The Center for Drug Evaluation ("the CDE") of the
China Food and Drug Administration ("CFDA") recently
published a long-awaited guidance document for companies seeking to
develop biosimilars. This document, titled Draft Technical
Guideline for the Research, Development and Evaluation of
Biosimilars ("the Draft Guideline"), is open for
public comment through November 29, 2014. The Chinese news media
has reported that the CFDA had been drafting this guideline since
2012. This first-ever biosimilars guideline issued by the CDE sets
forth requirements for research, development and evaluation of
biosimilars, covering such areas as pharmacological assessment,
preclinical studies, and clinical studies of biosimilars.
Under the Draft Guideline, a biosimilar is defined as a
therapeutic biologic that is similar to an approved innovator
biologic in quality, safety and efficacy, and that has the same
amino acid sequence. Notably, the reference product (including
active ingredients used for production or extracted from finished
products) to which a biosimilar product is compared must be
approved in China. Approved biosimilars cannot themselves act as
reference products. The Draft Guideline generally applies to
therapeutic recombinant proteins with structures and functions that
are distinct enough to permit comparison of the biosimilar and
The Draft Guideline further sets forth the following basic
principles for the technical review of biosimilars: (i) the
comparison principle: comparative safety, effectiveness and quality
data will be necessary to support the similarity to the reference
product; (ii) the stepwise approach principle: biosimilarity must
be demonstrated in a stepwise approach to justify exemption or
simplification of a comprehensive comparative study; (iii) the
consistency principle: consistency is required for samples used in
and methodology applied to a comparative study; and (iv) the
biosimilarity evaluation principle: biosimilarity will be evaluated
based on comparison of pharmacology, pre-clinical and clinical
Biosimilarity is proven through (a) analytical studies that
demonstrate similarity in features such as physical and chemical
properties, bioactivity, and purity as compared to the reference
product, (b) animal studies, including PK/PD
(pharmacokinetic/pharmacodynamic) studies and toxicological
assessment, and (c) clinical studies in human subjects.
Under certain circumstances, extrapolation to approved
indications of the innovator reference product may be possible even
where the biosimilar has not been tested for that particular
indication. Extrapolated indications and the indications under
development must address identical disease mechanisms or receptors
and have the same mechanism of action for both the biosimilar and
reference products. The safety and immunogenicity of the biosimilar
product for extrapolated indications must also be sufficiently
assessed during research and development.
Currently, all biologics in China are subject to the new drug
approval pathway. The time for approval of new drug applications
can be as long as 5-6 years. The CDE's issuance of the Draft
Guideline suggests that the CFDA may be considering creating a
separate pathway for biosimilars in the Drug Registration Rules and
the Drug Administration Law.
The content of this article is intended to provide a general
guide to the subject matter. Specialist advice should be sought
about your specific circumstances.
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