d*********e
发帖数: 15 | 1 我做实验测蛋白浓度， 发现 Genentech's Trastuzumab 剂量不对, 一瓶只有 54 mg
抗体, 不是 440 mg. 我给Genentech 发了email, 没有回音。
请问我该报告FDA吗？ |
m******l
发帖数: 7 | 2 你用什么方法测的？差那么多
【在 d*********e 的大作中提到】
: 我做实验测蛋白浓度， 发现 Genentech's Trastuzumab 剂量不对, 一瓶只有 54 mg
: 抗体, 不是 440 mg. 我给Genentech 发了email, 没有回音。
: 请问我该报告FDA吗？
|
d*********e
发帖数: 15 | 3 I used UV280 nm, Bradford assay as well as running a SDS-Gel, all leading to
same concentration.
I know antibody protein expression and purification is very expensive, but
do you think Genentech is trying to save the cost by using less amount of
antibody ? After all, it is vey unlikely that patients or doctors would
find out the true quantity of the antibody. It is only us, the biology
researchers, who would happen to find out the truth, by accident.
Do we have responsibility to ask Genentech
【在 m******l 的大作中提到】
: 你用什么方法测的？差那么多
|
b**u
发帖数: 2761 | 4 did you repeat? is your result reliable?
【在 d*********e 的大作中提到】
: 我做实验测蛋白浓度， 发现 Genentech's Trastuzumab 剂量不对, 一瓶只有 54 mg
: 抗体, 不是 440 mg. 我给Genentech 发了email, 没有回音。
: 请问我该报告FDA吗？
|
r***o
发帖数: 162 | 5 I am impressed by your confidence. However, I do feel that you are over-
confident.
In the pharmaceutical industry, there is something called CMC, chemistry
manufacture and control. CMC is under super-tight federal regulation. No ONE
would dare to play with such regulations. If your case below were true, the
fine to DNA alone would be billion dollar level and the payer and patient
legal actions would cost DNA tens of billions if not hundreds.
Check their CMC section of BLA (biologic license appl
【在 d*********e 的大作中提到】
: I used UV280 nm, Bradford assay as well as running a SDS-Gel, all leading to
: same concentration.
: I know antibody protein expression and purification is very expensive, but
: do you think Genentech is trying to save the cost by using less amount of
: antibody ? After all, it is vey unlikely that patients or doctors would
: find out the true quantity of the antibody. It is only us, the biology
: researchers, who would happen to find out the truth, by accident.
: Do we have responsibility to ask Genentech
|
K******S
发帖数: 10109 | 6 Start Forwarding...................
发信人: Dailybreeze (Sam), 信区: Biology
标 题: Re: Genentech's Trastuzumab 剂量不对，一瓶只有 54 mg 抗体,
发信站: BBS 未名空间站 (Mon Oct 20 02:23:51 2008)
我没有称，一瓶全溶在20 ml 水里。 混匀， 等了几天才测蛋白。
ONE
the |
h*****t
发帖数: 1226 | 7 hehehe...
【在 K******S 的大作中提到】
: Start Forwarding...................
: 发信人: Dailybreeze (Sam), 信区: Biology
: 标 题: Re: Genentech's Trastuzumab 剂量不对，一瓶只有 54 mg 抗体,
: 发信站: BBS 未名空间站 (Mon Oct 20 02:23:51 2008)
: 我没有称，一瓶全溶在20 ml 水里。 混匀， 等了几天才测蛋白。
:
: ONE
: the
|
d*********e
发帖数: 15 | 8 I used the provided bacteriostatic water for injection. It should be stable
for 28 days.
【在 h*****t 的大作中提到】
: hehehe...
|
d*********e
发帖数: 15 | 9 I repeated three times with uv280 , bradford, and running a SDS-Gel.
The reason is that my result is inconsistent with the labeled concentration.
So I have to find out the reason why the concentration is so low, 8-fold
less that the stated amount.
stable
【在 d*********e 的大作中提到】
: I used the provided bacteriostatic water for injection. It should be stable
: for 28 days.
|
m**b
发帖数: 617 | 10 Did you repeat these all on the same bottle of samples? Suggest you to test
it on samples from different bottles, different production batch. You need
more solid evidence before you reach such a serious accusation. From what
I can see from your post, digradation is a very likely cause that you did
not rule out.
concentration.
【在 d*********e 的大作中提到】
: I repeated three times with uv280 , bradford, and running a SDS-Gel.
: The reason is that my result is inconsistent with the labeled concentration.
: So I have to find out the reason why the concentration is so low, 8-fold
: less that the stated amount.
:
: stable
|
|
|
v*******y
发帖数: 1362 | 11 你有计量对的以前的样品吗? 对比一下就可以了啊. 还有啊, SDS 可以定量吗?
【在 d*********e 的大作中提到】
: 我做实验测蛋白浓度， 发现 Genentech's Trastuzumab 剂量不对, 一瓶只有 54 mg
: 抗体, 不是 440 mg. 我给Genentech 发了email, 没有回音。
: 请问我该报告FDA吗？
|
i*n
发帖数: 9793 | 12 测蛋白有很多办法，但是针对不同的情况要用不同的办法，不是随便一个都能一样管用
的，估计你多半是测定蛋白的方法不对。Genentech没这么大狗胆弄虚作假搞这么大水分
【在 d*********e 的大作中提到】
: 我做实验测蛋白浓度， 发现 Genentech's Trastuzumab 剂量不对, 一瓶只有 54 mg
: 抗体, 不是 440 mg. 我给Genentech 发了email, 没有回音。
: 请问我该报告FDA吗？
|
s**u
发帖数: 137 | 13 最好确认一下你的实验方法是否正确，同时换一个新的样品重测，避免任何可能的degr
adation.
如果结果重复的话，这是极端严重的问题。不是说他们故意掺假，而是工艺控制上有了
致命的漏洞，必须立即改变。
【在 d*********e 的大作中提到】
: 我做实验测蛋白浓度， 发现 Genentech's Trastuzumab 剂量不对, 一瓶只有 54 mg
: 抗体, 不是 440 mg. 我给Genentech 发了email, 没有回音。
: 请问我该报告FDA吗？
|
c******n
发帖数: 16403 | 14 如果是真的, 那么楼主要么暴富, 要么会被人灭口, 哈哈
degr
【在 s**u 的大作中提到】
: 最好确认一下你的实验方法是否正确，同时换一个新的样品重测，避免任何可能的degr
: adation.
: 如果结果重复的话，这是极端严重的问题。不是说他们故意掺假，而是工艺控制上有了
: 致命的漏洞，必须立即改变。
|
d*********e
发帖数: 15 | 15 I emailed my finding to DNA and they did not reply my email.
It should not be degraded because I stored it at 4 C degree for just a few
days after adding the provided dilulent.
I am not sure if I will get rich, even if this low concentration of antibody
finding is proved. Unless patients would file a class action and ask me as
a witness.
I do not have other batch or lot of the bottle. I will post log number
tomorrow. I believe this should not be just this lot number.
Anyone has the antibody p
【在 c******n 的大作中提到】
: 如果是真的, 那么楼主要么暴富, 要么会被人灭口, 哈哈
:
: degr
|
m**b
发帖数: 617 | 16 I can't believe Genetech would intentionally reduce the amount of antibody.
Anyone in the pharma industry would know it's totally unworthy of the risk
to do some stupid dirty trick like this. FDA often pays unanounced visits
to manufaturing sites and R&D sites to do tests. If a company was found out
to intentionally lower the dose, it will cause them big problem. If you
are really confident about your findings, why not contact FDA?
antibody
as
【在 d*********e 的大作中提到】
: I emailed my finding to DNA and they did not reply my email.
: It should not be degraded because I stored it at 4 C degree for just a few
: days after adding the provided dilulent.
: I am not sure if I will get rich, even if this low concentration of antibody
: finding is proved. Unless patients would file a class action and ask me as
: a witness.
: I do not have other batch or lot of the bottle. I will post log number
: tomorrow. I believe this should not be just this lot number.
: Anyone has the antibody p
|
h*****t
发帖数: 1226 | 17 You have your evedience and thoughts.
However, certain protein/antibody are very sensitive to the buffer condition,
your protein maybe decomposed or aggreated in the solution. A clear band
of the light chain and heavy chain on the reducing gel is not solid enough
to draw conclusion.
antibody
as
【在 d*********e 的大作中提到】
: I emailed my finding to DNA and they did not reply my email.
: It should not be degraded because I stored it at 4 C degree for just a few
: days after adding the provided dilulent.
: I am not sure if I will get rich, even if this low concentration of antibody
: finding is proved. Unless patients would file a class action and ask me as
: a witness.
: I do not have other batch or lot of the bottle. I will post log number
: tomorrow. I believe this should not be just this lot number.
: Anyone has the antibody p
|
m******l
发帖数: 7 | 18 不知道你的结果可靠不可靠，你还change buffer，有没有丢掉MAb?
从你的描述来看，你对药厂的运作是绝对外行
antibody
as
【在 d*********e 的大作中提到】
: I emailed my finding to DNA and they did not reply my email.
: It should not be degraded because I stored it at 4 C degree for just a few
: days after adding the provided dilulent.
: I am not sure if I will get rich, even if this low concentration of antibody
: finding is proved. Unless patients would file a class action and ask me as
: a witness.
: I do not have other batch or lot of the bottle. I will post log number
: tomorrow. I believe this should not be just this lot number.
: Anyone has the antibody p
|
K******S
发帖数: 10109 | 19 what kind of desaling column you used?
antibody
as
【在 d*********e 的大作中提到】
: I emailed my finding to DNA and they did not reply my email.
: It should not be degraded because I stored it at 4 C degree for just a few
: days after adding the provided dilulent.
: I am not sure if I will get rich, even if this low concentration of antibody
: finding is proved. Unless patients would file a class action and ask me as
: a witness.
: I do not have other batch or lot of the bottle. I will post log number
: tomorrow. I believe this should not be just this lot number.
: Anyone has the antibody p
|
v*******y
发帖数: 1362 | 20 难道是部分留在column里面了?
【在 K******S 的大作中提到】
: what kind of desaling column you used?
:
: antibody
: as
|
|
|
d*********e
发帖数: 15 | 21 I measured original solution without desalting too and uv 280 reading was
consistent with concentration after desalting. Just very very high uv260
reading. What would cause high uv 260 reading ? It is not nucleic acid.
After desalting, uv280 >uv260.(something like uv280 0.4, uv260 0.2.).
Did FDA come to measure protein concentration ? I doubt it.
FDA should measure protein concentration from samples randomly taking from
phamacy.
There are a lot of pharma dirty things exposed before, such as
【在 v*******y 的大作中提到】
: 难道是部分留在column里面了?
|
m**s
发帖数: 145 | |
m**b
发帖数: 617 | 23 Pharma tend to play tricks in R&D, i.e. before drug approval. But after
drug approval, they have little incentive to mess with manufacturing process
. The cost of a drug is largely the cost of R&D, manufacturing cost is a
just a small fraction. Why risk retraction from the market by intentionally
lower the dosage? It just doesn't make any good business sense.
scence.
【在 d*********e 的大作中提到】
: I measured original solution without desalting too and uv 280 reading was
: consistent with concentration after desalting. Just very very high uv260
: reading. What would cause high uv 260 reading ? It is not nucleic acid.
: After desalting, uv280 >uv260.(something like uv280 0.4, uv260 0.2.).
: Did FDA come to measure protein concentration ? I doubt it.
: FDA should measure protein concentration from samples randomly taking from
: phamacy.
: There are a lot of pharma dirty things exposed before, such as
|
d******m
发帖数: 199 | |
S**********l
发帖数: 30 | 25 That's only true for small molecules. Biologicals are very expensive to
produce, so the manufacturers do have incentive to reduce the protein.
process
intentionally
【在 m**b 的大作中提到】
: Pharma tend to play tricks in R&D, i.e. before drug approval. But after
: drug approval, they have little incentive to mess with manufacturing process
: . The cost of a drug is largely the cost of R&D, manufacturing cost is a
: just a small fraction. Why risk retraction from the market by intentionally
: lower the dosage? It just doesn't make any good business sense.
:
: scence.
|
E****e
发帖数: 315 | 26 可能你的样品浓度太高,UV signal saturate了,算出的浓度就低了 |
E****e
发帖数: 315 | 27 440mg/20mL = 22 mg/mL
需要稀释很多倍才好测UV,除非你用的是特殊的CUVETTE |
n******0
发帖数: 49 | 28 混这版的有么有药厂的啊？还有带这种想法的。你大概对生产流程一点不懂。出个产品
，几十人的cmc team来保证流程质量，process每一步都有限定的合格标准。谁会有
incentive去mess up。
【在 S**********l 的大作中提到】
: That's only true for small molecules. Biologicals are very expensive to
: produce, so the manufacturers do have incentive to reduce the protein.
:
: process
: intentionally
|
i*n
发帖数: 9793 | 29 就是，从原料进厂到生产每一步流程到ＱＣ到发运，每一步都有记录在案，不是谁想搞
手脚就能搞的
【在 n******0 的大作中提到】
: 混这版的有么有药厂的啊？还有带这种想法的。你大概对生产流程一点不懂。出个产品
: ，几十人的cmc team来保证流程质量，process每一步都有限定的合格标准。谁会有
: incentive去mess up。
|
t**n
发帖数: 4365 | 30 某site生产的final product，API忘加的事都出过。。。
【在 n******0 的大作中提到】
: 混这版的有么有药厂的啊？还有带这种想法的。你大概对生产流程一点不懂。出个产品
: ，几十人的cmc team来保证流程质量，process每一步都有限定的合格标准。谁会有
: incentive去mess up。
|
|
|
r***o
发帖数: 162 | 31 Yes, the consequence is that: it was fined by the FDA and other government
agencies $500million dollars. The incentive of doing so on purpose is very
low.
【在 t**n 的大作中提到】
: 某site生产的final product，API忘加的事都出过。。。
|
I*****y
发帖数: 6402 | 32 this adulteration in GMP-regulated pharmaceutical companies will cost them
injunction, product seizure, and even criminal prosecution.
【在 r***o 的大作中提到】
: Yes, the consequence is that: it was fined by the FDA and other government
: agencies $500million dollars. The incentive of doing so on purpose is very
: low.
|
w**z
发帖数: 123 | 33 I don't believe any sizable pharma will do this purposely because of the
huge cost associated with it. Either your method did not pick it up or some
accident(s) associated with the manufacture process.
However, I believe every pharma has a complain center and they should
respond to you. Supposely your complain is recorded (required by regulator). |
i*n
发帖数: 9793 | 34 对，所有正式的投诉都会记录在案进行调查的，如果楼主是正式的投诉，不应该没有反
映的
some
).
【在 w**z 的大作中提到】
: I don't believe any sizable pharma will do this purposely because of the
: huge cost associated with it. Either your method did not pick it up or some
: accident(s) associated with the manufacture process.
: However, I believe every pharma has a complain center and they should
: respond to you. Supposely your complain is recorded (required by regulator).
|
d*********e
发帖数: 15 | 35 I have not yet received responses from either FDA or DNA.
I filled out an online form (non-emergent) in FDA website, and sent an email
to DNA on its website website.
DNA is such huge biotech company that I do not wish to get retaliated.
Anyone would like to confirm it, just check the concentration if you happen
to have one.
Thanks,
【在 i*n 的大作中提到】
: 对，所有正式的投诉都会记录在案进行调查的，如果楼主是正式的投诉，不应该没有反
: 映的
:
: some
: ).
|
h*****t
发帖数: 1226 | 36 Genentech will not after you for sure.
Just curious, what is the EC you used for concentration calculation?
email
happen
【在 d*********e 的大作中提到】
: I have not yet received responses from either FDA or DNA.
: I filled out an online form (non-emergent) in FDA website, and sent an email
: to DNA on its website website.
: DNA is such huge biotech company that I do not wish to get retaliated.
: Anyone would like to confirm it, just check the concentration if you happen
: to have one.
: Thanks,
|
s**********y
发帖数: 122 | 37 I only worked in pharm for a few months. As what I have learned, it is
impossible. The drug was retested many times for the shelf-life stability
before putting on the market, with so many hands involved in QC/QA. This
scenario is mission impossible in reality. period. |
f*******e
发帖数: 689 | 38 UV, Bradford are not precise methods for some specific proteins. I don't
think that Genentech would make that stupid mistake. |
