Blood Plasma Safety: Plasma Product Risks and Manufacturers' Compliance
(Testimony, 09/09/1998, GAO/T-HEHS-98-242).

Limiting the number of donors whose plasma is pooled for production into
plasma products helps to lower the risk of viral transmission. More
significantly, viral clearance techniques have made the risk of
receiving an infected blood plasma product extremely low when
manufacturers follow procedures to ensure safety. Viral removal and
inactivation procedures can virtually eliminate enveloped viruses, such
as those responsible for AIDS, hepatitis B, and hepatitis C. However,
recent Food and Drug Administration (FDA) inspection reports have cited
many instances of noncompliance with good manufacturing practices, which
could pose a risk for those who rely on plasma products. These problems
have led to the imposition of consent decrees between FDA and two
manufacturers, the temporary suspension of production at one
manufacturing plant, and shortages of some plasma products. This
testimony summarizes the September 1998 report, GAO/HEHS-98-205.

--------------------------- Indexing Terms -----------------------------

 REPORTNUM:  T-HEHS-98-242
     TITLE:  Blood Plasma Safety: Plasma Product Risks and
	     Manufacturers' Compliance
      DATE:  09/09/1998
   SUBJECT:  Infectious diseases
	     Acquired immunodeficiency syndrome
	     Health hazards
	     Consent decrees
	     Product safety
	     Quality control
	     Testing
	     Safety regulation
	     Medical supplies
IDENTIFIER:  AIDS

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GAO/T-HEHS-98-242

Cover
================================================================ COVER

Before the Subcommittee on Human Resources, Committee on Government
Reform and Oversight, House of Representatives

For Release on Delivery
Expected at 10:00 a.m.
Wednesday, September 9, 1998

BLOOD PLASMA SAFETY - PLASMA
PRODUCT RISKS AND MANUFACTURERS'
COMPLIANCE

Statement of Bernice Steinhardt, Director
Health Services Quality and Public Health Issues
Health, Education, and Human Services Division

GAO/T-HEHS-98-242

GAO/HEHS-98-242T

(108384)

Abbreviations
=============================================================== ABBREV

  FDA - Food and Drug Administration
  HAV - hepatitis A
  HBV - hepatitis B
  HCV - hepatitis C
  HIV - human immunodeficiency virus

BLOOD PLASMA SAFETY:  PLASMA
PRODUCT RISKS AND MANUFACTURERS'
COMPLIANCE
============================================================ Chapter 0

Mr.  Chairman and Members of the Subcommittee:

We appreciate the opportunity to be here to discuss blood plasma
safety.  In the 1980s before the mechanism of human immunodeficiency
virus (HIV) transmission was understood, many hemophiliacs used
plasma products made from donations by HIV-infected individuals,
which consequently infected 63 percent of all hemophiliacs in the
United States.  Many more such patients contracted hepatitis B (HBV)
and hepatitis C (HCV).  Although the introduction of antibody tests
and viral inactivation and removal processes has reduced the number
of people contracting these diseases from plasma products, some
safety concerns remain.

One of these concerns relates to plasma donors, who may be paid or
unpaid.  A long-standing concern exists that paid donors might have
higher infectious disease rates than those of volunteer donors
because paid donors may have a financial incentive to conceal risk
factors that would prevent them from donating.  Concerns have also
been raised about the number of donors to whom a recipient is exposed
because manufacturers of plasma products pool donations from many
donors.  Furthermore, the efficacy of viral clearance procedures
manufacturers use and the manufacturers' safety record can clearly
affect the ultimate safety of plasma products.

Because of these concerns, you asked us to discuss the results of our
recent report on blood plasma safety.\1 In that report, done at the
Subcommittee's request, we (1) compared the risks of incorporating a
plasma unit infected with HIV, HBV, and HCV--from donations from
volunteer donors with those from paid donors--into the manufacturing
process; (2) examined the impact on frequent and infrequent plasma
users when pooling large numbers of plasma donations into
manufactured plasma products; (3) assessed the safety of end products
from plasma after they have undergone further manufacturing and
inactivation steps to kill or remove viruses; and (4) examined the
recent regulatory compliance history of plasma manufacturers.

In summary, viral clearance techniques have made the risks of
receiving an infected plasma product extremely low when manufacturers
follow all the procedures in place to ensure safety.  Although paid
plasma donors are over one and a half times more likely to donate
potentially infectious units (1 in every 3,834 units), several recent
initiatives by the paid plasma industry have greatly reduced the
chances (to 1 in every 10,959 units) of these units being included in
the plasma production pool.  These initiatives include using only
repeat donors (who have been found to have lower rates of viral
infection than first-time donors) and a 60-day inventory hold on all
units to allow manufacturers to retrieve units from donors who
subsequently test positive for disease or are otherwise disqualified.
Nonetheless, even with these initiatives in place, plasma units
donated by paid donors pose a somewhat higher risk of infection than
those from volunteer donors (in which 1 in every 15,662 units are
potentially infectious).

Limiting the number of donors whose plasma is pooled for production
into plasma products helps to reduce the risks of viral transmission
for recipients of these products.  Currently, the industry has a
limit of 60,000 donors for each finished plasma product.  This effort
has minimized infrequent users' exposure to a certain number of
donors for the few times they would receive a plasma product.  For
frequent users of plasma products, such as hemophiliacs, however,
this donor limit has little impact because such patients receive a
large number of infusions and are therefore exposed to a large number
of pools during their lifetimes.

A more significant step in reducing risk of infection takes place in
manufacturing, during which all plasma products undergo viral removal
or inactivation procedures, which virtually eliminate enveloped
viruses such as HIV, HBV, and HCV.  Epidemiological data on the
transmission of viruses through plasma products since the
introduction of viral removal and inactivation procedures in the late
1980s support the value of these procedures as do laboratory data
characterizing the effectiveness of viral clearance through these
procedures.  The effectiveness of these processes is limited,
however, in reducing transmission of nonlipid enveloped viruses, such
as hepatitis A (HAV), and human parvovirus.

Voluntary initiatives by the commercial plasma industry,
technological advances from increasingly sophisticated screening
tests that close the "window period" (the interval between when a
donor becomes infected and when a particular laboratory test becomes
positive), and viral removal and inactivation procedures are only
effective if manufacturers of finished plasma products adhere to
current good manufacturing practices.  Not all of the major
manufacturing companies producing plasma products adhere to these
practices, however.  In fact, recent FDA inspection reports highlight
many instances of noncompliance with current good manufacturing
practices.  This has led to consent decrees between FDA and two
manufacturing companies, temporary suspensions of production at one
manufacturing company's facility, and shortages of some plasma
products.  Although no known cases of HIV, HBV, or HCV from plasma
products have been transmitted during the time FDA identified these
problems, instances of companies' noncompliance with current good
manufacturing practices have been many.  A lack of strict adherence
to these practices related to viral removal and inactivation
procedures could compromise the safety of plasma products.  Actions
being taken by FDA and the plasma manufacturers since these problems
were identified should help to alleviate some of these problems.

--------------------
\1 Blood Plasma Safety:  Plasma Product Risks Are Low If Good
Manufacturing Practices Are Followed (GAO/HEHS-98-205, Sept.  9,
1998).

   BACKGROUND
---------------------------------------------------------- Chapter 0:1

Plasma is the liquid portion of blood, containing nutrients,
electrolytes (dissolved salts), gases, albumin, clotting factors,
hormones, and wastes.  Many different parts of plasma are used in
treating the trauma of burns and surgery and for replacing blood
elements that are lacking due to diseases such as hemophilia.
According to estimates, each year about one million people in the
United States receive products manufactured from human plasma.

Plasma-derived products are purified from plasma pools by a process
known as fractionation.  This procedure involves a series of steps so
that a single plasma pool yields several different protein products
such as albumin and immune globulins.

Plasma used for plasma-derived products manufactured and distributed
in the United States may only be collected at facilities licensed and
registered with the FDA.  Centers require donors to provide proof
that they are in the United States legally and have a local permanent
residence.  About 85 percent of plasma comes from paid donors in a
commercial setting and is known as source plasma.  The remaining 15
percent of plasma comes from volunteer donors and is known as
recovered plasma.  Units of plasma collected as source plasma contain
approximately 825 milliliters; recovered plasma from whole blood
donations contains approximately 250 milliliters.  Thus, more than
three times as many donated units of recovered plasma are required to
make up a plasma pool equal in volume to one comprising only source
plasma.

Approximately 370 paid plasma collection centers collect about 11
million liters of plasma from 1.5 million donors annually, involving
a total of approximately 13 million separate donations each year.
Four companies process the vast majority of source plasma:  Alpha
Therapeutic Corporation, Baxter Healthcare Corporation, Bayer
Corporation, and Centeon LLC.

An additional 1.8 million liters of plasma are collected from
approximately 8 million volunteer (not paid) donors, who contribute
12 to 13 million whole blood donations each year.  These donors give
blood at American Red Cross blood centers and independent blood
centers represented by the trade group, America's Blood Centers, and
the plasma is recovered for further manufacturing.  Plasma collected
by the American Red Cross is fractionated under contract by Baxter
Healthcare and the Swiss Red Cross and returned to the American Red
Cross for distribution.  Plasma collected at centers represented by
America's Blood Centers is sold only to the Swiss Red Cross, which
manufactures the various plasma products and sells them through U.S.
distributors.

Paid donors typically receive between $15 and $20 for the 2 hours of
time required to remove whole blood, separate the plasma from the
cells and serum, and reinfuse the latter back into the donor.  Source
plasma donors may donate once every 48 hours but no more than twice a
week.  Whole blood donors may only donate once every 56 days because
their red cells are not reinfused as they are with paid donors.

All donors are tested for certain viruses known to be transmitted
through blood, including HBV, HCV, and HIV.  The specific screening
tests check for the presence of hepatitis B surface antigen (HBsAg),
antibodies to hepatitis C (anti-HCV), HIV-1 antigen, and antibodies
to HIV types 1 and 2 (anti-HIV).\2 Donors with positive test results
are rejected from making further donations.  The positive unit and
all previously donated plasma units not pooled for manufacture in the
preceding 6 months are retrieved, and those professional services
that receive the plasma products are notified according to federal
regulations (21 CFR 610.46).\3

--------------------
\2 Antibody tests detect antibodies that the human body produces in
its immune response to a virus; antigen tests detect a part of the
actual virus.  Because it takes time for the body to develop
antibodies, antigen tests detect infection earlier than antibody
tests.

\3 In addition, tests are performed to examine the level of the liver
enzyme alanine aminotransferase (ALT).  ALT may be an indicator of
liver disease or a viral infection.  Units with unacceptable ALT
levels are not used.  Donors with elevated ALT levels are also
deferred from donating in the future.  In addition, whole blood
donations are tested for antibodies to human lymphotropic virus types
I and II, but source plasma is not screened for this because it is
cell associated and not found in plasma.

   RISK OF INFECTIOUS UNITS
   ENTERING PLASMA POOLS IS
   SOMEWHAT HIGHER FOR DONATIONS
   FROM PAID PLASMA DONORS THAN
   FOR DONATIONS FROM VOLUNTEERS
---------------------------------------------------------- Chapter 0:2

The risk of incorporating a potentially infectious plasma unit into a
plasma pool for HIV, HBV, or HCV is somewhat higher for donations
from paid donors than for donations from volunteer donors.
Information we obtained on viral marker rates for volunteer donors
from the American Red Cross and for paid donors from the American
Blood Resources Association (which represents paid plasma collection
centers) showed viral marker rates among individuals who offer
donations to paid plasma centers to be one and a half times higher
than rates among those who come to volunteer blood centers.\4 This is
due to higher HCV rates among paid donors.

In addition, incidence rates of HIV, HBV, or HCV are higher among
paid donors than they are for volunteer donors, according to our
review.  These rates include donors who pass the initial screening
tests and donate but who subsequently seroconvert and whom a
screening test later detects during another donation as being
positive.\5 Thus, potentially infectious units from these donors
could be incorporated into a plasma pool for manufacturing.  HIV
incidence rates are 19 times higher for paid donors than for
volunteer donors; HBV and HCV rates are 31 times and 4 times higher,
respectively.

Finally, the residual risk of incorporating an infectious plasma unit
into a plasma pool is somewhat higher for donations from paid donors
than for donations from volunteer donors, according to our review.
The residual risk represents the incidence rate and other factors
that, in the final analysis, could result in a potentially infectious
unit being incorporated into a plasma pool.  The overall residual
risk of incorporating an infectious HIV, HBV, or HCV plasma unit into
a plasma pool is about 43 percent higher for donations from paid
plasma donors than for donations from volunteer donors (1 in every
10,959 donations compared with 1 in every 15,662 donations,
respectively).\6 This difference is statistically significant.  Thus,
we calculated that about 3.8 infectious units would be included in a
plasma pool of 60,000 donations if the pool were made exclusively
from donations from volunteers; however, 5.5 infectious units would
be included in that pool if it were made exclusively from donations
from paid donors.

--------------------
\4 The term "viral marker rates" refers to the rate at which a
particular group has confirmed-positive tests for particular viruses,
in this case for HIV, HBV, and HCV.

\5 Seroconverting donors are recently infected donors who test
negative on a currently licensed test.

\6 The calculations for the volunteer sector are based on the
possibility that donors infected with HBV may have transient
antigenemia, of which a portion would be found positive by the HBsAg
test.  If this calculation is not made, the risk of incorporating an
infectious HIV, HBV, or HCV unit into a plasma pool becomes 1 in
20,872.  This would mean that donations from paid donors would be
about twice as likely to be potentially infected with HIV, HBV, or
HCV and incorporated into a plasma pool as units from volunteer
donors (1 in 10,959 compared with 1 in 20,872, respectively).

   MANUFACTURER REDUCTIONS IN
   PLASMA POOL SIZES TEND NOT TO
   BENEFIT FREQUENT USERS
---------------------------------------------------------- Chapter 0:3

Concerns have been raised about the size of plasma pools because
larger pools expose recipients of plasma products to more donors,
raising the risk of infection.  Manufacturers have recently taken
steps to reduce the size of the plasma pools they use for producing
plasma derivatives.  Modeling techniques indicate that this effort
can affect infrequent users of these products by minimizing their
exposure to a certain number of donors.  Frequent users of plasma
products, such as hemophiliacs, however, tend not to benefit from
these techniques because of the large number of different pools to
which they are exposed during their lives.

As recently as a year ago, FDA believed that initial fractionation
pools contained 1,000 to 10,000 source plasma units or as many as
60,000 recovered plasma units.  In response to inquiries from your
Subcommittee, however, FDA obtained information from plasma
manufacturers showing that after adjusting for the combination of
intermediates, pooling of material from several hundred thousand
donors for single lots of some products sometimes took place.  For
example, albumin can be added during intermediate processing steps or
to a final product, such as factor VIII, for use as an excipient or
stabilizer.\7 This albumin often comes from another plasma pool
containing donations that are not in the original pool.

Because of concerns about pool size, the four major plasma
fractionators voluntarily committed to reducing the size of plasma
pools, measured by total number of donors, to 60,000 for all
currently licensed U.S.  plasma products, including factor VIII,
factor IX, albumin, and immune globulin intravenous.  This
measurement takes into account the composition of starting pools,
combining of intermediates from multiple pools, and use of plasma
derivatives as additives or stabilizers in the manufacturing process.
Prior production streams are still being processed and distributed,
however, so that products distributed through the end of 1998 may
still be produced from pools that exceeded the 60,000-donor limit.

The American Red Cross has also voluntarily reduced the size of the
plasma pools from which its products are manufactured.  As a policy,
the American Red Cross has a 60,000-donor limit for plasma products
that are further manufactured by Baxter Healthcare.  Seventy-five
percent of all American Red Cross plasma manufactured by the Swiss
Red Cross is now at the 60,000-donor limit, with plans for all
production to adhere to the limit in the near future.

In a study employing the modeling technique noted above, researchers
found that limiting the number of donors in a pool may only be
marginally beneficial for infrequent recipients, who might be exposed
to an emergent unknown infectious agent with a low prevalence in the
donor population, which current manufacturing processes did not
inactivate or remove.\8 As an example, the researchers calculated
that for an agent with a prevalence of 1 in 500,000 (for example, a
rare or emerging virus), a pool comprising 10,000 donations would
yield a 2 in 100 chance of exposure to that agent for a one-time
recipient.  For frequent users of plasma products (that is, 100
infusions during a lifetime), however, this same pool size of 10,000
would yield an 86 in 100 chance of exposure to that agent, assuming
that the products would come from different pools.  Reducing the
number of donors in a pool does not significantly decrease this
effect.  Thus, these modeling data suggest that smaller plasma pool
sizes will reduce the likelihood of transmission of viral agents to
infrequent users of plasma products but will have only a minor impact
on frequent recipients of such products.

In addition, risk of exposure does not always equate with risk of
infection.  In fact, risk of exposure is always greater than or equal
to risk of infection.  For example, the recent transmission of HCV by
a plasma derivative that had not undergone viral inactivation
procedures showed that the risk of seroconversion for recipients of
this product increased with the number of positive HCV lots infused
and the quantity of HCV viral material infused.  Not all recipients
were infected, however, because the highest percentage of
seroconversions seen with the highest levels of HCV virus infused did
not exceed 30 percent.  Not all recipients experience seroconversions
because of two factors:  (1) each recipient's dose and (2) the
reduction of infectiousness due to steps in the manufacturing process
in addition to viral removal and inactivation.

--------------------
\7 Excipients are additives, other than the active ingredient of a
drug, that confer a desired property on the final dosage form.  This
may include a preservative to prevent microbial growth or a
stabilizer that maintains potency.  A stabilizer maintains the
integrity of the active ingredient against chemical degradation or
physical denaturation.

\8 Thomas Lynch and others, "Considerations of Pool size in the
Manufacture of Plasma Derivatives," Transfusion, Vol.  36, No.  9
(1996), pp.  770-75.

   RISK OF INFECTION REDUCED
   THROUGH VIRAL INACTIVATION AND
   REMOVAL TECHNIQUES
---------------------------------------------------------- Chapter 0:4

As mentioned, certain infectious units could make it through the
donor screening, deferral, and testing process.  Manufacturers have,
therefore, introduced additional steps in the fractionation process
to inactivate or remove viruses and bacteria that may have gotten
into plasma pools.  These techniques virtually eliminate enveloped
viruses such as HIV, HBV, and HCV.  They are only partly effective,
however, against nonenveloped viruses such as HAV and human
parvovirus.\9

All types of plasma derivatives undergo viral inactivation or
removal.\10 The two main methods of inactivation are heat treatment
and solvent-detergent treatment.  To be effective, inactivation
techniques must disrupt the virus, rendering it noninfectious.  Heat
treatment is accomplished either by exposing the freeze-dried product
to dry heat or suspending it in a solution.  Another technique heats
the completely soluble liquid product with the addition of various
stabilizers such as sucrose and glycine.  The second technique,
solvent-detergent washing, exposes the product to an organic solvent
to dissolve the lipid coat of viruses, rendering them inactive
without destroying the plasma-derived products.  The lipid membrane
contains critical viral proteins needed for infection of host cells.
Disrupting the viral lipid envelope renders the virus noninfectious.
Solvent-detergent inactivation is only partly effective, however, in
eliminating nonlipid-coated viruses such as HAV or human parvovirus.

Assessing the amount of viral clearance obtained through a particular
inactivation or removal process determines the effectiveness of these
different procedures.  This assessment is based on the amount of
virus that is killed or removed and therefore the extent to which
these processes eliminate viruses through manufacturing.  Individual
manufacturing steps can be specifically designed for viral clearance,
or they may be intended primarily as a purification process that will
also help in killing or removing viral agents.  To meet FDA approval
of their particular inactivation or removal technique, manufacturers
must separately validate each clearance step.

The viral inactivation and removal steps now in use have all been
demonstrated to reduce the levels of virus and, in many cases, most
likely eliminate them.  Even if the virus is not completely
eliminated, reducing it significantly is of value.  Although
theoretically even a single virus can cause infection, research has
shown that infection is much more likely to occur with higher
concentrations of virus.  Proper viral inactivation and removal steps
have resulted in no documented cases of HIV, HCV, or HBV transmission
from plasma products since 1988.

--------------------
\9 Parvovirus is the cause of Fifth disease, a common childhood
illness, which is usually mild and brief.  Approximately 50 percent
of the population has been infected by parvovirus at some time.

\10 Currently, only two immune globulin intramuscular products are
manufactured without the use of viral inactivation procedures.

   RECENT NONCOMPLIANCE WITH
   CURRENT GOOD MANUFACTURING
   PRACTICES COULD JEOPARDIZE
   PLASMA PRODUCTS' SAFETY
---------------------------------------------------------- Chapter 0:5

Although viral inactivation and removal techniques have proven to be
highly effective, they are only useful if the steps in the
manufacturing process are carried out properly.  Recent FDA
inspections of plasma fractionation facilities have found many
violations of current good manufacturing practices.  The lack of
strict adherence to these practices could compromise the safety of
plasma products.

The objective of good manufacturing practices is to ensure that
plasma products are safe, effective, adequately labeled, and possess
the quality purported.  Plasma manufacturers should operate in
compliance with applicable regulations, which require adherence to
current good manufacturing practices and quality assurance
principles.  In addition, each manufacturer must adhere to the
standard operating procedures it has established for its facilities.

To ensure that manufacturing processes, including inactivation
procedures, follow current good manufacturing procedures, FDA is
authorized to inspect plasma fractionation establishments.  If the
inspectors identify problems, FDA has a range of actions it may take.
For violations deemed serious, these actions can include issuing
warning letters, seeking a consent decree, or suspending a facility's
license.

When an inspection reveals deficiencies, FDA may issue a warning
letter to the facility, which does not suspend operations but gives
the facility an opportunity to correct deficiencies.  A warning
letter notifies a firm that FDA considers its activities to be
violating statutory or regulatory requirements and that failure to
take appropriate and prompt corrective action may result in further
FDA action.  For some serious violations, FDA may seek a consent
decree against a firm or individual--a court-ordered action that
either mandates corrective actions that must be taken or prohibits
the firm's operation unless and until such actions are taken.  FDA
may pursue an action to suspend a facility's license if the agency
has documented deficiencies that constitute a danger to health,
necessitating immediate corrective action.  In such instances, the
manufacturer would not be conforming to the standards in its license
or the regulations.

Recent FDA inspections conducted at the four major fractionation
companies found many potential deviations in each company's adherence
to current good manufacturing practices.  A recent inspection by FDA
of Alpha Therapeutic's facility observed 139 potential deviations
from current good manufacturing practices or standard operating
procedures; this has recently resulted in a consent decree with FDA.
An FDA inspection of Baxter Healthcare's fractionation facility
observed 96 potential deviations.  Bayer Corporation's Berkeley,
California, facility was cited for 30 potential deviations, and an
inspection of Bayer's Clayton, North Carolina, facility observed 77
potential deviations.  Finally, an inspection of Centeon's facility
observed 87 potential deviations, which resulted in a consent decree
filed in January 1997.  The consent decree required Centeon to cease
distribution of all but two of its products, while it brought its
manufacturing standards into compliance with FDA statutes and
regulations.  In May 1997, FDA authorized the distribution of
Centeon's products from the facility, but, in a subsequent inspection
completed in July 1998, FDA found that Centeon had failed to fully
comply with the consent decree, and the company was notified to
immediately cease manufacturing, processing, packing, holding, and
distributing all biological and drug products manufactured at that
facility.  The company may, however, manufacture products deemed
medically necessary.

Examples of potential deviations from current good manufacturing
practices found by FDA inspectors include the following:

  -- in-house-developed software that had not been validated being
     used for performance of finished product testing;

  -- often incomplete and sometimes inaccurate calibration and
     preventive maintenance records;

  -- reports of problems with plasma products after distribution not
     being reviewed and investigated in a timely manner;

  -- undetected or not corrected deviations found in viral
     inactivation processes used on several lots of factor VIII;\11

  -- no validation of reprocessing steps used for repooling of
     albumin product lots that failed final container testing for
     sterility;

  -- no validation of the cleaning process and removal of cleaning
     agent residues from fractionation kettles, bulk tanks, buffer
     tanks, or centrifuge bowls; and

  -- no validation of albumin manufacturing processes and final
     products that did not consistently conform to the release
     specifications.  In 1997, 54 percent of albumin lots for one
     company failed final container inspection because of visible
     evidence of protein material.

To overcome these problems, the major fractionation companies have
taken certain steps, such as increasing quality assurance and quality
control and production staff and training, implementing capital
investments at the fractionation facilities, and validating equipment
processes.  Many of the facilities slowed production as the firms
reallocated resources to work on their corrective actions.

In addition, FDA has taken several actions within the last year to
better ensure manufacturer compliance with current good manufacturing
practices.  In a previous study examining the safety of the blood
supply, we found inconsistencies in FDA's inspection practices.  As a
result of this and an Office of Inspector General study examining
FDA's regulatory role in the field of biologics, FDA adopted a new
inspection program.  Under this program, FDA has designated two
groups of investigators:  one to focus on blood banks and source
plasma collection centers and another to focus on plasma
fractionation and manufacturers of allergenic products, therapeutics,
licensed in vitro diagnostics, and vaccines.  This approach is
intended to ensure that all FDA current good manufacturing practice
inspections are conducted by a single agency unit using a similar
approach.  If properly implemented, these actions by plasma
manufacturers and FDA should help alleviate the problems related to
adherence to current good manufacturing practices and quality
assurance.

This concludes my prepared statement, Mr.  Chairman.  I will be happy
to respond to any questions that you or Members of the Subcommittee
may have.

--------------------
\11 Factor VIII is the antihemophilic factor concentrate used to
treat hemophilia A bleeding episodes.
*** End of document ***