Ensuring vaccines are free of "contaminants"


Excerpts from the testimony of Dr. Allen Albright, concluding speaker at the FDA NATIONAL CANCER INSTITUTE WORKSHOP ON TUMOR VACCINES
Thursday, December 10, 1998.
http://www.fda.gov/cber/minutes/tumor121098.doc


Some highlights on vaccine testing:
"I want to touch on first of all the regulatory authority that we have
for viral vaccines, give some examples of viral vaccines. We'll spend
a great deal of time, not too much time, on safe viral vaccine
production, mainly covering issues of cell substrate, viral seeds as
well as product testing." . . .

"Okay, in terms of safe, viral vaccine production, we use a
complementary approach and what I mean by that is there is
characterization of a cell substrate for identity, endogenous and
adventitious agents. We have certification of cell culture media,
viral C history and characterization, your validation of manufacturing
process for removal and activation of viruses, release testing of bulk
and final products." ...

"Also, there's in-process testing for adventitious agents to see
whether those are introduced.
In terms of cell substrates, again, each manufacturer must
characterize a cell substrate, banked and used in production. In
terms of history and isolation of the bank, growth characterizations,
karyology and tumor genicity, freedom from adventitious agents. And
these pertain to master, working and end of production cells.
In terms of identity testing, we have morphologies, species of origin,
cell passage number, copy number and physical state of expression
construct and again, these would pertain to recombinant proteins made
from cell substrates." . . .

". . . issues such as bacterial and fungal sterility, mycoplasma,
spiroplasma in the case of insect cell substrate, mycoplasma testing
for cultable and noncultable mycoplasma, mycobacteria testing these
both in animals and in culture, looking for adventitious viruses both
in vitro and in vivo techniques, again, looking for acute lytic
viruses as well as latent viruses such as retroviruses or other
oncogenic viruses.". . .

"There are in vivo tests for adventitious viruses in your cell
substrates including adult encephaline mice, embryonated hen's eggs
and when appropriate in vivo assays including guinea pigs, rabbits
and/or monkeys." . . .

"In addition, you're going to look for lymphocytic choriomeningitis
virus or LCM. If you're using a human cell substrate and we may ask
for tests for viruses such as Epstein-Barr virus, CMV, hepatitis B and
C, maybe there are others. You can use in vitro techniques, sometimes
to look for these such as PCR." . . .

"These tests are performed on monolayers of at least three different
cell types including same species, tissues of substrate, human diploid
cells, monkey kidney cells. There are tests for hemoabsorbate,
hemoabsorbing and hemagglutinating viruses and again, as mentioned
earlier, testing of your raw materials such as fetal bovine serum and
Trypsin for bovine and porcine paraviruses as outlined in 9 CFR. " . .

"Okay, other adventitious virus tests, retroviruses is an important
category and usually retroviruses tests are done by transmission,
electron microscopy or TEM. Reverse transcriptase assays are used, as
well as infectivity assays. And if appropriate, depending again on
your cell line, we may ask for papilloma virus tests, adenoviruses,
HHV 6 and others which become known to us." . . .

"Okay, once your cell substrate is characterized again another level
of safety again would be your viral seed testing. And again, this
would apply for live viral vaccines as well as inactivated vaccines,
where you use viral seeds." . . .

"You do control cells where you look for observation, hemadsorption
and identity. You do supernatant of control cells looking at
inoculation on cell cultures, microplasma and sterility. Once you've
titered your virus or your viral stock, you do a viral suspension test
where you look at sterility, microplasma, cell culture testing,
embryonated egg inoculation, animal inoculation, RT testing, titer and
tuberculosis and identity. Again, a lot of tests, but you want to
make sure that these viral seeds are safe as well as the cell
substrate."
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Bottom line: powerful tools are available that are used to ensure
that supposed "stealth" viruses are not present.

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