DEPARTMENT OF HEALTH & HUMAN SERVICES

Food and Drug Administration

Rockville MD 20 857

The Honorable Nancy L . Johnson

House of Representatives
Washington, D . C . 20515-0705 MAY 1 1 200 6

Dear Ms . Johnson:

Thank you for the letter of January 19, 2005, co-signed by fifty-one of your colleagues, in
which you express your views about the Food and Drug Adiriinistration's (FDA or the
Agency) processing of the supplemental new drug application from Barr Laboratories (now
owned by Duramed Research, Inc .) that proposes to change the marketing status of the drug,
Plan B, from prescription only to over-the-counter (OTC) . We would like to take this
opportunity to clarify below the current status of the Agency's activities concerning this
application .

As you know, FDA is charged by Congress with reviewing new drug applications (NDA) to
determine a proposed new product's safety and effectiveness for the uses put forth by the
manufacturer in the application . As a science-based agency, it is FDA that must make that
final determination on whether an application for a product adequately demonstrates that the
data presented supports the proposed uses stated by the manufacturer in the proposed labeling .
A product cannot be approved until FDA determines that the product is safe and effective for
the indications stated in the proposed labeling .

Your letter referenced the 23-4 vote taken at the joint advisory committee meeting in
December 2003, recommending that Plan B be sold OTC . Advisory committee opinions are
advisory in nature and are not binding on the Agency . Since the final determination on any
NDA always is the responsibility of FDA, it is up to the Agency to clarify any unanswered -
questions that may remain after the close of an advisory committee meeting or that were
identified during the meeting, even though a vote may have been taken on the main
question(s) before the committee . The busy schedules of the committee members require that
advisory committee meetings be scheduled well in advance . We certainly value the input
from advisory committee members and the opportunity to hear an exchange of ideas on
proposed new products from experts in their respective scientific fields . It should not be
presumed, however, that a favorable vote by an advisory committee automatically means that
a product is ready to go to the pharmacy shelves .

In May of 2004, FDA completed its first review of the NDA to switch Plan B to OTC, and
concluded that the application could not be approved at that time because : 1) adequate data
were not provided to support a conclusion that young adolescent women can safely an d
effectively use Plan B for emergency contraception without the professional supe rvision of a
licensed practitioner, and 2) an amended proposal submi tt ed by the sponsor during the review
Page 2 - The Honorable Nancy L . Johnson

cycle to change the requested indication to allow for marketing of Plan B as a prescription
only product for women under 16 years of age an d a nonpresc ri ption product for women 16
years and older was incomplete and inadequate for a full review. This message wa s
conveyed to the sponsor by the then-Acting Director of FDA's Center for Drug Evaluation
an d Research (CDER) with a full explana ti on of the reasons behind FDA's decision in a Not
Approvable le tter dated May 6, 2004, (copy enclosed) an d available online at:
www .fda .gov/cder/drug/infopage/pZanB NALetter.pdf.

That decision by the Acting Director of CDER was made after full review of all the
underlying data and analysis and after discussions with all of the appropriate Agency
personnel . . This decision was based on his assessment that the data in the supplemental
application did not contain sufficient information about whether younger adolescent women
could understand the label and use the product safely and effectivelyfor emergency
contraception without the professional supervision of a licensed practitioner . Therefore, the
data in the application did not support approval of the supplement . In its Not Approvable
letter to the sponsor, FDA outlined some additional information that would be required for
approval to market Plan B as an OTC drug . The issuance of a Not Approvable letter did not
mean that a supplemental application could not or would not be approved in the future .

In July 2004, the drug's sponsor amended its supplemental application seeking to make
Plan B an OTC product for women age 16 and over, and to have it remain prescription only
for women under age 16 . The company also sought to market Plan B in a single package,
and sold either as prescription only or OTC, depending on the age of the purchaser .

In August 2005, FDA wrote a letter to the Duramed Research, Inc ., (copy enclosed and
available at : http ://www.fda .gov/cder/drug/infopage/p1anB/Plan B_Ietter20050826.pdJ)
-
stating that FDA had completed its review of the application and that the scientific data
supported the safe and effective use of Plan B as an OTC product for women ages 17 and
over . FDA also stated, however, that it was unable at that time to reach a final decision on
the approvability of the application due to unresolved issues that related to the application .

In the letter to the sponsor, FDA identified three difficult and novel issues presented by the
application, issues for which the Agency is committed to a process for resolving . That
process was initiated with the publication on September 1, 2005, of an Advance Notice of
Proposed Rulemaking (ANPRM) in the Federal Register seeking comment on questions
related to section 503(b) of the Federal Food, Drug, and Cosmetic (FD&C) Act (T'itle 21,"
United States Code section 353(b)) . The questions the interested parties were asked to
respond to concern when an active ingredient of a drug may be simultaneously marketed as
both a prescription and as an OTC drug product, whether and how OTC availability of a
product could be restricted to a particular subpopulation, and whether the same packaged
product could be sold either as prescription only or OTC, depending on the age of the
purchaser . A related concern is how, as a practical matter, an age-based distinction could be
enforced .

As the Agency has said many times during the course of the review of this application, the
questions that FDA was asked to answer, and the proposal that was put forward by the
Page 3 - The Honorable Nancy L . Johnso n

sponsor, presented the Agency with many very difficult and novel policy and regulatory
questions . In some cases, the questions requiring an FDA response were unp re cedented for
this Agency .

An ANPRM is a mechanism to ask for public comments on whether the Agency should
initiate a rulemaking to codify our interpretation of section 503(b) of the FD&C Act regarding
when an active ingredient can simultaneously be marketed in both a prescription drug product
and an OTC drug product for the same indication, strength, dosage form and route of
administration . Although the Agency typically solicits public comment for a minimum of 90
days when initiating this type of process, in the interest of moving quickly on this issue, the
comment period was shortened to 60 days for this ANPRM . The public comment period on
these questions closed as of November 1, 2005, and FDA is reviewing the comments and
letters it received . While we cannot put an exact timeline on how long it will take to process
these comments, we are committed to moving forward as quickly as possible .

Notwithstanding the outcome of the rulemaking process, there remain deficiencies in the
sponsor's application . For example, as set forth in the letter FDA sent to Duramed Research,
Inc., on August 26, 2005, while the application sought approval for the switch for ages 16 and
older, CDER found that the data supported only for ages 17 and older. Moreover, the
outcome of FDA's rulemaking process may impact the approvability of the proposed
packaging and the use of age as a criterion on which to base a distinction between OTC and
prescription use . Accordingly, Duramed may need to amend its supplemental application .
Please note, however, that as FDA's August 26 letter to Duramed describes, CDER has
completed its scientific review of their pending supplemental application .

The Agency has found that considerable misinformation has circulated about this application
and the reasons FDA has taken the actions it has to this point . So there will be no confusion
about the public statements FDA actually has made concern ing the Barr/Duramed Pl an
B/OTC application, in addition to the two le tt ers to the sponsor mentioned above, we are
enclosing copies of the two press releases dated May 7, 2004, and August 26, 2005, that the
Agency issued concern ing this application .

Thank you again for your interest in this matter . If we can be of further assistance, please let
us know . A similar response is being sent to each of the other co-signers of your letter.

Sincerely,

vid W . Boyer
Assistant Commissioner
for Legislation

4 Enclosures
 uancU_

DEPARTMENT OF HEALTH & HUMAN SERVICES

~r.,...o
Food and Drug Administration
Rockville MD 20857

The Honorable Steven R. Rothman

House of Representatives
MAY 1 1 200 6
Washington, D . C. 20515-300 9

Dear Mr . Rothman :

Thank you for the letter of January 19, 2005, co-signed by fifty-one of your colleagues, in
which you express your views about the Food and Drug Administration's (FDA or the-
Agency) processing of the supplemental new drug application from Barr Laboratories (now
owned by Duramed Research, Inc .) that proposes to change the marketing status of the drug,
Plan B, from prescription only to over-the-counter (OTC) . We would like to take this
opportunity to clarify below the current status of the Agency's activities concerning this
application .

As you know, FDA is charged by Congress with reviewing new drug applications (NDA) to
determine a proposed new product's safety and effectiveness for the uses put forth by the
manufacturer in the application . As a science-based agency, it is FDA that must make that
final determination on whether an application for a product adequately demonstrates that the
data presented supports the proposed uses stated by the manufacturer in the proposed labeling .
A product cannot be approved until FDA determines that the product is safe and effective for
the indications stated in the proposed labeling .

Your letter referenced the 23-4 vote taken at the joint advisory committee meeting in
December 2003, recommending that Plan B be sold OTC . Advisory comniittee opinions are
advisory in nature and are not binding on the Agency . Since the final determination on any
NDA always is the responsibility of FDA, it is up to the Agency to clarify any unanswered
questions that may remain after the close of an advisory committee meeting or that were
identified during the meeting, even though a vote may have been taken on the main
question(s) before the committee . The busy schedules of the committee members require that
advisory committee meetings be scheduled well in advance . We certainly value the input
from advisory committee members and the opportunity to hear an exchange of ideas on
proposed new products from experts in their respective scientific fields . It should not be
presumed, however, that a favorable vote by an advisory committee automatically means that
a product is ready to go to the pharmacy shelves .

In May of 2004, FDA completed its first review of the NDA to switch Plan B to OTC, and
concluded that the application could not be approved at that time because : 1) adequate data
were not provided to support a conclusion that young adolescent women can safely and
effectively use Plan B for emergency contraception without the professional supervision of a
licensed practitioner, and 2) an amended proposal submitted by the sponsor during the review
Page 2 - The Honorable Steven R . Rothman

cycle to ch ange the requested indication to allow for marketing of Plan B as a prescription
only product for women under 16 years of age an d a nonprescription product for women 16
years an d older was incomplete an d inadequate for a full review. This message was
conveyed to the sponsor by the then-Acting Director of FDA's Center for Drug Evaluation
and Research (CDER) with a full explan ation of the reasons behind FDA's decision in a Not
Approvable letter dated May 6, 2004,, (copy enclosed) and available online at :
www.fda .gov/cder/drug/infopage/p1anB_NALetter .pdf.

That decision by the Acting Director of CDER was made after full review of all the
underlying data an d analysis and after discussions with all of the appropri ate Agency
personnel . This decision was based on his assessment that the data in the supplemental
application did not contain su fficient information about whether younger adolescent women
could understan d the label an d use the product safely and effectively for emergency
contraception without the professional supervision of a licensed practitioner . Therefore, the
data in the application did not support approval of the supplement. In its Not Approvable
lett er to the sponsor, FDA outlined some additional informa ti on that would be required for
approval to market Plan B as an OTC drug . The issuance of a Not Approvable letter did not
mean that a supplemental applicati on could not or would not be approved in the future .

In July 2004, the drug's sponsor amended its supplemental application seeking to make
Plan B an OTC product for women age 16 and over, and to have it remain prescription only
for women under age 16 . The company also sought to market Plan B in a single package,
and sold either as prescription only or OTC, depending on the age of the purchaser .

In August 2005, FDA wrote a lett er to the Duramed Research, Inc ., (copy enclosed and
available at : http ://www.fda .gov/cder/drug/infopage/planB/Plan B Ietter20050826 .pdf)
stating that FDA had completed its review of the applicati on and that the scientific data
suppo rted the safe and effective use of Pl an B as an OTC product for women ages 17 and
over . FDA also stated, however, that it was unable at that time to reach a fi nal decision on
the approvability of the application due to unresolved issues that related to the application .

In the letter to the sponsor, FDA identified three difficult and novel issues presented by the
application, issues for which the Agency is committed to a process for resolving . That
process was initiated with the publication on September 1, 2005, of an Advance Notice of
Proposed Rulemaking (ANPRM) in the Federal Register seeking comment on questions
related to section 503(b) of the Federal Food, Drug, and Cosmetic (FD&C) Act (Title 21,
United States Code, section 353(b)) . The questions the interested parties were asked to
respond to concern when an active ingredient of a drug may be simultaneously marketed as
both a prescription and as an OTC drug product, whether and how OTC availability of a
product could be restricted to a particular subpopulation, and whether the same packaged
product could be sold either as prescription only or OTC, depending on the age of the
purchaser . A related concern is how, as a practical matter, an age-based distinction could be
enforced .

As the Agency has said many times during the course of the review of this application, the
questions that FDA was asked to answer, and the proposal that was put forward by the
Page 3 - The Honorable Steven R . Rothman

sponsor, presented the Agency with many very difficult and novel policy and regulatory
questions . In some cases, the questions requiring an FDA response were unprecedented for
this Agency .

An ANPRM is a mechanism to ask for public comments on whether the Agency_ should
initiate a rulemaking to codify our interpretation of section 503(b) of the FD&C Act regarding
when an active ingredient can simultaneously be marketed in both a prescription drug product
and an OTC drug product for the same indication, strength, dosage form and route of
administration . Although the Agency typically solicits public comment for a minimum of 9 0
days when initiating this type of process, in the interest of moving
. . quickly on this issue, the
comment period was shortened to 60 days for this ANPRM . ~The public commentperi od on
these questions closed as of November 1, 2005, and FDA is reviewing the comments and
letters it received . While we cannot put an exact timeline on how long it will take to process
these comments, we are committed to moving forward as quickly as possible .

Notwithstanding the outcome of the rulemaking process, there remain deficiencies in the
sponsor's application. For example, as set forth in the letter FDA sent to-DuraniedResearch,
Inc ., on August 26, 2005, while the application sought approval for the switch for ages 16 an d
older, CDER found that the data supported only for ages 17 and older . Moreover, the
outcome of FDA's rulemaking process may impact the approvability of the proposed
packaging and the use of age as a criterion on which to base a distinction between OTC and
prescription use . Accordingly, Duramed may need to amend its supplemental application .
Please note, however, that as FDA's August 26 letter to Duramed describes, CDER has
completed its scientific review of their pending supplemental application . "

The Agency has found that considerable misinformation has circulated about this applica ti on
an d the reasons FDA has taken the actions it has to this point. So there will be no confusion
about the public statements FDA actually has made concerning the Barr/Duramed Plan
B/OTC application, in addition to the two letters to the sponsor mentioned above, we are
enclosing copies of the two press releases dated May 7, 2004, and August 26, 2005, that the
Agency issued concern ing this application .

Thank you again for your interest in this matter . If we can be of further assistance, please let
us know . A similar response is being sent to each of the other co-signers of your letter .

Sincerely,

avid W . Boyei•
Assistant Commissioner
for Legislation

4 Enclosures
 i

* 6tII17C[f
(i'rs

~r
V
DEPARTMENT OF HEALTH & HUMAN SERVICE S

+tir~" Food and Drug Administration

Rockville MD 20857

The Honorable John W . Olver

House of Representatives
Washington, D . C . 20515-210 1 MAY 1 1 2006

Dear Mr. Olver :

Thank you for the letter of January 19, 2005, co-signed by fifty-one of your colleagues, in
which you express your views about the Food and Drug Administration's (FDA or the
Agency) processing of the supplemental new drug application from Barr Laboratories (now
owned by Duramed Research, Inc .) that proposes to change the marketing status of the drug,
Plan B, from prescription only to over-the-counter (OTC) . We would like to take this
opportunity to clarify below the current status of the Agency's activities concerning this
application .

As you know, FDA is charged by Congress with reviewing new drug applications (NDA) to
determine a proposed new product's safety and effectiveness for the uses put forth by the
manufacturer in the application . As a science-based agency, it is FDA that must make that
final determination on whether an application for a product adequately demonstrates that the
data presented supports the proposed uses stated by the manufacturer in the proposed labeling .
A product cannot be approved until FDA determines that the product is safe and effective for
the indications stated in the proposed labeling .

Your letter referenced the 23-4 vote taken at the joint advisory committee meeting in
December 2003, recommending that Plan B be sold OTC . Advisory committee opinions are
advisory in nature and are not binding on the Agency . Since the final determination on any
NDA always is the responsibility of FDA, it is up to the Agency to clarify any unanswered
questions that may remain after the close of an advisory committee meeting or that were
identified during the meeting, even though a vote may have been taken on the main
question(s) before the committee . The busy schedules of the committee members require that
advisory committee meetings be scheduled well in advance . We certainly value the input
from advisory committee members and the opportunity to hear an exchange of ideas on
proposed new products from experts in their respective scientific fields . It should not be
presumed, however, that a favorable vote by an advisory committee automatically means that
a product is ready to go to the pharmacy shelves .

In May of 2004, FDA completed its first review of the NDA to switch Plan B to OTC, and
concluded that the application could not be approved at that time because : 1) adequate data
were not provided to support a conclusion that young adolescent women c an safely and
effectively use Plan B for emergency contraception without the professional supervision of a
licensed practitioner, and 2) an amended proposal submitted by the sponsor du ri ng the review
i

Page 2 - The Honorable John W . Olver

cycle to change the requested indication to allow for marketing of Plan B as a prescription
only product for women under 16 years of age and a nonprescription product for women 16
years and older was incomplete and inadequate for a full review . This message was
conveyed to the sponsor by the then-Acting Director of FDA's Center for Drug Evaluation
and Research (CDER) with a full explanation of the reasons behind FDA's decision in a Not
Approvable letter dated May 6, 2004, (copy enclosed) and available online at :
www.fda.gov/cder/drug/infopage/plan8 NALetter.pdf.

That decision .by the Acting Director of CDER was made after full review of all the
underlying data and analysis and after discussions with all of the appropriate Agency
personnel . This decision was based on his assessment that the data in the supplemental
application did not contain sufficient information about whether younger adolescent women
could understand the label and use the product safely and effectively for emergency
contraception without the professional supervision of a licensed practitioner. Therefore, the
data in the application did not support approval of the supplement . In its Not Approvable
letter to the sponsor, FDA outlined some additional information that would be required for
approval to market Plan B as an OTC drug . The issuance of a Not Approvable letter did not
mean that a supplemental application could not or would not be approved in the future .

In July 2004, the drug's sponsor amended its supplemental application seeking to make
Plan B an OTC product for women age 16 and over, and to have it remain prescription only
for women under age 16 . The company also sought to market Plan B in a single package,
and sold either as prescription only or OTC, depending on the age of the purchaser .

In August 2005, FDA wrote a letter to the Duramed Research, Inc ., (copy enclosed and
available at : http ://www.fda.gov/cder/drug/infopage/p1anB/Plan B_Ietter20050826.pdJ)
stating that FDA had completed its review of the application and that the scientific data
supported the safe and effective use of Plan B as an OTC product for women ages 17 and
over . FDA also stated, however, that it was unable at that time to reach a final decision on
the approvability of the application due to unresolved issues that related to the application .

In the letter to the sponsor, FDA identified three difficult and novel issues presented by the
application, issues for which the Agency is committed to a process for resolving . That
process was initiated with the publication on September 1, 2005, of an Advance Notice of
Proposed Rulemaking (ANPRM) in the Federal Register seeking comment on questions
related to section 503(b) of the Federal Food, Drug, and Cosmetic (FD&C) Act (Title 21,
United States Code, section 353(b)) . The questions the interested parties were asked to
respond to concern when an active ingredient of a drug may be simultaneously marketed as
both a prescription and as an OTC drug product, whether and how OTC availability of a
product could be restricted to a particular subpopulation, and whether the same packaged
product could be sold either as prescription only or OTC, depending on the age of the
purchaser . A related concern is how, as a practical matter, an age-based distinction could be
enforced .

As the Agency has said many times during the course of the review of this application, the
questions that FDA was asked to answer, and the proposal that was put forward by the
Page 3 - The Honorable John W . Olver

sponsor, presented the Agency with many very difficult and novel policy an d regulato ry
questions . In some cases, the questions requi ri ng an FDA response were unprecedented for
this Agency .

An ANPRM is a mechanism to ask for public comments on whether the Agency should
initiate a rulemaking to codify our interpretation of section 503(b) of the FD&C Act regarding
when an active ingredient c an simultaneously be marketed in both a presc ription drug product
and an OTC drug product for the same indication, strength, dosage form and route of
administration. Although the Agency typically solicits public comment for a minimum of 90
days when initiati ng this type of process, in the interest of moving quickly on this issue, the
comment peri od w as short ened to 60 days for this ANPRM . The public comment pe ri od on
these questions closed as of November 1, 2005, and FDA is reviewing the comments an d
lett ers it received . While we cannot put an exact timeline on how long it will take to process
these comments, we are committed to moving forward as quickly as possible .

Notwithstanding the outcome of the rulemaking process, there remain deficiencies in the
sponsor's application . For example, as set forth in the letter FDA sent to Duramed Research,
Inc ., on August 26, 2005, while the application sought approval for the switch for ages 16 and
older, CDER found that the data supported only for ages 17 and older . Moreover, the
outcome of FDA's rulemaking process may impact the approvability of the proposed
packaging and the use of age as a criterion on which to base a distinction between OTC and
prescription use . Accordingly, Duramed may . need to amend its supplemental application .
Please note, however, that as FDA's August 26 letter to Duramed describes, CDER has
completed its scientific review of their pending supplemental application .

The Agency has found that considerable misinformation has circulated about this application
and the reasons FDA has taken the actions it has to this point . So there will be no confusion
about the public statements FDA actually has made concerning the Barr/Duramed Plan
B/OTC application, in addition to the two letters to the sponsor mentioned above, we are
enclosing copies of the two press releases dated May 7, 2004, and August 26, 2005, that the
Agency issued concerning this application .

Thank you again for your interest in this matter . If we can be of further assistance, please let
us know . A similar response is being sent to each of the other co-sign ers of your letter.

Sincerely ,

avid W . Boyer
Assistant Commissioner
for Legislation

4 Enclosures
 SIxwF+ .
~41

~a ~ DEPARTMENT OF HEALTH & HUMAN SERVICE S

N Food and Drug Administration

Rockville MD 2085 7

The Honorable Lloyd Doggett

house of Representatives
Washington, D . C . 20515-4325 M AY 1 1 200 6

Dear Mr. Doggett :

Thank you for the letter of January 19, 2005, co-signed by fifty-one of your colleagues, in
which you express your views about the Food and Drug Administration's (FDA or the
Agency) processing of the supplemental new drug application from Barr Laboratories (now
owned by Duramed Research, Inc .) that proposes to change the marketing status of the drug,
Plan B, from prescription only to over-the-counter (OTC) . We would like to take this
opportunity to clarify below the current status of the Agency's activities concerning this
application .

As you know, FDA is charged by Congress with reviewing new drug applications (NDA) to
determine a proposed new product's safety and effectiveness for the uses put forth by the
manufacturer in the application . As a science-based agency, it is FDA that must make that
final determination on whether an application for a product adequately demonstrates that the
data presented supports the proposed uses stated by the manufacturer in the proposed labeling-
A product cannot be approved until FDA determines that the product is safe and effective for
the indications stated in the proposed labeling .

Your letter referenced the 23-4 vote taken at the joint advisory committee meeting in
December 2003, recommending that Plan B be sold OTC . Advisory committee opinions are
advisory in nature and are not binding on the Agency . Since the final determination on any
NDA always is the responsibility of FDA, it is up to the Agency to clarify any unanswered
questions that may remain after the close of an advisory committee meeting or that were
identified during the meeting, even though a vote may have been taken on the main
question(s) before the committee . The busy schedules of the committee members require that
advisory committee meetings be scheduled well in advance . We certainly value the input
from advisory committee members and the opportunity to hear an exchange of ideas on
proposed new products from experts in their respective scientific fields . It should not be
presumed, however, that a favorable vote by an advisory committee automatically means that
a product is ready to go to the pharmacy shelves .

In May of 2004, FDA completed its fi rst review of the NDA to switch Pl an B to OTC, and
concluded that the application could not be approved at that time because : 1) adequate data
were not provided to support a conclusion that young adolescent women can safely and
effectively use Pl an B for emergency contraception without the professional supe rv ision of a
licensed practitioner, and 2) an amended proposal submitted by the sponsor during the review
Page 2 - The Honorable Lloyd Doggett

cycle to change the requested indication to allow for marketing of Plan B as a prescription
only product for women under 16 years of age and a nonprescription product for women 16
years and older was incomplete and inadequate for a full review . This message was
conveyed to the sponsor by the then-Acting Director of FDA's Center for Drug Evaluation
and Research (CDER) with a full explanation of the reasons behind FDA's decision in a No t
Approvable le tt er dated May 6, 2004, (copy enclosed) and available online at :
www. fda . gov/cder/drug/infopage/pl anB_NALetter .pdf.

That decision by the Acting Director of CDER was made after full review of all the
underlying data and analysis and after discussions with all of the appropriate Agency
personnel . This decision was based on his assessment that the data in the supplemental
application did not contain sufficient information about whether younger adolescent women
could understand the label and use the product safely and effectively for emergency
contraception without the professional supervision of a licensed practitioner . Therefore, the
data in the application did not support approval of the supplement. In its Not Approvable
letter to the sponsor, FDA outlined some additional information that would be required for
approval to market Plan B as an OTC drug . The issuance of a Not Approvable letter did not
mean that a supplemental application could not or would not be approved in the future .

In July 2004, the drug's sponsor amended its supplemental application seeking to make
Plan B an OTC product for women age 16 and over, and to have it remain prescription only
for women under age 16 . The company also sought to market Plan B in a single package,
and sold either as prescription only or OTC, depending on the age of the purchaser .

In August 2005, FDA wrote a letter to the Duramed Research, Inc ., (copy enclosed and
available at : http ://www .fda .gov/cder/drug/infopage/planB/Plan_B_letter200S0826 .pdf)
stating that FDA had completed its review of the application and that the scientific data
supported the safe and effective use of Plan B as an OTC product for women ages 17 and
over. FDA also stated, however, that it was unable at that time to reach a final decision on
the approvability of the application due to unresolved issues that related to the application .

In the letter to the sponsor, FDA identified three difficult and novel issues presented by the
application, issues for which the Agency is committed to a process for resolving . That
process was initiated with the publication on September 1, 2005, of an Advance Notice of
Proposed Rulemaking (ANPRM) in the Federal Register seeking comment on questions
related to section 503(b) of the Federal Food, Drug, and Cosmetic (FD&C) Act (Title 21,
United States Code , section 353(b)) . The questions the interested parties were asked to
respond to concern when an active ingredient of a drug may be simultaneously marketed as
both a prescription and as an OTC drug product, whether and how OTC availability of a
product could be restricted to a particular subpopulation, and whether the same packaged
product could be sold either as prescription only or OTC, depending on the age of the
purchaser . A related concern is how, as a practical matter, an age-based distinction could be
enforced .

As the Agency has said many times during the course of the review of this application, the
questions that FDA was asked to answer, and the proposal that was put forward by the
Page 3 - The Honorable Lloyd Dogget t

sponsor, presented the Agency with many very difficult and novel policy and regulato ry
questions . In some cases, the questions requiring an FDA response were unprecedented for
this Agency.

An ANPRM is a mechanism to ask for public comments on whether the Agency should
initiate a rulemaking to codify our interpretation of section 503(b) of the FD&C Act regarding
when an active ingredient can simultaneously be marketed in both a prescription drug product
and an OTC drug product for the same indication, strength, dosage form and route of
administration . Although the Agency typically solicits public comment for a minimum of 90
days when initiating this type of process, in the interest of moving quickly on this issue, the
comment period was shortened to 60 days for this ANPRM . The public comment period on
these questions closed as of November 1, 2005, and FDA is reviewing the comments and
letters it received . While we cannot put an exact timeline on how long it will take to process
these comments, we are committed to moving forward as quickly as possible . .

Notwithstanding the outcome of the rulemaking process, there remain deficiencies in the
sponsor's application. For example, as set forth in the letter FDA sent to Duramed Research,
Inc ., on August 26, 2005, while the application sought approval for the switch for ages 16 and
older, CDER found that the data supported only for ages 17 and older . Moreover, the
outcome of FDA's rulemaking process may impact the approvability of the proposed
packaging and the use of age as a criterion on which to base a distinction between OTC and
prescription use . Accordingly, Duramed may need to amend its supplemental application .
Please note, however, that as FDA's August 26 letter to Duramed describes, CDER has
completed its scientific review of their pending supplemental application .

The Agency has found that considerable misinformation has circulated about this application
and the reasons FDA has taken the actions it has to this point . So there will be no confusion
about the public statements FDA actually has made concerning the Barr/Duramed Plan
B/OTC application, in addition to the two letters to the sponsor mentioned above, we are
enclosing copies of the two press releases dated May 7, 2004, and August 26, 2005, that the
Agency issued concerning this application .

Thank you again for your interest in this matter . If we can be of further assistance, please let
us know. A similar response is being sent to each of the other co-signers of your letter.

Sincerely ,

Da*f'd W . Boyer
Assistant Commissioner
for Legislatio n

4 Enclosures
J+~ SlsVlces
.o

DEPARTMENT OF HEALTH & HUMAN SERVICES

.,a Food and Drug Admin~stration

Rockville MD 2085 7

The Honorable Howard L . Berman

House of Representatives MAY 1 1 2006
Washington, D . C . 20515-052 8

Dear Mr . Berman :

Thank you for the letter of January 19, 2005, co-signed by fifty-one of your colleagues, in
which you express your views about the Food and Drug Administration's (FDA or the
Agency) processing of the supplemental new drug application from Barr Laboratories (now
owned by Duramed Research, Inc .) that proposes to change the marketing status of the drug,
Plan B, from prescription only to over-the-counter (OTC) . We would like to take this
opportunity to clarify below the current status of the Agency's activities concerning this
application .

As you know, FDA is charged by Congress with reviewing new drug applications (NDA) to
determine a proposed new product's safety and effectiveness for the uses put forth by the
manufacturer in the application . As a science-based agency, it is FDA that must make that
final determination on whether an application for a product adequately demonstrates that the
data presented supports the proposed uses stated by the manufacturer in the proposed labeling .
A product cannot be approved until FDA determines that the product is safe and effective for
the indications stated in the proposed labeling .

Your letter referenced the 23-4 vote taken at the joint advisory committee meeting in
December 2003, recommending that Plan B be sold OTC . Advisory committee opinions are
advisory in nature and are not binding on the Agency . Since the final determination on any
NDA always is the responsibility of FDA, it is up to the Agency to clarify any unanswered
questions that may remain after the close of an advisory committee meeting or that were
identified during the meeting, even though a vote may have been taken on the main
question(s) before the committee. The busy schedules of the committee members require that
advisory committee meetings be scheduled well in advance . We certainly value the input
from advisory committee members and the opportunity to hear an exchange of ideas on
proposed new products from experts in their respective scientific fields . It should not be
presumed, however, that a favorable vote by an advisory committee automatically means that
a product is ready to go to the pharmacy shelves .

In May of 2004, FDA completed its first review of the NDA to switch Plan B to OTC, and
concluded that the application could not be approved at that time because : 1) adequate data
were not provided to support a conclusion that young adolescent women can safely and
effectively use Plan B for emergency contraception without the professional supervision of a
licensed practitioner, and 2) an amended proposal submitted by the sponsor during the review
Page 2 - The Honorable Howard L . Berman

cycle to chan ge the requested indication to allow for marketing of Pl an B as a presc ri ption
only product for women under 16 years of age an d a nonprescription product for women 16
years and older was incomplete an d inadequate for a full review . This message was
conveyed to the sponsor by the then-Acting Director of FDA's Center for Drug Evaluation
and Research (CDER) with a full expl an ation of the reasons behind FDA's decision in a Not
Approvable le tter dated May 6, 2004, (copy enclosed) and available online at :
www.fda .gov/cder/drug/infopage/p1anB NALetter .pdf.

That decision by the Acting Director of CDER was made after full review of all the
underlying data and an alysis and after discussions with all of the approp ri ate Agency
personnel . This decision was b as ed on his assessment that the data in the supplemental
application did not contain sufficient information about whether younger adolescent women
could understand the label an d use the product safely and effec tively for emergency
contraception without the professional supe rvision of a licensed practitioner. Therefore, the
data in the application did not support approval of the supplement . In its Not Approvable
lett er to the sponsor, FDA outlined some additional information .that would be required for
approval to market Pl an B as an OTC drug . The issuance of a Not App rovable le tter did not
mean that a supplemental application could not or would not be approved in the future .

In July 2004, the drug's sponsor amended its supplemental application seeking to make
Plan B an OTC product for women age 16 and over, and to have it remain prescription only
for women under age 16 . The company also sought to market Plan B in a single package,
and sold either as prescription only or OTC, depending on the age of the purchaser .

In August 2005, FDA wrote a letter to the Duramed Research, Inc ., (copy enclosed and
available at: http ://www.fda.gov/cder/drug/infopage/planB/Plan_B_Ietter20050826 .pd,f)
stating that FDA had completed its review of the application and that the scientific data
supported the safe and effective use of Plan B as an OTC product for women ages 17 and
over. FDA also stated, however, that it was unable at that time to reach a final decision on
the approvability of the application due to unresolved issues that related to the application .

In the letter to the sponsor, FDA identified three difficult and novel issues presented by the
application, issues for which the Agency is committed to a process for resolving . That
process was initiated with the publication on September 1, 2005, of an Advance Notice of
Proposed Rulemaking (ANPRM) in the Federal Register seeking comment on questions
related to section 503(b) of the Federal Food, Drug, and Cosmetic (FD&C) Act (Title 21,
United States Code , section 353(b)) . The questions the interested parties were asked to
respond to concern when an active ingredient of a drug may be simultaneously marketed as
both a prescription and as an OTC drug product, whether and how OTC availability of a
product could be restricted to a particular subpopulation, and whether the same packaged
product could be sold either as prescription only or OTC, depending on the age of the
purchaser . A related concern is how, as a practical matter, an age-based distinction could be
enforced.

As the Agency has said many times during the course of the review of this application, the
questions that FDA was asked to answer, and the proposal that was put forward by the
Page 3 - The Honorable Howard L . Berman

sponsor, presented the Agency with many very difficult and novel policy and regulatory
questions . In some cases, the questions requiring an FDA response were unprecedented for
this Agency.

An ANPRM is a mechanism to ask for public comments on whether the Agency should
initiate a rulemaking to codify our interpretation of section 503(b) of the FD&C Act regarding
when an active ingredient can simultaneously be marketed in both a prescription drug product
and an OTC drug product for the same indication, strength, dosage form and route of
administration . Although the Agency typically solicits public comment for a minimum of 9
e 0dayswhenitgsypeofrc,inthesofmvingqucklythse,
comment period was shortened to 60 days .for this ANPRM . The public comment period on
these questions closed as of November 1, 2005, and FDA is reviewing the comments and
letters it received . While we cannot put an exact timeline on how long it will take to process
these comments, we are committed to moving forward as quickly as possible .

Notwithstanding the outcome of the rulemaking process, there remain deficiencies in the
sponsor's application . For example, as set forth in the letter FDA sent to Duramed Research,
Inc., on August 26, 2005, while the application sought approval for the switch for ages 16 and
older, CDER found that the data supported only for ages 17 and older . Moreover, the
outcome of FDA's rulemaking process may impact the approvability of the proposed
packaging and the use of age as a criterion on which to base a distinction between OTC and
prescription use . Accordingly, Duramed may need to amend its supplemental application .
Please note, however, that as FDA's August 26 letter to Duramed describes, CDER has
completed its scientific review of their pending supplemental application .

The Agency has found that considerable misinformation has circulated about this application
and the reasons FDA has taken the actions it has to this point . So there will be no confusion
about the public statements FDA actually has made concerning the Barr/Duramed Plan
B/OTC application, in addition to the two letters to the sponsor mentioned above, we are
enclosing copies of the two press releases dated May 7, 2004, and August 26, 2005, that the
Agency issued concerning this application .

Thank you again for your interest in this matter . If we can be of further assistance, please let
us know . A similar response is being sent to each of the other co-signers of your letter.

Sincerely,

d W. Boyer
Assistant Commissioner
for Legislation

4 Enclosures
 , ►0 WhRs .
614

_ DEPARTMENT OF HEALTH & HUMAN SERVICES

s ^J ~
10 . : ., . . . ._ . ,,. .
~~t ►•.,a -
Food and Drug Administration
Rockville MD 20857

The Honorable Raul M . Grijalva

House of Representatives
Washington, D . C . 20515-030 7 MAY 1 1 2006

Dear Mr. Grijalva :

Thank you for the letter of January 19, 2005, co-signed by fifty-one of your colleagues, in
which you express your views about the Food and Drug Administration's (FDA or the
Agency) processing of the supplemental new drug application from Barr Laboratories (now
owned by Duramed Research, Inc .) that proposes to change the marketing status of the drug,
Plan B, from prescription only to over-the-counter (OTC) . We would like to take this
opportunity to clarify below the current status of the Agency's activities concerning this
application .

As you know, FDA is charged by Congress with reviewing new drug applications (NDA) to
determine a proposed new product's safety an d effectiveness for the uses put forth by the
m anufacturer in the application. As a science-based agency, it is FDA that must make that
final determination on whether an application for a product adequately demonstrates that the
data presented support s the proposed uses stated by the manufacturer in the proposed labeling .
A product cannot be approved until FDA determines that the product is safe and effective for
the indications stated in the proposed labeling .

Your letter referenced the 23-4 vote taken at the joint advisory committee meeting in
December 2003, recommending that Plan B be sold OTC . Advisory committee opinions are
advisory in nature and are not binding on the Agency . Since the final determination on any
NDA always is the responsibility of FDA, it is up to the Agency to clarify any unanswered
questions that may remain after the close of an advisory committee meeting or that were
identified during the meeting, even though a vote may have been taken on the main
question(s) before the committee . The busy schedules of the committee members require that
advisory committee meetings be scheduled well in advance . We certainly value the input
from advisory committee members and the opportunity to hear an exchange of ideas on
proposed new products from experts in their respective scientific fields : It should not be
presumed, however, that a favorable vote by an advisory committee automatically means that
a product is ready to go to the pharmacy shelves .

In May of 2004, FDA completed its first review of the NDA to switch Plan B to OTC, and
concluded that the application could not be approved at that time because : 1) adequate data
were not provided to support a conclusion that young adolescent women can safely and
effectively use Plan B for emergency contraception without the professional supervision of a
licensed practitioner, and 2) an amended proposal submitted by the sponsor during the review
Page 2 - The Honorable Raul M. Grijalva

cycle to change the requested . indication to allow for marketing of Plan B as a prescriptio n
only product for women under 16 years of age and a nonpresc ri ption product for women 16
years and older was incomplete and inadequate for a full review . This message was
conveyed to the sponsor by the then-Acting Director of FDA's Center for Drug Evaluation
and Research (CDER) with a full explanation of the reasons behind FDA's decision in a Not
Approvable lett er dated May 6, 2004, (copy enclosed) and available online at :
www .fda .gov/cder/drug/infopage/p1anB_NALetter .pdf.

That decision by the Acting Director of CDER was made after full review of all the
underlying data and analysis and after discussions with all of the appropriate Agenc y
personnel . This decision was based on his . assessment that the data in the supplemental
application did not contain sufficient information about whether younger adolescent women
could understand the label and use the product safely and effectively for emergency'
contraception without the professional supervision of a licensed practitioner . Therefore, the
data in the application did not support approval of the supplement . In its Not Approvable
-
letter to the sponsor, FDA outlined some additional information that would lie required for
approval to market Plan B as an OTC drug . The issuance of a Not Approvable letter did not
mean that a supplemental application could not or would not be approved in the future .

In July 2004, the drug's sponsor amended its supplemental application seeking to make
Plan B an OTC product for women age 16 and over, and to have it remain p rescription only
for women under age 16 . The company also sought to market Plan B in a single package,
and sold either as prescription only or OTC, depending on the age of the purchaser .

In Augiist 2005, FDA wrote a le tt er to the Duramed Research, Inc ., (copy enclosed and
available at : http ://www.fda.gov/cder/drug/infopage/p1anB/Plan_B'7etter20050826.pdf)
stating that FDA had completed its review of the application an d that the scienti fi c data
supported the safe and effective use of Plan B as an OTC product for women ages 17 and
over. FDA also stated, however, that it was unable at that time to reach a final decision on
the approvability of the application due to unresolved issues that related to the application .

In the letter to the sponsor, FDA identified three difficult and novel issues presented by the
application, issues for which the Agency is committed to a process for resolving . That
process was initiated with the publication on September 1, 2005, of'an Advance
_ . . _ _ Notice . o.,f.
Proposed Rulemaking (ANPRM) in the Federal Register seeking comment on questions
related to section 503(b) of the Federal Food, Drug, and Cosmetic (FD&C) Act (Title 21,
United States Code, section 353(b)) . The questions the interested parties were asked to
respond to concern when an active ingredient of a drug may be simultaneously marketed as
both a prescription and as an OTC drug product, whether and how OTC availability of a
product could be restricted to a particular subpopulation, and whether the same packaged
product could be sold either as prescription only or OTC, depending on the age of th e
purchaser . A related concern is how, as a practical matter, an age-based distinction could be
enforced.

As the Agency has said many times during the course of the review of this application, the
questions that FDA was asked to answer, and the proposal that was put forward by the
Page 3 - The Honorable Raul M . Grijalva

sponsor, presented the Agency with many very difficult and novel policy and regulatory
questions . In some cases, the questions requiring an FDA response were unprecedented for
this Agency.

An ANPRM is a mechanism to ask for public comments on whether the Agency should
initiate a rulemaking to codify our interpretation of section 503(b) of the FD&C Act regarding
when an active ingredient can simultaneously be marketed in both a prescription drug product
and an OTC drug product for the same indication, strength, dosage form and route of
administration . Although the Agency typically solicits public comment for a minimum of 90
days when initiating this type of process, in the interest of moving quickly on this issue, the
comment period was shortened to 60 days for this ANPRM . The public comment period on
these questions closed as of November 1, 2005, and FDA is reviewing the comments and
letters it received. While we cannot put an exact timeline on how long it will take to process
these comments, we are committed to moving forward as quickly as possible .

Notwithstanding the outcome of the rulemaking process, there remain deficiencies in the
sponsor's application . For example, as set forth in the letter FDA sent to Duramed Research,
Inc ., on August 26, 2005, while the application sought approval for the switch for ages 16 and
older, CDER found that the data supported only for ages 17 and older . Moreover, the
outcome of FDA's rulemaking process may impact the approvability of the proposed
packaging and the use of age as a criterion on which to base a distinction between OTC and
prescription use . Accordingly, Duramed may need to amend its supplemental application .
Please note, however, that as FDA's August 26 letter to Duramed describes, CDER has
completed its scientific review of their pending supplemental application .

The Agency has found that considerable misinformation has circulated about this application
and the reasons FDA has taken the actions it has to this point . So there will be no confusion
about the public statements FDA actually has made concerning the Banr/Duramed Plan
B/OTC application, in addition to the two letters to the sponsor mentioned above, we are
enclosing copies of the two press releases dated May 7, 2004, and August 26, 2005, that the
Agency issued concerning this application .

Thank you again for your interest in this matter . If we can be of further assistance, please let
us know . A similar response is being sent to each of the other co-signers of your -letter .

Sincerely ,

avid W . Boyer
Assistant Commissioner
for Legislatio n

4 Enclosures
 DEPARTMENT OF HEALTH & HUMAN SERVICES

Food and Drug Administration

Rockville MD 2085 7

The Honorable Steve Israel

House of Representatives
Washington, D . C . 20515-3202 MAY 11 2006

Dear Mr. Israel :

Thank you for the letter of January 19, 2005, co-signed by fifty-one of your colleagues, in
which you express your views about the Food and Drug Administration's (FDA or the
Agency) processing of the supplemental new drug application from Barr Laboratories (now
owned by Duramed Research, Inc .) that proposes to change the marketing status of the drug,
Plan B, from prescription only to over-the-counter (OTC) . We would like to take this
opportunity to clarify below the current status of the Agency's activities concerning this
application .

As you know, FDA is charged by Congress with reviewing new drug applications (NDA) to
determine a proposed new product's safety and effectiveness for the uses put forth by the
manufacturer in the application . As a science-based agency, it is FDA that must make that
final determination on whether an application for a product adequately demonstrates that the
data presented supports the proposed uses stated by the manufacturer in the proposed labeling .
A product cannot be approved until FDA determines that the product is safe and effective for
the indications stated in the proposed labeling .

Your letter referenced the 23-4 vote taken at the joint advisory committee meeting in
December 2003, recommending that Plan B be sold OTC . Advisory committee opinions are
advisory in nature and are not binding on the Agency . Since the final determination on any
NDA always is the responsibility of FDA, it is up to the Agency to clarify any unanswered
questions that may remain after the close of an advisory committee meeting or that were
identified during the meeting, even though a vote may have been taken on the main
question(s) before the committee . The busy schedules of the committee members require that
advisory committee meetings be scheduled well in advance . We certainly value the input
from advisory committee members and the opportunity to hear an exchange of ideas on
proposed new products from experts in their respective scientific fields . It should not be
presumed, however, that a favorable vote by an advisory committee automatically means that
a product is ready to go to the pharmacy shelves .

In May of 2004, FDA completed its first review of the NDA to switch Plan B to OTC, and
concluded that the application could not be approved at that time because : 1) adequate data
were not provided to support a conclusion that young adolescent women can safely and
effectively use Plan B for emergency contraception without the professional supervision of a
licensed practitioner, and 2) an amended proposal submitted by the sponsor during the review
Page 2 - The Honorable Steve Israe l

cycle to chan ge the requested indication to allow for marketing of Pl an B as a presc ri ption
only product for women under 16 years of age an d a nonprescription product for women 16
years and older was incomplete and inadequate for a full review . This message was
conveyed to the sponsor by the then-Acting Director of FDA's Center for Dru g Evaluation
and Research (CDER) with a full expl an ation of the re asons behind FDA's decision in a Not
Approvable le tt er dated May 6, 2004, (copy enclosed) an d available online at :
www.fda .gov/cder/drug/infopage/planB NALetter .pdf.

That decision by the Acting Director of CDER was made after, ffull review of all the . .
underlying data and analysis and after discussions with all of.the appropriate Agency
personnel . This decision was based on his assessment that the .data_in the supplemental
application did not contain sufficient information about whether younger adolescent women
could understand the label and use the product safely and effectively for emergency
contraception without the professional supervision of a licensed practitioner . Therefore, the
data in the application did not support approval of the supplement . In its Not Approvable
letter to the sponsor, FDA outlined some additional information that would be required for
approval to market Plan B as an OTC drug. The issuance of a Not Approvable letter did not
mean that a supplemental application could not or would not be approved in the future .

In July 2004, the drug's sponsor amended its supplemental application seeking to make
Pl an B an OTC product for women age 16 an d over, and to have it remain prescription only
for women under age 16 . The comp any also sought to market Plan B in a single package,
and sold either as prescription only or OTC, depending on the age of the purchaser .

In August 2005, FDA wrote a lett er to the Duramed Research, Inc ., (copy enclosed and
available at : http ://www .fda .gov/cder/drug/infopage/planB/Plan_B_Ietter20050826 .pdf)
stating that FDA had completed its review of the application and that the scientific data
supported the safe and effective use of Plan B as an OTC product for women ages 17 and
over. FDA also stated, however, that it was unable at that time to reach a final decision on
the approvability of the application due to unresolved issues that related to the application .

In the le tt er to the sponsor, FDA identified three difficult and novel issues presented by the
application, issues for which the Agency is commi tted to a process for resolving . That
process was initiated with the publication on September 1, 2005, of an Advance Notice of
Proposed Rulemaking (ANPRM) in the Federal Register seeking comment on questions
related to section 503(b) of the Federal Food, Drug, an d Cosmetic (FD&C) Act (Title 21,
United States Code, section 353(b)) . The questions the interested pa rt ies were asked to
respond to concern when an active ingredient of a drug may be simultaneously marketed as
both a prescri ption and as an OTC drug product, whether and how OTC availability of a
product could be restricted to a particular subpopulation, and whether the same packaged
product could be sold either as presc ription only or OTC, depending on the age of the
purchaser. A related conce rn is how, as a practical ma tter, an age-based distinction could be
enforced.

As the Agency has said many times during the course of the review of this application, the
questions that FDA was asked to answer, and the proposal that was put forward by the
Page 3 - The Honorable Steve Israel

sponsor, presented the Agency with many very difficult and novel policy and regulatory
questions . In some cases, the questions requiring an FDA response were unprecedented for
this Agency.

An ANPRM is a mechanism to ask for public comments on whether the Agency should
initiate a rulemaking to codify our interpretation of section 503(b) of the FD&C Act regarding
when an active ingredient can simultaneously be marketed in both a prescription drug product
and an OTC drug product for the same indication, strength, dosage form and route of
administration . Although the Agency typically solicits public comment for a minimum of 90
days when initiating this type of process, in the interest of moving quickly on this issue, the
comment period was shortened to 60 days for this ANPRM . The public comment period on
these questions closed as of November 1, 2005, and FDA is reviewing the comments and
letters it received. While we cannot put an exact timeline on how long it will take to process
these comments, we are committed to moving forward as quickly as possible .

Notwithstanding the outcome of the rulemaking process, there remain deficiencies in the
sponsor's application. For example, as set forth in the letter FDA sent to Duramed Research,
Inc ., on August 26, 2005, while the application sought approval for the switch for ages 16 and
older, CDER found that the data supported only for ages 17 and older. Moreover, the
outcome of FDA's rulemaking process may impact the approvability of the proposed
packaging and the use of age as a criterion on which to base a distinction between OTC and
prescription use . Accordingly, Duramed may need to amend its supplemental application .
Please note, however, that as FDA's August 26 letter to Duramed describes, CDER has
completed its scientific review of their pending supplemental application .

The Agency has found that considerable misinformation has circulated about this application
and the reasons FDA has taken the actions it has to this point . So there will be no confusion
about the public statements FDA actually has made concerning the Barr/Duramed Pla n
B/OTC application, in addition to the two letters to the sponsor mentioned above, we are
enclosing copies of the two press releases dated May 7, 2004, and August 26, 2005, that the
Agency issued concerning this application .

Thank you again for your interest in this matter . If we can be of further assistance, please let
us know . A similar response is being sent to each of the other co-signers of your letter .

Sincerely,

id W . Boyer
Assistant Commissioner
for Legislation

4 Enclosures
J~~ ssmcts.~~

DEPARTMENT OF HEALTH & HUMAN SERVICES

~~.3 o
Food and Drug Administration
Rockville MD 20857

The Honorable Anthony D . Weiner

House of Representatives MAY Y 1 2006
Washington, D . C . 20515-320 9

Dear Mr. Weiner:

Thank you for the letter of January 19, 2005, co-signed by fifty-one of your colleagues, in
which you express your views about the Food and Drug Administration's (FDA or the
Agency) processing of the supplemental new drug application from Barr Laboratories (now
owned by Duramed Research, Inc .) that proposes to change the marketing status of the drug,
Plan B, from prescription only to over-the-counter (OTC) . We would like to take this
opportunity to clarify below the current status of the Agency's activities concerning this
application .

As you know, FDA is charged by Congress with reviewing new drug applications (NDA) to
determine a proposed new product's safety and effectiveness for the uses put forth by the
manufacturer in the application . As a science-based agency, it is FDA that must make that
final determination on whether an application for a product adequately demonstrates that the
data presented supports the proposed uses stated by the manufacturer in the proposed labeling .
A product cannot be approved until FDA determines that the product is safe and effective for
the indications stated in the proposed labeling .

Your letter referenced the 23-4 vote taken at the joint advisory committee meeting in
December 2003, recommending that Plan B be sold OTC . Advisory committee opinions are
advisory in nature and are not binding on the Agency . Since the final determination on any
NDA always is the responsibility of FDA, it is up to the Agency to clarify any unanswered
questions that may remain after the close of an advisory committee meeting or that were
identified during the meeting, even though a vote may have been taken on the main
question(s) before the committee . The busy schedules of the committee members require that
advisory committee meetings be scheduled well in advance . We certainly value the input
from advisory committee members and the opportunity to hear an exchange of ideas on
proposed new products from experts in their respective scientific fields . It should not be
presumed, however, that a favorable vote by an advisory committee automatically means that
a product is ready to go to the pharmacy shelves .

In May of 2004, FDA completed its first review of the NDA to switch Pl an B to OTC, and
concluded that the application could not be approved at that time because : 1) adequate data
were not provided to suppo rt a conclusion that young adolescent women can safely and
effectively use Plan B for emergency contraception without the professional supe rvision of a
licensed practitioner, and 2) an amended proposal submi tt ed by the sponsor during the review
Page 2 - The Honorable Anthony D . Weine r

cycle to change the requested indication to allow for marketing of Plan B as a prescription
only product for women under 16 years of age and a nonprescription product for women 16
years and older was incomplete and inadequate for a- full review . This message was
conveyed to the sponsor by the then-Acting Director of FDA's Center for Drug Evaluation
and Research (CDER) with a full explanation of the reasons behind FDA's decision in a Not
Approvable letter dated May 6, 2004, (copy enclosed) and available online at :
www.fda .gov/cder/drug/infopage/planB_NALetter .pdf.

That decision by the Acting Director of CDER was made after full review of all the
underlying data and analysis and after discussions with all of the appropriate Agency
personnel . This decision was based on his assessment that the data in the supplemental
application did not contain sufficient information about whether younger adolescent women
could understand the label and use the product safely and effectively for emergency
contraception without the professional supervision of a licensed practitioner . Therefore, the
data in the application did not support approval of the supplement . In its Not Approvable
letter to the sponsor, FDA outlined some additional information that would be required for
approval to market Plan B as an OTC drug . The issuance of a Not Approvable letter did not
mean that a supplemental application could not or would not be approved in the future.

In July 2004, the drug's sponsor amended its supplemental application seeking to make
Plan B an OTC product for women age 16 and over, and to have it remain prescription only
for women under age 16 . The company also sought to market Plan B in a single package,
and sold either as prescription only or OTC, depending on the age of the purchaser .

In August 2005, FDA wrote a letter to the Duramed Research, Inc ., (copy enclosed an d
available at : http ://www .fda .gov/cder/drug/infopage/planB/Plan_B_letter20050826 .pdf)
stating that FDA had completed its review of the application and that the scientific data
support ed the safe an d effective use of Plan B as an OTC product for women ages 17 and
over . FDA also stated, however, that it was unable at that time to reach a final decision on
the approvability*of the application due to unresolved issues that related to the application.

In the letter to the sponsor, FDA identified three difficult and novel issues presented by the
application, issues for which the Agency is committed to a process for resolving. That
process was initiated with the publication on September 1, 2005, of an Advance Notice of
Proposed Rulemaking (ANPRM) in the Federal Register seeking comment on questions
related to section 503(b) of the Federal Food, Drug, and Cosmetic (FD&C) Act (Title 21,
United States Code section 353(b)) . The questions the interested parties were asked to
respond to concern when an active ingredient of a drug may be simultaneously marketed as
both a prescription and as an OTC drug product, whether and how OTC availability of a
product could be restricted to a particular subpopulation, and whether the same packaged
product could be sold either as prescription only or OTC, depending on the age of the
purchaser . A related concern is how, as a practical matter, an age-based distinction could be
enforced .

As the Agency has said many times during the course of the review of this application, the
questions that FDA was asked to answer, and the proposal that was put forward by the
Page 3 - The Honorable Anthony D . Weine r

sponsor, presented the Agency with many very difficult and novel policy and regulato ry
questions . In some cases, the questions requiring an FDA response were unprecedented for
this Agency.

An ANPRM is a mechanism to ask for public comments on whether the Agency should
initiate a rulemaking to codify our interpretation of section 503(b) of the FD&C Act regarding
when an active ingredient can simultaneously be marketed in both a prescription drug product
and an OTC drug product for the same indication, strength, dosage form and route of
administration . Although the Agency typically solicits public comment for a minimum of 90
days when initiating this type of process, in the interest of moving quickly on this issue, the
comment period was shortened to 60 days for this ANPRM . The public comment period on
these questions closed as of November 1, 2005, and FDA is reviewing the comments and
letters it received . While we cannot put an exact timeline on how long it will take to process
these comments, we are committed to moving forward as quickly as possible .

Notwithstanding the outcome of the rulemaking process, there remain deficiencies in the
sponsor's application. . For example, as set forth in the letter FDA sent to Durame .d .Research,
Inc., on August 26, 2005, while the application sought approval for the switch for ages 16 and
older, CDER found that the data supported only for ages 17 and older. Moreover, the
outcome of FDA's rulemaking process may impact the approvability of the proposed
packaging and the use of age as a criterion on which to base a distinction between OTC and
prescription use . Accordingly, Duramed may need to amend its supplemental application .
Please note, however, that as FDA's August 26 letter to Duramed describes, CDER has
completed its scientific review of their pending supplemental application .

The Agency has found that considerable misinformation has circulated about this application
and the reasons FDA has taken the actions it has to this point . So there will be no confusion
about the public statements FDA actually has made concerning the Barr/Duramed Plan
B/OTC application, in addition to the two letters to the sponsor mentioned above, we are
enclosing copies of the two press releases dated May 7, 2004, and August 26, 2005, that the
Agency issued concerning this application .

Thank you again for your interest in this matter . If we can be of further assistance, please let
us know . A similar response is being sent to each of the other co-signers of your letter.

Sincerely,

d W . Boye r
Assistant Commissioner
for Legislatio n

4 Enclosures
,~~s[w~cts .~~
z f

DEPARTMENT OF HEALTH & HUMAN SERVICES

na

Food and Drug Administration

Rockville MD 20857

The Honorable Sherrod Brown

House of Representatives
Washington, D. C . 20515-351 3 MAY 11 2006

Dear Mr . Brown :

Thank you for the letter of January 19, 2005, co-signed by fifty-one of your colleagues, in
which you express your views about the Food and Drug Administration's (FDA or the
Agency) processing of the supplemental new drug application from Barr Laboratories (now
owned by Duramed Research, Inc .) that proposes to change the marketing status of the drug,
Plan B, from prescription only to over-the-counter (OTC) . We would like to take this
opportunity to clarify below the current status of the Agency's activities concerning this
application .

As you know, FDA is charged by Congress with reviewing new drug applications (NDA) to
determine a proposed new product's safety and effectiveness for the uses put forth by the
manufacturer in the application . As a science-based agency, it is FDA that must make that
final determination on whether an application for a product adequately demonstrates that the
data presented supports the proposed uses stated by the manufacturer in the proposed labeling .
A product cannot be approved until FDA determines that the product is safe and effective for
the indications stated in the proposed labeling .

Your letter referenced the 23-4 vote taken at the joint advisory committee meeting in
December 2003, recommending that Plan B be sold OTC . Advisory committee opinions are
advisory in nature and are not binding on the Agency . Since the final determination on any
NDA always is the responsibility of FDA, it is up to the Agency to clarify any unanswered
questions that may remain after the close of an advisory committee meeting or that were
identified during the meeting, even though a vote may have been taken on the main
question(s) before the committee . The busy schedules of the committee members require that
advisory committee meetings be scheduled well in advance . We certainly value the input
from advisory committee members and the opportunity to hear an exchange of ideas on
proposed new products from experts in their respective scientific fields . It should not be
presumed, however, that a favorable vote by an advisory committee automatically means that
a product is ready to go to the pharmacy shelves .

In May of 2004, FDA completed its first review of the NDA to switch Plan B to OTC, and
concluded that the application could not be approved at that time because : 1) adequate data
were not provided to support a conclusion that young adolescent women can safely and
effectively use Plan B for emergency contraception without the professional supervision of a
licensed practitioner, and 2) an amended proposal submitted by the sponsor during the review
i

Page 2 - The Honorable Sherrod Brow n

cycle to change the requested indication to allow for marketing of Plan B as a prescription
only product for women under 16 years of age and a nonprescription product for women 16
years and older was incomplete and inadequate for a full review . This message wa s
conveyed to the sponsor by the then-Acting Director of FDA's Center for Drug Evaluation
and Research (CDER) with a full explanation of the reasons behind FDA's decision -in a . Not
Approvable letter dated May 6, 2004, (copy enclosed) and available online at :
www.fda.gov/cder/drug/infopage/planB_NALetter.pdf.

That decision by the Acting Director of CDER was made after full review of all the
underlying data and analysis and after discussions with all of the appropriate Agency
personnel . This decision was based on his assessment that the data in the supplemental
application did not contain sufficient information about whether younger adolescent women
could understand the label and use the .product safely and effectively for emergency
contraception without the professional supervision of a licensed practitioner. Therefore, the
data in the application did not support approval of the supplement . In its Not Approvable
letter to the sponsor, FDA outlined some additional information that would be required for
approval to market Plan B as an OTC drug . The issuance of a Not Approvable letter did not
mean that a supplemental application could not or would not be approved in the future .

In July 2004, the drug's sponsor amended its supplemental application seeking to make
Plan B an OTC product for women age 16 and over, and to have it remain prescription only
for women under age 16 . The company also sought to market Plan B in a single package,
and sold either as prescription only or OTC, depending on the age of the purchaser .

In August 2005, FDA wrote a letter to the Duramed Research, Inc ., (copy enclosed and
available at : http ://www.fda .gov/cder/drug/infopage/planB/Plan_B_letter20050826.pdf)
stating that FDA had completed its review of the application and that the scientific data
supported the safe and effective use of Plan B as an OTC product for women ages 17 and
over . FDA also stated, however, that it was unable at that time to reach . a final decision on
the approvability of the application due to unresolved issues that related to the application .

In the letter to the sponsor, FDA identified three difficult and novel issues presented by the
application, issues for which the Agency is committed to a process for resolving . That
process was initiated with the publication on September 1, 2005, of an Advance Notice of
Proposed Rulemaking (ANPRM) in the Federal Register seeking comment on questions
related to section 503(b) of the Federal Food, Drug, and Cosmetic (FD&C) Act (Title 21,
United States Code, section 353(b)) . The questions the interested parties were asked to
respond to concern when an active ingredient of a drug may be simultaneously marketed as
both a prescription and as an OTC drug product, whether and how OTC availabilityof a
product could be restricted to a particular subpopulation, and whether the same packaged
product could be sold either as prescription only or OTC, depending on the age of the
purchaser. A related concern is how, as a practical matter, an age-based distinction could be
enforced .

As the Agency has said many times during the course of the review of this application, the
questions that FDA was asked to answer, and the proposal that was put forward by the
 Page 3 - The Honorable Sherrod Brow n

sponsor, presented the Agency with many very difficult and novel policy and regulatory
questions . In some cases, the questions requiring an FDA response were unprecedented for
this Agency .

An ANPRM is a mechanism to ask for public comments on whether the Agency should
initiate a rulemaking to codify our interpretation of section 503(b) of the FD&C Act regarding
when an active ingredient can simultaneously be marketed in both a prescription drug product
and an OTC drug product for the same indication, strength, dosage form and route of
administration. Although the Agency typically solicits public comment for a minimum of 90
days when initiating this type of process, in the interest of moving quickly on this issue, the
comment period was shortened to 60 days for this ANPRM . The public comment period on
these questions closed as of November 1, 2005, and FDA is reviewing the comments and
letters it received. While we cannot put an exact timeline on how long it will take to process
these comments, we are committed to moving forward as quickly as possible .

Notwithstanding the outcome of the rulemaking process, there remain deficiencies in the
sponsor's application . For example, as set forth in the letter FDA sent to Duramed Research,
Inc ., on August 26, 2005, while the application sought approval for the switch for ages 16 and
older, CDER found that the data supported only for ages 17 and older . Moreover, the
outcome of FDA's rulemaking process may impact the approvability of the proposed
packaging and the use of age as a criterion on which to base a distinction between OTC and
prescription use. Accordingly, Duramed may need to amend its supplemental application .
Please note, however, that as FDA's August 26 letter to Duramed describes, CDER has
completed its scientific review of their pending supplemental application.

The Agency has found that considerable misinformation has circulated about this application
and the reasons FDA has taken the actions it has to this point . So there will be no confusion
about the public statements FDA actually has made concerning the Barr/Duramed Plan
B/OTC application, in addition to the two letters to the sponsor mentioned above, we are
enclosing copies of the two press releases dated May 7, 2004, and August 26, 2005, that the
Agency issued concerning this application .

Thank you again for your interest in this matter . If we can be of further assistan ce, please let
us know . A similar response is being sent to each of the other co-signers of your letter .

Sincerely,

id W . Boyer
Assistant Commissioner
for Legislation

4 Enclosures
 i

DEPARTMENT OF HEALTH & HUMAN SERVICES

,~ _ _ . . _ _ .: . . _. . _._ .. . _ . _ . . _ . . .~ ,.. __.:__ ~ . .. .. __ _ ._

,~~i►na
Food and Drug Administration
Rockville MD 20857

The Honorable Patrick J . Kennedy

House of Representatives
MAY 1 I 2006
Washington, D . C . 20515-390 1

Dear Mr . Kennedy :

Thank you for the letter of January 19, 2005, co-signed by fifty-one of your colleagues, in
which you express your views about the Food and Drug Administration's (FDA or the
Agency) processing of the supplemental new drug application from Barr Laboratories (now
owned by Duramed Research, Inc .) that proposes to change the marketing status of the drug,
Plan B, from prescription only to over-the-counter (OTC) . We would like to take this
opportunity to clarify below the current status of the Agency's activities concerning this
application .

As you know, FDA is charged by Congress with reviewing new drug applications (NDA) to
determine a proposed new product's safety and effectiveness for the uses put forth by the
manufacturer in the application. As a science-based agency, it is FDA thatrnust make that
final determination on whether an application for a product adequately demonstrates that the
data presented supports the proposed uses stated by the manufacturer in the proposed labeling .
A product cannot be approved until FDA determines that the product is safe and effective for
the indications stated in the proposed labeling .

Your letter referenced the 23-4 vote taken at the joint advisory committee meeting in
December 2003, recommending that Plan B be sold OTC . Advisory committee opinions are
advisory in nature and are not binding on the Agency . Since the final determination on any
NDA always is the responsibility of FDA, it is up to the Agency to clarify any unanswered
questions that may remain after the close of an advisory committee meeting or that were
identified during the meeting, even though a vote may have been taken on the main
question(s) before the committee . The busy schedules of the committee members require that
advisory committee meetings be scheduled well in advance . We certainly value the input
from advisory committee members and the opportunity to hear an exchange of ideas on
proposed new products from experts in their respective scientific fields . It should not be
presumed, however, that a favorable vote by an advisory committee automatically means that
a product is ready to go to the pharmacy shelves .

In May of 2004, FDA completed its first review of the NDA to switch Plan B to OTC, and
concluded that the application could not be approved at that time because : 1) adequate data
were not provided to support a conclusion that young adolescent women can safely and
effectively use Plan B for emergency contraception without the professional supervision of a
licensed practitioner, and 2) an amended proposal submitted by the sponsor during the review
 Page 2 - The Honorable Patrick J. Kenned y

cycle to change the requested indication to allow for marl, :: B as a prescription

only product for women under 16 years of age and a nonf• ., ..:. . . oduct for women 16
years and older was incomplete and inadequate for a full :: message was
conveyed to the sponsor by the then-Acting Director of F :: :or Drug Evaluation
and Research (CDER) with a full explanation of the reaso ;, A's decision in a Not
Approvable letter dated May 6, 2004, (copy enclosed) and . ., : line at :
www.fda .gov/cder/drug/infopage/p1anB_NALetter.pdf.

That decision by the Acting Director of CDER was made -, • •. _ of all the
underlying data and analysis and after discussions with all iri ate Agency
personnel . This decision was based on his assessment that the supplemental
application did not contain sufficient information about w1- - ; ;:.r adolescent women
could understand the label and use the product safely and e . _~r emergency
contraception without the professional supervision of a lic~ : ioner. Therefore, the
data in the application did not support approval of the sup~ .• :ts Not Approvable
letter to the sponsor, FDA outlined some additional inforrr :- ~uld be required for
approval to market Plan B as an OTC drug . The issuance rovable letter did not
mean that a supplemental application could not or woul d ed in the future .

In July 2004, the drug's sponsor amended its supplementa i seeking to mak e
Plan B an OTC product for women age 16 and over, and t o zin prescription only
for women under age 16 . The company also sought to mi . : In a single package,
an d sold either as prescription only or OTC, depending on .e purchaser.

In August 2005, FDA wrote a le tt er to the Duramed Resea r py enclosed and

available at : http.//www.fda.gov/cder/drug/infopage/planB- `ter20050826.pdf)
stating that FDA had completed its review of the applicat i c e scientific data
support ed the safe and effective use of Pl an B as an OTC c- -omen ages 17 and
over. FDA also stated, however, that it was unable at that a final decision on
the approvability of the application due to unresolved issr. :: 1 to the application.

In the letter to the sponsor, FDA identified three difficult _ :es presented by the
application, issues for which the Agency is committed to .: , :~ : . . esolving . That
process was initiated with the publication on September 1, Advance Notice of
Proposed Rulemaking (ANPRM) in the Federal Register s ., nent on questions
related to section 503(b) of the Federal Food, Drug, and C , : .-PzC) Act (Title 21,
United States Code, section 353(b)) . The questions the were asked to
respond to concern when an active ingredient of a drug ma ; wously marketed as
both a prescription and as an OTC drug product, whether z~ ; .~ availability of a
product could be restricted to a particular subpopulation, a : ; he same packaged
product could be sold either as prescription only or OTC, ( the age of the
purchaser . A related concern is how, as a practical matter . . : :d distinction could be
enforced .

As the Agency has said m an y times during the course of ;his a pplication, the
questions that FDA was asked to an swer, and the propos ,~ forward by the
Page 3 - The Honorable Patrick J . Kenned y

sponsor, presented the Agency with many very difficult and novel policy and regulato ry
questions . In some cases, the questions requi ri ng an FDA response were unprecedented for
this Agency.

An ANPRM is a mechanism to ask for public comments on whether the Agency should
initiate a rulemaking to codify our interpretation of section 503(b) of the FD&C Act regarding
when an active ingredient can simultaneously be marketed in both a prescription drug product
and an OTC drug product for the same indication, strength, dosage form and route of
administration. Although the Agency typically solicits public comment for a minimum of 90
days when initiating this type of process, in the interest of moving quickly on this issue, the
comment period was shortened to 60 days for this ANPRM . The public comment period on
these questions closed as of November 1, 2005, and FDA is reviewing the comments and
letters it received. While we cannot put an exact timeline on how long it will take to process
these comments, we are committed to moving forward as quickly as possible .

Notwithstanding the outcome of the rulemaking process, there remain deficiencies in the
sponsor's application. For example, as set forth in the letter FDA sent to Duramed Research,
Inc ., on August 26, 2005, while the application sought approval for the switch for ages 16 and
older, CDER found that the data supported only for ages 17 and older. Moreover, the
outcome of FDA's rulemaking process may impact the approvability of the proposed
packaging and the use of age as a criterion on which to base a distinction between OTC and
prescription use. Accordingly, Duramed may need to amend its supplemental application .
Please note, however, that as FDA's August 26 letter to Duramed describes, CDER has
completed its scientific review of their pending supplemental application .

The Agency has found that considerable misinformation has circulated about this application
and the reasons FDA has taken the actions it has to this point . So there will be no confusion
about the public statements FDA actually has made concerning the Barr/Duramed Pla n
B/OTC application, in addition to the two letters to the sponsor mentioned above, we are
enclosing copies of the two press releases dated May 7, 2004, and August 26, 2005, that the
Agency issued concerning this application .

Thank you again for your interest in this matter. If we can be of further as sist an ce, please let
us know. A similar response is being sent to each of the other co-signers of your letter.

Sincerely ,

DAV-id W . Boyer
Assistant Commissioner
for Legislatio n

4 Enclosures
i

JM 1

DEPARTMENT OF HEALTH & HUMAN SERVICES

At+vtrc
Food and Drug Administration
Rockville MD 2085 7

The Honorable Carolyn McCarthy

House of Representatives
Washington, D . C . 20515-320 4 MAY 1 1 2006

Dear Ms. McCarthy :

Thank you for the letter of January 19, 2005, co-signed by fifty-one of your colleagues, in
which you express your views about the Food and Drug Administration's (FDA or the
Agency) processing of the supplemental new drug application from Barr Laboratories (now
owned by Duramed Research, Inc .) that proposes to change the marketing status of the drug,
Plan B, from prescription only to over-the-counter (OTC) . We would like to take this
opportunity to clarify below the current status of the Agency's activities concerning this
application .

As you know, FDA is charged by Congress with reviewing new drug applications (NDA) to
determine a proposed new product's safety and effectiveness for the uses put forth by the
m anufacturer in the application . As a science-based agency, it is FDA that must- make that
final determination on whether an application for a product adequately demonstrates that the
data presented supports the proposed uses stated by the manufacturer in the proposed labeling .
A product cannot be approved until FDA determines that the product is safe and effective for
the indications stated in the proposed labeling .

Your letter referenced the 23-4 vote taken at the joint advisory committee meeting in
December 2003, recommending that Plan B be sold OTC . Advisory committee opinions are
advisory in nature and are not binding on the Agency . Since the final determination on any
NDA always is the responsibility of FDA, it is up to the Agency to clarify any unanswered
questions that may remain after the close of an advisory committee meeting or that were
identified during the meeting, even though a vote may have been taken on the main
question(s) before the committee . The busy schedules of the committee members require that
advisory committee meetings be scheduled well in advance . We certainly value the input
from advisory committee members and the opportunity to hear an exchange of ideas on
proposed new products from experts in their respective scientific fields . It should not be
presumed, however, that a favorable vote by an advisory committee automatically means that
a product is ready to go to the pharmacy shelves .

In May of 2004, FDA completed its first review of the NDA to switch Plan B to OTC, and
concluded that the application could not be approved at that time because : 1) adequate data
were not provided to support a conclusion that young adolescent women can safely and
effectively use Plan B for emergency contraception without the professional supervision of a
licensed practitioner, and 2) an amended proposal submitted by the sponsor during the review
 Page 2 - The Honorable Carolyn McCarthy

cycle to change the requested indication to allow for marketing of Plan B as a prescription
only product for women under 16 years of age and a nonprescription product for women 16
years and older was incomplete and inadequate for a full review . This message wa s
conveyed to the sponsor by the then-Acting Director of FDA's Center for Drug Evaluation
and Research (CDER) with a full explanation of the reasons behind FDA's decision in a Not
Approvable letter dated May 6, 2004, (copy enclosed) and available . online at :
www.fda.gov/cder/drug/infopage/planB NALetter.pdf.

That decision by the Acting Director of CDER was made after full review of all the
underlying data and analysis and after discussions with all of the appropriate Agency
personnel . This decision was based on his assessmentthat the, data in the supplemental
application did not contain sufficient information about whether younger adolescent women
could understand the label and use the product safely and effectively for emergency
contraception without the professional supervision of a licensed practitioner . Therefore, the
data in the application did not support approval of the supplement . In its Not Approvable
letter to the sponsor, FDA outlined some additional information that would be required for
approval to market Plan B as an OTC drug . The issuance of a Not Approvable letter did not
mean that a supplemental application could not or would not be approved in the future .

In July 2004, the drug's sponsor amended its supplemental application seeking to make
Plan B an OTC product for women age 16 and over, and to have it remain prescription only
for women under age 16 . The company also sought to market Plan B in a single package,
and sold either as prescription only or OTC, depending on the age of the purchaser .

In August 2005, FDA wrote a letter to the Duramed Research, Inc ., (copy enclosed and
available at : http : //www.fda.gov/cder/drug/infopage/planB/Plan_B_letter200S0826 .pdJ)
stating that FDA had completed its review of the application and that the scientific data
supported the safe and effective use of Plan B as an OTC product for women ages 17 and
over. FDA also stated, however, that it was unable at that time to reach a final decision on
the approvability of the application .due to unresolved issues that related to the application.

In the letter to the sponsor, FDA identified three difficult and novel issues presented by the
application, issues for which the Agency is committed to a process for resolving . That
process was initiated with the publication on September 1, 2005, of an Advance Notice of
Proposed Rulemaking (ANPRM) in the Federal Register seeking comment on questions
related to section 503(b) of the Federal Food, Drug, and Cosmetic (FD&C) Act (Title 21,
United States Code , section 353(b)). The questions the interested parties were asked to
respond to concern when an active ingredient of a drug may be simultaneously marketed as
both a prescription and as an OTC drug product, whether and how OTC availability of a
product could be restricted to a particular subpopulation, and whether the same packaged
product could be sold either as prescription only or OTC, depending on the age of the
purchaser . A related concern is how, as a practical matter, an age-based distinction could be
enforced.

As the Agency has said many times during the course of the review of this application, the
questions that FDA was asked to answer, and the proposal that was put forward by the
Page 3 - The Honorable Carolyn McCarthy

sponsor, presented the Agency with many very difficult and novel policy and regulatory
questions. In some cases, the questions requiring an FDA response were unprecedented for
this Agency.

An ANPRM is a mechanism to ask for public comments on whether the Agency should
initiate a rulemaking to codify our interpretation of section 503(b) of the FD&C Act regarding
when an active ingredient can simultaneously be marketed in both a prescription drug product
and an OTC drug product for the same indication, strength, dosage form and route of
administration. Although the Agency typically solicits public comment for a minimum of 90
days when initiating this type of process, in the interest of moving quickly on this issue, the
comment period was shortened to 60 days for this ANPRM . The public comment period on
these questions closed as of November 1, 2005, and FDA is reviewing the comments and
letters it received. While we cannot put an exact timeline on how long it will take to process
these comments, we are committed to moving forward as quickly as possible.

Notwithstanding the outcome of the rulemaking process, there remain deficiencies in the
sponsor's application . For example, as set forth in the letter FDA sent to Duramed Research,
Inc ., on August 26, 2005, while the application sought approval for the switch for ages 16 and
older, CDER found that the data supported only for ages 17 and older . Moreover, the
outcome of FDA's rulemaking process may impact the approvability of the proposed
packaging and the use of age as a criterion on which to base a distinction between OTC and
prescription use . Accordingly, Duramed may need to amend its supplemental application .
Please note, however, that as FDA's August 26 letter to Duramed describes, CDER has
completed its scientific review of their pending supplemental application .

The Agency has found that considerable misinformation has circulated about this application
and the reasons FDA has taken the actions it has to this point . So there will be no confusion
about the public statements FDA actually has made concerning the Barr/Duramed Pla n
B/OTC application, in addition to the two letters to the sponsor mentioned above, we are
enclosing copies of the two press releases dated May 7 ; 2004, and August 26, 2005, that the
Agency issued concerning this application.

Thank you again for your interest in this ma tt er. If we can be of further assistance, please let
us know . A similar response is being sent to each of the other co-signers of your letter.

Sincerely,

id W . Boyer
Assistant Commissioner
for Legislatio n

4 Enclosures
DEPARTMENT OF HEALTH & HUMAN SERVICES

Food and Drug Administration

Rockville MD 20857

The Honorable Hilda L . Solis

house of Representatives MAY 1 1 200 6
Washington, D . C . 20515-053 2

Dear Ms. Solis :

Thank you for the letter of January 19, 2005, co-signed by fifty-one of your colleagues, in
which you express your views about the Food and Drug Administration's (FDA or the
Agency) processing of the supplemental new drug application from Barr Laboratories (now
owned by Duramed Research, Inc .) that proposes to change the marketing status of the drug,
Plan B, from prescription only to over-the-counter (OTC) . We would like to take this
opportunity to clarify below the current status of the Agency's activities concerning this
application .

As you know, FDA is charged by Congress with reviewing new drug applications (NDA) to
determine a proposed new product's safety and effectiveness for the uses put forth by the
manufacturer in the application . As a science-based agency, it is FDA that must make that
final determination on whether an application for a product adequately demonstrates that the
data presented supports the proposed uses stated by the manufacturer in the proposed labeling .
A product cannot be approved until FDA determines that the product is safe and effective for
the indications stated in the proposed labeling .

Your letter referenced the 23-4 vote taken at the joint advisory committee meeting in
December 2003, recommending that Plan B be sold OTC . Advisory committee opinions are
advisory in nature and are not binding on the Agency . Since the final determination on any
NDA always is the responsibility of FDA, it is up to the Agency to clarify any unanswered
questions that may remain after the close of an advisory committee meeting or that were
identified during the meeting, even though a vote may have been taken on the main
question(s) before the committee . The busy schedules of the committee members require that
advisory committee meetings be scheduled well in advance . We certainly value the input
from advisory committee members and the opportunity to hear an exchange of ideas on
proposed new products from experts in their respective scientific fields . It should not be
presumed, however, that a favorable vote by an advisory committee automatically means that
a product is ready to go to the pharmacy shelves .

In May of 2004, FDA completed its first review of the NDA to switch Plan B to OTC, and
concluded that the application could not be approved at that time because : 1) adequate data
were not provided to support a conclusion that young adolescent women can safely and
effectively use Plan B for emergency contraception without the professional supervision of a
licensed practitioner, and 2) an amended proposal submitted by the sponsor during the review
Page 2- The Honorable Hilda L . Solis

cycle to change the requested indication to allow for marketing of Pl an B as a prescription

only product for women under 16 years of age and a nonpresc ri ption product for women 16
years and older was incomplete an d inadequate for a full review . This message wa s
conveyed to the sponsor by the then-Acting Director of FDA's Center for Drug Evaluation
an d Research (CDER) with a full explana ti on of the reasons behind FDA's decision in a Not
Approvable lett er dated May 6, 2004, (copy enclosed) an d available online at :
www.fda.gov/cder/drug/infopage/p1anB NALetter.pdf.

That decision by the Acting Director of CDER was made after full review of all the
underlying data and analysis and after discussions with all of the appropriate Agency
personnel . This decision was based on his assessment that the data_in the-supplemental
application did not contain sufficient information about whether younger adolescent women
could understand the label and use the product safely and effectively for emergency
contraception without the professional supervision of a licensed practitioner . Therefore, the
data in the application did not support approval of the supplement . In its Not Approvable
letter to the sponsor, FDA outlined some additional information that would be required for
approval to market Plan B as an OTC drug . The issuance of a Not Approvable letter did not
mean that a supplemental application could not or would not be approved in the future .

In July 2004, the drug's sponsor amended its supplemental application seeking to make
Plan B an OTC product for women age 16 and over, and to have it remain prescription only
for women under age 16 . The company also sought to market Plan B in a single package,
and sold either as prescription only or OTC, depending on the age of the purchaser .

In August 2005, FDA wrote a lett er to the Duramed Research, Inc ., (copy enclosed and
available at : http ://www.fda .gov/cder/drug/infopage/p1anB/Plan_B_Ietter200 .50826.pdf)
stating that FDA had completed its review of the application and that the scienti fi c data
supported the safe and effective use of Plan B as an OTC product for women ages 17 an d
over. FDA also stated, however, that it was unable at that time to reach a fi nal decision on
the approvability of the application due to unresolved issues that related to the application .

In the letter to the sponsor, FDA identified three difficult and novel issues presented by the
application, issues for which the Agency is committed to a process for resolving . That
process was initiated with the publication on September 1, 2005, of an Advance Notice of
Proposed Rulemaking (ANPRM) in the Federal Register seeking comment on questions
related to section 503(b) of the Federal Food, Drug, and Cosmetic (FD&C) Act (Title 21,
United States Code , section 353(b)) . The questions the interested parties were asked to
respond to concern when an active ingredient of a drug may be simultaneously marketed as
both a prescription and as an OTC drug product, whether and how OTC availability of a
product could be restricted to a particular subpopulation, and whether the same packaged
product could be sold either as prescription only or OTC, depending on the age of the
purchaser . A related concern is how, as a practical matter, an age-based distinction could be
enforced .

As the Agency has said many times duri ng the course of the review of this application, the
questions that FDA was asked to answer, and the proposal that was put forward by the
Page 3 - The Honorable Hilda L . Soli s

sponsor, presented the Agency with many very difficult and novel policy and regulato ry
questions . In some cases, the questions requi ri ng an FDA response were unprecedented for
this Agency .

An ANPRM is a mechanism to ask for public comments on whether the Agency should
initiate a rulemaking to codify our interpretation of section 503(b) of the FD&C Act regarding
when an active ingredient can simultaneously be marketed in both a prescription drug product
and an OTC drug product for the same indication, strength, dosage form and route of
administration . Although the Agency typically solicits public comment for a minimum of 90
days when initiating this type of process, in the interest of moving quickly on this issue, the
comment period was shortened to 60 days for this ANPRM . The public comment period on
these questions closed as of November 1, 2005, and FDA is reviewing the comments and
letters it received . While we cannot put an exact timeline on how long it will take to process
these comments, we are committed to moving forward as quickly as possible .

Notwithstanding the outcome of the rulemaking process, there remain deficiencies in the
sponsor's application . For example, as set forth in the letter FDA sent to Duramed Research,
Inc ., on August 26, 2005, while the application sought approval for the switch for ages 16 and
older, CDER found that the data supported only for ages 17 and older . Moreover, the
outcome of FDA's rulemaking process may impact the approvability of the proposed
packaging and the use of age as a criterion on which to base a distinction between OTC and
prescription use . Accordingly, Duramed may need to amend its supplemental application .
Please note, however, that as FDA's August 26 letter to Duramed describes, CDER has
completed its scientific review of their pending supplemental application .

The Agency has found that considerable misinformation has circulated about this application
and the reasons FDA has taken the actions it has to this point . So there will be no confusion
about the public statements FDA actually has made concerning the Barr/Duramed Pla n
B/OTC application, in addition to the two letters to the sponsor mentioned above, we are
enclosing copies of the two press releases dated May 7, 2004, and August 26, 2005, that the
Agency issued concerning this application .

Thank you again for your interest in this matter . If we can be of further assistance, please let
us know. A similar response is being sent to each of the other co-signers of your letter.

Sincerely,

David W . Boyer
Assistant Commissione r
for Legislation

4 Enclosures
J+'p ssmRr,`J'

DEPARTMENT OF HEALTH & HUMAN SERVICE S

~ - -_
1j►+1G
Food and Drug Administrati-^
Rockville MD 20857

The Honorable Peter A . Defazio

House of Representatives MAY 1 1 2006
Washington, D . C . 20515-3704

Dear Mr. Defazio :

Thank you for the letter of January 19, 2005, co-signed by fifty-one of your colleagues, in
which you express your views about the Food and Drug Administration's (FDA or the
Agency) processing of the supplemental new drug application from Barr Laboratories (now
owned by Duramed Research, Inc .) that proposes to change the marketing status of the drug,
Plan B, from prescription only to over-the-counter (OTC).' We would like to take_ tfus , " "
opportunity to clarify below the current status of the Agency's activities' concerning this
application .

As you know, FDA is charged by Congress with reviewing new drug applications (NDA) to
determine a proposed new product's safety and effectiveness 'for the uses put forth'by the
manufacturer in the application . As a science-based agency, it is FDA that must make that
final determination on whether an application for a product adequately demonstrates that the
data presented supports the proposed uses stated by the manufacturer in the proposed labelir , .
A product cannot be approved until FDA determines that the product is safe arid effective fo . i
the indications stated in the proposed labeling .

Your lett er referenced the 23-4 vote taken at the joint adviso ry commi tt ee meeting in .
December 2003, recommending that Plan B be sold OTC. Advisory committee opinion s ar :_
advisory in nature and are not binding on the Agency . Since the final determination on any
NDA always is the responsibility of FDA, it is up to the Agency to clarify any unanswered
questions that may remain after the close of an advisory committee meeting or that were
identified du ring the meeting, even though a vote may have been taken on the main'
question(s) before the commi tt ee . The busy schedules of the committee members require th : :
advisory committee meetings be scheduled well in advance . We cert ainly value the input
from advisory committee members an d the opportunity to hear an exchange of ideas on
proposed new products from experts in their respective scientific fi elds . It should not be
presumed, however, that a favorable vote by an advisory committee automatically means that
a product is ready to go to the pharmacy shelves .

In May of 2004, FDA completed its first review of the NDA to switcfr Pl'an B to OTC, and
concluded that the application could not be approved at that time because : 1) adequate data
were not provided to support a conclusion that young adolescent women can safely and
effectively use Plan B for emergency contraception without the professional supervision of a
licensed practitioner, and 2) an amended proposal submitted by the sponsor during the review
Page 2 - The Honorable Peter A . Defazi o

cycle to change the requested indication to allow for marketing of Plan B as a prescription
only product for women under 16 years of age and a nonprescription product for women 16
years and older was incomplete and inadequate for a full review . This message was
conveyed to the sponsor by the then-Acting Director of FDA's Center for Drug Evaluation
and Research (CDER) with a full explanation of the reasons behind FDA's decision in aNot
Approvable letter dated May 6, 2004, (copy enclosed) and available online at :
www.fda .gov/cder/drug/infopage/p1anB_NALetter.pdf.

That decision by the Acting Director of CDER was made after fu ll review of all. the
underlying data and analysis and after discussions with all of the appropriate Agency
personnel . This decision was based on his assessment that the data in the, supplemental
application did not contain sufficient information about whether younger adolescent women `
could understand the label and use the product safely and effectively for emergency
contraception without the professional supervision of a licensed practitioner . Therefore, the
data in the application did not support approval of the supplement. In its Not Approvable
letter to the sponsor, FDA outlined some additional information, that would be required for
approval to market Plan B as an OTC drug . The issuance of a Not Approvable letter did not
mean that a supplemental application could not or would not be approved in the future.

In July 2004, the drug's sponsor amended its supplemental application seeking to make
Plan B an OTC product for women age 16 and over, and to have it remain prescription only
for women under age 16 . The company also sought to market Plan B in a single package,
and sold either as prescription only or OTC, depending on the age of the purchaser .

In August 2005, FDA wrote a le tter to the Duramed Research, Inc ., (copy enclosed and
available at : http : //www.fda.gov/cder/drug/infopage/p1anB/Plan_B_Ietter20050826 .pdJ)
stating that FDA had completed its review of the application an d that the scientific data
supported the safe and effective use of Pl an B as an OTC product for women ages 17 and
over. FDA also stated, however, that it was unable at that time to reach a fi nal decision on
the approvability-of the application due to unresolved issues that related to the application .

In the . letter to the sponsor, FDA identified three difficult and novel issues presented by the
application, issues for which the Agency is committed to a process for resolving . That .
process was initiated with the publication on September 1, 2005, of an Advance Notice of
Proposed Rulemaking (ANPRM) in the Federal Register seeking comment on questions
related to section 503(b) of the Federal Food, Drug, and Cosmetic (FD&C) Act (Title 21,
United States Code , section 353(b)) . The questions the interested parties were asked to
respond to concern when an active ingredient of a drug may be simultaneously marketed as
both a prescription and as an OTC drug product, whether and how OTC availability of a
product could be restricted to a particular subpopulation, and whether the same packaged
product could be sold either as prescription only or OTC, depending on the age of the
purchaser . A related concern is how, as a practical matter, an age-based distinction could be
enforced.

As the Agency has said many times during the course of the review of this application, the
questions that FDA was asked to answer, and the proposal that was put forward by the
Page 3 - The Honorable Peter A . Defazi o

sponsor, presented the Agency with many very difficult and novel policy and regulatory
questions . In some cases, the questions requiring an FDA resporise were unprecedented for
this Agency .

An ANPRM is a mechanism to ask for public comments on whether the Agency should
initiate a rulemaking to codify our interpretation of section 503(b) of the FD&C Act regarding
when an active ingredient can simultaneously be marketed in both a prescription drug product
and an OTC drug product for the same indication, strength, dosage form and route of
administration. . Although the Agency typically solicits public comment . . for a minimum of 90 ,
days when initiating this type of process, in the interest of moving quickly on this issue, the
comment period was shortened to 60 days for this ANPRM . The public comment period on
these questions closed as of November 1, 2005, and FDA is reviewing the comments and
letters it received . While we cannot put an exact timeline on how long it will take to process
these comments, we are committed to moving forward as quickly as possible .

Notwithstanding the outcome of the rulemaking process, there remain deficiencies in the
sponsor's application . For example, as set forth in the letter FDA sent to Duramed_Research,
Inc ., on August 26, 2005, while the application sought approval for the switch for ages 16 and
older, CDER found that the data supported only for ages 17 and older . Moreover, the
outcome of FDA's rulemaking process may impact the approvability of the proposed
packaging and the use of age as a criterion on which to base a distinction, between OTC, and
prescription use . Accordingly, Duramed may need to amend its supplemental application .
Please note, however, that as FDA's August 26 letter to Duramed describes, CDER has
completed its scientific review of their pending supplemental application .

The Agency has found that considerable misinformation has circulated about this application
and the reasons FDA has taken the actions it has to this point . So there will be no confusion
about the public statements FDA actually has made concerning the Barr/Duramed Pla n
B/OTC application, in addition to the two le tters to the sponsor mentioned above, we are
enclosing copies of the two press releases dated May 7, 2004, an d August 26, 2005, that the
Agency issued conce rn ing this application .

Thank you again for your interest in this matter . If we can be of. further assistance, please let
us know . A similar response is being sent to each of the other co-signers of your letter.

Sincerely,

d W . Boyer
-;Z~
Assistant Commissioner
for Legislation

4 Enclosures
DEPARTMENT OF HEALTH & HUMAN SERVICES

Food and Drug Administration

Rockville MD 2085 7

The Honorable Sheila Jackson Lee

House of Representatives MAY 1 1 200 6
Washington, D . C. 20515-431 8

Dear Ms . Lee :

Thank you for the letter of January 19, 2005, co-signed by fifty-one of your colleagues, in
which you express your views about the Food and Drug Administration's (FDA or the
Agency) processing of the supplemental new drug application from Barr Laboratories (now
owned by Duramed Research, Inc .) that proposes to change the marketing status of the drug,
Plan B, from prescription only to over-the-counter (OTC) . We would like to take this
opportunity to clarify below the current status of the Agency's activities concerning this
application .

As you know, FDA is charged by Congress with reviewing new drug applications (NDA) to
determine a proposed new product's safety and effectiveness for the uses put forth by the
manufacturer in the application . As a science-based agency, it is FDA that must make that
final determination on whether an application for a product adequately demonstrates that the
data presented supports the proposed uses stated by the manufacturer in the proposed labeling .
A product cannot be approved until FDA determines that the product is safe and effective for
the indications stated in the proposed labeling .

Your letter referenced the 23-4 vote taken at the joint advisory committee meeting in
December 2003, recommending that Plan B be sold OTC . Advisory committee opinions are
advisory in nature and are not binding on the Agency . Since the final determination on any
NDA always is the responsibility of FDA, it is up to the Agency to clarify any unanswered
questions that may remain after the close of an advisory committee meeting or that were
identified during the meeting, even though a vote may have been taken on the main
question(s) before the committee . The busy schedules of the committee members require that
advisory committee meetings be scheduled well in advance . We certainly value the input
from advisory committee members and the opportunity to hear an exchange of ideas on
proposed new products from experts in their respective scientific fields . It should not be
presumed, however, that a favorable vote by an advisory committee automatically means that
a product is ready to go to the pharmacy shelves .

In May of 2004, FDA completed its first review of the NDA to switch Plan B to OTC, and
concluded that the application could not be approved at that time because : 1) adequate data
were not provided to support a conclusion that young adolescent women can safely and
effectively use Plan B for emergency contraception without the professional supervision of a
licensed practitioner, and 2) an amended proposal submitted by the sponsor during the review
Page 2 - The Honorable Sheila Jackson Lee

cycle to change the requested indication to allow for marketing of Plan B as a presc ri ption
only product for women under 16 years of age an d a nonprescription product for women 16
years and older was incomplete and inadequate for a full review . This message was
conveyed to the sponsor by the then-Acting Director of FDA's Center for Drug Evaluation
and Research ( CDER) with a full explanation of the reasons behind FDA's decision in a Not
Approvable lett er dated May 6, 2004, (copy enclosed) and available online at:
www;fda.gov/cder/drug/infopage/p1anB NALetter .pdf.

That decision by the Acting Director of CDER was made after full review of all the
underlying data and analysis and after discussions with all of the appropriate Agency
personnel . This decision was based on his assessment that the data in the supplemental
application did not contain sufficient information about whether younger adolescent women
could understand the label and use the product safely and effectively for emergency
contraception without the professional supervision of a licensed practitioner . Therefore, the
data in the application did not support approval of the supplement . In its Not Approvable
letter to the sponsor, FDA outlined some additional information that would be required for
approval to market Plan B as an OTC drug . The issuance of a Not Approvable letter did not
mean that a supplemental application could not or would not be approved in the future .

In July 2004, the drug's sponsor amended its supplemental application seeking to make
Plan B an OTC product for women age 16 and over, and to have it remain prescription only
for women under age 16 . The company also sought to market Plan B in a single package,
and sold either as prescription only or OTC, depending on the age of the purchaser .

In August 2005, FDA wrote a letter to the Duramed Research, Inc ., (copy enclosed and
available at : http ://www.fda.gov/cder/drug/in. f'opage/planB/Plan_B_letter20050826.pdf)
stating that FDA had completed its review of the applica ti on and that the scientific data
supported the safe and effective use of Plan B as an OTC product for women ages 17 and
over. FDA also stated, however, that it was unable at that time to reach a fi nal decision on
the approvability of the application due to unresolved issues that related to the applicati on .

In the le tter to the sponsor, FDA iden ti fied three difficult and novel issues presented by the
application, issues for which the Agency is commi tt ed to a process for resolving . That
process was initiated with the publication on September 1, 2005, of an Advance Notice of
Proposed Rulemaking (ANPRM) in the Federal Register seeking comment on questions
related to section 503(b) of the Federal Food, Drug, an d Cosmetic (FD&C) Act (Title 21,
United States Code , section 353(b)). The questions the interested part ies were asked to
respond to concern when an active ingredient of a drug may be simultaneously marketed as
both a presc ription and as an OTC drug product, whether and how OTC availability of a
product could be rest ri cted to a particular subpopulation, and whether the same packaged
product could be sold either as prescription only or OTC, depending on the age of the
purchaser . A related concern is how, as a practical ma tt er, an age-based distinction could be
enforced .

As the Agency has said many times during the course of the review of this application, the
questions that FDA was asked to answer, and the proposal that was put forward by the
Page 3 - The Honorable Sheila Jackson Lee

sponsor, presented the Agency with many very difficult and novel policy and regulatory
questions . In some cases, the questions requiring an FDA response were unprecedented for
this Agency.

An ANPRM is a mechanism to ask for public comments on whether the Agency should
initiate a rulemaking to codify our interpretation of section 503(b) of the FD&C Act regarding
when an active ingredient can simultaneously be marketed in both a prescription drug product
and an OTC drug product for the same indication, strength, dosage form- and route of
administration . Although the Agency typically solicits public comment for a minimum of 90
days when initiating this type of process, in the interest of moving quickly on this issue, the
comment period was shortened to 60 days for this ANPRM . The public comment period on
these questions closed as of November 1, 2005, and FDA is reviewing the comments and
letters it received . While we cannot put an exact timeline on how long it will take to process
these comments, we are committed to moving forward as quickly as possible .

Notwithstanding the outcome of the rulemaking process, there remain deficiencies in the
sponsor's application . For example, as set forth in the letter FDA sent to Duramed Research,
Inc ., on August 26, 2005, while the application sought approval for the switch for ages 16 and
older, CDER found that the data supported only for ages 17 and older . Moreover, the
outcome of FDA's rulemaking process may impact the approvability of the proposed
packaging and the use of age as a criterion on which to base a distinction between OTC and
prescription use. Accordingly, Duramed may need to amend its supplemental application .
Please note, however, that as FDA's August 26 letter to Duramed describes, CDER has
completed its scientific review of their pending supplemental application .

The Agency has found that considerable misinformation has circulated about this application
and the reasons FDA has taken the actions it has to this point . So there will be no confusion
about the public statements FDA actually has made concerning the Barr/Duramed Plan
B/OTC application, in addition to the two letters to the sponsor mentioned above, we are
enclosing copies of the two press releases dated May 7, 2004, and August 26, 2005, that the
Agency issued concerning this application .

Thank you again for your interest in this matter . If we can be of further assistance, please let
us know . A similar response is being sent to each of the other co-signers of your letter.

Sincerely ,

id W . Boyer
Assistant Commissioner
for Legislation

4 Enclosures
DEPARTMENT OF HEALTH & HUMAN SERVICES

Food and Drug Administration

Rockville MD 20857

The Honorable Dennis J . Kucinich

House of Representatives
Washington, D . C . 20515-3510 MAY 1 1 200 6

Dear Mr. Kucinich :

Thank you for the letter of January 19, 2005, co-signed by fifty-one of your colleagues, in
which you express your views about the Food and Drug Administration's (FDA or the
Agency) processing of the supplemental new drug application from Barr Laboratories (now
owned by Duramed Research, Inc .) that proposes to change the marketing status of the drug,
Plan B, from prescription only to over-the-counter (OTC) . We would like to take this
opportunity to clarify below the current status of the Agency's activities concerning this
application .

As you know, FDA is charged by Congress with reviewing new drug applications (NDA) to
determine a proposed new product's safety and effectiveness for the uses put forth by the
manufacturer in the application . As a science-based agency, it is FDA that must make that
final determination on whether an application for a product adequately demonstrates that the
data presented supports the proposed uses stated by the manufacturer in the proposed labeling .
A product cannot be approved until FDA determines that the product is safe and effective for
the indications stated in the proposed labeling .

Your lett er referenced the 23-4 vote taken at the joint advisory committee meeting in
December 2003, recommending that Pl an B be sold OTC. Advisory commi ttee opinions are
advisory in nature an d are not binding on the Agency. Since the final determination on any
NDA always is the responsibility of FDA, it is up to the Agency to clarify any unanswered
questions that may remain after the close of an advisory commi ttee meeting or that were
identified during the meeting, even though a vote may have been taken on the main
question(s) before the commi ttee . The busy schedules of the commi ttee members require that
advisory committee meetings be scheduled well in advance . We certainly value the input
from advisory commi tt ee members and the opportunity to hear an exchange of ideas on
proposed new products from expe rt s in their respective scienti fi c fields . It should not be
presumed, however, . that a favorable vote by an adviso ry committee automatically me ans that
a product is ready to go to the pharmacy shelves .

In May of 2004, FDA completed its first review of the NDA to switch Plan B to OTC, an d
concluded that the application could not be approved at that time because : 1) adequate data
were not provided to support a conclusion that young adolescent women can safely and
effectively use Plan B for emergency contraception without the professional supervision of a
licensed practitioner, and 2) an amended proposal submitted by the sponsor during the review
Page 2 - The Honorable Dennis J . Kucinich

cycle to chan ge the requested indication to al low for marketing of Plan B as a presc ription
only product for women under 16 years of age an d a nonpresc ri ption product for women 16
years and older was incomplete and inadequate for a full review . This message was
conveyed to the sponsor by the then-Acting Director of FDA's Center for Drug Evaluation
and Research (CDER) with a full explanation of the reas ons behind FDA's decision in a Not
Approvable le tter dated May 6, 2004, (copy enclosed) and available online at :
www.fda .gov/cder/drug/infopage/p1anB_NALetter .pdf.

That decision by the Acting Director of CDER was made after full review of all the
underlying data and analysis and after discussions with all of the appropriate Agency
personnel . This decision was based on his assessment that the data in the supplemental
application did not contain sufficient information about whether younger adolescent women
could understand the label and use the product safely and effectively for emergency
contraception without the professional supervision of a licensed practitioner . Therefore, the
data in the application did not support approval of the supplement . In its Not Approvable
letter to the sponsor, FDA outlined some additional information that would be required for
approval to market Plan B as an OTC drug . The issuance of a Not Approvable letter did not
mean that a supplemental application could not or would not be approved in the future . '

In July 2004, the drug's sponsor amended its supplemental application seeking to make
Plan B an OTC product for women age 16 and over, and to have it remain prescription only
for women under age 16 . The compan y also sought to market Pl an B in a single package,
and sold either as prescri ption only or OTC, depending on the age of the purchaser.

In August 2005, FDA wrote a lett er to the Duramed Research, Inc ., ( copy enclosed and
available at : http ://www.fda .gov/cder/drug/infopage/p1anB/Plan_B letter20050826 .pdJ)
stating that FDA had completed its review of the application and that the scientifi c data
supported the safe and effective use of Plan B as an OTC product for women ages 17 an d
over . FDA also stated, however, that it was unable at that time to reach a final decision on
the approvability of the application due to unresolved issues that related to the application .

In the letter to the sponsor, FDA identified three di fficult and novel issues presented by the
application, issues for which the Agency is commi tt ed to a process for resolving . That
process was initiated with the publication on September 1, 2005, of an Advance Notice of
Proposed Rulemaking (ANPRM) in the Federal Register seeking comment on questions
related to section 503(b) of the Federal Food, Drug, and Cosmetic (FD&C) Act (Title 21,
United States Code section 353(b)). The questions the interested pa rties were asked to
respond to concern when an active ingredient of a drug may be simultaneously marketed as
both a prescription and as an OTC drug product, whether an d how OTC availability of a
product could be restricted to a particular subpopulation, and whether the same packaged
product could be sold either as prescri ption only or OTC, depending on the age of the
purchaser . A related conce rn is how, as a practical ma tter, an age-based distinction could be
enforced .

As the Agency has said many times during the course of the review of this application, the
questions that FDA was asked to answer, and the proposal that was put forward by the
Page 3 - The Honorable Dennis J . Kucinich

sponsor, presented the Agency with many very difficult and novel policy and regulatory
questions . In some cases, the questions requiring an FDA response were unprecedented for
this Agency .

An ANPRM is a mechanism to ask for public comments on whether the Agency should
initiate a rulemaking to codify our interpretation of section 503(b) of the FD&C Act regarding
when an active ingredient can simultaneously be marketed in both a prescription drug product
and an OTC drug product for the same indication, strength, dosage form and route of
administration. Although the Agency typically solicits public comment for a minimum of 90
days when initiating this type of process, in the interest of moving quickly on this issue, the
comment period was shortened to 60 days for this ANPRNI : The public comment period on
these questions closed as of November 1, 2005, and FDA is reviewing the comments and
letters it received . While we cannot put an exact timeline on how long it will take to process
these comments, we are committed to moving forward as quickly as possible .

Notwithstanding the outcome of the rulemaking process, there remain deficiencies in the
sponsor's application . For example, as set forth in the letter FDA sent to Duramed Research,
Inc ., on August 26, 2005, while the application sought approval for the switch for ages 16 and
older, CDER found that the data supported only for ages 17 and older . Moreover, the
outcome of FDA's rulemaking process may impact the approvability of the proposed
packaging and the use of age as a criterion on which to base"a distinction between OTC and'
prescription use . Accordingly, Duramed may need to amend its supplemental application .
Please note, however, that as FDA's August 26 letter to Duramed describes, CDER has
completed its scientific review of their pending supplemental application .

The Agency has found that considerable misinformation has circulated about this application
and the reasons FDA has taken the actions it has to this point . So there will be no confusion
about the public statements FDA actually has made concerning the Barr/Duramed Plan
B/OTC application, in addition to the two letters to the sponsor mentioned above, we are
enclosing copies of the two press releases dated May 7, 2004, and August 26, 2005, that the
Agency issued concerning this application .

Thank you again for your interest in this matter . If we can be of further assistance, please let
us know . A similar response is being sent to each of the other co-signers of your letter .

Sincerely,

id W . Boyer
Assistant Commissioner
for Legislation

4 Enclosures .
 DEPARTMENT OF HEALTH & HUMAN SERVICE S
$~ _ .. .. : - . . .- . ,.>: ..:- .

Food and Drug Administration

Rockville MD 20857

The Honorable Jim McDermo tt

House of Representatives
W ashington, D. C . 20515-470 7 MAY 1 1 200 6

Dear Mr. McDermott :

Thank you for the letter of January 19, 2005, co-signed by fifty-one of your colleagues, in
which you express your views about the Food and Drug Administration's (FDA or the
Agency) processing of the supplemental new drug application from Barr Laboratories (now
owned by Duramed Research, Inc .) that proposes to change the marketing status of the drug,
Plan B, from prescription only to over-the-counter (OTC) . We would like to take this
opportunity to clarify below the current status of the Agency's activities concerning this
application.

As you know, FDA is charged by Congress with reviewing new drug applications (NDA) to
determine a proposed new product's safety and effectiveness for the uses put forth by the
manufacturer in the application . As a science-based agency, it is FDA that must make that
final determination on whether an application for a product adequately demonstrates that the
data presented supports the proposed uses stated by the manufacturer in the proposed labeling .
A product cannot be approved until FDA determines that the product is safe and effective for
the indications stated in the proposed labeling .

Your letter referenced the 23-4 vote taken at the joint advisory committee meeting in
December 2003, recommending that Plan B be sold OTC . Advisory committee opinions are
advisory in nature and are not binding on the Agency . Since the final determination on any
NDA always is the responsibility of FDA, it is up to the Agency to clarify any unanswered
questions that may remain after the close of an advisory committee meeting or that were
identified during the meeting, even though a vote may have been taken on the main
question(s) before the committee . The busy schedules of the committee members require that
advisory committee meetings be scheduled well in advance . We certainly value the input
from advisory committee members and the opportunity to hear an exchange of ideas on
proposed new products from experts in their respective scientific fields . It should not be
presumed, however, that a favorable vote by an advisory committee automatically means that
a product is ready to go to the pharmacy shelves .

In May of 2004, FDA completed its first review of the NDA to switch Plan B to OTC, and
concluded that the application could not be approved at that time because : 1) adequate data
were not provided to support a conclusion that young adolescent women can safely and
effectively use Plan B for emergency contraception without the professional supervision of a
licensed practitioner, and 2) an amended proposal submitted by the sponsor during the review
Page 2 - The Honorable Jim McDermot t

cycle to change the requested indication to allow for marketing of Plan B as a prescription
only product for women under 16 years of age and a nonprescription product for women 16
years and older was incomplete and inadequate for a full review. This message wa s
conveyed to the sponsor by the then-Acting Director of FDA's Center for Drug Evaluation
and Research (CDER) with a full explanation of the reasons behind FDA's decision in "a Not
Approvable letter dated May 6, 2004, (copy enclosed) and available onlme at :
www .fda .gov/cder/drug/infopage/planB_NALetter .pdf.

That decision by the Acting Director of CDER was made after full review of all the
underlying data and analysis and after discussions with all of the appropriate Agency
personnel . This decision was based on his assessment that the data in the supplemental
application did not contain sufficient information about whether younger adolescent women
could understand the label and use the product safely and effectively for emergency
contraception without the professional supervision of a licensed practitioner. Therefore, the
data in the application did not support approval of the supplement . In its Not Approvable
letter to the sponsor, FDA outlined some additional information that would be required for
approval to market Plan B as an OTC drug . The issuance of a Not Approvable Ietter did not
mean that a supplemental application could not or would not be approved in the future.

In July 2004, the drug's sponsor amended its supplemental application seeking to make
Plan B an OTC product for women age 16 and over, and to have it remain presc ription only
for women under age 16 . The company also sought to market Plan B in a single package,
and sold either as prescription only or OTC, depending on the age of the purchaser .

In August 2005, FDA wrote a letter to the Duramed Research, Inc ., (copy enclosed and
available at : http ://www.fda.gov/cder/drug/infopage/plan)Plan_B_Zetter20050826pdf)
stating that FDA had completed its review of the applicarion'and that the scientific_ data
supported the safe and effective use of Plan B as an OTC product for women ages 17 and
over, FDA also stated, however, that it was unable at that time to reach a final decision on
the approvability of the application due to unresolved issues that related to the application .

In the letter to the sponsor, FDA identified three difficult and novel issues presented by the
application, issues for which the Agency is committed to a process for resolving . That
process was initiated with the publication on September 1, 2005, of an Advance Notice of
Proposed Rulemaking (ANPRM) in the Federal Register seeking comment on questions
related to section 503(b) of the Federal Food, Drug, and Cosmetic'(FD&C) Act (Title 21 ;
United States Code , section 353(b)) . The questions the interested parties were asked to
respond to concern when an active ingredient of a drug may be simultaneously marketed as
both a prescription and as an OTC drug product, whether and how OTC availability of a'
product could be restricted to a particular subpopulation, and whether the same packaged
product could be sold either as prescription only or OTC, depending on the age of the
purchaser . A related concern is how, as a practical matter, an age-based distinction could be
enforced .

As the Agency has said many times during the course of the review of this application, the
questions that FDA was asked to answer, and the proposal that was put forward by the
Page 3 - The Honorable Jim McDermot t

sponsor, presented the Agency with many very difficult and novel policy and regulatory
questions . In some cases, the questions requiring an FDA response were unprecedented for
this Agency.

An ANPRM is a mechanism to ask for public comments on whether the Agency should
initiate a rulemaking to codify our interpretation of section 503(b) of the FD&C Act regarding
when an active ingredient can simultaneously be marketed in both a prescription drug product
and an OTC drug product for the same indication, strength, dosage form and route of
administration . Although the Agency typically solicits public comment for a minimum of 90
days when initiating this type of process, in the interest of moving quickly on this issue, the
comment period was shortened to 60 days for this ANPRM . The public comment period on
these questions closed as of November 1, 2005, and FDA is reviewing the comments and
letters it received . While we cannot put an exact timeline on how long it will take to process
these comments, we are committed to moving forward as quickly as possible .

Notwithstanding the outcome of the rulemaking process, there remain deficiencies in the
sponsor's application . For example, as set forth in the letter FDA sent to Duramed Research,
Inc., on August 26, 2005, while the application sought approval for the switch for ages 16 and
older, CDER found that the data supported only for ages 17 and older . Moreover, the
outcome of FDA's rulemaking process may impact the approvability of the proposed
packaging and the use of age as a criterion on which to base a distinction between OTC and
prescription use . Accordingly, Duramed may need to amend its supplemental application .
Please note, however, that as FDA's August 26 letter to Duramed describes, CDER has
completed its scientific review of their pending supplemental application.

The Agency has found that considerable misinformation has circulated about this application
and the reasons FDA has taken the actions it has to this point . So there will be no confusion
about the public statements FDA actually has made concerning the Barr/Duramed Plan
B/OTC application, in addition to the two le tt ers to the sponsor mentioned above, we are
enclosing copies of the two press releases dated May 7, 2004, and August 26, 2005; that the
Agency issued conce rn ing this application .

Thank you again for your interest in this matter . If we can be of further assistance, please let
us know. A similar response is being sent to each of the other co-signers of your letter .

Sincerely,

id W . Boyer
Assistant Commissioner
for Legislatio n

4 Enclosures
DEPARTMENT OF HEALTH & HUMAN SERVICE S

Food and Drug Administration

Rockville MD 20857

The Honorable Adam Smith

House of Representatives MAY 1 1 2006
Washington, D . C . 20515-470 9

Dear Mr . Smith :

Thank you for the letter of January 19, 2005, co-signed by fifty-one of your colleagues, in
which you express your views about the Food and Drug Administration's (FDA or the
Agency) processing of the supplemental new drug application from Barr Laboratories (now
owned by Duramed Research, Inc .) that proposes to change the marketing status of the drug,
Plan B, from prescription only to over-the-counter (OTC) . We would like to take this
opportunity to clarify below the current status of the Agency's activities concerning this
application .

As you know, FDA is charged by Congress with reviewing new drug applications (NDA) to
determine a proposed new product's safety and effectiveness for the uses put forth by the
manufacturer in the application . As a science-based agency, it is FDA that must make that
final determination on whether an application for a product adequately demonstrates that the
data presented supports the proposed uses stated by the manufacturer in the proposed labeling .
A product cannot be approved until FDA determines that the product is safe and effective for
the indications stated in the proposed labeling .

Your letter referenced the 23-4 vote taken at the joint advisory committee meeting in
December 2003, recommending that Plan B be sold OTC . Advisory committee opinions are
advisory in nature and are not binding on the Agency . Since the
__ ._final
. : . ,_.determination
. . ._ on any
NDA always is the responsibility ofFDA, it is up to the Agency to clarify anyunanswered
questions that may remain after the close of an advisory committee meeting or that were
identified during the meeting, even though a vote may have been taken on the main
question(s) before the committee . The busy schedules of the committee members require that
advisory committee meetings be scheduled well in advance . We certainly value the input
from advisory committee members and the opportunity to hear an exchange of ideas on
proposed new products from experts in their respective scientific fields . It should not be
presumed, however, that a favorable vote by an advisory committee automatically means that
a product is ready to go to the pharmacy shelves .

In May of 2004, FDA completed its first review of the NDA to switch Plan B to OTC, and
concluded that the application could not be approved at that time because : 1) adequate data
were not provided to support a conclusion that young adolescent women can safely and
effectively use Plan B for emergency contraception without the professional supervision of a
licensed practitioner, and 2) an amended proposal submitted by the sponsor during the review
Page 2 - The Honorable Adam Smith

cycle to change the requested indication to allow for marketing of Plan B as a presc ription
only product for women under 16 years of age and a nonprescription product for women 16
years and older was incomplete and inadequate for a full review . This message wa s
conveyed to the sponsor by the then-Acting Director of FDA's Center for Drug Evaluation
an d Research (CDER) with a full explanation of the reasons behind FDA's decision in a Not
Approvable lett er dated May 6, 2004, (copy enclosed) and available online at :
www.fda .gov/cder/drug/infopage/planB NALetter .pdf.

That decision by the Acting Director of CDER was made after full review of all the
underlying data an d an alysis and after discussions with all of the approp riate Agency
personnel . This decision was based on his assessment that the data in the supplemental
application did not contain sufficient information about whether younger adolescent women
could understand the label and use the product safely and effectively for emergency
contraception without the professional supervision of a licensed practitioner . Therefore, the
data in the application did not support approval of the supplement . In its Not Approvable
letter to the sponsor, FDA outlined some additional information that would be required for
approval to market Plan B as an OTC drug . The issuance of a Not Approvable letter did not
mean that a supplemental application could not or would not be approved in the future .

In July 2004, the drug's sponsor amended its supplemental application seeking to make
Plan B an OTC product for women age 16 and over, and to have it remain prescription only
for women under age 16 . The compan y also sought to market Plan B in a single package,
an d sold either as presc ription only or OTC, depending on the age of the purchaser.

In August 2005, FDA wrote a letter to the Duramed Research, Inc ., (copy enclosed and
available at : http ://www.fda .gov/cder/drug/infopage/planB/Plan B_letter20050826 .pdf)
stating that FDA had completed its review of the application an d that the scientific dat a
supported the safe and effective use of Plan B as an OTC product for women ages 17 and
over. FDA also stated, however, that it was unable at that time to reach a final decision on
the approvability of the application due to unresolved issues that related to the application .

In the lett er to the sponsor, FDA identified three difficult and novel issues presented by the
application, issues for which the Agency is committed to a process for resolving. That
process was initiated with the publication on September 1, 2005, of an Advance Notice of
Proposed Rulemaking (ANPRM) in the Federal Register seeking comment on questions
related to section 503(b) of the Federal Food, Drug, an d Cosmetic (FD&C) Act (Title 21,
United States Code , section 353(b)) . The questions the interested parties were asked to
respond to concern when an active ingredient of a drug may be simult aneously marketed as
both a prescription and as an OTC drug product, whether and how OTC availability of a
product could be rest ri cted to a pa rticular subpopulation, and whether the same packaged
product could be sold either as prescription only or OTC, depending on the age of the
purchaser. A related concern is how, as a practical ma tter, an age-based distinction could be
enforced .

As the Agency has said many times during the course of the review of this application, the
questions that FDA was asked to answer, and the proposal that was put forward by the
Page 3 - The Honorable Adam Smith

sponsor, presented the Agency with many very difficult and novel policy and regulatory
questions . In some cases, the questions requiring an FDA response were unprecedented for
this Agency .

An ANPRM is a mechanism to ask for public comments on whether the Agency should
initiate a rulemaking to codify our interpretation of section 503(b) of the FD&C Act regarding
when an active ingredient can simultaneously be marketed in both a prescription drug product
and an OTC drug product for the same indication, strength, dosage form and route of
administration . Although the Agency typically solicits public comment for a minimum of 90
days when initiating this type of process, in the interest of moving quickly on this issue, the
comment period was shortened to 60 days for this ANPRM . The public comment period on
these questions closed as of November 1, 2005, and FDA is reviewing the comments and
letters it received . While we cannot put an exact timeline on how long it will take to process
these comments, we are committed to moving forward as quickly as possible .

Notwithstanding the outcome of the rulemaking process, there remain deficiencies in the
sponsor's application . For example, as set forth in the letter FDA sent to Duramed Research,
Inc ., on August 26, 2005, while the application sought approval for the switch for ages 16 and
older, CDER found that the data supported only for ages 17 and older . Moreover, the
outcome of FDA's rulemaking process may impact the approvability of the proposed
packaging and the use of age as a criterion on which to base a distinction between OTC and
prescription use . Accordingly, Duramed may need to amend its supplemental application .
Please note, however, that as FDA's August 26 letter to Duramed describes, CDER has
completed its scientific review of their pending supplemental application .

The Agency has found that considerable misinformation has circulated about this application
and the reasons FDA has taken the actions it has to this point . So there will be no confusion
about the public statements FDA actually has made concerning the Barr/Duramed Pla n
B/OTC application, in addition to the two letters to the sponsor mentioned above, we are
enclosing copies of the two press releases dated May 7, 2004, and August 26, 2005, that the
Agency issued concerning this application .

Thank you again for your interest in this matter . If we c an be of further assist ance, please let
us know . A similar response is being sent to each of the other co-signers of your le tter .

Sincerely ,

id W . Boyer
Assistant Commissioner
for Legislatio n

4 Enclosures
 , uRVrct
,e~ G~
DEPARTMENT OF HEALTH & HUMAN SERVICES
a~.iM1 Z
Food and Drug Administration
Rockville MD 2085 7

The Honorable John Conyers, Jr .

House of Representatives MAY 1 1 2006
Washington, D . C . 20515-221 4

Dear Mr . Conyers :

Thank you for the letter of January 19, 2005, co-signed by fifty-one of your colleagues, in
which you express your views about the Food and Drug Admiriistration's (FDA or the
Agency) processing of the supplemental new drug application from Barr Laboratories (now
owned by Duramed Research, Inc .) that proposes to change the marketing status of the drug,
Plan B, from prescription only to over-the-counter (OTC) . We would like to take this
opportunity to clarify below the current status of the Agency's activities concerning this
application .

As you know, FDA is charged by Congress with reviewing new drug applications (NDA) to
determine a proposed new product's safety and effectiveness for the uses put forth by the
manufacturer in the application. As a science-based agency, it is FDA that must make that
final determination on whether an application for a product adequately demonstrates that the
data presented supports the proposed uses stated by the manufacturer in the proposed labeling .
A product cannot be approved until FDA determines that the product is safe and effective for
the indications stated in the proposed labeling .

Your letter referenced the 23-4 vote taken at the joint advisory committee meeting in
December 2003, recommending that Plan B be sold OTC . Advisory committee opinions are
advisory in nature and are not binding on the Agency . Since the final determination on any
NDA always is the responsibility of FDA, it is up to the Agency to clarify any unanswered
questions that may remain after the close of an advisory committee meeting or that were
identified during the meeting, even though a vote may have been taken on the main
question(s) before the committee . The busy schedules of the committee members require that
advisory committee meetings be scheduled well in advance . We certainly value the input
from advisory committee members and the opportunity to hear an exchange of ideas on
proposed new products from experts in their respective scientific fields . It should not be
presumed, however, that a favorable vote by an advisory committee automatically means that
a product is ready to go to the pharmacy shelves .

In May of 2004, FDA completed its first review of the NDA to switch Plan B to OTC, and
concluded that the application could not be approved at that time because : 1) adequate data
were not provided to support a conclusion that young adolescent women . . can
. . safely an d
effectively use Plan B for emergency contraception without the professional supervision of a
licensed practitioner, and 2) an amended proposal submitted by the sponsor during the review
Page 2 - The Honorable John Conyers, Jr.

cycle to ch ange the requested indication to allow for marketing of Plan B as a presc ription
only product for women under 16 years of age and a nonprescription product for women 16
years an d older was incomplete and inadequate for a full review . This message wa s
conveyed to the sponsor by the then-Acting Director of FDA's Center for Drug Evaluation
an d Research (CDER) with a full explanation of the reasons behind FDA's decision in a Not
Approvable letter dated May 6, 2004, ( copy enclosed) and available online at :
www .fda .gov/cder/drug/infopage/planB NALetter .pdf.

That decision by the Acting Director of CDER was made after full review of all the
underlying data and analysis and after discussions with all of the appropriate Agency
personnel . This decision was based on his assessment that the data in the supplemental
application did not contain sufficient information about whether younger adolescent
.1._., . . wome n :
. ._, ._ ._
could understand the label and use the product safely and effectively for emergenc y
contraception without the professional supervision of a licensed practitioner . Therefore, the
data in the application did not support approval of the supplement . In its Not Approvable
letter to the sponsor, FDA outlined some additional information that would be required for
approval to market Plan B as an OTC drug . The issuance of a Not Approvable letter did not
mean that a supplemental application could not or would not be approved in the future .

In July 2004, the drug's sponsor amended its supplemental application seeking to make
Plan B an OTC product for women age 16 and over, and to have it remain prescription only
for women under age 16 . The company also sought to market Plan B in a single package,
and sold either as prescription only or OTC, depending on the age of the purchaser .

In August 2005, FDA wrote a letter to the Duramed Research, Inc ., (copy enclosed and
available at : http ://www.fda.gov/cder/drug/infopage/planB/Plan_B_letter20050826 .pd~
stating that FDA had completed its review of the application and that the scientific data
supported the safe and effective use of Plan B as an OTC product for women ages 17 and
over . FDA also stated, however, that it was unable at that time to reach a final decision on
the approvability of the application due to unresolved issues that related to the application .

In the letter to the sponsor, FDA identified three difficult and novel issues presented by the
application, issues for which the Agency is committed to a process for resolving . That
process was initiated with the publication on September 1, 2005, of an Advance Notice of
Proposed Rulemaking (ANPRM) in the Federal Register seeking comment on questions
related to section 503(b) of the Federal Food, Drug, and Cosmetic (FD&C) Act (Title 21,
United States Code , section 353(b)) . The questions the interested parties were asked to
respond to concern when an active ingredient of a drug may be simultaneously marketed as
both a prescription and as an OTC drug product, whether and fiow OTC availability of a
product could be restricted to a particular subpopulation, and whether the same packaged
product could be sold either as prescription only or OTC, depending on the age of the
purchaser. A related concern is how, as a practical matter, an age-based distinction could be
enforced .

As the Agency has said many times during the course of the review of this application, the
questions that FDA was asked to answer, and the proposal that was put forward by the
Page 3 - The Honorable John Conyers, Jr.

sponsor, presented the Agency with many very difficult and novel policy and regulatory
questions . In some cases, the questions requi ri ng an FDA response were unprecedented for
this Agency .

An ANPRM is a mechanism to ask for public comments on whether the Agency should
initiate a rulemaking to codify our interpretation of section 503(b) of the FD&C Act regardin_ g
when an active ingredient can simultaneously be marketed in both a prescription drug product
and an OTC drug product for the same indication, strength, dosage form and route of .:. .._ .
administration . Although the Agency typically solicits public comment for aminimum of 90
days when initiating this type of process, in the interest of moving quickly on this issue, the
comment period was shortened to 60 days for this ANPRM . The public comment period on
these questions closed as of November 1, 2005, and FDA is reviewing the comments and
letters it received . While we cannot put an exact timeline on how long it will take to process
these comments, we are committed to moving forward as quickly as possible .

Notwithstanding the outcome of the rulemaking process, there remain deficiencies in the
sponsor's application . For example, as set forth in the letter FDA sent to Duramed Research,
Inc., on August 26, 2005, while the application sought approval for the switch for ages 16 and
older, CDER found that the data supported only for ages 17 and older . Moreover, the
outcome of FDA's rulemaking process may impact the approvability of the proposed
packaging and the use of age as a criterion on which to base a distinction between OTC and
prescription use . Accordingly, Duramed may need to amend its supplemental application .
Please note, however, that as FDA's August 26 letter to Duramed describes, CDER fias
completed its scientific review of their pending supplemental application .

The Agency has found that considerable misinformation has circulated about this application
and the reasons FDA has taken the actions it has to this point. So there will be no confusion
about the public statements FDA actually has made concerning theBai7/Duramed Pla n
B/OTC application, in addition to the two letters to the sponsor mentioned above, we are
enclosing copies of the two press releases dated May 7, 2004, and August 26, 2005, that the
Agency issued concerning this application .

Thank you again for your interest in this matter . If we can be of further assist ance, please let
us know . A similar response is being sent to each of the other co-signers of your l~tter
e ~ .'

Sincerely,

07 David W . Boyer
Assistant Commissione r
for Legislation

4 Enclosures