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Omnitrope (somatropin [rDNA origin])
Questions and Answers
What is Omnitrope?
Omnitrope (somatropin [rDNA origin]), is a recombinant human growth hormone
product indicated for long-term treatment of pediatric patients who have growth
failure due to an inadequate secretion of endogenous growth hormone, and for
long-term replacement therapy in adults with GHD of either childhood- or adult
onset.
Is Omnitrope a generic biologic?
No. Omnitrope is not rated as therapeutically equivalent to (and therefore
substitutable for) any of the other approved human growth hormone products.
Omnitrope is more appropriately characterized as a "follow-on protein product."
What is a follow-on protein product?
The
term follow-on protein products generally refers to protein and
peptide products that are intended to be sufficiently similar to a product
already approved or licensed to permit the applicant to rely for approval on
certain existing scientific knowledge about the safety and effectiveness of the
approved protein product. Follow-on protein products may be produced
through biotechnology or derived from natural sources.
Is this FDA's first approval of a follow-on protein product?
No. FDA has approved other follow-on protein products under section 505
of the Food, Drug, and Cosmetic Act. These include GlucaGen (glucagon
recombinant for injection), Hylenex (hyaluronidase recombinant human), Hydase
and Amphadase (hyaluronidase), and Fortical (calcitonin salmon recombinant)
Nasal Spray.
Does today’s approval of Omnitrope create a new pathway for follow-on
versions of all protein products?
No. The approval of Omnitrope in a 505(b)(2) application does not
establish a pathway for approval of follow-on products for biological products
licensed under section 351 of the Public Heath Service Act, nor does it mean
that more complex and/or less well understood proteins approved as drugs under
the Food, Drug, and Cosmetic Act could be approved as follow-on products.
The majority of protein products are licensed as biological products under
the Public Health Service Act, not approved as drugs under the Food, Drug, and
Cosmetic Act. There is no abbreviated approval pathway analogous to 505(b)(2)
or 505(j) of the Act for protein products licensed under section 351 of the
Public Health Service Act. Such a pathway for the approval or licensure of
follow-on protein products under the Public Health Service Act would require new
legislation.
Why could FDA approve Omnitrope as a follow-on product?
Among other things, human growth hormone (hGH) has several characteristics
that enable one rhGH product to be adequately compared to another for purposes
of approval under section 505(b)(2) of the Act. For example:
- hGH is well characterized and non-glycosylated (in other
words, sugar molecules are not added to the protein, which would
increase the complexity of a protein and make it more difficult to
compare the structures from one version of the protein to another
using standard tools such as mass spectrometry)
- The primary structure of hGH is known, and physicochemical
tests exist for the determination of an hGH product’s secondary
and tertiary structures (how the protein folds upon itself)
- Clinically relevant bioassays and qualified biomarkers are
available for hGH
- hGH has a long and well documented history of clinical use as
a replacement for endogenous growth hormone deficiency
- hGH’s mechanism of drug action is known, and its human
toxicity profile is well understood
Has FDA's authority to approve follow-on protein products been
questioned?
We have received citizen petitions raising regulatory, legal, and scientific
issues associated with these approvals and requesting that the Agency use a
public process to obtain input from industry. We have used a public process to
gather additional information. This process consisted of convening two public
meetings (September 2004 and February 2005) and establishing a related public
docket for the submission of written comments (docket # 2004N-0355)
In conjunction with today's approval, we are issuing a response to the
questions raised in the citizen petitions and in the public process that apply
to the approval of this recombinant human growth hormone product.
Approval of Omnitrope does not involve the regulatory and legal questions
that may be associated with approval of follow-on products licensed under the
Public Health Service Act. It also does not raise the scientific issues,
of the type identified during the public meetings and in the public comments,
that are associated with protein products that have unknown or multiple active
ingredients (rhGH products have one known active ingredient, somatropin);
protein products that have an unknown mechanism of action (rhGH’s mechanism of
action related to hGH's efficacy for pediatric and adult GHD is well
understood); protein products that are difficult to characterize (currently
available technologies allow rhGH to be extensively characterized); or protein
products that are glycosylated (rhGH is not glycosylated).
Why has it taken so long to take an action on Omnitrope?
Sandoz submitted its new drug application for Omnitrope in July 2003.
In August 2004, the FDA notified Sandoz in a letter that it had completed its
review of the Omnitrope application but was unable to reach a final decision
because of uncertainty about scientific and legal issues relating to follow-on
protein products raised in the citizen petitions and expected to be addressed
through a public process.
FDA has now completed its analysis of the issues pertaining to the Omnitrope
approval that were raised in the citizen petitions and in the public meetings
and docket. The Agency has also reviewed additional data submitted recently to
the Omnitrope NDA. FDA has determined that the Sandoz application provides
the evidence of safety and effectiveness necessary for approval under the Act.
Was there a court case involved with this application?
Yes, Sandoz, Inc. filed a lawsuit against the FDA in September 2005. On
April 10, 2006, a federal judge in Washington, D.C. ruled that the FDA must make
a decision on the Omnitrope application.
What is a 505(b)(2) application?
Section 505(b)(2) of the Food, Drug, and Cosmetic Act permits an applicant to
rely for approval of a drug on information from published scientific literature
or on the fact that the agency has already found a similar drug to be safe and
effective. A 505(b)(2) application, like an application under 505(j) for
approval of a generic drug, can only be approved when the applicable patent and
marketing exclusivity protections for the innovator drug have expired.
What is section 351 of the Public Health Service Act?
Biological products such as vaccines, blood products, allergenic products,
and certain other products such as monoclonal antibodies are licensed by FDA
under section 351 of the Public Health Service Act. There is no
abbreviated approval pathway similar to 505(b)(2) or 505(j) for products
licensed under the Public Health Service Act.
Does FDA believe it has the authority to develop an abbreviated
pathway for licensed biological products?
For products approved under section 505 of the Food, Drug, and Cosmetic Act,
we believe there is existing authority to allow applications for follow-on
protein products to be approved under section 505(b)(2) of the Act through a
process that relies on the earlier approval of the innovator product. In
contrast, there is no abbreviated approval pathway analogous to 505(b)(2) or
505(j) of the Act for protein products licensed under section 351 of the Public
Health Service Act.
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Date created: May 30, 2006 |
