FDA is working to develop guidelines for documenting the similarity and interchangeability of copycat versions of biotech
therapies, a process that is drawing considerable scrutiny from a broad spectrum of manufacturers. There are a host of thorny
issues to resolve related to reference products, interchangeability, labeling, and exclusivity. One area of agreement is that
producing biosimilars is vastly more complex and costly than manufacturing conventional generic drugs, and that FDA will require
broader testing to license a product as biosimilar or interchangeable. Developing a follow-on biotech therapy will require
considerable investment in time, resources, and expertise, running up a tab of some $75-$250 million and typically taking
seven to eight years, according to Ameet Mallik, global head of Novartis's Sandoz biopharmaceutical division, during an investor
call in May 2011.
Even so, the prospect of biopharmaceuticals capturing a greater share of the global drug market is drawing interest from many
pharmaceutical and biotech companies. The worldwide market for biosimilars is projected to grow to $3.7 billion by 2015, up
from about $250 million last year, according to Datamonitor. As more biotechnology product patents expire and regulatory authorities
clarify requirements, biosimilar development is projected to soar. Leading pharmaceutical companies, such as Novartis and
Merck, aim to be major players in the field, and even innovator biotech companies like Amgen are eyeing the follow-on market.
SETTING A PATHWAY
FDA officials are under pressure from Congress, government agencies, and payers to develop an abbreviated regulatory pathway
for approving biosimilars, as authorized by the Biologics Price Competition and Innovation Act (BPCI), which was approved
as part of the Affordable Care Act (ACA) of 2010. The legislation aims to reduce spending on prescription drugs by permitting
"highly similar" versions of biotech therapies to come to market based on less-extensive nonclinical and clinical data than
was required to approve the original reference drug. Manufacturers talk of marketing biosimilars at discounts of 25–30% off
branded products, but reimbursement experts say that prices that are just 10% lower will be able to gain market share, particularly
for therapies that have high price tags to start.
BPCI gives FDA the task of establishing a process that will encourage development of biosimilars that meet all standards for
product safety, purity, and potency. No "clinically meaningful differences" should exist between the new biologic and the
reference product. Both should use the same mechanism of action and have the same route of administration, dosage form, and
strength. A biosimilar also has to be manufactured, processed, packaged, and stored in facilities that meet GMP standards.
FDA began the formal guidance-development process for evaluating biosimilars at a November 2010 public meeting. Janet Woodcock,
director of the Center for Drug Evaluation and Research (CDER), recently indicated that general guidance should appear before
the end of 2011, and that requirements for human testing will vary according to how well a biosimilar can document similarity
to the innovator product.
FDA also is moving forward with a user-fee schedule for biosimilars. The agency proposes to set fees similar to those for
innovator drugs and biologics, but will take a new approach to help finance FDA's extensive involvement in steering sponsors
through the development process. The plan is for manufacturers to pay a product development fee of $150,000 with submission
of an investigational new drug application and annually thereafter; those upfront payments would be subtracted from the eventual
application fee. Performance goals for approving applications would apply to applications submitted within two years of the
expiration of exclusivity for the reference product, but not to applications for products that have years to wait before they
can enter the market.