板块主题窝 --- 生物和化学制药

maomi

From my point of view, biosimilar industry is not as mature as generic small molecule based drug. that's why FDA does not even have a established pathway to approval biosimilar. In general, it is easier to get biosimilar or new drug approved by EMEA than FDA.

one of my colleagues went to a bio-related conference last year. She came back and told us a story last year about how a India research produce a biosimilar. He uses only one analytical method to prove that it is biosimilar. Our whole group cannot help laughing, as he is too naive about proving the equivalency between two biomolecule. I am afraid that that is the stage that India and China are in.
MAB is absolutely right, we normally use multiple orthogonal analytical methods to prove the equivalency. Can you believe that we applied more than 20 analytical methods for a biomolecule new drug for FDA approval?

Biomolecule production is through molecular biology to insert the DNA sequence of protein of interest to other expression system, including mammlian cell, E.Coli, yeast or insect cell. post-translation modification of protein of interest is possible in some of the expression system, including glycolation, phosphorylation, etc... Sometime, after recombinant protein is purified, we need pegylate the protein to increase its circulatory time in human body (we have protease in our body to chew protein), to reduce the immunogenicity and to improve solubility. Pegylation will bring in more variation of the molecule. Even FDA does not set criteria for pegylation. That's why it is very difficult to produce exact same biomolecule.

spy2009

76# maomi

That's really too bad for that chemist.

maomi

76# maomi

That's really too bad for that chemist.
spy2009 发表于 2009-3-1 14:05

I know, I am glad that I did not apply that position. Well, I am not keen on being a VP or director. I like technical side, feel it is more rewarding that way.

mab

From my point of view, biosimilar industry is not as mature as generic small molecule based drug. that's why FDA does not even have a established pathway to approval biosimilar. In general, it is easi ...
maomi 发表于 2009-3-1 14:05

Learned a lot from you. Thanks!

spy2009

81# maomi

感觉买SSRX，有点赌中国和欧洲对biosimilar的限制，起码两三年内不会增加。

maomi

79# spy2009

It does not sound right to me to have your drug product on market while it is going through clinical trials.

a biosimilar of EPIAO (Recombinant Human Erythropoietin Injection) was approved in Europe in 2007 already.
ZT
Biopharmaceuticals: Approval Trends in 2007
More than 70% of the products were produced in mammalian cells.
Oct 1, 2008
By: Gary Walsh, PhD
BioPharm International

PRODUCTS APPROVED
Abseamed (recombinant human erythropoietin alfa) is a recombinant form of human erythropoietin (EPO) produced in a Chinese hamster ovary (CHO) cell line. Native human EPO is a 165 amino acid, 36 kDa glycoprotein housing three N-linked and one O-linked glycosylation sites. It is synthesized almost exclusively in the kidney and is primarily responsible for stimulating and regulating erythropoiesis (red blood cell production). Abseamed is a biosimilar product, with Janssen-Cilag's erythropoietin Eprex/Erypo having served as reference medicine. The product is identical to both reference and native EPO in amino-acid sequence, but does differ in exact glycosylation detail. Compared to Eprex it displays somewhat higher sialylation levels, particularly associated with its O-linked glycan chain. The biosimilar product also displays higher levels of mannose-6-phosphate containing glycans associated with the Asn 24 N-linked glycosylation site. However, these specific glycans display only weak binding affinity for the mannose-6-phosphate receptor, and therefore are unlikely to trigger rapid product uptake from circulation.

Abseamed gained approval in the EU in August 2007. It is indicated for the treatment of anemia associated with chronic renal failure and for anemia accompanying chemotherapy of certain cancer types. It also can be used to reduce exposure of patients undergoing major orthopedic surgery to blood transfusions if transfusion related complications are anticipated.

The product is manufactured by batch cell culture in media supplemented with recombinant human insulin. After recovery from the cell media, the product is purified to homogeneity by a combination of standard chromatographic techniques. Downstream processing also incorporates a nanofiltration-based viral-removal step.

spy2009

I know, I am glad that I did not apply that position. Well, I am not keen on being a VP or director. I like technical side, feel it is more rewarding that way.
maomi 发表于 2009-3-1 14:08

呵呵，在美国做技术，可以做到退休。在国内，不一样，四十岁以后得做官了。

还做技术，谁来做你的领导？中国人，年龄观念很重。年纪小的，不能领导，年纪大的。

IT方面更明显了，三十岁就没有人还写程序了。

笑口常开

69# maomi


Well generic drug company usually don't need organic synthesis chemist since they usually buy raw API from other big chemical and big generic drug company like Teva.
Generic drug doesn't need clinical trial but it does need to do bioequivalence study. So Formulation is most important part of generic drug development.
Generic drug company make big chunck of money during 180 day excluxivity so they fight to get first filing. After this period, the profit margin was greatly decreased.
For example: Norvac a high blood pressure drug
                      brand name    $58/month
                      Exclusive generic:$35/month
                      Flooded with tons of generic: 8$/ 3 month

Just FYI

spy2009

So Formulation is most important part of generic drug development.
笑口常开 发表于 2009-3-1 14:23

Nod，认识一个大学教授(中国人)，是搞缓释的。没有缓释，每天都要打针；有了缓释，一个月打一次针；这个美国人喜欢。

就是没赶上好时候，找风险投资找得很辛苦。

mab

69# maomi


Well generic drug company usually don't need organic synthesis chemist since they usually buy raw API from other big chemical and big generic drug company like Teva.
Generic drug doe ...
笑口常开 发表于 2009-3-1 14:23

You mean the first generic drug has 180 day exclusive right?

spy2009

88# 笑口常开

感觉国内药厂，大多还是做原料仿制药，而做制剂做得牛的，还是美国这儿的药厂。现在情况是否不同了？

maomi

88# 笑口常开

that's very informative. Thank you for correcting me. I guess it depends on the business strategy of generic drug company. Some generic drug company will have one subdivision to synthesis active pharmecutical ingredient (API), and another subdivision will do the final finishing and formulation. like my friend's company, she works in API subdivision. Whereas some generic drug company just buy API.

笑口常开

68# spy2009
I can not agree with you about generic drug application. Generic drug company usually file the application several years before patent expiration. They usually have very good lawyer to do patent challenging. If they suceed it, they can push into the market earlier even before patent expiration to grap big profit or get authosized generic ( kind of settlement with brand name pharm ( eg Fosmax Merk with Whatson).

If you just synthesized same small molecule, it doesn't mean it has same bioequvalence as brand name drug. You have to have right formulation then do in vivo bioequvalence study to prove generic drug has same bioequvalence as brand name. Then can go filing to get approve.

Have a friend who has been working with FDA to review ANDA application and myself working in generic drug company.

笑口常开

89# spy2009


Yes.

spy2009

93# 笑口常开

Well said, 谢谢纠正原来的看法。

笑口常开

91# spy2009

Yes. Big generic drug company has subdivision to synthesize API such as MYL ( they have it in India), Teva and Norvatis ( Sandoz).

maomi

yes, I refer to collect clinical data as to demonstrate bioequvalency, that's the key part as a generic drug. sorry for being vague there.

It is interesting to know that "Generic drug company usually file the application several years before patent expiration", has this been development in terms generic drug application? maybe I just recalled wrong. If this is true, this practice simply put innovator to a bad situation, as the generic drug company simply chips in innovator's big profit.

spy2009

NND，研发小分子新药，越来越象撞大运了。而利用已有的小分子仿制药，搞搞制剂，
增强点性能，如果还能弄出点新性能，那就更爽了。

不是有鸡尾酒料法吗？用好几种小分子仿制药，一起攻击，或者依次分批攻击等等，
还是很有搞头的。

笑口常开

64# spy2009

WX is a leading customized outsourcing company. The big pharma such as Schering, Merk outsource their starting material, intermediate of early stage development compound to WX by providing them recipe. They produce large quantity and this is just part of it but big money. Also big pharm even provide funding for hiring in China ( it is called FTE ( full tim equavalient)). Of course WX also do research portion.

笑口常开

96# 笑口常开
The generic drug company is very aggressive. That is why brl was growing very fast by this way but last year BRL was bought out by TEVA.