrently maintained with the performance of each significant step in the
[collection] [processing] [compatibility testing]
[storage] [distribution] of each unit of blood and blood components so that all steps can be clearly traced.
Specifically, ***

Cited in 13 inspections
Records are [ illegible ] [ not indelible ]
Specifically, ***

Cited in 22 inspections
Failure to maintain [donor] [processing]
[storage and distribution] [compatibility testing]
[ quality control ] [general] records .
Specifically, ***

Cited in 15 inspections
Failure to use supplies and reagents in a manner consistent with instructions provided by the manufacturer .
Specifically, ***

Cited in 15 inspections
Equipment used in the [ collection ] [ processing ]
[compatibility testing] [ storage and distribution] of blood and blood components is not
[ observed ] [standardized] [ calibrated ] on a regularly scheduled basis as prescribed in the
SOP Manual.
Specifically, ***

Cited in 15 inspections
The personnel responsible for the [collection]
[processing] [compatibility testing] [storage]
[distribution] of blood or blood components are not adequate in [number] [educational background]
[ training and experience, including professional training as necessary ] 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.
Specifically, ***

Cited in 13 inspections
Failure to submit a biological product deviation report [ within 45 days from the date you acquired information suggesting that a reportable event occurred]
Specifically, ***

Top 10 Biologics Observations Used in Turbo EIR Between 01/01/2012 And 12/31/2012

FDA Enforcement Statistics Summary
Fiscal Year 2012
Seizures
Injunctions
Warning Letters
Recall Events
Recalled Products
Debarments
8
17
4,882
4,075
9,469
20

Seizures by FDA Center
Fiscal Year 2012
14
12
10
8
6
4
2
0
CD
RH
1
2
CD
ER
CF
SAN
5
CB
ER
0
CVM
0
CT
P
0

20
Injunctions by FDA Center
Fiscal Year 2012
15
10 9
5
0
2
CDRH
2
CDER CFSAN
0
CBER
4
CVM
0
CTP

Warning Letters by FDA Center
Fiscal Year 2012
5000
4146
4000
3000
2000
1000
0
CD
RH
210
95
335
CD
ER
CF
SAN
CB
ER
20
CVM
76
CT
P

Total Recalled Products by FDA Center
Fiscal Year 2012
4,000
3,500
3,000
2,500
2,000
1,500
1,000
500
0
2,475
1,703
2,464
2,615
212
0
CDRH CDER CFSAN CBER CVM CTP
Class I, II and III

Recalled Products – All Centers
Fiscal Years 2007 – 2012
9,000
6,000
3,000
0
5,585
2007
5,778
8,065
9,361 9,288
9,469
2008 2009 2010
Recalls: Class I, II, and III
2011 2012

FDA Recalls By Center - All Classes
Fiscal Year 2012
4,000
3,000
2,000
1,000
1,190
2,475
1,703
2,464
1,794
2,615
704
316
0
CDRH CDER CFSAN CBER
Events Products
67
212
CVM
0 0
CTP

900
600
300
0
1500
FDA Recalls – Class I By Center
Fiscal Year 2012
1,105 1200
57 124
28
54
317
1
4
28
76
0 0
CD
RH
CD
ER
CFS
AN
CBE
R
Events Products
CVM
CTP

3,600
3,000
2,400
1,800
1,200
600
0
FDA Recalls - Class II By Center
Fiscal Year 2012
1,043
2,210
197
1,518
309
1,174
1,226
1,794
26 88
0 0
CDR
H
CDE
R
CF
SA
N
CBE
R
Events Products
CV
M
CTP

FDA Recalls - Class III By Center
Fiscal Year 2012
1000
817
800
567
600
400
200
0
90
141
95 131
78
185
13
48
CDRH CDER CFSAN CBER CVM
Events Products
0 0
CTP

140
123
120
106
100
80
60
40
48
46
PROC
WL
UTL
Reg Meeting
Import Alerts
Seizure
Shut-Down
Close-out
Cessation Order
Post-insp ltr
20
0
8 8 9
1 1
FY 11
8
18
6 2
0 0
8
1 1
FY 12

CBER - Blood and Plasma Branch CSOs:
(301) 827-3543
FLA-DO: Biologics Specialist:
(904) 281-1924 ext. 116
FLA-DO District Office:
(407) 475-4700