Anticipated US biosimilar legislation
• strength;
• bioavailability (ie, it must be bioequivalent); and
In order to fully understand the current debate over biosimilar
• labelling.
legislation in the US, it is helpful to take a brief look back at the
history of drug regulation in that market.
Patent certifi cations Under Waxman-Hatch
The Public Health Service Act
In addition to showing “sameness,” the sponsor of an ANDA
must submit one of the following four certifi cations with regard
Biological products have been regulated in the US for more than
to each patent listed in the FDA’s “Approved Drug Products with
100 years. At the turn of the last century, after more than 20
Therapeutic Equivalence Evaluations” (commonly known as the
children died in two separate incidents involving contaminated
“Orange Book”) for the reference listed drug:
vaccines, the US Congress passed the Biologics Control Act of
1902. This was the fi rst major pharmaceutical legislation in the US. I. that no patents have been submitted;
This law was enacted to ensure the purity and safety of serums, II. that the patent has expired;
vaccines and similar products. Under the Biologics Control Act, III. that the patent will expire on a specifi ed date; or
biologics approvals encompassed not only the product itself, IV. that the patent is invalid or will not be infringed by the
but also the facility where the product was manufactured. This manufacture, use or sale of the product for which the ANDA
was in recognition of the particularly signifi cant impact that the is submitted.
manufacturing process can have on biologics’ safety, purity and
If a certifi cation is made under paragraph I or II, the FDA is
potency. The Biologics Control Act was recodifi ed in 1944 as section
authorised to approve the ANDA application whenever all of the
351 of the Public Health Service Act (PHSA), which continues to
other requirements for approval have been met. If the sponsor
govern biologics licensing to this day.
makes a paragraph III certifi cation, the FDA will make approval of
The Federal Food, Drug, and Cosmetic Act
the ANDA effective on the date the patent expires. Paragraph IV
certifi cations, by contrast, trigger a number of additional statutory
In 1938, Congress passed the Federal Food, Drug, and Cosmetic
requirements that provide a framework for the resolution of any
Act (FDCA). Under this law, pharmaceutical companies had to prove
patent disputes between the innovator and the generic applicant.
that all new drugs were safe before marketing. The FDCA also
required that companies submit NDAs for unapproved new drugs.
Waxman-Hatch exclusivity
Under the 1938 Act, no “new drug” could lawfully be introduced
Waxman-Hatch also created several exclusivity periods for which
into interstate commerce unless, and until, an NDA for that product
30 innovative and generic drugs may be eligible. Market or data
had been fi led with the FDA and become effective. If the FDA did
exclusivity is a statutory mechanism under the FDCA that delays the
not refuse approval of the NDA within 60 days, it was automatically
approval or bars the acceptance of certain types of applications for
deemed effective. Importantly, the NDA provisions of the 1938 Act
set periods of time.
only applied to small-molecule drugs. Those approval provisions
did not apply to vaccines and other biological products, which
Perhaps most signifi cantly, after a product is approved under an
continued to be licensed under the Biologics Control Act.
NDA, it may be eligible for new chemical entity (NCE) exclusivity.
Under the FDCA, a drug that has not been previously approved
The Drug Price Competition and Patent Term Restoration Act
(including any ester or salt of the active ingredient) may receive
In September 1984, the new drug provisions of the FDCA fi ve years of exclusivity. The effect of this exclusivity period is that
were amended by the Drug Price Competition and Patent Term no ANDA that contains the same active moiety as the approved
Restoration Act of 1984, (the “Waxman-Hatch Amendments” drug and that includes a paragraph I, II or III certifi cation may be
or “Waxman-Hatch”). It is commonly recognised that Waxman- submitted with FDA until the expiration of fi ve years after the date
Hatch represented a compromise by which Congress sought to that the innovator NDA was approved.
balance the consumers’ need for lower priced drug products with
ANDAs that include a paragraph IV certifi cation may be fi led four
the innovator industry’s need to receive a suffi cient return on its
years after the NDA approval. However, if the NDA sponsor initiates
investment to develop new products and improve existing products.
patent infringement litigation within 45 days of receiving notice of
Under Waxman-Hatch, the FDA is authorised to approve generic the paragraph IV certifi cation from the generic company, the FDA
products, without requiring original safety and effectiveness data, may not approve the ANDA for 30 months from the notifi cation
if the generic is shown under an abbreviated new drug application date (a provision known as the “30-month stay”).
(ANDA) to be “the same as” the pioneer. Generally, a proposed
However, if the innovator initiates infringement litigation before
generic drug must be the same as the pioneer reference drug with
the end of its fi ve-year exclusivity period, the FDA may not
respect to:
approve the ANDA sooner than seven and a half years from the
• active ingredient(s); date the NDA was approved (fi ve years of NCE exclusivity plus the
• dosage form; additional 30 months). The FDA may approve an ANDA application
• route of administration; earlier, however, if before expiration of the 30-month stay, the
Scrip World Pharmaceutical News Supplement August 2009
cphi.com | icsexpo.com | p-mec.com | bioph-online.com
wherepharmameets.com | scripnews.com
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