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Hi Alan,
Here's the information about Lantus, et. al. and the animal products
used in their production. Note there are bovine materials, porcine
materials and bird feathers used to produce GE insulin/analogs. Here
also is the validation process for bovine insulin.
Novo Actraphane (GE) Scientific discussion-
http://www.emea.eu.int/humandocs/Humans/EPAR/actraphane/actraphane.htm
page 4--Viral safety and TSE assessment
A number of animal derived raw materials are used in the production of
insulin human,rDNA. These are peptone, beef extract and pepticase
which are used in the preparation and storage of cell banks,
L-threonine and trypsin- used in the purification process and protamine
sulphate used as excipient in the final product. L-threonine is
sourced from avian feathers and porcine gelatine, trypsin from porcine
pancreas and protamine sulphate from salmon.
Pepticase falls outside the scope of the TSE Guideline as it is derived
from casein from milk from healthy cows only and no other ruminant
materials are used in its preparation.
For peptone (CEP-2000-175) and beef extract (CEP-2000-181) Certificates
of Suitability of the EDQM have been submitted.
The risk of transmission of TSE from Actraphane in human beings has
been appropriately addressed in accordance with CPMP/CVMP/ Note for
Guidance for minimising the risk of transmitting animal spongiform
encephalopathy via medicinal products (EMEA/410/01).
Viral safety issues have been addressed and compliance with relevant
guidelines are considered to be met.
Novo Actrapid (GE)--scientific discussion
www.emea.eu.int/humandocs/Humans/EPAR/actrapid/actrapid.htm">http://www.emea.eu.int/humandocs/Humans/EPAR/actrapid/actrapid.htm
page 4--Viral Safety and TSE Assessment
A number of animal derived raw materials are used in the production of
human insulin, (rDNA). These are peptone, beef extract and pepticase
which are used in the preparation and storage of cell banks, and
L-threonine and trypsin used in the purification process to convert
human insulin precursor to human insulin methyl ester.
Pepticase falls outside the scope of the TSE Guideline as it is derived
from casein from milk from healthy cows only and no other ruminant
materials are used in its preparation.
For peptone (CEP-2000-175) and beef extract (CEP-2000-181) Certificates
of Suitability of the EDWM have been submitted.
L-threonine is sourced from avian feathers and porcine gelatine and
trypsin from porcine pancreas.
The risk of transmission of TSE from Actrapid to human beings has been
appropriately addressed in accordance with CPMP/CVMP Note for Guidance
for minimising the risk of transmitting animal spongiform
encephalopathy via medicinal products (EMEA/410/01).
Viral safety issues have been addressed and compliance with relevant
guidelines is considered to be met.
Lantus--insulin glargine (GE analog) scientific discussion
www.emea.eu.int/humandocs/PDFs/EPAR/Lantus/061500en6.pdf">http://www.emea.eu.int/humandocs/PDFs/EPAR/Lantus/061500en6.pdf
page 4 Viral safety.
No starting material from human or animal origin is used. Due to the
usage of prokaryotic cells no viral contamination is expected. Trypsin
is used in the production of the active ingredient. Trypsin is
isolated from a homogenate of porcine pancreas. The process comprises
treatment with organic solvents and nanofiltration or acidification of
the extract. The trypsin manufacturing process ensures that no viruses
are introduced into the production process by trypsin. Glycerol used
as ingredient or for the preparation of the second WCB (Working Cell
Bank) is of plant or synthetic origin. Glycerol used for the
preparation of the MCB (Master Cell Bank) and the first WCB (Working
Cell Bank) is of bovine origin and the processing conditions for this
glycerol are in accordance with the "Note for Guidance on minimising
the risk of transmitting animal spongiform encephalopathy agents via
medicinal products" (CPMPBWP/1230/98). After further investigation it
was confirmed through a type II variation application that glycerol
used as ingredient for the preparation of the MCB (Master Cell Bank) of
synthetic origin.
This then means that they are still using bovine glycerol in the first
Working Cell Bank.
Novo Levemir (GE analog)--scientific discussion
www.emea.eu.int/humandocs/PDFs/EPAR/levemir/093604en6.pdf">http://www.emea.eu.int/humandocs/PDFs/EPAR/levemir/093604en6.pdf
page 4- TSE and Viral Safety
Three components in the storage medium for the WCB (Working Call Bank)
are from bovine origin, i.e. peptone, beef extract and pepticase.
Peptone is also used in the propagation of the MCB (Master Call Bank).
For the beef extract and peptone, EDQM Certificates of suitability are
presented. The pepticase has been produced from bovine milk, sourced
from USA, Australia or New Zealand, fit for human consumption. In the
production of pepticase, two secondary raw materials of animal origin
are used. these are bovine derived lactose and a material of porcine
origin.
Two additional raw materials of bovine origin, amicase and lactose are
used in the manufacture of the enzyme Achromobacter lyticus protease
(ALP). Both are produced from bovine milk from healthy animals and are
considered acceptable.
Validation studies on virus removal/inactivation have not been
performed on the basis that viruses are unable to replicate in the
yeast cell line. Furthermore, the production processes for all
materials contain steps that are considered virus inactivating (high
temperature treatment (all materials) to high pH treatment (peptone)).
Novomix-(GE analog) scientific discussion
www.emea.eu.int/humandocs/PDFs/EPAR/Novomix/136300en6.pdf">http://www.emea.eu.int/humandocs/PDFs/EPAR/Novomix/136300en6.pdf
page 3 TSE risk assessment & Virus risk assessment
No animal derived raw materials have been used directly in the
production of the active substance or the finished product. The
requirements of EMEA/410/01 are met.
The important word here is "directly". You see how bird feathers are
used to make L-threonine for other Novo insulins. This is an indirect
use of the animal materials. They do not say no animal derived raw
materials are used at all to make Novomix--they just say they are not
used directly.
The risk of transmission of viruses is negligible as no primary animal
or human sourced materials have been used in the preparation of either
active substance or finished product.
They could say there was no risk at all if they did not use animal
sourced material indirectly somewhere in the making of Novomix--if
there was none, there would be no need to address the virus risk.
Novo Ultratard (GE)--Scientific Discussion--
www.emea.eu.int/humandocs/PDFs/EPAR/ultratard/211702en6.pdf">http://www.emea.eu.int/humandocs/PDFs/EPAR/ultratard/211702en6.pdf
pages 3 and 4--Viral Safety and TSE Risk Assessment
A number of animal derived raw materials are used in the production of
human insulin, rDNA. These are peptone, beef extract and pepticase
which are used in the preparation and storage of cell banks,
L-threonine and trypsin used in the purification process to convert
human insulin precursor to human insulin methyl ester. Bovine insulin
microcrystals are use for seeding the crystals in the product.
L-threonine is sourced from avian feathers and porcine gelatine,
trypsin from porcine pancreas, and bovine insulin from bovine pancreas.
Pepticase falls outside the scope of the TSE Guideline as it is derived
from casein from milk from healthy cows only and no other ruminant
materials are used in its preparation.
For peptone (CEF-2000-175) and beef extract (CEF-2000-181) Certificates
of Suitability of the EDQM have been submitted.
Although a certificate of suitability has been provided by the
applicant for bovine insulin from German sourced pancreas (RO-CEP
200-135-Rev-00), suitability of the material for its intended use in
the finished product must be taken into consideration. The change of
contamination of German sourced pancreas used to produce the current
batch of microcrystals is remote. In addition, the manufacturing
process for bovine insulin is stated to provide a total reduction of
8.7 logs for BSE-agents in the early steps of insulin extraction.
Therefore, it is considered that the risk of transmission of BSE is
highly unlikely. However, the applicant should undertake to source
glands from lands catagorised as GBR 1 or 2 in future.
The risk of transmission of TSE from Ultratard to human beings has been
appropriately addresses in accordance with CPMP/CVMP Note for Guidance
for minimising the risk of transmitting animal spongiform
encephalopathy via medicinal products (EMEA/410/01).
Viral safety issues have been addressed and compliance with relevant
guidelines are considered to be met.
Novo Insulatard (GE) Scientific Discussion
www.emea.eu.int/humandocs/PDFs/EPAR/insulatard/206002en6.pdf">http://www.emea.eu.int/humandocs/PDFs/EPAR/insulatard/206002en6.pdf
page 4-Viral Safety and TSE Risk Assessment
A number of animal derived raw materials are used in the production of
human insulin, rDNA. These are peptone, beef extract and pepticase
which are used in the preparation and storage of cell banks, and
L-threonine and trypsin used in the purification process to convert
human insulin precursor to human insulin methyl ester. In addition,
protamine sulphate derived from salmon is used as excipient in the
finished product.
Pepticase falls outside the scope of the TSE Guideline as it is derived
from casein from milk from healthy cows only and no other ruminant
materials are used in its preparation.
For peptone (CEF-2000-175) and beef extract (CEF-2000-1181)
Certificates of Suitability of the EDQM have been submitted.
L. threonine is sourced from avian feathers and porcine gelatine and
trypsin from porcine pancreas.
The risk of transmission of TSE from Insulatard to human beings has
been appropriately addressed in accordance with CPMP/CVMP Note for
Guidance for minimising the risk of transmitting animal spongiform
encephalopathy via medicinal products (EMEA/410/01).
Viral safety issues have been addressed and compliance with relevant
guidelines are considered to be met.
Novo Mixtard (GE) Sicentific Discussion
www.emea.eu.int/humandocs/Humans/EPAR/mixtard/mixtard.htm">http://www.emea.eu.int/humandocs/Humans/EPAR/mixtard/mixtard.htm
page 4--Viral Safety and TSE Risk Assessment
A number of animal derived raw materials are used in the production of
insulin human, rDNA. These are peptone, beef extract and pepticase
which are used in the preparation and storage of cell banks,
L-threonine and trypsin used in the purification process, and protamine
sulfate used as excipient in the final product. L-threonine is sourced
from avian feathers and porcine gelatine, trypsin from porcine pancreas
and protamine sulfate from salmon.
Pepticase falls outside the scope of the TSE Guideline as it is derived
from casein from milk from healthy cows only and no other ruminant
materials are used in its preparation.
For peptone (CEP-2000-175) and beef extract (CEP-2000-181) Certificates
of Suitability of the EDQM have been submitted.
The risk of transmission of TSE from Mixtard to human beings has been
appropriately addressed in accordance with CPMP/CVMP Note for Guidance
for minimising the risk of transmitting animal spongiform
encephalopathy via medicinal products (EMEA/410/01).
Viral safety issues have been addressed and compliance with relevant
guidelines are considered to be met.
Novo Monotard (GE) Scientific Discussion
www.emea.eu.int/humandocs/Humans/EPAR/monotard/monotard.htm">http://www.emea.eu.int/humandocs/Humans/EPAR/monotard/monotard.htm
Pages 3 and 4--Viral Safety and TSE Risk Assessment--
A number of animal derived raw materials are used in the production of
human insulin, rDNA. These are peptone, beef extract and pepticase
which are used in the preparation and storage of cell banks,
L-threonine and trypsin used in the purification process to convert
human insulin precursor to human insulin methyl ester. Bovine insulin
microcrystals are used for seeding the crystalline fraction.
L-threonine is sourced from avian feathers and porcine gelatine,
trypsin form porcine pancreas, and bovine insulin from bovine pancreas.
Papticase falls outside the scope of the TSE Guideline as it is derived
from casein from milk from healthy cows only and no other ruminant
materials are used in its preparation.
For peptone (CEP-2---175) and beef extract (CEP-2000-181) Certificates
of Suitability of the EDQM have been submitted.
Although a certificate of suitability has been provided by the
applicant for bovine insulin from German sourced pancreas (RO-CEP
200-135-Rev-OO), suitability of the material for its intended use in
the finished product must be taken into consideration. The chance of
contamination of German sourced pancreas used to produce the current
batch of microcrystals is remote. In addition, the manufacturing
process for bovine insulin is stated to provide a total reduction of
8.7 logs for BSE-agents in the early steps of insulin extraction.
Therefore, it is considered that the risk of transmission of BSE is
highly unlikely. However, the applicant should undertake to source
glands from lands categorised as GBR 1 or 2 in future.
The risk of transmission of TSE from Mixtard to human beings has
appropriately addressed in accordance with CPMP/CVMP Note for Guidance
for minimising the risk of transmitting animal spongiform
enecephalopathy via medicinal products (EMEA/410/01).
Viral safety issues have been addressed and compliance with relevant
guidelines are considered to be met.
Novo Velosulin (GE) Scientific Discussion
www.emea.eu.int/humandocs/Humans/EPAR/velosulin/velosulin.htm">http://www.emea.eu.int/humandocs/Humans/EPAR/velosulin/velosulin.htm
Pages 3 and 4--Viral Safety and TSE Risk Assessment
A number of animal derived raw materials are used in the preparation of
insulin human (rDNA). These are peptone, beef extract and pepticase
which are used in the preparation and storage of cell banks, and
L-threonine and trypsin used in the purification process to convert
human insulin precursor to human insulin methyl ester.
Pepticase falls outside the scope of the TSE Guideline as it is derived
from casein from milk from healthy cows only and no other ruminant
materials are used in its preparation.
For peptone (CEP-2000-175) and beef extract (CEP-2000-181) Certificates
of suitability of the EDQM have been submitted.
L-threonine is sourced from avian feathers and porcine gelatine and
trypsin-calcium acetate solution from porcine pancreas.
The risk of transmission of TSE from Velosulin to human beings has been
appropriately addressed in accordance with CPMP/CVMP Note for Guidance
for minimising the risk of transmitting animal spongiform
encephalopathy via medicinal products (EMEA/410/01).
Viral safety issues have been addressed and compliance with relevant
guidelines is considered to be met.
Aventis Optisulin (insulin glargine with another trade
name--analog)--Scientific Discussion
www.emea.eu.int/humandocs/PDFs/EPAR/Optisulin/209700en6.pdf">http://www.emea.eu.int/humandocs/PDFs/EPAR/Optisulin/209700en6.pdf
Page 4 Viral Safety
No starting material from human or animal origin is used. Due to the
usage of prokaryotic cells no viral contamination is expected. Trypsin
is used in the production of the active ingredient. Trypsin is
isolated from a homogenate of porcine pancreas. The process comprises
treatment with organic solvents and nonfiltration or acidification of
the extract. The trypsin manufacturing process ensures that no viruses
are introduced into the production process by trypsin. Glycerol used
as ingredient or for the preparation of the second WCB (Working Cell
Bank) is of plant or synthetic origin. Glycerol used for the
preparation of the MCB (Master Cell Bank) and the first WCB (Working
Cell Bank) is of bovine origin and the processing conditions for this
glycerol are in accordance with the "Note for Guidance on minimising
the risk of transmitting animal spongiform enecephalopathy agents via
medicinal products" (CPMP-BWP/1230/98). After further investigation it
was confirmed through a type II variation application that glycerol
used as ingredient for the preparation of the MCB is of synthetic
origin.
And, just as you saw with the Lantus information, this means the first
Working Cell Bank has bovine glycerol used for it.
Aventis Apidra (GE analog)--Scientific Discussion
www.emea.eu.int/humandocs/PDFs/EPAR/apidra/121804en6.pdf">http://www.emea.eu.int/humandocs/PDFs/EPAR/apidra/121804en6.pdf
Page 6 Adventitious Agents Safety Evaluation
No excipients of human or animal origin are used in the product
manufacture and therefore there is not risk of contamination with viral
or TSE agents by these ingredients. No animal ingredients are used for
preparation of the cell banks or in the fermentation process. During
downstream processing, enzymes are used, which are derived from porcine
pancreas. All pigs used are suitable for human consumption and each
batch of product must contain a certificate of animal origin and
species in addition to the certificate of analysis. Viral validation
studies were carried out to test the ability of the production process
of the enzymes to remove and inactivate viruses. The submitted viral
clearance study data demonstrate that the enzyme manufacturing
processes are capable of inactivating/removing viruses. The choice of
viruses, production steps investigated and the validity of the scale
down process have been satisfactorily addressed. Based on these
results, the possibility of viral contamination with the use of these
enzymes in the production process of insulin glulisine is considered
negligible.
But no one says there is NO risk and yes, the porcine enzyme IS used to
make Apidra, so the statement that no animal products are used is
false. If there are no real pigs' enzymes used, then why say they
could be eaten and have certificates of origin for them?
www.diosynth.com/site/biochem/classical/index.html">http://www.diosynth.com/site/biochem/classical/index.html
Diosynth pays special attention to the source of the materials to avoid
contamination with pathogenic microorganisms or toxic substances. For
instance, supplier slaughterhouses, inspected by European or North
American government agencies, reject any material taken from animals
showing signs of illness. Furthermore, our manufacturing processes have
undergone virus validations - studies in which virus removal is proven
- just in case a virus is present despite all precautions. Bovine
starting material originates from BSE-free countries only.
www.iddtindia.org/bsetse.asp">http://www.iddtindia.org/bsetse.asp
Diosynth B. V., as manufacturer of
BOVINE INSULIN
hereby confirms that this product is manufactured from pancreas glands
of bovine origin. Only starting material collected exclusively from
BSE/TSE free countries is used as a source.
Moreover, the manufacturing process has been validated for potential
prion removal and/or inactivation and was shown to be sufficiently
effective.(see enclosed summary report).
Validation of Bovine Insulin Manufacturing process.
Inveresk Research, Scotland
www.inveresk.com/services/b_virusandtsevalid.asp">http://www.inveresk.com/services/b_virusandtsevalid.asp
www.dotpharmacy.co.uk/mar30.html#b">http://www.dotpharmacy.co.uk/mar30.html#b
Novo Nordisk says that, in a trial, no traces of a deliberately
introduced SE pathogen could be detected after the fourth stage of its
standard 15-stage insulin purification process.
CP Pharmaceuticals, manufacturer of Hypurin beef insulin, derived from
the pancreas, says this organ has a low risk of infectivity with regard
to spongiform encephalopathies. This is also the case for its heparin
products, derived from lung and intestine, and hyaluronidase, from
testes.
Note that the Dot Pharmacy URL dates back to the '90's when the first
rumblings of BSE/TSE began.
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