I 
109TH CONGRESS 
2D SESSION 
H. R. 6257 
To amend the Public Health Service Act to provide for the licensing of 
comparable biological products, and for other purposes. 
IN THE HOUSE OF REPRESENTATIVES 
SEPTEMBER 29, 2006 
Mr. WAXMAN (for himself and Mr. BROWN of Ohio) introduced the following 
bill; which was referred to the Committee on Energy and Commerce, and 
in addition to the Committees on the Judiciary and Ways and Means, 
for a period to be subsequently determined by the Speaker, in each case 
for consideration of such provisions as fall within the jurisdiction of the 
committee concerned 
A BILL 
To amend the Public Health Service Act to provide for 
the licensing of comparable biological products, and for 
other purposes. 
Be it enacted by the Senate and House of Representa-
tives of the United States of America in Congress assembled, 
SECTION 1. SHORT TITLE. 
This Act may be cited as the ‘‘Access to Life-Saving 
Medicine Act’’. 
SEC. 2. DEFINITIONS. 
Section 351(i) of the Public Health Service Act (42 
U.S.C. 262(i)) is amended— 
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(1) by striking ‘‘In this section, the term ‘bio-
logical product’ means’’ and inserting the following: 
‘‘In this section: 
‘‘(1) The term ‘biological product’ means’’; and 
(2) by adding at the end the following: 
‘‘(2) The term ‘comparable biological product 
application’ means an abbreviated application for a 
license of a biological product containing the same, 
or similar, active ingredient as a biological product 
for which a license has been approved under sub-
section (a). A comparable biologic application is a 
human drug application under section 735(1)(C) of 
the Federal Food, Drug, and Cosmetic Act. 
‘‘(3) The term ‘reference product’ under this 
Act means the single licensed biological product, ap-
proved under subsection (a) or subsection (k), 
against which a comparable biological product is 
evaluated for demonstration of safety, potency, or 
purity. 
‘‘(4) The term ‘comparable’ in reference to a 
comparable biological product application means the 
absence of clinically meaningful differences between 
the comparable biological product and the reference 
product in terms of the safety, purity, and potency 
of the product based upon— 
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‘‘(A) data derived from chemical, physical, 
and biological assays, other non-clinical labora-
tory studies; and 
‘‘(B) data from any necessary clinical 
study or studies sufficient to confirm safety, 
purity, and potency in one or more appropriate 
conditions of use for which the reference prod-
uct is licensed and intended to be used. 
Any studies under subparagraph (B) shall be de-
signed to avoid duplicative and unethical clinical 
testing. 
‘‘(5) The term ‘thorough characterization’ 
means an analysis of structural features based upon 
appropriate analytical and functional testing suffi-
cient to identify differences between a new and ref-
erence biological product relevant to safety, purity or 
potency. 
‘‘(6) The term ‘interchangeable’ means that a 
biological product contains an active ingredient or 
ingredients with principal molecular structural fea-
tures comparable to the reference product, and that 
the comparable biological product can be expected to 
produce the same clinical result as the reference 
product in any given patient in the condition or con-
ditions of use for which both products are labeled. 
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‘‘(7) The term ‘process for the review of a com-
parable biological product application’ means, with 
respect to a comparable biological product applica-
tion, the procedural activities of the Secretary with 
respect to the review of human drug applications 
and supplements as defined in section 735(6) of the 
Federal Food, Drug, and Cosmetic Act, except as 
otherwise defined herein. 
‘‘(8) The term ‘final action’ means, with respect 
to a comparable biological product application, the 
Secretary’s issuance on the final action date of a 
final action letter to the sponsor of a comparable bi-
ological product application under this Act which— 
‘‘(A) approves the application, or 
‘‘(B) disapproves the application and sets 
forth in detail an enumeration of the specific 
deficiencies in the particular application and of 
the specific, enumerated actions the sponsor 
would be required to take in order for the spon-
sor to receive a final action letter that approves 
such application. 
‘‘(9) The term ‘final action date’ means, with 
respect to an abbreviated comparable biological 
product application, the date that is eight calendar 
months following the sponsor’s submission of such 
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application, or 180 days following the Secretary’s 
notification of the sponsor that its application has 
been accepted for filing, whichever is earlier, except 
that the final action date hereunder may be ex-
tended for such period of time as is agreed to by the 
Secretary and the sponsor of such application in a 
jointly executed written agreement that is counter- 
signed by the Secretary and the sponsor of such ap-
plication no later than 30 days prior to the final ac-
tion date provided for by this subsection. 
‘‘(10) The term ‘reviewing division’ means the 
division responsible for the review of an application 
for approval of a biological product (including all sci-
entific and medical matters, chemistry, manufac-
turing, and controls).’’. 
SEC. 3. REGULATION OF CERTAIN BIOLOGICAL PRODUCTS. 
(a) IN GENERAL.—Section 351 of the Public Health 
Service Act (42 U.S.C. 262) is amended— 
(1) in subsection (a)(1)(A), by inserting after 
‘‘biologics license’’ the following: ‘‘, or comparable 
biologics license,’’; and 
(2) by adding at the end the following sub-
section: 
‘‘(k) REGULATION
OF COMPARABLE BIOLOGICAL 
PRODUCTS.— 
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‘‘(1) SUBMISSION OF A COMPARABLE BIOLOGI-
CAL PRODUCT APPLICATION.—Any person may file 
with the Secretary an abbreviated comparable bio-
logical product application that includes the fol-
lowing: 
‘‘(A) Data demonstrating that the com-
parable biological product is comparable to the 
reference product. 
‘‘(B) Data demonstrating that the com-
parable biological product and reference product 
contain comparable principal molecular struc-
tural features as demonstrated by thorough 
characterization of the two products, notwith-
standing minor differences in heterogeneity pro-
file, impurities, or degradation patterns. The 
Secretary shall find the following types of prod-
ucts to contain comparable principal molecular 
structural features: 
‘‘(i) Two protein biological products 
with differences in structure between them 
solely due to post-translational events, infi-
delity of translation or transcription, or 
minor differences in amino acid sequence. 
‘‘(ii) Two polysaccharide biological 
products with similar saccharide repeating 
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units, even if the number of units differ 
and even if there are differences in post- 
polymerization modifications. 
‘‘(iii) Two glycosylated protein prod-
ucts with differences in structure between 
them 
solely 
due 
to 
post-translational 
events, infidelity of translation or tran-
scription, or minor differences in amino 
acid sequence, and if they had similar sac-
charide repeating units, even if the number 
of units differ and even if there were dif-
ferences in post-polymerization. 
‘‘(iv) Two polynucleotide biological 
products with identical sequence of purine 
and pyrimidine bases (or their derivatives) 
bound to an identical sugar backbone (ri-
bose, deoxyribose, or modifications of these 
sugars). 
‘‘(v) Closely related, complex partly 
definable biological products with similar 
therapeutic intent, such as two live viral 
products for the same indication. 
The principal molecular structural features of 
two biological products not enumerated in the 
foregoing clauses may be demonstrated to be 
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comparable based upon such data and other in-
formation characterizing the two products as 
the Secretary determines to be necessary. 
‘‘(C) Data demonstrating that the com-
parable biological product and reference product 
utilize the same mechanism or mechanisms of 
action for the conditions of use prescribed, rec-
ommended, or suggested in the proposed label-
ing, but only to the extent the mechanism or 
mechanisms of action are known for the ref-
erence product. 
‘‘(D) Information to show that the condi-
tion or conditions of use prescribed, rec-
ommended, or suggested in the labeling pro-
posed for the comparable biological product 
have been previously approved for the reference 
product. 
‘‘(E) Information to show that the route of 
administration, the dosage form, and the 
strength of the comparable biological product 
are the same as those of the reference product. 
‘‘(F) Data demonstrating that the facility 
in which the comparable biological product is 
manufactured, processed, packed, or held meets 
standards designed to assure that the com-
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parable biological product continues to be safe, 
pure, and potent. 
‘‘(G) At the applicant’s option, publicly- 
available information regarding the Secretary’s 
previous determination that the reference prod-
uct is safe, pure, and potent. 
‘‘(H) Any additional data and information 
in support of the application, including publicly- 
available information with respect to the ref-
erence product or another biological product. 
‘‘(2) OTHER APPLICATIONS.—A person who has 
not conducted and does not have a right of reference 
to the studies in the application for a reference prod-
uct may submit an application under this section for 
a biologic product that differs from, or incorporates 
a change to, the reference product with respect to 
one or more characteristics described in subpara-
graphs (A) through (E) of paragraph (1), including 
a difference in safety, purity, or potency, so long as 
the application contains sufficient information to es-
tablish the safety, purity, and potency of the biologi-
cal product relative to the reference product for its 
proposed condition or conditions of use. 
‘‘(3) POSTMARKETING
STUDIES.—If the Sec-
retary has agreed with the sponsor of the reference 
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product that the sponsor shall conduct one or more 
postmarketing safety studies, the applicant may 
agree with the Secretary to conduct a similar post-
marketing safety study or studies upon a reasonable 
showing that such study or studies would provide 
relevant information not available from the studies 
on the reference product. The Secretary shall not, as 
a condition of approval, propose any additional post-
marketing studies. 
‘‘(4) FDA REVIEW OF COMPARABLE BIOLOGI-
CAL PRODUCT APPLICATIONS.— 
‘‘(A) GUIDANCE
REGARDING
REVIEW
OF 
APPLICATIONS.—The Secretary shall issue guid-
ance for the individuals who review applications 
submitted under paragraph (1) or (2), which 
shall relate to promptness in conducting the re-
view, technical excellence, lack of bias and con-
flict of interest, and knowledge of regulatory 
and scientific standards, and which shall apply 
equally to all individuals who review such appli-
cations. 
‘‘(B) MEETINGS WITH SPONSORS AND AP-
PLICANTS.—The Secretary shall meet with a 
sponsor of an investigation or an applicant for 
approval of a comparable biological product 
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under this subsection if the sponsor or appli-
cant makes a reasonable written request for a 
meeting for the purpose of reaching agreement 
on the design and size of studies needed for ap-
proval of such application. The sponsor or ap-
plicant shall provide information necessary for 
discussion and agreement on the design and 
size of such studies. Minutes of any such meet-
ing shall be prepared by the Secretary and 
made available to the sponsor or applicant. 
‘‘(C) AGREEMENTS.—Any agreement re-
garding the parameters of design and size of 
the studies of a biological product under this 
paragraph that is reached between the Sec-
retary and a sponsor or applicant shall be re-
duced to writing and made part of the adminis-
trative record by the Secretary. Such agreement 
shall not be changed after the testing begins, 
except— 
‘‘(i) with the written agreement of the 
sponsor or applicant; or 
‘‘(ii) pursuant to a decision, made in 
accordance with subparagraph (D) by the 
director of the reviewing division, that a 
substantial scientific issue essential to de-
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termining the safety, purity, and potency 
of the biological product has been identi-
fied after the testing has begun. 
‘‘(D) PROCEDURE
REGARDING
CERTAIN 
DECISIONS.—A decision under subparagraph 
(C)(ii) by the director shall be in writing and 
the Secretary shall provide to the sponsor or 
applicant an opportunity for a meeting at which 
the director and the sponsor or applicant will be 
present and at which the director will document 
the scientific issue involved. 
‘‘(E) EFFECT OF DECISIONS.—The written 
decisions of the reviewing division shall be bind-
ing upon, and may not directly or indirectly be 
changed by, the field or compliance office per-
sonnel unless such field or compliance office 
personnel demonstrate to the reviewing division 
why such decision should be modified. 
‘‘(F) DELAYS BY REVIEWING DIVISIONS.— 
No action by the reviewing division may be de-
layed because of the unavailability of informa-
tion from or action by field personnel unless the 
reviewing division determines that a delay is 
necessary to assure the marketing of a safe, 
pure, and potent biological product. 
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‘‘(5) APPROVAL OF COMPARABLE BIOLOGICAL 
PRODUCTS.—The Secretary shall review the informa-
tion submitted in the application and any other in-
formation available to the Secretary and shall issue, 
subject to paragraph (9), a comparable biological 
product license for all conditions of use of the ref-
erence product sharing the same mechanism of ac-
tion for which the applicant has demonstrated com-
parability for a single condition of use, or, if the 
mechanism of action is unknown, for the condition 
or conditions of use for which the data submitted es-
tablishes comparability, unless the Secretary finds 
and informs the applicant that— 
‘‘(A) information submitted in the applica-
tion or any other information available to the 
Secretary is insufficient to show that the com-
parable biological product and the reference 
product contain comparable principal molecular 
structural features as demonstrated by thor-
ough characterization of the two products; 
‘‘(B) information submitted in the applica-
tion or any other information available to the 
Secretary is insufficient to show that the com-
parable biological product is comparable to the 
reference product for the condition or condi-
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tions of use prescribed, recommended, or sug-
gested in the labeling proposed in the applica-
tion; 
‘‘(C) information submitted in the applica-
tion or any other information available to the 
Secretary is insufficient to show that the com-
parable biological product and reference product 
utilize the same mechanism or mechanisms of 
action for the conditions of use prescribed, rec-
ommended, or suggested in the labeling pro-
posed for the comparable biological product, un-
less the mechanism or mechanisms of action are 
not known for the reference product for such 
condition or conditions; 
‘‘(D) information submitted in the applica-
tion or any other information available to the 
Secretary is insufficient to show that the route 
of administration, the dosage form, and the 
strength of the comparable biological product 
are the same as those of the reference product; 
‘‘(E) information submitted in the applica-
tion or any other information available to the 
Secretary is insufficient to show that the condi-
tion or conditions of use prescribed, rec-
ommended, or suggested in the labeling pro-
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posed for the comparable biological product are 
limited to one or more of the same use or uses 
as have been previously approved for the ref-
erence product; 
‘‘(F) information submitted in the applica-
tion or any other information available to the 
Secretary shows (i) the inactive ingredients of 
the comparable biological product are unsafe for 
use under the conditions prescribed, rec-
ommended, or suggested in the labeling pro-
posed for the biological product, or (ii) the com-
position of the comparable biological product is 
unsafe under such conditions because of the 
type or quantity of inactive ingredients included 
or the manner in which the inactive ingredients 
are included; 
‘‘(G) information submitted in the applica-
tion or any other information available to the 
Secretary fails to demonstrate that the facility 
in which the comparable biological product is 
manufactured, processed, packed, or held meets 
standards designed to assure that the com-
parable biological product continues to be safe, 
pure, and potent; 
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‘‘(H) the Secretary has withdrawn or sus-
pended the license of the reference product, for 
safety or effectiveness reasons, or has published 
a notice of opportunity for hearing to withdraw 
such license for safety or effectiveness reasons, 
or the Secretary has determined that the ref-
erence product has been withdrawn from sale 
for safety or effectiveness reasons; or 
‘‘(I) the application contains an untrue 
statement of material fact; and 
provides the applicant with a detailed explanation 
for the decision. 
‘‘(6) OTHER APPROVAL PROVISIONS.—The Sec-
retary shall approve, under the provisions of para-
graph (5), an application for a license submitted 
under paragraph (2), except that the Secretary shall 
approve such an application that would otherwise be 
disapproved by reason of one or more of subpara-
graphs (A) through (E) of paragraph (5), if the ap-
plication and any other information available to the 
Secretary contains sufficient information to establish 
the safety, purity, and potency of the comparable bi-
ological product relative to the reference product for 
the proposed condition or conditions of use for such 
product. 
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‘‘(7) INTERCHANGEABILITY
DETERMINATIONS 
FOR COMPARABLE BIOLOGICAL PRODUCTS.—An ap-
plicant may request in an original application or 
supplement to an application that the Secretary 
make a determination as to the interchangeability of 
a comparable biological product and the reference 
product. An applicant may withdraw a request for a 
determination at any time. A request for an inter-
changeability determination submitted after the fil-
ing of an application shall be considered a major 
amendment to the application. In response to such 
a request, the Secretary shall, at such time as the 
application or supplement is approved, publish a 
therapeutic comparability evaluation code indicating 
either that the comparable biological product has 
been shown to be interchangeable with the reference 
product, or that interchangeability has not been es-
tablished. Nothing in this subsection shall be con-
strued to prohibit the Secretary from making a de-
termination of interchangeability at any time after 
approval. 
‘‘(8) INTERCHANGEABILITY
LABELING
FOR 
COMPARABLE BIOLOGICAL PRODUCTS.—Upon a de-
termination of interchangeability under paragraph 
(7), the label of the comparable biological product at 
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the time of licensure may include a statement, if re-
quested by the sponsor, that it is interchangeable 
with the biological reference product to which the 
sponsor of the comparable biological product applica-
tion has demonstrated comparability to the reference 
product for the conditions of use prescribed, rec-
ommended, or suggested in the labeling proposed for 
the comparable biological product. 
‘‘(9) EXCLUSIVITY.— 
‘‘(A) IN GENERAL.—Notwithstanding any 
other provision of law, the Secretary shall not 
approve a second or subsequent comparable bio-
logical product application, and no holder of a 
biologic product license approved under sub-
section (a) shall manufacture, market, sell, or 
distribute a rebranded interchangeable biologic, 
directly or indirectly, or authorize any other 
person to manufacture, market, sell, or dis-
tribute a rebranded interchangeable biologic 
that is interchangeable with the reference prod-
uct, until the earlier of— 
‘‘(i) 180 days after the first commer-
cial marketing of the first interchangeable 
comparable biological product to be ap-
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proved as interchangeable for that same 
reference product; 
‘‘(ii) one year after— 
‘‘(I) a final court decision on all 
patents in suit in an action instituted 
under paragraph (16)(C) against the 
applicant that submitted the applica-
tion for the first approved inter-
changeable 
comparable 
biological 
product; or 
‘‘(II) the dismissal with or with-
out prejudice of an action instituted 
under paragraph (16)(C) against the 
applicant that submitted the applica-
tion for the first approved inter-
changeable 
comparable 
biological 
product; or 
‘‘(iii)(I) 36 months after approval of 
the first interchangeable comparable bio-
logical product if the applicant has been 
sued under paragraph (16)(C) and such 
litigation is still ongoing within such 36- 
month period; or 
‘‘(II) one year after approval in the 
event that the first approved interchange-
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