WARNING LETTER
Stratus BioSystems, LLC
MARCS-CMS 581032 —
July 01, 2019
Delivery Method:
VIA UNITED PARCEL SERVICE
SIGNATURE CONFIRMED DELIVERY
Reference #:
OBPO 19-08
Product:
Biologics
Recipient:
Recipient Name
Gene Elliot
Recipient Title
Chief Operating Officer
Stratus BioSystems, LLC
918 S Main St
Ste 215
Grapevine
,
TX
76051-7575
United States
Issuing Office:
Office of Biological Products and Operations Division 2
550 W. Jackson Chicago
Chicago
,
IL
60661
United States
Dear Mr.
Elliot:
The United States Food and Drug Administration (FDA) conducted an inspection
of
your firm, Stratus Biosystems, LLC, located at 918 S Main Street, Ste 215, Grapevine, Texas, from February 6 through February 28, 2019. During the inspection. FDA Investigators documented
significant
deviations
from
the regulations
for
human cells, tissues, and cellular and tissue-based products (HCT/Ps)
set forth
in Title 21,
Code of Federal Regulations,
Part 1271 (21 CFR 1271), and issued under
the
authority of Section 361 of the Public Health Service Act (42 U.S.C.
§
264).
The deviations documented on a Form FDA 483, List of lnspectional Observations, were presented to and discussed with you at the conclusion of the inspection. The items of concern include, but are not
limited
to the following:
1. Failure to validate and approve a process
acco
rding
to
established procedures where the results of processing cannot be fully verified
by
subsequent
inspection and tests. The validation activities and results must be documented, including the date and signature of the individual(s) approving the
validation [21
CFR
1271.230(a)].
For example,
you
failed to adequately validate
the
Amniotic Membrane Patch Allograft manufacturing process, which cannot be fully verified, to ensure that your process removes contamination that
is
present,
and
to
ensure
that processing prevents the introduction, transmission, or
spread of
communicable disease through the use of the HCT/P. Since March 2018, your firm has processed HCT/Ps into Amniotic Membrane Patch Allografts and distributed those products without a validated process.
2. You must not make available for distribution an HCT/P that is in quarantine, is contaminated, is
recovered
from a donor who has been determined to be ineligible or for whom a donor eligibility determination has not been completed, or that otherwise does not meet
release
criteria designed to prevent communicable disease transmission [21 CFR 1271.265(c)(2)]. For example:
a. Donor
(b)(4)
,
(b)(6)
had a positive pre-processing culture on
the
amniotic membrane for
Staphylococcus aureus,
a
Class
3 organism
on
your Bacter
i
a Acceptance Criteria chart. According to your procedures
,
HCT/Ps with positive pre-processing cultures for a Class 3
organism
should be discarded, however you did not discard th
is
tissue and processed and distributed Amniotic Membrane Patch Allografts manufactu
r
ed from this donor.
b. You distributed Amniotic Membrane Patch
Allografts
manufactured from donor
(b)(4)
,
(b)(6)
after receiving a positive p
o
st-processing culture result
for
Clostridium perfringens
on a different product manufactured from the
same
donor.
Clostridium perfringens
is a Class
3
organism (on
your
Bacteria Acceptability Criteria list) that requires discard o
f
culture positive tissue from the don
o
r
,
i.e. in this case, the amnion. We also note that this organism is not generally a contaminant introduced during processing
,
the source
was
likely
the donor.
3.  Failure of a responsible person to determine and document the eligibility
of a
cell or tissue donor based upon the
results
of donor
screening
and donor testing [21 CFR 1271.50(a)]
.
For examp
l
e
,
since operations began in March 2018, your
firm
has
failed
to document whether donors of amniotic
membrane
are eligible. Although you receive relevant medical records from your recovery agency, including a donor medical history
i
nterview and a physical examination, you do not use the results of donor
screening
in accordance with Sec.
1
271.75 and donor testing in accordance with Secs. 1271.80 and 1271
.
85 to
document
that a donor has been determined to be
eligible.
4
.
Failure to retain the accompanying records with
the
HCT/Ps at all times follow
i
ng a donor eligibility determination including a statement whether, based on the
results
o
f screening and
testing,
the donor has
been
determined to be el
i
g
i
ble
or
ineligible; and a summary of records used to make the donor
eligibility
determination [21 CFR 1271.55(a)]. Specifically, all Amniotic Membrane Patch Allograft products distributed since your
firm's
manufacturing operation began in February 2018, were distr
i
buted without a
statement
of donor eligibility and without
a
summary of records used to make the donor eligibility determ
i
nation
.
5. Failure to clean, sanitize
,
and maintain equipment according to
established
schedules [21 CFR 1271.200(a)]. For example, you do not maintain your
(b)(4)
(SN
(b)(4)
, model #
(b)(4)
to ensure proper functioning. This
(b)(4)
is
used to
sterilize
your
processing equipment and supplies for the Amniotic Membrane Patch Allograft products. According to the owner's manual, the
(b)(4)
requires
(b)(4)
maintenance. You have not performed
(b)(4)
maintenance on this
equipment since
you began
operations
in March 2018.
6. Fa
i
lure to establish and maintain procedures appropriate
to
meet core current good tissue practice (CGTP
)
requirements for all steps that you perform in the manufacture of HCT/Ps. You must design these procedures to prevent circumstan
c
es that increase the risk of the introduction, transm
i
ssion,
or
spread
of
communicable diseases through the use of HCT/Ps [21 CPR 1271
.1
80(a)].
For example,
you do not have a procedure providing guidance on what to do if an unknown bacterium (not
i
ncluded on
your
Bacteria Acceptability
Criteria
list) is
i
dent
i
fied on a post-processing culture.
The deviations ident
i
fied above are not intended to be an all-inclusive list of deficiencies at your facility. It is your responsibility to ensure that your establishment
is
in compliance
with
all applicable requirements of
the federal regulations. You are responsible for reviewing your firm's operat
i
on
s
as a whole to assure
t
hat you are
i
n compliance with all of the FDA regulatory requirements
.
This Warning Letter only addresses your Amniotic Membrane Patch Allograft product. At th
i
s time, FDA has not evaluated the compliance status of the Suspension Allografts or Purified Fluid Allografts manufactured by
Stratus Biosystems. Accordingly, references to HCT
/
Ps in this letter do not include such products. Please be advised that it remains your responsibility to ensure that all your products, whether specifically men
t
ioned in this letter or n
o
t, ar
e
manufactured in accordance with the law, including all applicable FDA regulations.
We acknowledge receipt of your written response, dated March 8, 2019, which provide
s
a response and corrective actions to FDA's inspectiona
l
observations (FDA-483)
.
We note that you have ceased pr
o
cess
i
ng of HCT/Ps and have committed to implementing new
p
rocedures and re-training your staff. The effectivenes
s
of your corrective actions will be evaluated during the next inspection. We als
o
have the following comments regarding your responses
:
1. You st
a
ted th
a
t part of your corrective action
s
included the e
s
tablishment of new procedures and forms for your operations. We remind you that you in acc
o
rdance with 21 CFR 1271.
1
80(a), you must ensure that you establish and maintain procedures
fo
r all steps you perform in the manufacture of HCT/Ps.
2. In response to Observations 3 and 7.a., you noted that you have written a validation protocol and completed process va
li
dat
io
n
.
We request that you
s
ubmit your validation protocol and results o
f
val
i
dation for the Amniotic Membrane Patch Allograft process to FDA for review
.
Additionally, we note that if you have not already written a new procedure for the Amniotic Membrane Patch All
o
graft process following validation
, s
uch a pro
c
edure will also need to be established and maintained.
3
.
In response to Observation 2, you sta
t
ed that you are updating SOP F-SB-021 to include all bacteria that may affect your validation and that you will
reject any tissue that is positive on preprocessing cultures for o
r
ganisms not already on your Bacteria Acceptability Criteria list. However
,
we note that your Bacteria Acceptability Criteria list classifies organisms as Class 1
,
2, or 3 based on their pathogenicity and
(b)(4)
.
According to your procedure
Donor Eligibility Review,
C
l
ass 3 organisms require discard of culture-positive tissues. However, for Class 1 and 2 organisms
,
your procedure states
th
at tissues with posit
i
ve cultures for either class of organism "shall be considered incidentally contaminated." Your procedure does not
i
ndicate if additional processing steps are required when Class 1 or 2 organisms are identified. Please explain how you manage tissues when pre-processing cu
l
tures identify such organisms.
You should take prompt action to correct the violations addressed in this letter and prevent their recurrence. Failure to promptly correct these violations may result in regulat
o
ry action being initiated by the FDA without further notice.
We request that you respond in writing within fifteen (15) wor
k
ing days from your receipt o
f
this letter, outlining the specific steps you have taken or plan to take to correct the noted violations and prevent their recurrence. If you cannot complete all corrections within fifteen (15) working days, please explain the reason for your delay and the time frame within which the remaining corrections will be completed.
Your response should be sent to the
following
address: Sam Labinjo,
U.S.
Food and Drug Administration, 550 W.
Jackson,
Ste. 1500 Chicago I
L
60661 or emailed to Samuel.labinjo@fda.hhs.gov. If you
shoul
d
have any questions, please contact Sam Labinjo, Compliance Officer at 312-596-4254
or
via e-mail.
Sincerely,
/S/
Karlton Watson
Program Division Director
Office of Biological
Products
Operations - Division 2
Content current as of:
07/23/2019
Regulated Product(s)
Biologics