Note: Although this FDA-483 is an
accurate representation of the original FDA-483 issued to the firm, it is not an exact
copy. Slight modifications to the original FDA-483 have been made to accommodate its
conversion to the HTML format. A scanned copy of the original FDA-483 is available in PDF format on this website. |
DEPARTMENT
OF HEALTH AND HUMAN SERVICES
FOOD AND DRUG ADMINISTRATION |
DISTRICT OFFICE ADDRESS AND PHONE NUMBER
International Compliance Team, DMPQ/OC/CDER, FDA
White Oak Building 51, 4th FLoor
10903 New Hampshire Avenue
Silver Spring, MD 20993 USA
[Handwritten #1: adding the phone number "(301)
827-8942"] |
DATE(S)
OF INSPECTION
Feb 20, 21, 22, 25 & 26, 2008 |
FEI
NUMBER
|
NAME
AND TITLE OF INDIVIDUAL TO WHOM REPORT IS ISSUED
TO: Mr. Yan Wang, General Manager |
FIRM NAME
Changzhou SPL Company, Ltd. |
STREET ADDRESS
3 Changhong West Road |
CITY, STATE
AND ZIP CODE
Wujing, Changzhou City, Jiangsu Province,
China |
TYPE OF
ESTABLISHMENT INSPECTED
API (animal origin) Manufacturer |
THIS DOCUMENT LISTS OBSERVATIONS
MADE BY THE FDA REPRESENTATIVE(S) DURING THE INSPECTION OF YOUR FACILITY.
THEY ARE INSPECTIONAL OBSERVATIONS, AND DO NOT REPRESENT A FINAL AGENCY
DETERMINATION REGARDING YOUR COMPLIANCE. IF YOU HAVE AN OBJECTION REGARDING
AN OBSERVATION, OR HAVE IMPLEMENTED. OR PLAN TO IMPLEMENT. CORRECTIVE
ACTION IN RESPONSE TO AN OBSERVATION. YOU MAY DISCUSS THE OBJECTION
OR ACTION WITH THE FDA REPRESENTATIVE(S) DURING THE INSPECTION OR SUBMIT
THIS INFORMATION TO FDA AT THE ADDRESS ABOVE. IF YOU HAVE ANY QUESTIONS,
PLEASE CONTACT FDA AT THE PHONE NUMBER AND ADDRESS ABOVE.
DURING AN INSPECTION OF YOUR FIRM (I) (WE) OBSERVED:
- There have been no critical processing steps identified for the
Heparin Sodium USP [Redacted] process, and, the repeated
and efficient removal of impurities, such as proteins, nucleotides,
virus, endotoxin, bacteria and heavy metals at the appropriate, specified,
process steps has not been evaluated. There was no report for
annual [Redacted]
test results available.
The improvements offered by removal of a raw material [Redacted] test
@ [Redacted] a batch size increase, an added [Redacted] step,
a change in [Redacted] for the [Redacted] step
and [Redacted] and parameter
changes, approved in a 1/05 process validation report for Heparin Sodium
USP, were not demostrated.
- There has been no impurity profile established for Heparin Sodim
USP and no evaluation for degradants during stability program testing.
- The manufacturing instructions for Heparin Sodium USP are incomplete
in that they do not include a description of manual manipulations of
the [Redacted] during processing steps, they do not
include the actual, manually entered [Redacted] set
temperatures and times and, operator observations such as level measurements,
used in calculations, during the [Redacted] step are
not recorded.
- There has been no test method verification performed for the reported
USP test methods, Nitrogen Determination, Protein and Total Aerobic
Microbial Count, employed in testing of Heparin Sodium USP and Heparin
Crude materials, to show that the methods are suitable under actual
conditions of use. In addition, there is no routine test for [Redacted]
residue amount at the time of release.
- Investigations into failed lots and out of trend lots were approved
as complete, but did not identify a cause for the problem. For example,
Heparin Sodium USP batch [Redacted] failed the Nitrogen Determination
test and was reprocessed to make [Redacted] without finding the reason
for the slightly high, OOS Nitrogen result.
Investigations into [Handwritten
#2: cross out a word, added "OOT"]
of customer [Redacted]
specification @[Redacted] for Heparin Sodium USP lots
[Handwritten #3: cross out word(s)] [Redacted] and [Handwritten
#4: cross out word.] were
performed without knowing what the failed test measurement actually
represented.
[Redacted][Handwritten #5: added "and
the failure of lot"][Redacted]
Investigations into ROI out of trend results for Heparin Sodium USP
lots [Redacted] identified both results inappropriately
as outliers.
- Heparin Crude lots [Redacted] received 8/06 from
vendor [Handwritten #6: cross out word(s)]
[Redacted] that included material from an unacceptable workshop vendor were used
in Herapin Sodium USP [Redated] marketed to the USA. In
addition, prior to 3/06 there are no
[Redacted] records from vendor [Redacted] showing
the source for their crude materials.
- The inside surface of large, "cleaned" [Redacted] tanks
used in the final [Redacted] step, after both [Redacted] were
very scratched, with unidentified material adhering to the insides
and, the inverted handles held liquid, which spilled to the bottom
of the tank when it was uprighted. There was no written procedure
showing that the tanks were dedicated to a particular process step. There
was no data collected to verify marker and tape volume markings on
the outside of the tanks and, the cleaning method was not validated. It
was noted that equipment cleaning tags were made of paper and taped
to the piece of equipment unprotected from liquids used in the processing
room environments.
- Raw material inventory records were incomplete in that samples removed
from the containers and the status and amount of materials returned
from use by the production processing department were not recorded. For
[Redacted] stored in a freezer, the amount, condition and date of return
was not recorded.
- Control of material flow in the processing area was inadequate in
that waste [Redacted] was carted through a door to the outside in the
processing area and not provided for by the material flow written procedure.
- The outer foil bags containing Heparin Sodium USP lot [Redacted]
manufactured and held since 5/25/07, are not labeled. The drum lid
showed the only indications of the lot number.
- There is no report or data to show that leachables for the [Redacted]
bags used to hold Heparin Sodium USP lot, have been evaluated.
|
SEE
REVERSE OF THIS PAGE |
EMPLOYEE(S)
SIGNATURE
[Signed]
Regina T. Brown, Investigator
Zi-Qiang Gu, Chemist
|
EMPLOYEE(S) NAME AND TITLE (Print or Type)
Regina T. Brown, Investigator
Zi-Qiang Gu, Chemist |
DATE ISSUED
02/26/2008 |
FORM FDA 483
(4/03) PREVIOUS
EDITION OBSOLETE (PSC Media Arts (301) 443-1090 EF) INSPECTIONAL
OBSERVATIONS
Reverse Text on Page: The observations of objectional conditions and practices listed
on the front of this form are reported:
- Pursuant to Section 704(b) of the Federal Food, Drug and
Cosmetic Act, or
- To assist firms inspected in complying with the Acts and
regulations enforced by the Food and Drug Administration.
|
Section 704(b) of the Federal Food, Drug, and Cosmetic
Act (21 USC374(b)) provides: "Upon
completion of any such inspection of a factory, warehouse, consulting laboratory, or other
establishment, and prior to leaving the premises, the officer or employee making the
inspection shall give to the owner, operator, or agent in charge a report in writing
setting forth any conditions or practices observed by him which, in his judgement,
indicate that any food, drug, device, cosmetic in such establishment (1) consists in whole
or in part of any filthy, putrid, or decomposed substance or (2) has been prepared,
packed, or held under insanitary conditions whereby it may have become contaminated with
filth, or whereby it may have been rendered injurious to health. A copy of such report
shall be sent promptly to the Secretary." |
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