IA #57-01 - REVISED 2/3/97, IMPORT ALERT #57-01, "AUTOMATIC DETENTION OF
"BLOOD AND BLOOD COMPONENTS INCLUDING HUMAN PLASMA AND SERUM"
NOTE: *This Import Alert is reissued to delete the inappropriate
CFR citation for nonlicensed human source materials under the
GUIDANCE section.* Revisions and Updates are marked with an
asterisk (*).
TYPE OF ALERT : Guidance
(Note: This import alert contains guidance to FDA field
personnel only. It does not establish any requirements, or
create any rights or obligations on FDA or on regulated
entities.)
PRODUCT : Blood and Blood Components
PRODUCT CODE : 57DY[][][]
HARMONIZED
CODE : 3002
PROBLEM : Unlicensed biologics, misbranding, labeling
PAC : 42R800 and *42R825*
COUNTRY : Multiple countries (ZZ,999)
MANUFACTURER/
SHIPPER : All
MANUFACTURER
SHIPPER I.D.# : N/A
IMPORTERS
I.D.# : N/A
CHARGE : The article is subject to refusal of admission pursuant to
Section 801(a)(3) in that it appears to be misbranded in
that (give reason)[Misbranded, Section 502] or adulterated
in that [give reason] [Adulterated, Section 501].รพ
It is also appropriate to include a PHS Act, Section 351 (b)
charge regarding false labeling or marking, if applicable.
RECOMMENDING
OFFICE : *CBER, Office of Compliance, Division of Case Management,
Import/Export Team (HFM-610)*
REASON FOR
ALERT : *Blood and blood components have entered the United States
without FDA notification as required. Importer/broker
filings of inaccurate entry papers and inaccurate Harmonized
Tariff Codes have been noted.
This revised import alert will provide guidance to the FDA
import districts as part of efforts to eliminate improper
entries of blood and blood components.*
*GUIDANCE*
Blood and blood components applicable to the prevention,
treatment, or cure of diseases or injuries of man are
biological products as defined by the Public Health Service
Act (42 U.S.C. 262). Section 351(b) of the Public Health
Service (PHS) Act prohibits the false labeling or marking of
any package or container of any biological product such as
blood, plasma, or serum.
Blood and blood components are also drugs or medical devices
as defined by Sections 201(g) and (h) of the Federal Food,
Drug, and Cosmetic (FD&C) Act, depending on their intended
use. The FD&C Act (Section 502(a)) requires that the
labeling for drugs and devices must not contain any
statement which is false or misleading in any particular.
Standards for labeling blood and blood products are found at
21 CFR 606.120. Since 21 CFR Part 606 was promulgated under
both drug and device authorities contained in the FD&C Act,
labeling standards apply to blood, plasma, or serum, whether
they fall within the drug definition or device definition of
the FD&C Act.
*DEFINITIONS*
The two major sources of human blood plasma are Source
Plasma and Recovered Plasma.
Source Plasma is plasma collected by plasmapheresis (21 CFR
640.60), and is subject to the licensure provisions of
Section 351 of the PHS Act. Source Plasma cannot be
lawfully shipped interstate or imported into or exported
from this country *for sale, barter or exchange* unless the
collection facility holds an unsuspended and unrevoked U.S.
license for Source Plasma. Source Plasma, while considered
a final product for purposes of licensure, is intended for
use as source material in the manufacture of either
injectable or non-injectable products. Irrespective of the
drug or device use, a U.S. license is required for the
product.
Recovered Plasma is obtained as a by-product of red blood
cell production from units of Whole Blood. Current policy is
that Recovered Plasma is not required to be licensed.
Recovered Plasma intended for further manufacture into
licensed biological products (injectables or noninjectables)
may be shipped interstate only as prescribed by 21 CFR
601.22 - Short Supply. Recovered Plasma intended for
further manufacture into in-vitro diagnostic reagents not
subject to license (e.g., clinical chemistry controls) may
be shipped interstate *provided the Whole Blood from which
the Recovered Plasma was derived has been manufactured in
accordance with applicable good manufacturing standards and*
is properly labeled as in the INSTRUCTIONS section below.
*OTHER BLOOD DERIVED SOURCE MATERIALS*
Another possible source of plasma may include out-dated
units of plasma that were initially intended for intravenous
use (e.g., Fresh Frozen Plasma.)
Serum is a component of plasma, i.e., plasma without
fibrinogen. *While serum is a biological product subject to
GMP's, it is not required to be licensed at this time.* The
standards for labeling serum intended for further
manufacturing use are identical to those for Recovered
Plasma.
*CONCERNS*
In the past, the Center for Biologics Evaluation and
Research (CBER) has received reports that *"clinical
samples" (i.e., plasma and/or pooled serum from hospitals
and clinical laboratories) have* been labeled "Reagent Use
Only" and exported out the United States. *These "clinical
samples"* may be diverted for unacceptable use, or *they*
may be shipped back into the United States as source
materials for injectable products. *Districts should be
alert to the potential of deverting "clinical samples" for
manufacturing use.*
In December 1989, a report received by CBER indicated that
large amounts of blood and/or blood products were entering
the United States from Mexico, Costa Rico, Guatemala,
Panama, Japan, and Europe, among other countries. The blood
and/or blood products were characterized by United States
Customs according to the Harmonized Tariff Schedule codes
which includes nine (9) categories. These categories are:
(1) Human blood plasma (3002.10.0010); (2) normal human
blood sera (3002.10.0020); (3) human normal blood sera
(3002.10.0030); (4) other blood fractions (3002.10.0050);
(5) vaccine for human medicines (3002.20.0000); (7) ferments
(3002.90.1000); (8) anti-allergenic preparations
(3002.90.5020); (9) toxins, culture of microorganisms and
similar products (3002.90.5050). As a result, FDA
surveillance activities in the area of blood products
increased. *More recently, shipments into the United States
of Source Plasma, collected and distributed by non-U.S.
licensed foreign firms, have occurred.* Local Customs
offices *are* requested to notify the FDA of every entry of
blood and blood products regardless of monetary value.
GUIDANCE : Blood and blood components bearing a U.S. license number may
be permitted entry after it has been confirmed that the
collection facility is indeed a licensed establishment and
that the establishment holds an unsuspended and unrevoked
license for the particular product being entered. For
unlicensed products (e.g., plasma, serum, and/or red blood
cells) bearing the label statement "Caution: for
Manufacturing Use Only", verify that there is a current
short supply agreement between the collection facility and
the manufacturer of the finished licensed product. Short
supply agreements are not valid if they are entered into
between the broker and the manufacturer of the final,
licensed product.
*Nonlicensed human source materials of blood and blood
components, intended for use in the manufacture of
unlicensed in vitro diagnostic devices (reagents) are
regulated by CBER. Once the component materials have been
incorporated into a manufacturing step whereby they are
irrecoverable as original material or are packaged in a
device container, these materials become the regulatory
responsibility of CDRH and will be regulated as medical
devices under the Medical Device Authorities.*
For blood and blood components that are not covered by an
unsuspended and unrevoked U.S. license or a valid short
supply agreement, the immediate container label for the
*component* shall contain all of the following information
listed below.
1. Appropriate descriptive name of the product; e.g.,
Human Serum, or if pooled, Human Serum Pooled;
Recovered Plasma, or if pooled, Recovered Plasma
Pooled.
2. The statement of intended use; e.g., "Caution: For Use
in Manufacturing Noninjectable Products Only."
3. The total volume or weight of plasma or serum and the
quantity and type of anticoagulant used.
4. Name and quantity of additives, if any.
5. The donor number or individual bleed number or both.
If plasma or serum is pooled from two or more donors,
either all donor numbers, all bleed numbers, or a pool
number that is traceable to each individual unit
comprising the pool.
6. Date of collection, or if pooled, collection date of
oldest material in the pool.
7. Storage temperature adequate for the intended use of
product.
8. *The statement: "Nonreactive for HBsAg by FDA
required test" or "Reactive for HBsAg by FDA required
test and may transmit viral hepatitis."*
9. *The statement: "Negative for antibody to HIV by an
FDA approved test."*
10. *The statement: "Not tested for antibody to HIV or
HBsAg by an FDA approved test."*
11. The statement: "Not for use in products subject to
license under Section 351 of the Public Health Service
Act."
12. Immunizing antigen when applicable.
13. Name(s) and address(es) of establishment(s)
collecting, preparing, labeling, or pooling the source
material such as "Manufactured by ",
"Distributed by ", or any other wording
that expresses these facts.
NOTE: These items have been derived from labeling
requirements stated in 21 CFR 606.120(b), 606.121, 801.122,
and 809.10(a) promulgated under the authority of the Uniform
Labeling of Blood and Blood Components.
*OTHER BIOLOGICAL MATERIALS NOT SUITABLE FOR FURTHER
MANUFACTURE*
*Biological specimens of human body fluids (e.g., Whole
Blood, plasma, serum, and urine) or tissues (Not For
Transplantation) being shipped interstate or imported for
testing only, or for non-clinical research only, are not
considered to be biological products subject to licensure in
accordance with Section 351(a) of the Public Health Service
Act (PHS Act), nor would they appear to be drugs or devices
as defined in Sections 201(g) and (h), respectively, of the
FD&C Act. The Food and Drug Administration would not object
to the entry or exportation of biological specimens for the
stated purpose of testing only, or for non-clinical research
only, provided the shipping documents, i.e., invoice,
manifest, clearly identifies the intended use of the human
body fluid or tissue.*
For additional guidance, contact the *CBER, Office of
Compliance, Division of Case Management, Import/Export Team,
(HFM-610) at (301) 827-6201.*
FOI : No purging is necessary.
KEYWORDS : Human plasma, blood components, blood, plasma, serum,
biologics, biological specimens, research.
PREPARED BY : Alwin W. Collins, Operations and Policy, DIOP, 301-443-6553.
DATE LOADED
INTO FIARS : FEBRUARY 3, 1997
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