Transcript SESSION 1 FDA - The Florida Association of Blood Banks

FABB - 2013
HOT TOPICS
Current Issues in Blood Banking
Ron Jackson
Director, Compliance Branch
FDA FLORIDA DISTRICT
June 7, 2013
New Labeling Regulations
New Labeling Regulations
• 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
Most Notable Changes
• 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
Most Notable Changes
• 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
Most Notable Changes
• 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
Most Notable Changes
• 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
Additional Information in
Preamble
• 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)
Most Notable Changes
• 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
Summary of Notable Changes
• 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)
References
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
New Apheresis Plasma
Products
New Apheresis Plasma Products
• 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)
Apheresis Devices approved
and/or cleared to manufacture new
Plasma products
• Fenwal ALYX
• Fenwal Amicus
• TerumoBCT Trima Accel
Plasma Frozen Within 24 Hours
After Phlebotomy (PF24)
• 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.
Plasma Frozen Within 24 Hours
After Phlebotomy Held At Room
Temperature Up To 24 Hours After
Phlebotomy (PF24RT24)
• 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.
Example of Instructions for Use
Circular of Information
21 CFR 606.122 Circular of information.
A circular of information must be available
for distribution if the product is intended for
transfusion.
Circular of Information
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
Please Note
• Whole Blood
– PF24 has been a licensable product for > 20
years
– PF24RT24 has NOT been cleared or
approved to be manufactured from Whole
Blood
Platelet Manufacturing
Rest Period and Agitation
The Science…
• 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.
The Regulations…
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 …
Additional Information 
• Trima Accel
Additional Information 
CaridianBCT Guide to Platelet and Plasma Collections 2001
Additional Information 
• Fenwal Amicus
Guidance for Industry
Implementation of an Acceptable
Abbreviated Donor History
Questionnaire (aDHQ) and
Accompanying Materials for Use in
Screening Frequent Donors of Blood
and Blood Components
Defined Donor Criteria for Frequent
Donor
• 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.
Eligibility for using the aDHQ
• 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
Methods of Administration
• 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
Day of Donation (aDHQ)
• 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
Common Problems in
Biologics Inspections
Source:
Turbo EIR Database
Scope
Timeframe
01/2012 to 12/2012
Approx. # of Inspections in Database
1,038
Approx. # of Observations in Database
343
Applicable Regulations
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
Frequency of Observations
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
606.100(b) – SOPs
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, ***
606.100(c)
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, ***
606.160(a)(1)
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, ***
606.160(a)(1) cont’d:
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, ***
606.160(a)(1) cont’d:
Cited in 13 inspections
Records are [illegible] [not indelible]
Specifically, ***
606.160(b)
Cited in 22 inspections
Failure to maintain [donor] [processing]
[storage and distribution] [compatibility testing]
[quality control] [general] records.
Specifically, ***
606.65(e)
Cited in 15 inspections
Failure to use supplies and reagents in a manner
consistent with instructions provided by the
manufacturer.
Specifically, ***
606.60(b)
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, ***
606.20(b)
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, ***
606.171
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
8
Injunctions
17
Warning Letters
4,882
Recall Events
4,075
Recalled Products
9,469
Debarments
20
Seizures by FDA Center
Fiscal Year 2012
14
12
10
8
5
6
2
0
TP
V
BE
R
C
N
FS
A
C
D
ER
C
C
D
R
H
0
0
M
0
C
1
2
C
4
Injunctions by FDA Center
Fiscal Year 2012
20
15
10
9
5
4
2
2
0
0
CDRH
CDER
CFSAN
CBER
0
CVM
CTP
Warning Letters by FDA Center
Fiscal Year 2012
5000
4146
4000
3000
2000
P
T
M
ER
B
C
N
FS
A
C
D
ER
C
D
R
H
0
C
76
20
C
335
95
V
210
C
1000
Total Recalled Products by FDA Center
Fiscal Year 2012
4,000
3,500
3,000
2,500
2,000
2,475
2,464
2,615
1,703
1,500
1,000
212
500
0
CDRH CDER CFSAN CBER
Class I, II and III
CVM
0
CTP
Recalled Products – All Centers
Fiscal Years 2007 – 2012
9,000
9,361
9,288
9,469
8,065
6,000
5,585
5,778
3,000
0
2007
2008
2009
2010
2011
Recalls: Class I, II, and III
2012
FDA Recalls By Center - All Classes
Fiscal Year 2012
4,000
3,000
2,475
2,615
2,464
2,000
1,794
1,703
1,190
1,000
704
316
67
212
0
CDRH
CDER
CFSAN
Events
CBER
Products
CVM
0
0
CTP
FDA Recalls – Class I By Center
Fiscal Year 2012
1500
1,105
1200
900
600
317
Events
Products
76
TP
0
C
M
BE
R
4
C
N
FS
A
D
ER
C
D
R
H
0
C
1
28
28
V
54
C
57 124
C
300
0
FDA Recalls - Class II By Center
Fiscal Year 2012
3,600
3,000
2,400
1,800
2,210
1,794
1,518
1,043
1,174
1,200
600
197
1,226
309
26
88
0
0
CD
RH
ER
D
C
SA
F
C
N
Events
E
CB
R
Products
CV
M
P
CT
0
FDA Recalls - Class III By Center
Fiscal Year 2012
1000
817
800
567
600
400
200
185
141
90
95
131
48
78
13
0
0
CDRH
CDER
CFSAN
Events
CBER
Products
CVM
0
CTP
FLA-DO Legal Actions
PROC
WL
UTL
Reg Meeting
Import Alerts
Seizure
Shut-Down
Close-out
Cessation Order
Post-insp ltr
140
123
120
106
100
80
60
48
46
40
20
0
18
889
11
FY 11
8
8
6 2
00 11
FY 12
Questions??
Contact Information:
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