Transcript FDA Perspective on the Implementation of Electronic

CBER 510(k) Issues
Sheryl A. Kochman, MT(ASCP)
Chief, Devices Review Branch
DBA/OBRR/CBER
IVD Roundtable – OIVD Workshop April 23, 2003
C B
E R
Why does CBER review devices?
 Jurisdiction
for medical device review
is governed by the FDA Intercenter
Agreement between the Center for
Biologics Evaluation and Research
(CBER) and the Center for Devices
and Radiological Health (CDRH)
(October 31, 1991)
Available at:
http://www.fda.gov/cber/dap/devpubs.htm
C B
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Intercenter Agreement Between
CBER and CDRH
(October 31, 1991)
 CBER
will have the lead responsibility for
regulating medical devices used or indicated for
the collection, processing, testing, storage, or
administration of biological products (including
blood products, blood components, or analogous
products), and will use authorities under the
Public Health Service Act (PHS Act) and the
FD&C Act, as well as any other authorities
delegated to it, as appropriate.
C
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Intercenter Agreement (cont)
In vitro tests which are required for blood donor
screening and related blood banking practices (such
as donor re-entry) are licensed under the PHS Act
 Immunohematology
Reagents
• Blood Grouping Reagents
• Reagent Red Blood Cells
• Antihuman Globulins
 Limulus
(LAL)
amebocyte lysate
 Blood
Borne pathogen tests*
• HIV 1/2
• HIV Ag
• HBsAg
• HB core
• HCV
• HTLV I/II
* examples only, not a C B
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complete list
Intercenter Agreement (cont)
 CBER
also has the responsibility for regulating
all in vitro diagnostic tests and any other
medical devices intended for use for human
immunodeficiency virus, type 1 (HIV 1) and type
2 (HIV 2) and other retroviruses.
 These
devices, including but not limited to
collection devices, specimen containers, test kit
components or support materials and those used
or indicated for the inactivation of these viruses,
will be regulated by CBER under the Medical C
E
Device Authorities (MDA).
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R
What devices does CBER review ?*

Medical devices that are dedicated systems intended for
use in collection, processing, or administration of a
licensed biological or analogous product
 Includes
• Apheresis machines  Blood Warmers
 Plasma Thawers
• Filters
 Stem Cell Concentrator
• Refrigerators
 Excludes
• Administration sets
• Therapeutic devices
Dialysis machines
C
Intraoperative blood salvage devices
E
* As stated in the Intercenter Agreement
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Devices Reviewed at CBER (cont)*
Certain In Vitro Reagents
 Those
intended for use in the processing of
licensed biologicals and analogous products
 Lectins
 Protectins
 Bovine
albumin potentiating media
 Leukocyte
typing sera or other medical devices
intended for use in the determination of tissue type
 Quality assurance reagents intended for use in
conjunction with a licensed biological reagents
or
C B
in vitro tests
E R
Devices Reviewed at CBER (cont)*
 Medical
devices other than reagents intended for
use in the preparation of, in conjunction with, or
for the quality assurance of a blood bank related
licensed biological product or practice.
Clinical laboratory devices with separate blood
bank claims
Software programs for data management in a
blood establishment
Dosimeters and thermal indicators
Microwave ovens used for thawing blood
C
E
products
B
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Devices Reviewed at CBER (cont)
 See
also
21 CFR 864.9050 through 864.9875
List of Devices Regulated by CBER
• http://www.fda.gov/cber/dap/devlst.htm
• KSS/Blood Banking supplies consists of a
wide variety of devices, some of which are:
• Blood temperature indicator
• Tube stripper
• Isotonic saline labeled for BB use
• Blood irradiation label
• Blood component separator
C B
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Devices Reviewed at CBER (cont)
• ZZZ/Unclassified was used for devices for
which a firm could identify a predicate, and
therefore could submit a 510(k) but which
had not been formally classified. This group
also contains a wide variety of devices, such
as:
• HLA reagents
• CMV test kits
• Instrument software
• Syphilis tests
• Platelet antigen/antibody tests
• Leukocyte removal filters
C B
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What kinds of premarket device
submissions does CBER review ?
Everything
that CDRH does
But fewer of them
INDs and BLAs
C B
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Special Situations for IVDs*
 For
diagnostic use only (except HIV and
retroviruses), CDRH regulates under MDA
HIV and other retrovirus diagnostics
regulated by CBER under MDA
 For blood donor screening, CBER regulates
under MDA, i.e., 510(k)
CMV
*
As stated in the Intercenter Agreement
C B
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Special Situations for IVDs (cont)*
 For
diagnostic use AND blood donor screening,
CDRH is lead Center with each center reviewing
their respective data sets under MDA
CMV
 Required for use in blood donor testing, CBER
regulates under the PHS Act
Blood borne pathogen tests (IND/BLA)
• Syphilis is an exception (reviewed under 510(k))
Immunohematology reagents (BLA)
C B
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What are some of the public health
issues that are unique to CBER ?
Ensuring safety and efficacy of biological therapeutic products
 Management of those products
 Recalls
 Management of donors
 Temporary deferral and subsequent re-entry
 Permanent deferral
 Counseling
 Rapid response to emerging infectious agents
 TSEs
 West Nile Virus
C B
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 SARS

What are some of the outside groups
CBER deals with ?
 Significant
outside interactions with:
 Blood
Products Advisory Committee
 Advisory Committee on Blood Safety and Availability
 PHS Blood
• FDA, CDC, NIH, DOD
 Congress
 Public perception of blood safety
 Patient advocacy groups
C B
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Scope of the Blood Industry
Whole Blood
Source Plasma
13.9 million units
collected/yr
 18 million components
 8 million donors
 3000 registered facilities
 3.5 million recipients


12 million units collected/yr
 Manufactured into 35
different plasma derivative
products
 1 million donors
 80 licensed establishments
C B
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What are some of the review issues
that are important to CBER ?
Detection and identification of disease in a
population of “normal, healthy adults”
Versus
Diagnosis of disease in a patient showing signs
and symptoms of disease
Requires higher numbers of clinical trial samples
to assure statistical significance
C B
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What are some of the review issues
that are important to CBER ?


Many of our products are Combination Products because they are
linked by their labeling, i.e., a system
 Licensed reagent(s) (biologicals)
 Accessory reagents (devices)
 Accessory instruments (devices)
 Accessory software (devices)
 Ancillary goods (devices)
• Pipettes
• Tubes
• Micro-well plates
Others are combination products because of their packaging
C
 Therapeutic biological in a syringe
E
B
R
What are some of the procedural
issues that are different at CBER ?




We currently do not respond by e-mail to incoming e-mails that
contain proprietary or confidential information but are working
on a secure e-mail system to allow us to do so.
We have different submission binding and filing formats.
 Please see SOPPs 8007 and 8110 at:
 http://www.fda.gov/cber/regsopp/regsopp.htm
We have a different address:
FDA/CBER
Document Control Center, HFM-99, Suite 200N
1401 Rockville Pike
Rockville, MD 20852-1448
We usually need more than one copy; please send at least two
or call ahead and ask.
C B
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Recent CBER Process Changes
(To Enhance the Review Process)
 New
priority courier service for regulatory documents
 New bar-coded tracking of regulatory documents
 Close collaboration with CDRH
 Least Burdensome training
 Active problem solving during first cycle, not just
problem finding
 Down delegation to Division Directors
C B
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Recent CBER Process Changes (cont)
 Where
possible, use CDRH policies
 Set internal goals in parallel with CDRH
ex. 60 day response for 510(k) IVD submissions
 Increased pre-submission meetings
 Device subcommittee of RMCC
C B
E R
Is everything unique or different at
CBER ?
ABSOLUTELY NOT !
 We are subject to the same Congressional mandates as
CDRH
 FDAMA
 MDUFMA
 We support the use of pre-submittal (Pre-IDE) meetings
 CBER SOPP 8101.1
http://www.fda.gov/cber/regsopp/81011.htm
 We utilize:
 Standards & guidances
 Scientific workshops
C
E
 Advisory committee recommendations

B
R
How Do I Find a Predicate ?

Go to CBER’s web site for list of cleared devices 1st
 510(k)
Blood Establishment Computer Software
http://www.fda.gov/cber/products/510ksoft.htm
 Substantially Equivalent 510(k) Device Information
http://www.fda.gov/cber/efoi/510k.htm
 510(k) Device Applications (Cleared Since 1996)
http://www.fda.gov/cber/dap/510kman.htm

If you can’t find one on ours, try CDRH’s website
C B
E R
What about guidance documents ?
Most general CDRH guidances are applicable

Federal Register - FDA Modernization Act of 1997; List
of Documents Issued by the FDA That Apply to Medical
Devices Regulated by CBER - 4/26/1999
Several CBER-specific guidances exist.
The following are available at:
http://www.fda.gov/cber/dap/devpubs.htm

Federal Register - Medical Devices; Hematology and
Pathology Devices; Reclassification of Automated Blood
Cell Separator Device Operating by Filtration Principle
C
from Class III to Class II; Final rule - 2/28/2003
B
E R
CBER-specific guidances

Draft Guidance for Industry: Premarket Notifications
[510(k)s] for In Vitro HIV Drug Resistance Genotype
Assays: Special Controls - 8/28/2001

Draft Guidance for FDA Reviewers: Premarket
Notification Submissions for Automated Testing
Instruments Used in Blood Establishments - 8/3/2001

Guidance for FDA Reviewers: Premarket Notification
Submissions for Blood and Plasma Warmers - 7/19/2001

Guidance for FDA Reviewers: Premarket Notification
Submissions for Transfer Sets (Excluding Sterile
Connecting Devices) - 7/19/2001
C B
E R
CBER-specific guidances (cont)

Guidance for FDA Reviewers: Premarket Notification
Submissions for Empty Containers for the Collection
and Processing of Blood and Blood Components 7/19/2001

Draft Guidance for Industry: Clinical Development
Programs for Drugs, Devices, and Biological Products
Intended for the Treatment of Osteoarthritis (OA) –
7/15/1999

Guidance for Industry: Clinical Development Programs
for Drugs, Devices, and Biological Products for the
C
Treatment of Rheumatoid Arthritis – 2/17/1999
E
B
R
CBER-specific guidances (cont)
These CBER-specific guidances are available at:
http://www.fda.gov/cber/blood/bldguid.htm

Guidance for Industry: In the Manufacture and Clinical
Evaluation of In Vitro Tests to Detect Nucleic Acid Sequences
of Human Immunodeficiency Viruses Types 1 and 2 12/14/1999

Draft Guidance for Industry: Application of Current
Statutory Authority to Nucleic Acid Testing of Pooled Plasma11/26/1999
C B
E R
CBER-specific guidances (cont)

Draft Guidance for Industry: In the Manufacture and
Clinical Evaluation of In Vitro Tests to Detect Nucleic Acid
Sequences of Human Immunodeficiency Virus Type 1 7/10/1998

Guidance for Industry - The Sourcing and Processing of
Gelatin to Reduce the Potential Risk Posed by Bovine
Spongiform Encephalopathy (BSE) in FDA-Regulated
Products for Human Use - 10/07/1997

Reviewer Guidance for a Premarket Notification
Submission for Blood Establishment Computer Software 1/13/1997
C B
E R
CBER-specific guidances (cont)

Draft Guideline for the Validation of Blood Establishment
Computer Systems - 9/28/1993

Draft Points to Consider in the Manufacture and Clinical
Evaluation of In Vitro Tests to Detect Antibodies to the
Human Immunodeficiency Virus Type 1 - 8/8/1989
C B
E R
Contacting CBER About Submissions


For pre-submission help:
 Contact the person identified in the slides that follow
based on the device you wish to discuss
 If you cannot decide who to contact, contact the Center
Ombudsman, Dr. Sheryl L. Lard-Whiteford
For post-submission help:
 Contact your RPM first (see acknowledgement letter)
• The RPM can set up conference call or meeting with
the review team
 Contact Division management
 Contact Office management (Dr. Mary Beth Jacobs for
OBRR)
C
 Contact the Center Ombudsman
E
B
R
How to Contact CBER for Information
Contact the Office of Communication, Training &
Manufacturers Assistance at:
 Phone
301-827-1800 or 800-835-4709
 E-mail
[email protected]
 Web site
http://www.fda.gov/cber/pubinquire.htm
 See our current organization charts and lists at:
http://intranet.fda.gov/cber/admin/orgcht.htm
 Visit our web site: http://www.fda.gov/cber/
 Guidance: http://www.fda.gov/cber/dap/devpubs.htm

C B
E R
CBER Office of the Director
Jesse L. Goodman, M.D., M.P.H., Center Director,
 Previously Deputy for Medicine
 Spokesperson on West Nile Virus
 Mark A. Elengold, Deputy Director for Operations
 Robert A. Yetter, Ph.D., Associate Director for
Review Management
 Diane Maloney, J.D., Associate Director for Policy
 Sheryl L. Lard-Whiteford, Ph.D., Associate Director
for Quality Assurance and CBER Ombudsman

C B
E R
Office of Blood Research & Review
Jay S. Epstein, M.D., Director
 Richard M. Lewis, Ph.D., Deputy Director
 Mark J. Weinstein, Ph.D., Associate Deputy Director
 John S. Finlayson, Ph.D., Associate Director for
Science
 Mary Elizabeth Jacobs, Ph.D., Associate Director for
Regulatory Affairs
 Edward Tabor, Ph.D., Associate Director for Medical
Affairs
 Linda A. Smallwood, Ph.D., Associate Director
for
C B
Policy (BPAC contact)
E R

Division of Blood Applications
Alan E. Williams, Ph.D., Director
 Elizabeth G. Callaghan, Deputy Director
 Sayah Nedjar, Ph.D., Chief, Regulatory Program
Management Branch
 Sheryl A. Kochman, Chief, Devices Review
Branch
 Elizabeth G. Callaghan, Chief (Acting) Blood
and Plasma Branch

C B
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Division of Emerging &
Transfusion Transmitted Diseases
Hira L. Nakhasi, Ph.D., Director
 Paul A. Mied, Ph.D., Deputy Director
 Indira K. Hewlett, Ph.D., Chief, Laboratory of
Molecular Biology
 Gerardo Kaplan, Ph.D., Chief, Laboratory of
Hepatitis & Related Emerging Agents
 David Asher, M.D., Chief, Laboratory of Bacterial,
Parasitic, & Unconventional Agents

C B
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Division of Hematology
Basil (Dov) Golding, M.D., Director (Acting)
 Andrew Chang, Ph.D., Deputy Director (Acting)
 Jaro Vostal, M.D., Ph.D., Chief (Acting),
Laboratory of Cellular Hemostasis
 Dorothy E. Scott, M.D., Chief (Acting),
Laboratory of Cellular Hematology
 Andrew Chang, Ph.D., Chief (Acting),
Laboratory of Hemostasis
 Toby A. Silverman, M.D., Chief, Clinical
C B
Review Branch
E R

Office of Vaccines Research & Review
 Karen
Midthun, M.D., Director
 William M. Egan, Ph.D., Deputy Director
 Norman W. Baylor, Ph.D., Associate Director for
Regulatory Policy
 Richard I. Walker, Ph.D., Director Division of
Bacterial, Parasitic & Allergenic Products
 Jerry P. Weir, Ph.D., Director, Division of Viral
Products
 Karen L. Goldenthal, M.D., Division of Vaccines &
C B
Related Products Applications
E R
Office of Cellular, Tissue,
Gene Therapies
 Philip
&
D. Noguchi, M.D., Director (Acting)
 Joyce L. Frey-Vasconcells, Ph.D., Deputy Director
(Acting)
Andrea Wright, Regulatory Management Staff
 Raj K. Puri, M.D., Ph.D., Director (Acting),
Division of Cellular & Gene Therapies
 Cynthia A. Rask, M.D., Director (Acting), Division
of Clinical Evaluation & Pharmacology/Toxicology
 Ruth Solomon, M.D., Director (Acting),
C B
Division of Human Tissues
E R
Who Does What ?
 Office
of Blood Research & Review (OBRR)
Division of Blood Applications (DBA)
Devices Review Branch
• Immunohematology/HLA reagents, controls,
instruments, and accessories
• Blood Establishment Computer Software
(BECS)
• Meeting requests for the above
Call Sheryl Kochman or staff at 301-827-3503
C B
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Who Does What ?
 Office
of Blood Research & Review (OBRR)(cont)
Division of Blood Applications (DBA)(cont)
Regulatory Project Management Branch
• Blood collection, mixing, weighing, storage
systems
• Management and tracking of the reviews
• Meeting requests for all OBRR (except DRB)
submissions
Call Dr. Sayah Nedjar or staff at 301-827-5307
C B
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Who Does What ?
 Office
of Blood Research & Review (OBRR) (cont)
Division of Emerging & Transfusion Transmitted
Diseases (DETTD)
• Blood borne pathogen reagents, kits,
instruments
• HIV diagnostics, viral load test kits
• West Nile Virus
• TSEs
Call Dr. Sayah Nedjar or staff at 301-827-5307
C B
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Who Does What ?
 Office
of Blood Research & Review (OBRR) (cont)
Division of Hematology (DH)
• Blood containers, cell separators, processing
systems
• IVDs for platelet antigen/antibody testing
• Bacterial detection systems
• Cord/Stem cell collection, processing system
•Minimally manipulated
Call Dr. Sayah Nedjar or staff at 301-827-5307
C B
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Who Does What ?
 Office
of Cellular, Tissue & Gene Therapies (OCTGT)
Cord/Stem cell collection, processing system
• More than minimally manipulated
Call Dr. Stephanie L. Simek at 301-827-6536
 Office
of Vaccines Research & Review (OVRR)
Division of Vaccines & Related Products (DVRPA)
• Endotoxin testing supplies
(The kits themselves are licensed biologicals)
Call Dr. Paul Richman at 301-827-3070
C B
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CBER Device Submissions Received*
FY00
PMAs (Traditional)
3
PMSs (Traditional)
5
510(k)s (All Types)
34
BLAs (Original)
4
BLSs (Efficacy)
0
BLSs (Manufacturing, PAS) 124
FY01
3
8
37
2
0
47
FY02
1
5
42
2
0
35
*Includes RTAs/RTFs, Transfers, Withdrawals
C B
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CBER Device Submissions Received*
(from 10/1/02 – 3/31/03)
PMAs (Traditional)
PMSs (180 Day)
510(k)s (All Types)
BLAs (Original, Std)
BLSs (Efficacy)
BLSs (Manufacturing, PAS)
FY 03
1
1
35
0
3
31
ALL MDUFMA FY 05 GOALS MET*
*Data as of 4/15/03
C B
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510(k)s Received
45
Traditional
Abbreviated
Special
40
35
30
25
20
15
10
5
0
FY00
FY01
FY02
FY03 (6 mo)
C B
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CBER 510(k)s – Current Status*
(Receipts from 10/1/02 – 3/31/03)
Under 1st Cycle
510(k) Type
Traditional
Rec’d SE NSE Other Review Complete
21
10
0
3
5
3
Abbreviated
6
3
0
0
2
1
Special
8
7
1
0
0
0
Total
35
20
1
3
7
4
*All data as of 4/15/03
C B
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CBER 510(k) Cycles*
(from Receipt to Final Action)
510(k) Type
Traditional
(SE/NSE)
(Average)**
Under
1st Cycle
Review
Completed
10
1.1
5
3
Abbreviated
3
1.3
2
1
Special
8
1.0
0
0
21
1.1
7
4
Total
* All data as of 4/15/03
**Cycles will increase with completion of pendings
C B
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Time to Final Decision: FY 02*
(510(k) Receipt Cohort from 10/1/01 – 9/30/02)
FDA Time
Total Time
Cycles
510(k) Type
n (Days, Ave)
Traditional
18
141.2
175.5
1.89
Abbreviated
7
124.4
165.3
2.00
Special
4
38.8
50.0
1.50
Total
29
123.0
(Days, Ave)
155.7
* SE/NSEs Only; Data as of 4/15/03
(Average)
1.86
C B
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Time to Final Decision: Current*
(510(k) Receipt Cohort from 10/1/02 – 3/31/03)
FDA Time
Total Time
(Days, Ave)**
(Days, Ave)**
510(k) Type
n
Traditional
10
58.8
61.0
Abbreviated
3
60.0
69.3
Special
8
19.9
19.9
Total
21
44.1
46.5
* SE/NSEs Only; Data as of 4/15/03
**Times will increase with completion of pendings
C B
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Acknowledgements
 Dr.
Mary Beth Jacobs, Ph.D., CBER/OBRR/IOD
 Michael A. Calabro, Ph.D.; CBER/OBRR/IOD
C B
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