What Are Biosimilars? Should I Care ?

What Are biological products ?

A biological product is a substance derived from a living organism and used for the prevention or treatment of disease. Biologicals are usually too complex for chemical synthesis by a laboratory. These products include antitoxins, bacterial and viral vaccines, or may be living entities such as cells and tissues, blood products and hormone extracts.
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Example of biologics made with recombinant DNA technology :
Erythropoietin = Epogen / stimulation of red blood cell production
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BioByte 103 - What are biotech drugs?

.**This Guy Should Be In An Infomercial, Or Is He?

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What Are Biogenerics ?

Biogenerics also known as are generic versions of biotech drugs.

Whats The Debate On Biogenerics?

"It's no secret that the golden years for generic drugs have arrived, with billions of dollars worth of branded drugs losing their patents every year and an American public that's realizing that generic drugs perform as well as their branded counterparts. However, there's one area where the gold doesn't glisten quite as brightly, and that's in biogenerics, also known as biosimilars, and arguments continue from both sides about the establishment of an approval pathway for these drugs".

Source

"The healthcare reform law allows for the approval of so-called biosimilars after 12 years of patent exclusivity. However, critics have warned that the law provides the FDA with too much leeway to approve these drugs — including the flexibility to decide if clinical trials are even necessary. Biologics are medications and other medical products created through the biological process instead of chemistry."

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Note From Tina@HCV New Drugs : *Example A drug company may hold all rights to the biotech drug for 12 years, then it can be sold cheaper as a generic (deemed Biogenerics also known as biosimilars). The debate is these biotech drugs are too complex to be manufactured and sold as a generic without strong regulation by the FDA, which is currently being put in place. (more info below).

Biosimilars in the United States:
Implementation Challenges and Lessons Learned from the European Union
December 01, 2010 Length: 01:15:10
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Event Summary
The Patient Protection and Affordable Care Act established a legal framework for an abbreviated approval pathway for off-brand versions of biotech drugs, known in the United States as biosimilars, and charged the Food and Drug Administration (FDA) with the authority to implement the biosimilars pathway. Following the FDA’s recent public hearing on biosimilars, many questions remain unanswered: What are the key implementation issues associated with biosimilar entry in the United States? And what should government’s role be in regulating the process?
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On Wednesday, December 1, Brookings hosted a discussion on these key issues and experiences as the FDA considers an approach to implementing a U.S. biosimilars pathway. Moderated by Brookings Vice President and Director of Governance Studies Darrell West, a panel of experts addressed regulatory and implementation challenges and opportunities and provide a comparative analysis of the European Union’s experience in creating a biosimilars approval pathway. The European Union, as well as several countries around the globe, has already implemented an approval pathway for biosimilars.
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Transcript
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DARRELL WEST:
For those of you who are unfamiliar with the term "biosimilars," they are drugs that are similar to, but not identical to, innovator biologics. Unlike generic drugs, which could be determined to represent exact duplicates, biosimilars are more complex substances, and, therefore, raise interesting questions both for public policy as well as regulation.
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In March of this year, Congress passed legislation designed to encourage biologics, price competition and innovation, and, among other things, this bill gave the Food and Drug Administration the authority to establish scientific standards for the approval of biosimilars, and it also authorized the FDA to determine the analytical and clinical data needed to assure patient safety. Today we have brought together several experts to offer their views of the implementation challenges. Several other places, including the European Union, Canada and Japan have developed a pathway to approval for biosimilars.
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The European Medicines Agency, for example, already has established a process that is science driven and included the input of major stakeholders. Among the questions facing the FDA are how to identify and monitor adverse events, what kinds of clinical data are required for approval, and how to involve the various relevant stakeholders in these decisions. To help us better understand these issues, we are pleased to welcome three distinguished speakers, and they’re going to focus on the regulatory and implementation challenges and opportunities, as well as comparative analysis of the European Union and Canadian experiences in creating a biosimilars approval pathway.

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View Full Transcript » Full Audio Download Audio

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FDA Hears Comments on Biosimilar Approval Pathway
By Emily P. Walker, Washington Correspondent,
MedPage TodayPublished:
November 02, 2010
SILVER SPRING, Md. -- The FDA kicked off a two-day hearing on creating an approval pathway for follow-on biologics -- also known as biosimilars -- by listening to testimony from generic and brand-name drug companies, pharmacy groups, academics, and doctors who treat patients with biologics.
The agency is still years away from creating a framework for approving generic biologic products, called biosimilars, but the open public hearing gets the potentially lengthy process under way.
"To protect patients, comparative nonclinical and clinical testing of biosimilars is necessary," said Jim Shehan, vice president of legal, government, and quality affairs at Novo Nordisk, which makes biologics to treat diabetes.
"FDA should proceed particularly cautiously with respect to extrapolation, where individuals in the unstudied population may have different physiological responses to the drug," he said.
Continue Reading..............


FDA Page On Bioimilars
This page contains information (and links to additional information) about biosimilar biological products, which are biological prescription drugs that are demonstrated to be “highly similar” (biosimilar) to or “interchangeable” with an FDA-approved biological product.
The FDA held a 2-day public hearing on November 2 and 3, 2010 to obtain input on specific issues and challenges associated with the implementation of the Biologics Price Competition and Innovation Act of 2009 (BPCI Act).

CBER is the Center within FDA that regulates biological products for human use under applicable federal laws, including the Public Health Service Act and the Federal Food, Drug and Cosmetic Act. CBER protects and advances the public health by ensuring that biological products are safe and effective and available to those who need them. CBER also provides the public with information to promote the safe and appropriate use of biological products.

November 29, 2010
FDA faces conflicting views on how to develop drug approval pathway.
Download Untangling Biosimilars
Nov 29, 2010 Vol. 88 Issue 48 pp. 25-27)

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Biosimilars will be challenging for FDA, speakers say
By Jason Millman -
12/01/10 11:02 AM ET
The Food and Drug Administration (FDA) will face a number of challenging issues as it works to create a pathway to bring generic versions of biologics into the market, speakers said at a Brookings Institution panel Wednesday morning.
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The healthcare reform law allows for the approval of so-called biosimilars after 12 years of patent exclusivity. However, critics have warned that the law provides the FDA with too much leeway to approve these drugs — including the flexibility to decide if clinical trials are even necessary. Biologics are medications and other medical products created through the biological process instead of chemistry.
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Experts have warned that the biosimilar manufacturing processes can alter the drugs in ways that cannot be detected. Mary Pendergast, president of a biotech consulting firm, said the 12-year approval process raises the question of whether a generic biologic will be consistent with the original drug."If you have a pioneer in year 12 that has a product different from the biologic that was tested for a biosimilar in year two or three, at year 12, are they going to be biosimilar or not?" she said.
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The FDA is being asked to make "very tough scientific decisions" over whether one drug is biosimilar to another drug, Pendergast said, adding that she expects Congress will continue to battle the FDA over requirements for the biosimilar approval process. "Members of Congress have already told the FDA what they think they should do, which may or may not be identical to law as written," Pendergast said. "The FDA will be under pressure from the innovator and biosmilar industries one way or another. This is very difficult to the FDA."
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Yesterday From : The Big Red Biotech Blog
News and discussion on critical trends and issues in the biopharm and pharmaceutical industry
Dec 04
More on Biosimilar Approval Pathways
Bruce Lehr
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Chemical & Engineering News just published its take on the FDA's progress towards establishment of a biosimilars approval process. The publication writes, "Fights over testing requirements, data exclusivity, and even how to name these so-called biosimilars, or follow-on biologics, are delaying the agency from putting an approval process in place."FDA now has to decide how much testing is necessary to show that a biosimilar is as safe and effective as the original product. But there is much disagreement over exactly how much clinical testing FDA should require. Because of the complexity of protein-based drugs, FDA is finding it difficult to strike the right balance between the desire for low-cost biologics and the need for careful evaluation of safety and efficacy.
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On one side of the debate are the biotech companies and patient groups, which insist that the complexity of biological products makes animal toxicology studies and human clinical trials essential for establishing safety and efficacy. They argue that, “A biosimilar product will invariably be made up of a different mixture of related molecules than the product it is attempting to copy. The challenge with biosimilars is knowing which structural variations matter clinically and which do not.” Makes sense, huh?
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On the other side of the debate are the generic drug manufacturers that claim that clinical testing for biosimilars is redundant and unethical because it has already been performed on the original products. They argue that if biosimilars producers have confirmed that their product is “highly similar” to a reference biologic with state-of-the-art analytical tools, then that biosimilar “should be subject to clinical study requirements only to the same degree as is expected for originator products making manufacturing changes.” Such requirements typically do not involve clinical testing. Makes sense, huh? FDA has begun the process of establishing a biosimilars approval pathway, but observers say it will likely be several years before the agency sorts through all the challenges related to implementing the new law.So stay tuned, and read the whole article, entiled "Untangling Biosimilars".

Download Untangling Biosimilars

'Biosimilar' drugs poised to penetrate market
Draft regulations will pave the way for copycat antibodies and other large molecules.
Heidi Ledford
When is a copy good enough to be treated as the real thing? In recent days, regulators on both sides of the Atlantic have been grappling with the question as they try to develop guidelines that will expand the development of 'biosimilar' drugs: copycat versions of complex biological drugs, such as antibodies and other therapeutic proteins.

Biosimilars differ from generic drugs because their active ingredients are huge molecules with intricate structures. Such molecules are nearly impossible to replicate in every detail — even in the hands of the original manufacturer, minute variations in production yield slight differences. Unlike the relatively simple construction of a small-molecule drug, making a biosimilar is more like placing a complicated family recipe in the hands of a new chef. The overall result may be roughly the same, but it is not exactly how mother used to make it — and it may not precisely match the safety and therapeutic effects of the original.

Biosimilar medicines already have a toehold in Europe, but last week regulators there at the European Medicines Agency (EMA) hammered out draft guidelines that could drastically expand the market for these compounds. And in Washington DC, the US Food and Drug Administration (FDA), which in March received the authority to approve biosimilars as part of President Barack Obama's health-care reforms, is holding a public meeting this week to gather opinions on how it should evaluate such drugs. The new health-care act defines biosimilars as 'highly similar' to the original product; the FDA must now decide what that means, and how much extra testing will be required of a biosimilar before it can be marketed.

"This legislation was anticipated for so many years," says Deborah Shelton, a partner at the law firm Sheppard Mullin Richter & Hampton in Washington DC. "Now it's here and we're still in a black hole."

Meanwhile, some companies see biosimilars as a low-risk way to bolster dwindling drug pipelines. Biological drugs are expensive, and even with a 20–30% reduction in the original price, biosimilars can still pull in a huge profit. "Not a day goes by when you don't read a press release saying some company is getting into biosimilars," says Michael Malecki, head of the biosimilars group at Decision Resources, a market-research firm based in Burlington, Massachusetts. But if regulators require extensive testing, biosimilars could falter. For example, in 2006, the Croatian drug maker Pliva decided to abandon its copy of the best-selling anaemia drug erythropoietin after learning that the EMA would require more clinical trials than the company had anticipated.
Europe's framework for approving biosimilars was established in 2004, and copies of three drugs have already hit the European market. Some observers expect the FDA guidelines to be broadly similar to the European ones, which generally require clinical tests of biosimilars, but the extent and nature of the tests depends on the class of drugs being copied. A relatively simple and familiar molecule such as insulin, for example, may require less testing than a complex protein carrying several chemical modifications.

Yet biosimilars have had a slow start in Europe, says Huub Schellekens, who studies pharmaceutical development at Utrecht University in the Netherlands. The three drugs copied in Europe — human growth hormone, erythropoietin and granulocyte colony-stimulating factor, another treatment for anaemia — were selected because they command a huge market, their patents had expired, and they are relatively simple to make. But these drugs were already embroiled in a price war with second-generation longer-acting versions. Furthermore, the inability to tap the US drug market may ultimately have stifled industry enthusiasm. North America accounted for 39.8% of world pharmaceutical sales in 2009 compared with 30.6% for Europe.

At a meeting on 27–28 October in London, regulators at the EMA worked to finalize draft recommendations for biosimilar versions of the biggest moneymakers of the biological world: highly specific antibodies called monoclonal antibodies. In 2009, monoclonal antibodies brought in US$36.4 billion in sales worldwide. "These are blockbusters," says Falk Ehmann, the scientific secretariat for the Working Party for Biosimilar Medicinal Products at the EMA. "They are the hot molecules." The prospect of copying them — and selling the copies on the lucrative US market — could finally animate European biosimilars efforts, says Schellekens. The guidelines will be presented to the EMA's Committee for Medicinal Products for Human Use next week and, if accepted, will then be posted for public comment.

The first biosimilar monoclonal antibody is likely to be a copy of the cancer drug rituximab. Initially developed by Biogen Idec in Cambridge, Massachusetts, rituximab is expected to be one of the first monoclonal antibody therapies to go off patent, which Malecki says it may do in Europe as early as 2013. It is also one of the best-sellers: in 2009 the drug earned about $5.61 billion worldwide (see Table 1). In May, the Israeli generics maker Teva Pharmaceuticals announced that its biosimilar version of rituximab is ready for clinical trials, which are now expected to conclude in August 2011.

All biosimilars will probably require some clinical trials in the United States, says Mark McCamish, head of global biopharmaceutical development at Sandoz, a generics company based in Holzkirchen, Germany, but the FDA should expect a lively debate about how extensive those clinical trials must be.

On one side of this debate will be companies such as Denmark's Novo Nordisk, which derives at least 90% of its income from biologics and has no biosimilar programme. Jim Shehan, the company's general counsel for North America, urges stringent clinical trials that pit a biosimilar head-to-head with the product it aims to replaceMeanwhile, McCamish and others with a vested interest in marketing biosimilars — Sandoz already sells three in Europe and is developing about a dozen more — will argue that the FDA should use the variation in the original drug as a guide. Biologics are so complex that minor manufacturing changes often change the properties of the drug.

"There's going to be a range of how much a biosimilar company would have to do," says McCamish. "If the biosimilar falls within the goalposts of the originator's own changes, then you should have very abbreviated clinical testing."