The European Experience With

Follow-on Biologics Legislation

Federal Trade Commission Roundtable on

Follow-on Biologic Drugs: Framework for

Competition and Continued Innovation

Linda R. Horton, Partner

Hogan & Hartson LLP

Washington, DC

LRHorton@hhlaw.com

Washington, DC

November 21,2008

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The topics I have been asked to

address:

· European experience with the legislation

· European approach to exclusivity

· Exclusivity for new indications

· Exclusivity for product improvements and

second-generation products

· How interchangeability is handled

The views presented are mine, not those of Hogan & Hartson LLP or any

of our clients.

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Similarities and Differences: EU I U.S.

Relevant similarities

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• All biotech products, including biosimilars, go through centralized EMEA process

(national Member State agencies might approve non-biotech biosimilars if the

reference product was not one assessed by the EMEA)

• Rigorous review; much harmonization (ICH) and cooperation

• 20 years patent life; belief in strong IP system and in regulatory exclusivity

Relevant differences and a few cautionary notes

• Each of the 27 EU Member States has its own healthcare system and makes its

own decisions about reimbursement, pricing etc., and medicine substitutability

• In the EU, national differences persist in the patent system.

• No linkage, no Orange Book, no Paragraph IV, no 180-day generic exclusivity In

the EU: EU pharma regulators ignore patents and patent litigation

• Origin of EU 1O-year exclusivity was 1987 "EU Hatch Waxman" law; biosimilar

approval pathway came separately and much later (2004). In the U.S. we have the

benefit of studies that might more accurately predict timelines/cost for biologics

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"8+2+1"

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• 8 years data exclusivity dating from the European Commission authorization

decision: before that, no generic applications are fileable

• +2 years marketing protection: no generic applications approvable

• + 1 year: new indication(s) if it constitutes a significant clinical benefit

• For all products, regardless of centralized or Member State agency approval

procedure

• Not retroactive; does not affect exclusivity periods for products for which

applications were submitted before effective date (late 2005)

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Legal provisions on

improvements HOGAN &

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• All biotech biologicals, including biosimilars, go through the centralized EMEA route.

Therefore the exclusivity provision for centralized products is relevant.

• Art. 14.11 of the EMEA Regulation:

• Without prejudice to intellectual property law, medicinal products authorized under the

EMEA Regulation "shall benefit from an eight-year period of data protection and a

ten- year period of marketing protection, in which connection the latter period shall be

extended to a maximum of 11 years if, during the first 8 of the 10 years, the marketing

authorization holder obtains an authorization of one or more new therapeutic indications

which are held to bring a significant clinical benefit in comparison with existing therapies.

• It would appear that every medicinal product that enters the EU market via the EMEA

centralized procedure should receive a full 8+2+1 period. On the face of this provision, any

medicinal product authorized under the EMEA Regulation "shall" be eligible for 8+2+1.

Applicants wishing to market their own versions of biotech biologics already on the market

could, by submitting full applications, enjoy the benefits of Article 14.11.

This does not appear to be possible for applicants that use the biosimilar route.

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"Global marketing authorization" HOGAN &

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• There is debate as to whether a legal construct-"global marketing authorization"--

in the 2004 amendment to the Community Code on Medicinal Products (new

Article 6(1)) will apply to biosimilars authorized through the centralized EMEA

process.

• "When a medicinal product has been granted an initial marketing authorization ... ,

any additional strengths, pharmaceutical forms, administration routes,

presentations, as well as any variations and extensions shall also be granted an

authorization ... or be included in the initial marketing authorization. All these

marketing authorizations shall be considered as belonging to the same global

marketing authorization, in particular for the purpose of the application of Article

10(1 ).

• Note: European Commission guidance states that applications from different

marketing authorization holders are not treated as being under the same global

marketing authorization.

* Article 10(1) is the generics provision that includes the 8+2+1 provision. Article 6.1

was intended to codify case law that arose from generic applications under the

previous EU pharma laws (Generics case).

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"Global marketing authorization" HOGAN &

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• The term "a medicinal product" in the provision on "global marketing authorization"

is a key term.

• Changes that are treated as "line extensions" of the origination authorization (other

than the indication +1) do not entitle the marketing authorization holder to get a

new exclusivity period.

• However, where a 2nd generation product is a different product-e.g., a pegylated

version of an older biotech product-the EMEA has treated these products as

distinctive products and thus not the same "medicinal product." Therefore, the

concept of "global marketing authorization" should not stand in the way of a new

exclusivity period for the 2nd product.

• However, it should be noted that there is uncertainty on this point due to case law

interpreting the 1987 Directive (Novartis case).

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Guidance on 11 th year in 8+2+1

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• It is too soon for experience with this provision.

• However, the European Commission has issued guidance, Nov. 2007, applies to both

centrally authorized products and products authorized by Member States

• Guidance takes a broad view of significant benefit:

• New target disease, different stages or severity of disease, extended population for same

disease

• Change from 15t line to 2nd line treatment or vice versa or from combination therapy to

monotherapy

• Change from treatment to prevention or vice versa

• Change from short-term to maintenance treatment

• Improved safety, efficacy, contribution to patient care

• Applicant must justify 11 th year, address existing therapy

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Interchangeability - EMEA View

• "It is not possible we would guarantee a biosimilar is

interchangeable (with its originator). Substitution is a national

competency and needs to be discussed at the nationalleve/"

EMEA Executive Director Thomas L6nngren, 21 July 2006

• EMEA/74562/2006, 19 April 2007

"Since biosimilar and biological reference medicines are

similar but not identical, the decision to treat a patient with a

reference or a biosimilar medicine should be taken following

the opinion of a qualified healthcare professional."

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