EXHIBIT 10.46


 


RELIANT PHARMACEUTICALS-PPD MEDICAL COMMUNICATIONS

PRODUCT SAFETY/PHARMACOVIGILANCE SERVICES (PSPV) AGREEMENT


 


This AGREEMENT, executed this 25th day of February, 2003, by and between Reliant Pharmaceuticals,
LLC, a New Jersey limited liability company, having a place of business at 110 Allen Road, Liberty Corner. NJ 07938, (hereinafter referred to as “CLIENT”), and ATP, LLC, dba PPD Medical Communications, a North Carolina limited liability company
(hereinafter referred to as “PPD”).


 


W  I  T  N  E  S
S  E  T  H:


 


WHEREAS, CLIENT maintains the Company Core
Safety information and the regulatory
reporting responsibilities for
the post-marketing Pharmacovigilance functions pertaining to the products covered in this contract;


 


WHEREAS, CLIENT retains
all responsibilities associated
with Marketing Authorization Holder (MAH)
for the product/products managed by PPD;


 


WHEREAS, PPD provides a central processing facility staffed by health care professionals, research
assistants, and data entry
specialists to receive, review, process, and assess adverse events (AEs);


 


WHEREAS, CLIENT desires
to retain PPD (1) to utilize a
specified validated database for the purpose of data entry, coding, and generating regulatory
sumbission-ready reports for AEs, (2)
to perform medical review of all AEs on
a regular basis, along with line
listing review and coding review, unless otherwise specified by mutual written agreement, and (3) to
maintain dedicated toll-free telephone numbers for CLIENT to enable call return and to maintain a separate toll-free
telephone numbers for CLIENT to enable call return and to maintain a separate
toll-free number for inbound/outbound faxes;


 


WHEREAS, PPD provides services to facilitate
completion of periodic reports/periodic safety update reports (PSURs) for the
product(s) indicated in this contract; and


 


WHEREAS, CLIENT retains the responsibility to approve the
final periodic report/PSUR along with submission to appropriate agencies.


 


NOW, THEREFORE, in consideration of the premises and mutual covenants
herein contained and other valuable consideration. the sufficiency of which is
hereby acknowledged. the parties hereby
agree as follows:


 


1.             Services Provided by PPD.


 


A.            General
Services. PPD shall provide Product
Safety/Pharmacovigilance services as herein described. PPD personnel selected for staffing the project will
receive documented training on project-specific standard operating procedures (“SOPS”), along with additional mining on CLIENTS products. CLIENT-specific toll-free telephone number(s) will be accessed by PPD exclusively to provide
services for CLIENT. The PPD telephone
access system will include queuing/auto
attendant and voice mail features
that facilitate PPD’s handling
of calls, and CLIENT will review
and approve the


 


 

















 


telephone system scripting prior to implementation by PPD. If CLIENT so requests in writing, and on reasonable advance
notice from CLIENT, PPD shall also provide backup Staff as
necessary upon mutual agreement. Services provided by PPD shall conform
to applicable local, state, and federal
laws, rules, and regulations in addition to agreed project-specific standard operating
procedures.


 


B.            Staff
Responses. When the Staff receives
queries not pertaining to product safety issues from consumers or health care professionals (“HCPs”), Staff will refer the consumer/HCP
to the Medical Information group handling such inquiries, or to their respective
primary health care provider. At no time
will the Staff offer therapeutic
PPD Medical Communications.


 


C.            PSPV
Services. PPD will process AEs, including
Serious Adverse Events (SAEs), for CLIENT according to
mutually agreed upon standard operating procedures and project specific protocols.
PPD will produce draft MedWatch reports
for CLIENT critique and revision.
PPD will produce a final
MedWatch form and send it to CLIENT via overnight carrier for final submission
to the agency. Similarly, PPD will
produce draft periodic reports for specified products covered under this
contract. Upon receipt of critique and revisions, PPD will return a final report to CLIENT for submission to the
agency. Depending on regulatory requirements,
a mutually agreed time line will
be developed with CLIENT for turnaround
of these reports. PPD will
assign a safety physician for this project.


 


i)              Non-Serious
AEs. PPD will handle adverse events, both expected and unexpected, in
accordance with mutually agreed project-specific protocols. PPD will send CLIENT a daily summary report
of all AEs no later than the next business day, unless
otherwise specified by CLIENT, following receipt. CLIENT will instruct PPD whether further action is necessary. Follow-up will be performed in accordance with
mutually agreed project-specific standard operating protocols. Completed case files
and source documents will be retained for a period of time determined by mutual agreement and in
accordance with applicable laws and regulations, and cases will
have been entered into the specified validated safety database.


 


ii)             SAEs. PPD will handle expected or unexpected SAEs in
accordance with mutually agreed
project-specific protocols. PPD will send to CLIENT a [***] summary report of all SAEs no later than the [***] following receipt. For
reportable events, PPD will send a draft MedWatch report to CLIENT for review and
comment within [***] of the initial notification. CLIENT will be responsible for submitting
this report to the agency within defined regulatory time frames. Follow-up will be done in accordance with
mutually negotiated project-specific protocols. PPD will provide SAE narratives
in agreed upon format, if so
requested by CLIENT. Completed case files and source documents will be
retained for a period of time determined by mutual agreement
and in accordance with applicable laws and regulations, and cases
will have been entered into the specified
validated safety database.


 


iii)            Medical
Review, AE/SAE documentation
will be reviewed upon initial receipt
and whenever substantive follow-up information is received. The safety physician will finalize the
determination of seriousness and expectedness
for each event. The
safety physician will finalize
scientific rationale and discussion


 






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with the Commission.  Confidential
treatment has been requested with respect to the omitted portions.


 


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(with references to the biomedical
literature) for expedited reportable unexpected
SAEs. The safety physician will also
approve the final draft of the MedWatch report and event narrative. All AEs/SAEs will be reviewed at least [***] for
trend analysis and coding
evaluation.


 


iv)           Periodic
Scientific Literature Surveillance. PPD
will process all AE/SAEs identified
as a result of regularly
scheduled systematic scientific literature surveillance. Unless otherwise
specified by CLIENT, scientific literature
surveillance will be performed
using a minimum of two databases (REACTIONS, Medline) at least monthly.
If requested, CLIENT will be provided with photocopies of scientific literature
which cite safety issues, for which CLIENT will be charged article procurement fees and copyright
clearance fees, including
translation fees for non-English language
articles, as per Attachment A.


 


v)            Periodic
report/PSUR. Upon request, and in collaboration with CLIENT, PPD will prepare periodic reports in an agreed upon format as
mandated by applicable regulatory agencies. CLIENT will provide all necessary information to enable
completion of the periodic report prior to the due date for the report. Failure
by CLIENT to provide all the
necessary information will result in a periodic report that may not meet all
regulatory requirements, and CLIENT will
assume all responsibility for such deficiencies. CLIENT will receive the draft
copy of the report for critique
and revision followed by a final
copy of the report for submission to the regulatory agency. PPD will provide
all available line listings and
tabulations, accompanying MedWatch forms, and necessary scientific literature references available to PPD.


 


D.            Project
Management. PPD shall perform Project management support which includes,
but is not limited to, oral and written communication with CLIENT, procedure and protocol development,
procedure and protocol maintenance, report
generation, training plan development, staff training. staff supervision and development,
quality assurance (including review of AE and product complaint reports),
consultative services, meeting preparation and conduction, and communication
with other third parties necessary to business
operations. Such services may be provided by Supervisor(s), Safety Coordination Specialist(s), Product Safety Manager(s), Quality Assurance
Personnel, Trainer(s), Associated Director(s), Director(s), Executive
Director(s), and/or Vice-President(s) and will be charged as stated on Attachment A.


 


E.             FDA
Issues. Immediately upon
receipt, but in no event later than one
business day after receipt thereof, PPD shall
provide CLIENT with a copy of any correspondence or notice it receives
from the FDA relating to products or services covered by this Agreement. Further,
PPD agrees to cooperate with CLIENT,
if requested, in corresponding with the FDA
or in filing any documents with respect to the products covered by this Agreement, as CLIENT deems necessary or desirable.
Such services will be charged as stated on Attachment A.


 


F.             Quality Assurance Procedures. PPD shall implement and maintain
quality assurance procedures and
will provide copies of such assurance procedures to CLIENT
upon request. As mutually agreed by CLIENT
and PPD, the quality assurance processes shall incorporate any reasonable standards which CLIENT provides to PPD in writing. At


 






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minimum, PPD will perform quality assurance
on [***]% of the cases processed by PPD. At CLIENT’S specific request, PPD can
perform additional quality assurance measures at a mutually agreed upon fee.
The selection of cases subject to quality assurance assessment will be random
and will be determined by the supervisory staff. Additional quality assurance
may be performed as requested by CLIENT and as mutually agreed in writing.


 


G.            Hours
of Coverage. The parties agree to staffing and
hours of coverage will be from 9AM until 5PM. Monday - Friday. All
times are Eastern Time.


 


H.            Answering
Telephone Lines. Safety staff will answer
incoming telephone calls with a
mutually agreed statement, which will be provided to CLIENT prior to use, similar to: “CLIENT [Safety Department], I am a pharmacist/nurse, and my name is (consultant name).”  Simultaneous incoming calls on CLIENT lines
will be held in queue, and the Staff will answer telephone
calls in the order in which they
were received. Until such time that PPD
can answer the telephone call, if
desired by CLIENT, a
recorded message may be played. If requested
by CLIENT, PPD can establish
voice mail capability to capture inbound
call information while the Staff
is answering other telephone calls, or
to capture information after hours.
The Staff will access voice mail multiple times throughout each business day to ensure that no adverse event
reports are lost to untimely
follow-up.


 


I.              Records Kept by PPD. Information gathered shall include that which CLIENT reasonably requests or PPD deems
important. PPD shall maintain
either written or computerized records in
accordance with applicable regulatory requirements and approved CLIENT protocols.
Upon termination of this Agreement
by either party, all records shall be returned to each party, upon request by the other,
except for one copy, which may
be kept for archival purposes.


 


J.             Reports. PPD will provide CLIENT reports as requested, provided adequate advance notice is given. Requests for reports other than those
routinely produced during normal AE/SAE
processing and periodic report generation will be charged as mutually agreed in writing.


 


K.            Other Services Provided. CLIENT may request PPD’s support in performing various other
services during the term of this
Agreement. These services
include medical information inquiries, literature searches, medical letter writing.
product launch support, and contingency operations management services. Such services shall be provided under a separate agreement between PPD and
CLIENT or by Amendment to this Agreement.


 


L.             Commencement
Date. As of the date of execution of this Agreement, the commencement date
for PPD staff to perform start-up, training, and protocol development for PSPV Support Services will be on or
before September 16, 2002 (the “Commencement Date”).


 


M.           Implementation
Date. As of the date of
execution of this Agreement, the targeted implementation date for PSPV Support Services will be September 9, 2002 (the


 






[***]: 
Certain information on this page has been omitted and filed separately
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treatment has been requested with respect to the omitted portions.


 


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“Implementation Date”). The Implementation Date may be modified only upon mutual written agreement by both
CLIENT and PPD.


 


2.             Obligations of CLIENT.


 


A.            Maintenance
for Call Forwarding Capabilities.
If applicable, CLIENT is
responsible for maintaining the call forwarding
capabilities of the CLIENT toll-free number(s) and shall bear all reasonable expenses incurred for such capabilities and for the
CLIENT toll-free number(s) telephone charges used in connection with his
Agreement.


 


B.            Maintenance
for Computer Linkage Capabilities. If applicable. CLIENT is responsible for maintaining the computer linkage
capabilities and shall bear all
reasonable expenses incurred for
such capabilities used in
connection with this Agreement.


 


C.            Inform
PPD of Any Unusual Circumstances.
If a situation is anticipated that may create an
unusually high volume of adverse
events (e.g., adverse press, product recall),
CLIENT shall notify PPD
of such situation prior to its occurrence, if possible, and shall provide PPD with complete
up-to-date information necessary for processing such events.


 


D.            Training
of PPD Employees. While PPD employees have received
specialized training in providing services
set forth in Section 1A and 1B of
this Agreement, certain additional training will be needed on CLIENT’s
products and procedures. CLIENT, at CLIENT’s sole expense, shall provide
training personnel and/or necessary training materials to PPD for the express
purpose of familiarizing PPD employees with CLIENT’s products or other information required to provide services hereunder. Additional training after the Implementation Date will be conducted as needed and as
mutually agreed upon, in writing, by CLIENT and PPD. Fees shall be
charged according to Attachment A.


 


E.             Quality
Assurance. CLIENT has the authority to audit PPD processes and procedures
that relate to CLIENT and materially impact
PPD’s role in fulfilling services for CLIENT in accordance with
established quality assurance procedures. CLIENT may audit PPD at any time during regular business
hours and agrees to give at least three (3) business days notice to PPD. Such audits may include, but are not limited to, PPD procedures,
files, and records associated
with this project.


 


3.             Term of Agreement. The term of this Agreement shall commence upon execution of this Agreement by both parties upon Commencement
Date, whichever is earlier, and shall continue unless terminated according to
Section 4. The parties shall review and
make adjustments to Attachment A on an annual basis beginning December 31. 2003.


 


4.             Termination. This Agreement may be terminated as follows:


 


A.            By
CLIENT or PPD without cause upon sixty (60)
days written notice to the other party.


 


B.            By
CLIENT or PPD immediately on notice to the other, if the other party shall fail
to make any undisputed payments within
thirty (30) days of the date
when due hereunder.


 


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C.            By
CLIENT or PPD, if the other
party shall default in the performance
of any term or condition of this
Agreement (other than nonpayment or moneys
owed), on thirty (30) days prior written notice to the
other, specifying the nature of the default, unless such defaulting party shall
cure that default within the thirty (30) day period.


 


D.            By CLIENT or PPD immediately on notice
to the other, if the other party shall make
an assignment for the benefit of
creditors, shall file a petition
in bankruptcy, is adjudicated insolvent or bankrupt, or if a receiver or
trustee is appointed with respect to a substantial part of such other party’s property or a
proceeding is commenced against it which
reasonably will impair substantially its ability to perform hereunder.


 


Upon termination
both parties shall be relieved
of any further obligations hereunder except those set forth in Sections 7, 8,
9, 10, 11, and 13 and payment
for services rendered set forth in Section 5. Termination shall not affect the rights or obligations of either party
accrued as of such
termination.


 


5.             Payments for Services Rendered by PPD.


 


A.            Resource Costs. CLIENT shall
compensate PPD for performance of services
rendered by PPD pursuant to this Agreement on a monthly basis. The invoice will include cases submitted for the preceding month and billable
hours and costs applied to the project according to the rates stated in Attachment A. When off-site travel
is requested by CLIENT staff time
will be billed at rates shown in
Attachment A. On or before November 15 of each year of this Agreement, the PPD Fee Structure for the
period beginning the following
January 1 through the following December
31 shall be adjusted by mutual
agreement of CLIENT and PPD,
unless already specified in the then current Attachment A. Any such
adjustment shall be reflected in
a replacement Attachment A that shall be
signed by an authorized representative
of CLIENT and of PPD. Should the replacement Attachment A not be executed before November 15, PPD’s standard Fee Structure for the following January 1 through December 31 shall apply, pending the execution and implementation of the
replacement Attachment A.


 


B.            Start-up, Technology, Project Management, and Additional Costs. CLIENT shall compensate PPD
for Start-up, Technology, Resource Costs, Project Management, and Additional Costs as set forth in Attachment A. Technology Costs
shall only be incurred upon prior written approval by CLIENT.


 


C.            Billing
and Payment. PPD shall submit monthly invoices to CLIENT
setting forth Resource Costs in
addition to applicable Start-up, Technology,
Project Management, and Additional Costs. Payment shall be due within thirty
(30) days of receipt of the invoice. PPD’s
federal tax identification number is 56-2203444.


 


D.            Noncancelable
Obligations. If this Agreement is terminated pursuant to Section 4 hereof,
PPD shall be compensated for all fees
and costs accrued and unpaid through the
date of termination and reasonable
“wrap-up” period. Promptly upon sending or receiving notice of termination of this Agreement for any reason, PPD
shall use all reasonable efforts to minimize any further costs and to promptly cancel all cancelable
commitments. In addition, PPD shall be reimbursed for any and all noncancelable
and reasonable obligations owed to third parties and incurred by PPD in
rendering the Services.


 


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6.             Independent Contractor Status. PPD is and at all times shall
be an independent contractor in the
performance of this Agreement and is not authorized to bind CLIENT to any agreement
or contract, of in any other
manner, with any third party. PPD shall
exercise control over its employees and
agents and shall be solely responsible
for the verification of
identity and employment eligibility,
for the payment of any wages, salaries. or other remuneration of its employees
and agents, and for the payment
of any payroll taxes, contributions for unemployment or workers compensation,
social security, pensions, or annuities which are imposed as a result of the employment
of PPD’s employees and/or
agents.


 


7.             Rights to Program and Other Property. All computer programs, including any
documentation relating thereto, and all trade
secrets, copyrights, and other intellectual and proprietary
rights, developed by PPD in connection
with the performance of services hereunder, are owned by and shall remain the exclusive proprietary
property of PPD. Such materials
shall be deemed confidential business information of PPD and subject to the
limitations and restrictions of Section
8 of this Agreement. Any data
or information generated by PPD as a result of inquiries received through the CLIENT toll-free number(s),
documents and information supplied to PPD by CLIENT or any patients or health care professionals
purchasing, using, or prescribing CLIENT products, including product package inserts, protocols, training
materials, and any reports or compilation of data, inquiries, or responses prepared by PPD in performing the services for CLIENT shall be referred to as “CLIENT
Information.” CLIENT Information shall be owned by CLIENT and, to the extent that
it is reduced to written form, CLIENT shall be deemed owner of the
copyright in relation to such materials. Such materials shall be deemed confidential business information of CLIENT and
subject to the limitations and restrictions of Section 8 of this
Agreement. Within five (5) business days
after the termination of this Agreement for any reason, the
CLIENT Information shall be returned to CLIENT except for one copy which may be kept for archival purposes only. PPD shall not
use CLIENT Information for any purpose other than carrying out the terms of
this Agreement.


 


8.             Confidential Information. CLIENT and PPD hereby acknowledge that their businesses involve the
development of valuable and confidential business information. “CLIENT
Confidential Information” shall mean
any information treated by CLIENT as confidential, including without limitation
CLIENT date and information relating
to AE’s received through CLIENT
toll-free number(s) treated by PPD as confidential, including PPD’s use of telephone services to
provide access to a wide variety of information on a national basis. During the
term of this Agreement, and for
a period of five (5) years following the
implementation of this Agreement, PPD and CLIENT agree that. without the
prior written consent of the other party, it shall not disclose to any third party nor use for any purposes
whatsoever, other than that set forth herein, any CLIENT Confidential Information
or PPD Confidential Information which has been disclosed by the other party
or by any other person or entity
on behalf of the other party or learned in the performance hereof. All Confidential
Information containing personal data
shall be handled in accordance with all application law, including, but
not limited to the European Data
Protection Directive [EC/95/46]. In
addition, neither party shall disclose the
essential terms of this
Agreement to any other entity or person. This obligation of non-disclosure does not extend to Confidential Information which was in the
possession of or known by either party prior to their receipt of the information
from the other party as
evidenced by written records; is or becomes available to the general public by
acts not attributable to a breach or default of an agreement by the other party; is hereafter furnished
to CLIENT or PPD by a third party as a matter of right without restriction on
disclosure; or that CLIENT or PPD is obligated to produce under Court or governmental
order, limited to the purposes and extent of such order, in which case either party will notify the
other as far in advance as possible to allow
the other party to challenge such production.
In addition, each party further
agrees to use its reasonable precaution to safeguard the confidentiality of all proprietary information and trade
secrets of the other party. Upon termination of this Agreement by either party,
all Confidential Information shall be returned to each party, upon request by the other, except for one copy which may be kept for archival
purposes. Neither party


 


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shall make any press releases during the term of this Agreement with
respect to the existence of this Agreement,
without the prior consent of the other party,
unless such disclosure is required by Law.


 


9.             Noninterference with Employees. Each party acknowledges that
the other’s employees have
received special training and have expertise in rendering services and are a
valuable and unique asset of such party’s business. During the period this Agreement in effect and for a one (1) year
period following the termination of this Agreement, party agrees that, without
the prior written consent of the other, it
shall neither hire any person who has been under the employment of the other during the term of
this Agreement nor shall it solicit any such person (i) to terminate his
or her
employment with such party or (ii) to become
associated with the other or its affiliates.
The following shall not be
deemed to prohibit a party from hiring an employee of the other as a result of
an unsolicited response by such employee to an open advertisement for
employment.


 


10.           Remedies. No adequate remedy at law may exist or be
available in the event of a breach or threatened breach of the covenants contained in Sections 7, 8 and 9. In the event of any breach or threatened
breach by CLIENT or PPD, the
other party shall be entitled to
seek injunctive relief, including a temporary restraining order and preliminary
injunction, without the posting of bond or other security restraining
such breach by the other party;
provided, however, that nothing
herein shall be construed as
prohibiting the other party from pursuing any other remedies available with
respect to such breach or threatened breach, including the recovery of damages.


 


11.           Indemnification. CLIENT shall indemnify and save
PPD harmless from any claim, loss, liability, or expense, including
reasonable attorneys’ fees,
which may be incurred by or asserted against
PPD as a result of or arising
from CLIENT’s breach or default of this Agreement, the negligence or
misconduct of CLIENT or its employees, or on account of the CLIENT data. PPD shall indemnify
and save CLIENT harmless from any claim,
loss, liability, or expense, including
reasonable attorneys’ fees, which may be
incurred by or asserted against
CLIENT as a result of or
arising from PPD’s breach or
default of this Agreement or from the negligence or misconduct of PPD or its employees
in performance of the services hereunder. The indemnifying party, provided it
properly notifies in advance and protects
the interests of the
other party, shall have the sole control of the defense of any such action which shall be exercised reasonably and of all negotiations for its settlement
or compromise, and the other party will provide, at the
indemnifying party’s expense, reasonable assistance in defending, at the indemnifying party’s discretion,
any claim, suit, or action. Neither party
shall settle or admit liability with respect to any such claims,
charges, suits or
other actions (which
could result in injury to the other party without the prior written
consent of the other party) which consent shall not be unreasonably withheld or delayed; provided. however, neither
party may settle a claim or
action related to a liability without the consent of the other party if such
settlement would impose any monetary obligation an the other party or
require the other party to submit to an
injunction or otherwise limit the other party’s rights under this Agreement.


 


12.           Insurance of PPD.
During the term of this
Agreement, PPD shall maintain in full force
and effect comprehensive general
liability insurance, including professional and contractual liability coverages,
with aggregate coverage of no
less than $2,000,000 single limit. If so requested
by CLIENT, PPD shall provide
CLIENT a certificate evidencing such insurance.
If the insurance is on a “claims made” basis,
if commercially available at a reasonable premium, PPD shall obtain coverage for at least seven (7)
years after termination of this Agreement,


 


13.           Liability: Disclaimers.


 


A.            Liability.
Except for acts constituting gross negligence or willful misconduct, neither party
shall be liable to the other under or in connection with this Agreement for


 


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special, indirect, consequential, punitive, or exemplary damages of any nature, including lost profits or
savings.


 


B.            Force
Majeure. Neither party shall be liable, in any manner, for failure to meet
its obligations pursuant to this Agreement
to the extent that such failure is caused
by matters which are beyond the
reasonable control of such party, including, without limitations, any delay of
carriers, supplies, or telecommunication providers, any extreme weather, any Act of God, or any Change of Law. “Change of Law” means any change in, or
binding change, in the judicial or administrative
interpretation of, or adoption of, any Law, which is implemented after the date
hereof. “Law” means any federal,
state. local, or other constitution,
charter, act, Statute, law, ordinance,
code, rule, regulations, order,
specified standards or subjective
criteria contained in any applicable permit or approval, or other
legislative or administrative action of the United States of America or any
state law agency, department
authority, political subdivision of other
instrumentality of either thereof, or a final decree, judgement, or order of a court. If the Force Majeure continues for more than thirty (30) days,
the party not suffering  the Force Majeure may terminate this Agreement
upon five (5) days written notice to the other party.


 


14.           Assignment and  Delegation
of Duties. Neither party
hereto may assign any of its rights or delegate any of its duties
hereunder without the other party’s express written consent to such assignment
or delegation, except that CLIENT may, without consent, assign its rights and responsibilities
hereunder to any Affiliate of CLIENT or by any corporation, firm, or other business entity with or into
which CLIENT may merge or consolidate or to which CLIENT may sell or transfer all or substantially all of its assets.


 


15.           Governing Law. This Agreement
shall be construed
and governed under the laws
of the State of Delaware.


 


16.           Severability. Any invalidity or unenforceability
of any paragraph or part of any
paragraph herein shall not in
any way affect the validity or
enforceability of any other
paragraph or any part of any other paragraph, and this Agreement shall be construed in all respects as if such
invalid or unenforceable provisions were omitted.


 


17.           Entire Agreement. This Agreement, including all attachments
and schedules attached hereto, constitutes the entire Agreement among the
parties pertaining to the subject matter contained herein and supersedes any and all prior and contemporaneous agreements, representations, and understandings.
No supplement to or modification of this Agreement shall be binding unless executed
in writing by each of the parties hereto.


 


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IN WITNESS WHEREOF, each of the parties
hereto have caused this
Agreement to be signed by its duly authorized officers as of
the day and year; first above written.


 


	
  ATP, LLC

  	
   

  	
   

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  
	
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  RELIANT PHARMACEUTICALS, LLC

  	
   

  	
   

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  
	
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ATTACHMENT A


PPD FEE STRUCTURE


Page 1 of 2


 


	
   

  	
   

  	
  01/01/02

  -12/31/02

  	
   

  	
  01/01/03

  -12/31/03

  	
   

  
	
  START-UP
  COSTS (Hourly)

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Start-Up
  Costs Include: SOP Development and Approval and Project-Specific Training
  Development:

  	
   

  	
  $

  	
  95.00

  	
   

  	
  $

  	
  750.00

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  TECHNOLOGY
  COSTS (as Indicated)

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Workstation
  Set-up (per Station  :

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Information
  Systems Support, Database and Report Programming, Videoconferencing and
  Telephone Programming Rate (per hour):

  	
   

  	
  $

  	
  750.00

  	
   

  	
  $

  	
  750.00

  	
   

  
	
  After-Hours
  Laptop Hardware Set-Up (per Laptop):

  	
   

  	
  $

  	
  1,800.00

  	
   

  	
  $

  	
  1,926.00

  	
   

  
	
  RESOURCE
  COSTS (hourly unless otherwise indicated)

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Staff Rate
  for Travel/Training Period or Specified Hourly Services:

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Product
  Safety Specialist

  	
   

  	
  $

  	
  100.00

  	
   

  	
  $

  	
  106.00

  	
   

  
	
  Senior
  Product Safety Specialist

  	
   

  	
  $

  	
  110.00

  	
   

  	
  $

  	
  116.60

  	
   

  
	
  Safety
  Physician

  	
   

  	
  $

  	
  250.00

  	
   

  	
  $

  	
  268.00

  	
   

  
	
  Research
  Assistant/Data Entry

  	
   

  	
  $

  	
  75.00

  	
   

  	
  $

  	
  79.50

  	
   

  
	
  Management
  Rate

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Safety
  Coordination specialist, Supervisor, Trainer, Quality Assurance Personnel,
  Associate Director, Product Safety Manager

  	
   

  	
  $

  	
  135.00

  	
   

  	
  $

  	
  144.50

  	
   

  
	
  Medical
  Writer Rate:

  	
   

  	
  $

  	
   

  	
  $

  	
   

  
	
  Senior
  Medical Writer:

  	
   

  	
  $

  	
  100.00

  	
   

  	
  $

  	
  106.00

  	
   

  
	
  Quality
  Assurance Reviewer

  	
   

  	
  $

  	
  100.00

  	
   

  	
  $

  	
  106.00

  	
   

  
	
  Adverse
  Event Report Management Rate (per Event)

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Non-Serious
  Adverse Event:

  	
   

  	
  $

  	
  318.00

  	
   

  	
  $

  	
  318.00

  	
   

  
	
  Serious
  Adverse Event (SAE):

  	
   

  	
  $

  	
  848.00

  	
   

  	
  $

  	
  848.00

  	
   

  
	
  Expedited
  AEs (Serious/Unexpected)

  	
   

  	
  $

  	
  1,060.00

  	
   

  	
  $

  	
  1,060.00

  	
   

  
	
  Annual
  Report for [***] (per Drug):

  	
   

  	
  $

  	
  9,000.00

  	
   

  	
  $

  	
  9,000.00

  	
   

  
	
  Annual
  Report for [***] (per Drug):

  	
   

  	
  $

  	
  9,000.00

  	
   

  	
  $

  	
  9,000.00

  	
   

  
	
  Annual
  Report for [***] (per Drug):

  	
   

  	
  $

  	
  9,000.00

  	
   

  	
  $

  	
  9,000.00

  	
   

  
	
  PSUR Report
  for New Drug 1** (per Drug)

  	
   

  	
  $

  	
  9,000.00

  	
   

  	
  $

  	
  9,000.00

  	
   

  
	
  PSUR Report
  for New Drug 2** (per Drug)

  	
   

  	
  $

  	
  9,000.00

  	
   

  	
  $

  	
  9,000.00

  	
   

  







[***]      Certain
information on this page has been omitted and filed separately with the
Commission.  Confidential treatment has
been requested with respect to the omitted portions.


 


1

















 


	
  Monthly
  Product Safety/Pharmacovigilance (PSPV) Management Fee:

  	
   

  	
  $

  	
   

  	
  $

  	
   

  
	
  Literature
  Searches:

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Write Search
  Strategy (One-time per Chemical Entity)

  	
   

  	
  $

  	
  250.00

  	
   

  	
  $

  	
  267.50

  	
   

  
	
  Execute
  Monthly Search Strategy (per Chemical Entity)

  	
   

  	
  $

  	
  60.00

  	
   

  	
  $

  	
  64.20

  	
   

  
	
  Review
  Citations for Reportability (per Hour)

  	
   

  	
  $

  	
  101.00

  	
   

  	
  $

  	
  108.10

  	
   

  
	
   

  	
   

  	
  $

  	
   

  	
  $

  	
   

  
	
  ADDITIONAL
  COSTS (as Indicated)

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Telephone/Pager/Cell
  Phone Charges, Faxing, Outsourced Photocopying, Translation Services, Travel,
  Meals, Copyright Clearance, External Document Retrieval, Supplies, Postage
  and Fulfillment, Off-Site Storage:

  	
   

  	
  $

  	
  Cost+5

  	
  %

  	
  $

  	
  Cost+5

  	
  %

  
	
  Document
  Storage, Medical Record Retrieval:

  	
   

  	
  $

  	
  Cost+5

  	
  %

  	
  $

  	
  Cost+5

  	
  %

  
	
  Travel,
  Meals, Copyright Clearance, External Document Supplier:

  	
   

  	
  $

  	
  Cost

  	
   

  	
  $

  	
  Cost

  	
   

  
	
  Postage and
  Fulfillment:

  	
   

  	
  $

  	
  Cost+$.50/ piece

  	
   

  	
  $

  	
  Cost+$.50/ piece

  	
   

  
	
  Internal
  Document Procurement (per Document):

  	
   

  	
  $

  	
  15.00

  	
   

  	
  $

  	
  15.00

  	
   

  
	
  Videoconferencing
  (per Hour):

  	
   

  	
  $

  	
  135.00

  	
   

  	
  $

  	
  135.00

  	
   

  
	
  REACTIONS
  Database (per Year):

  	
   

  	
  $

  	
  1,000.00

  	
   

  	
  $

  	
  1,350.00

  	
   

  



 


 


 


2

















 


 


ATTACHMENT A


PPD FEE STRUCTURE


Page 2 of 2


 


“Annual report
charge is based on a base cost of $8,000 per report plus a surcharge that
depends on AE/SAE volume. The surcharge is $1,000 if there are no more than 100 reported events (80 AE’s and 20
SAE’s) per product during the reporting interval. Should the volume of AE/SAEs
exceed this threshold, additional charges would be calculated on a prorated
basis.


**It is
recommended that RELIANT request a waiver from FDA to allow filing of PSURs
instead of quarterly reports that are required for New Drugs #1 and #2 for the
3 years following FDA approval.  The
costs to RELIANT would be substantially less using the PSUR Format, as is
outlined in the example below:


EXAMPLE: New
Drug 1 QUARTERLY REPORTS:


•      $5,000 Basic
Cost for a periodic quarterly report = $20,000/yr


•      $1,000 per
drug for up to 100 AE’s = $4,000/yr


•      total cost
per drug for quarterly reports per year = $24,000/yr


 


New Drug 1
Semiannual PSUR Report:


•      $8,000 Basic
Cost for each PSUR Report = $16,000/yr.


•      $1,000 per
drug for up to 100 AE’s = $2,000/yr


•      Total cost
per drug for 2 semiannual PSUR reports = $18,000/yr


 


If granted a
waiver, RELIANT would not need to submit the quarterly reports for two years
but would instead file a PSUR semiannually for three years. The waiver also
provides that the NDA holder would not be required to submit the 3500A’s for
non-serious AE’s; only line listings would be required.


The total cost
savings to RELIANT if they are granted the waiver for New Drugs #1 & #2
would be $12,000/year.


Last, an
important point to remember is that a separate periodic report is required for each marketed formulation of the same drug, whereas a PSUR
is prepared for each molecular entity,
regardless of different formulations. 
For multiple drug formulations of the same molecular entity, PSUR
charges will be billed at a higher rate as follows:


$12,000 Basic
Cast for Each PSUR = $24,000/yr


$1000 for up
to 100 AEs including 20 SAEs = $2,000/yr


 


- NOTE: The following dates are
considered as holidays for the purpose of this Agreement. If requested by
CLIENT, in writing at least 60 working days in advance, PPD will provide
services to CLIENT on these days as mutually agreed at PPD’s Holiday rates.


 


	
  New Year’s Day (observed)

  	
   

  	
  Good Friday

  	 

	
  Memorial Day

  	
   

  	
  July Fourth (observed)

  	 

	
  Labor Day

  	
   

  	
  Thanksgiving

  	 

	
  Day After Thanksgiving

  	
   

  	
  Christmas Day (observed)

  
	
  Day After Christmas or Christmas Eve Day
  (observed)

  	
   

  	
  New Year’s Eve Day

  



 


Should the project operate on weekends, holiday rates will apply to
Easter Sunday and to weekend days on which the above-observed holidays actually
occur.


 


3






 










 


AMENDMENT
NO. 1


 


THIS AMENDMENT NO. 1 (“Amendment
No. 1”) is made this 15th day of January, 2004 (“Effective Date”) by and
between Reliant Pharmaceuticals, LLC (“CLIENT”) and ATP, LLC d/b/a PPD Medical
Communications (“PPD”).


 


WHEREAS, CLIENT and PPD
entered into a certain Product Safety/Pharmacovigilance Services Agreement
dated February 25, 2003 (“Agreement”) pursuant to which PPD provides certain
medical information services to CLIENT and


 


WHEREAS, CLIENT and PPD
wish to amend the Agreement as set forth herein.


 


NOW, THEREFORE, in
consideration of the premises and mutual covenants contained herein, the
receipt and sufficiency of which are hereby acknowledged, the parties agree as
follows:


 


1.                                       The last
sentence of Section 1C(i), Services Provided by PPD, PSPV Services, Non Serious
AEs, shall be deleted in its entirety and replaced with the following two (2)
sentences:


 


“Completed case files and source documents will be
retained for a period of time determined by mutual agreement and in accordance
with applicable laws and regulations. PPD’s validated safety platform will be
implemented during the first quarter of calendar year 2004, after which time
all non-serious AEs shall be processed, archived, and analyzed within this
system.”


 


2.                                       The last
sentence of Section 1C(ii), Services Provided by PPD, PSPV Services, SAEs,
shall be deleted in its entirety and replaced with the following two (2)
sentences:


 


“Completed case files and source documents will be
retained for a period of time determined by mutual agreement and in accordance
with applicable laws and regulations. PPD’s validated safety platform will be
implemented during the first quarter of calendar year 2004, after which time
all SAEs shall be processed, archived, and analyzed within this system.”


 


3.                                       Section 1C(iv),
Services Provided by PPD, PSPV Services, Periodic Scientific Literature
Surveillance, shall be deleted in its entirety and replaced with the following:


 


“(iv) Periodic Scientific Literature Surveillance.
PPD will process all AEs/SAEs identified as a result of regularly scheduled
systematic scientific literature surveillance. Unless otherwise specified by
CLIENT, scientific literature surveillance will be performed using a minimum of
two databases (EMBASE, Medline) at least [***]. If requested, CLIENT will be
provided with photocopies of scientific literature which cite safety issues,
for which CLIENT will be charged article procurement fees and copyright
clearance fees. In addition, upon CLIENT request, PPD will make provisions for
language translation, and translation fees will be charged for non-English
articles as specified in Attachment A. Should CLIENT not request translation
services, PPD will send


 






[***]:  Certain information on this page has been
omitted and filed separately with the Commission.  Confidential treatment has been requested
with respect to the omitted portions.


 

















 


photocopies of non-English articles to CLIENT, and
CLIENT will assume full responsibility for their further processing.”


 


4.                                       Section 1C(v)
is revised to include the title “Periodic Safety Reports” and shall be amended
to include the following:


 


“In order to be in full regulatory compliance, PPD
shall utilize a validated safety database for comprehensive management of
adverse events. This system shall comply with 21 CFR Part 11. PPD estimates
that CLIENT will require one dedicated license (user seat) for use by PPD
staff; with payment of additional setup fees, CLIENT may request secured
read-only access to CLIENT safety data from CLIENT premises. Any request for ad
hoc safety database query will be charged at time and materials by IT staff.
Such validated safety database shall be fully operational by March 31,
2004.”


 


5.                                       Section 1D,
Services Provided by PPD, Project Management, shall be deleted in its entirety
and replaced with the following:


 


“D. PSPV Project Management. PPD shall perform PSPV
Project Management support which includes, but is not limited to, oral and
written communication with CLIENT, procedure and protocol development,
procedure and protocol maintenance, report generation, training plan
development, staff training, staff supervision and development, quality
assurance (including review of AE and product complaint reports), consultative
services, meeting preparation and conduction, and communication with other
third parties necessary to business operations. Such services may be provided
by Supervisor(s), Safety Coordination Specialist(s), Product Safety Manager(s),
Quality Assurance Personnel, Trainer(s), Associate Director(s), Director(s),
Executive Director(s), and/or Vice-President(s). A monthly PSPV Project
Management fee shall be invoiced to CLIENT to cover ongoing costs for
performance of the above-listed activities in the provision of safety and
pharmacovigilance services required by regulatory agencies. Fees for the
processing of individual case safety reports (ICSRs) are invoiced on a ‘per
event’ basis according to the fee schedule presented in Attachment A of this
Amendment No. 1.”


 


6.                                       Section 5A of
the Agreement, Payments for Services Rendered by PPD, Resource Costs shall be
deleted in its entirety and replaced with the following:


 


“CLIENT shall compensate PPD for performance of
services rendered by PPD pursuant to this Agreement on a monthly basis. The
invoice will include cases submitted for the preceding month and billable hours
and costs applied to the project according to the rates stated in Attachment A.
When off-site travel is requested by CLIENT, staff time will be billed at rates
shown in Attachment A. The PPD Fee Structure attached to the Agreement as
Attachment A shall be revised by PPD on an annual basis during the term of the
Agreement. On or before October 15th of each year during the term of the
Agreement, PPD shall provide CLIENT with the revised PPD Fee Structure
reflecting PPD’s rates for the upcoming


 


2

















 


calendar year, which revised PPD Fee Structure shall
be attached to this Agreement and incorporated by reference herein. Unless
otherwise agreed to by the parties in writing, the new PPD Fee Structure shall
be in effect for the duration of such upcoming calendar year beginning on
January 1st and ending on December 31st.”


 


7.                                       Pursuant to
Paragraph 6 above, the 2004 PPD Fee Structure attached to this Amendment No. 1
shall be effective beginning January 1, 2004 and shall remain in effect until
December 31, 2004.


 


8.                                       In the event of
any inconsistency or conflict of terms between the Agreement and this
Amendment, the terms of this Amendment No. 1 shall control.


 


9.                                       Except as
provided herein, all other terms and conditions of the Agreement shall remain
in full force and effect.


 


IN WITNESS WHEREOF, the parties
hereto have caused this Amendment No. 1 to be executed as of the date first
above written.


 


	
  RELIANT PHARMACEUTICALS, INC.

  	
   

  	
  ATP, LLC

  
	
   

  	
   

  	
   

  
	
  By:

  	
   

  	
   

  	
  By:

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Name:

  	
   

  	
   

  	
  Name:

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Title:

  	
   

  	
   

  	
  Title:

  	
   

  	
   

  
												



 


3

















 


ATTACHMENT A

2004 PPD FEE STRUCTURE

01/01/2004 - 12/3l/2004

Page 1 of 1


 


	
  TECHNOLOGY COSTS (as
  indicated)

  	
   

  	
   

  	
   

  
	
  Information Systems Support, Database and
  Report Programming, Videoconferencing and Telephone Programming Rate (per
  hour):

  	
   

  	
  $

  	
  144.50

  	
   

  
	
  Bibliographic Database Access (MedLine,
  EMBASE, REACTIONS) (per year):

  	
   

  	
  $

  	
  1,500.00

  	
   

  
	
  Validated Safety Database (first year)
  single seat license, Database validation, and test scripts (invoiced upon
  implementation in Q1 2004):

  	
   

  	
  $

  	
  15,000.000

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
  RESOURCE COSTS (hourly unless otherwise
  indicated)

  	
   

  	
   

  	
   

  
	
  Management Rate

  	
   

  	
   

  	
   

  
	
  Supervisor, Trainer, Quality Assurance
  Personnel, Product Safety Specialist:

  	
   

  	
  $

  	
  109.00

  	
   

  
	
  Associate Director, Product Safety Manager:

  	
   

  	
  $

  	
  154.75

  	
   

  
	
  Director, Executive Director/Vice
  President:

  	
   

  	
  $

  	
  182.25

  	
   

  
	
  Periodic Safety Literature Searches*

  	
   

  	
   

  	
   

  
	
  Develop Search Strategy (One Time Fee per
  Chemical Entity):

  	
   

  	
  $

  	
  267.50

  	
   

  
	
  Execute Monthly Search Strategy (per
  Chemical Entity):

  	
   

  	
  $

  	
  64.20/search

  	
   

  
	
  Review Abstracted Citations/Retrieved
  Articles for Reportability:

  	
   

  	
  $

  	
  108.10

  	
   

  
	
  Clinical Communications Medical Writing
  Rates

  	
   

  	
   

  	
   

  
	
  Medical Writer:

  	
   

  	
  $

  	
  103.00

  	
   

  
	
  Senior Medical Writer:

  	
   

  	
  $

  	
  114.50

  	
   

  
	
  Editorial & Literature Search
  Coordinator:

  	
   

  	
  $

  	
  91.50

  	
   

  
	
  Adverse Event Report Management Rate (per
  event)

  	
   

  	
   

  	
   

  
	
  Non-Serious Adverse Event:

  	
   

  	
  $

  	
  449.00

  	
   

  
	
  Serious Adverse Event (SAE):

  	
   

  	
  $

  	
  949.00

  	
   

  
	
  Literature Adverse Event Report :

  	
   

  	
  $

  	
  849.00

  	
   

  
	
  Annual NDA Safety Reports

  	
   

  	
   

  	
   

  
	
  Annual Report for [***]**:

  	
   

  	
  $

  	
  9000.00

  	
   

  
	
  Annual Report for [***]**:

  	
   

  	
  $

  	
  9000.00

  	
   

  
	
  Annual Report for [***]**:

  	
   

  	
  $

  	
  9000.00

  	
   

  
	
  Monthly Product Safety/Pharmacovigilance
  (PSPV) Management Fee:

  	
   

  	
  $

  	
  5000.00

  	
   

  
	
  Staff Rate for Travel or Specified Hourly
  Services

  	
   

  	
   

  	
   

  
	
  Product Safety Specialist:

  	
   

  	
  $

  	
  106.00

  	
   

  
	
  Senior Product Safety Specialist:

  	
   

  	
  116.50

  	
   

  
	
  Medical Director:

  	
   

  	
  $

  	
  265.00

  	
   

  
	
  Research Assistant/Data Entry:

  	
   

  	
  $

  	
  79.50

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
  ADDITIONAL COSTS (as Indicated)

  	
   

  	
   

  	
   

  
	
  Telephone/Pager/Cell Phone Charges, Faxing,
  Outsourced Photocopying, Translation Services, Travel, Meals, Copyright
  Clearance, External Document Retrieval, Supplies, Postage and Fulfillment,
  Off-Site Storage:

  	
   

  	
  $

  	
  Cost

  	
   

  
	
  Internal Photocopying:

  	
   

  	
  $

  	
  0.08/copy

  	
   

  
	
  Internal Document Procurement:

  	
   

  	
  $

  	
  16.00/document

  	
   

  







*Literature Search service is
currently provided for Innopran XL. Scheduled literature searches for
identification of safety issues are charged per search per month. Review and
evaluation of abstracted citations and/or retrieved articles for reportability
are charged at actual time spent. If the search results in an identifiable
AE/SAE, it will be transitioned to PPD Safety Staff for further processing at
regular AE/SAE rates.


 


**Annual report charge is based
on a base cost of $8,000 per report plus a surcharge that depends on AE/SAE
volume. The surcharge is $1,000 if there are no more than 100 reported events
(80 AEs and 20 SAEs) per product during the reporting interval. Should the
volume of AE/SAEs exceed this threshold, additional charges would be calculated
on a prorated basis.


 


[***]:  Certain information on this page has been
omitted and filed separately with the Commission.  Confidential treatment has been requested
with respect to the omitted portions.


 


1














 


AMENDMENT NO. 2


 


THIS
AMENDMENT NO. 2 (“Amendment No. 2”) is made this 30th
day of March, 2004 (“Effective Date”) by and between Reliant Pharmaceuticals,
LLC (“CLIENT”) and ATP, LLC d/b/a PPD Medical Communications (“PPD).


 


WHEREAS,
CLIENT and PPD entered into a certain Product Safety/Pharmacovigilance Services
Agreement dated February 25, 2003 (“Agreement”) as amended by Amendment No. 1
dated January 15, 2004 (“Amendment 1”) pursuant to which PPD provides certain
medical information services to CLIENT; and


 


WHEREAS,
the Agreement together with Amendment 1 shall collectively be referred to
herein as the “Agreement”; and


 


WHEREAS,
CLIENT and PPD wish to further amend the Agreement as set forth herein.


 


NOW,
THEREFORE, in consideration of the premises and mutual
covenants contained herein, the receipt and sufficiency of which are hereby
acknowledged, the parties agree as follows:


 


1.                                       The
line item entitled “Annual NDA Safety Reports” on the 2004 PPD Fee Structure
pursuant to Amendment 1 of the Agreement shall be deleted in its entirety and
replaced with the following:


 




	
  “Periodic Safety Reports**

  	
   

  	
   

  	
   

  
	
  Annual NDA Report (per 21 CFR 314.81)***:

  	
   

  	
  $

  	
  9000.00

  	
   

  
	
  Quarterly NDA Report (per 21 CFR
  314.80)***:

  	
   

  	
  $

  	
  5500.00

  	
   

  
	
  Quarterly NDA Report (with 0 AE/SAE
  reports)***:

  	
   

  	
  $

  	
  1000.00

  	
   

  
						






 


2.                                       Pursuant
to paragraph 1 above, the Revised 2004 PPD Fee Structure attached to this
Amendment No. 2 as Attachment A shall remain in effect until December 31, 2004.


 


3.                                       Upon
execution, this Amendment 2 shall be made a part of the Agreement and
incorporated by reference herein.


 


4.                                       In
the event of any inconsistency or conflict of terms between the Agreement and
this Amendment, the terms of this Amendment No. 2 shall control.


 


5.                                       Except
as provided herein, all other terms and conditions of the Agreement shall
remain in full force and effect.


 


IN
WITNESS WHEREOF, the parties hereto have caused this
Amendment No. 2 to be executed as of the date first above written.


 


	
  RELIANT PHARMACEUTICALS, INC. 

  	
  ATP, LLC

  
	
   

  	
   

  
	
   

  	
   

  
	
  By:

  	
   

  	
   

  	
  By:

  	
   

  	
   

  
	
   

  	
   

  
	
  Name:

  	
   

  	
   

  	
  Name:

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Title:

  	
   

  	
   

  	
  Title:

  	
   

  	
   

  
								



 


 

















ATTACHMENT A

2004 PPD FEE STRUCTURE

01/01/2004 - 12/3l/2004

Page 1 of 1


 


	
  TECHNOLOGY COSTS (as indicated)

  	
   

  	
   

  	
   

  
	
  Information Systems Support, Database and
  Report Programming, Videoconferencing and Telephone Programming Rate (per
  hour):

  	
   

  	
  $

  	
  144.50

  	
   

  
	
  Bibliographic Database Access (MedLine,
  EMBASE, REACTIONS) (per year):

  	
   

  	
  $

  	
  1,500.00

  	
   

  
	
  Validated Safety Database (first year)
  single seat license, Database validation, and test scripts (invoiced upon
  implementation in Q1 2004):

  	
   

  	
  $

  	
  15,000.000

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
  RESOURCE COSTS (hourly unless otherwise
  indicated)

  	
   

  	
   

  	
   

  
	
  Management Rate

  	
   

  	
   

  	
   

  
	
  Supervisor, Trainer, Quality Assurance
  Personnel, Product Safety Specialist:

  	
   

  	
  $

  	
  109.00

  	
   

  
	
  Associate Director, Product Safety Manager:

  	
   

  	
  $

  	
  154.75

  	
   

  
	
  Director, Executive Director/Vice
  President:

  	
   

  	
  $

  	
  182.25

  	
   

  
	
  Periodic Safety Literature Searches*

  	
   

  	
   

  	
   

  
	
  Develop Search Strategy (One Time Fee per
  Chemical Entity):

  	
   

  	
  $

  	
  267.50

  	
   

  
	
  Execute Monthly Search Strategy (per
  Chemical Entity):

  	
   

  	
  $

  	
  64.20/search

  	
   

  
	
  Review Abstracted Citations/Retrieved
  Articles for Reportability:

  	
   

  	
  $

  	
  108.10

  	
   

  
	
  Clinical Communications Medical Writing
  Rates

  	
   

  	
   

  	
   

  
	
  Medical Writer:

  	
   

  	
  $

  	
  103.00

  	
   

  
	
  Senior Medical Writer:

  	
   

  	
  $

  	
  114.50

  	
   

  
	
  Editorial & Literature Search
  Coordinator:

  	
   

  	
  $

  	
  91.50

  	
   

  
	
  Adverse Event Report Management Rate (per
  event)

  	
   

  	
   

  	
   

  
	
  Non-Serious Adverse Event:

  	
   

  	
  $

  	
  449.00

  	
   

  
	
  Serious Adverse Event (SAE):

  	
   

  	
  $

  	
  949.00

  	
   

  
	
  Literature Adverse Event Report :

  	
   

  	
  $

  	
  849.00

  	
   

  
	
  Periodic Safety Reports**

  	
   

  	
   

  	
   

  
	
  Annual NDA Report (per 21 CFR 314.81)***:

  	
   

  	
  $

  	
  9000.00

  	
   

  
	
  Quarterly NDA Report (per 21 CFR
  314.80)***:

  	
   

  	
  $

  	
  5500.00

  	
   

  
	
  Quarterly NDA Report (with 0 AE/SAE
  reports)***:

  	
   

  	
  $

  	
  1000.00

  	
   

  
	
  Monthly Product Safety/Pharmacovigilance
  (PSPV) Management Fee:

  	
   

  	
  $

  	
  5000.00

  	
   

  
	
  Staff Rate for Travel or Specified Hourly
  Services

  	
   

  	
   

  	
   

  
	
  Product Safety Specialist:

  	
   

  	
  $

  	
  106.00

  	
   

  
	
  Senior Product Safety Specialist:

  	
   

  	
  $

  	
  116.50

  	
   

  
	
  Medical Director:

  	
   

  	
  $

  	
  265.00

  	
   

  
	
  Research Assistant/Data Entry:

  	
   

  	
  $

  	
  79.50

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
  ADDITIONAL COSTS (as indicated)

  	
   

  	
   

  	
   

  
	
  Telephone/Pager/Cell Phone Charges, Faxing,
  Outsourced Photocopying, Translation Services, Travel, Meals, Copyright
  Clearance, External Document Retrieval, Supplies, Postage and Fulfillment,
  Off-Site Storage:

  	
   

  	
  $

  	
  Cost

  	
   

  
	
  Internal Photocopying:

  	
   

  	
  $

  	
  0.08/copy

  	
   

  
	
  Internal Document Procurement:

  	
   

  	
  $

  	
  16.00/document

  	
   

  







*Literature Search service
is currently provided for InnoPran XL. Scheduled literature searches for
identification of safety issues are charged per search per month. Review and
evaluation of abstracted citations and/or retrieved articles for reportability
are charged at actual time spent. If the search results in an identifiable
AE/SAE, it will be transitioned to PPD Safety Staff for further processing at
regular AE/SAE rates.


**Refer to Appendix for
listing of drug products subject to annual or quarterly NDA periodic reports.


***Annual report charge is
based on a base cost of $8,000 per report plus a surcharge that depends on
AE/SAE volume. The surcharge is $1,000 if there are no more than 100 reported
events (80 AEs and 20 SAEs) per product during the reporting interval. Should
the volume of AE/SAEs exceed this threshold, additional charges would be
calculated on a prorated basis.  Routine
line listings and summary tabulations for annual reports are provided upon
client request at no additional charge.


Quarterly report charge is
based on a base cost of $5,000 per report plus a surcharge that depends on
AE/SAE volume.  The surcharge is $500 if
there are no more than 50 reported events (40 AEs and 10 SAEs) per product
during the reporting interval.  Should
the volume of AE/SAEs exceed this threshold, additional charges would be
calculated on a prorated basis.  If there
are no reported events, AE or SAE, then the charge for the quarterly report is
$1,000


 


 


 

















 


 


APPENDIX


 


Periodic NDA Reporting
Obligations


 


Annual Report


[***]


[***]


[***]


[***]


 


Quarterly Report


[***]


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 






[***]:  Certain information on this page has been
omitted and filed separately with the Commission. Confidential treatment has been
requested with respect to the omitted portions.


 


 

















 


AMENDMENT NO. 3


 


THIS
AMENDMENT NO. 3 (“Amendment”) is made this 29th
day of November, 2004 (“Effective Date”) by and between Reliant
Pharmaceuticals, Inc. (“Reliant” or “CLIENT”) and ATP, LLC d/b/a PPD Medical
Communications (“PPD”)


 


WHEREAS,
CLIENT and PPD entered into a certain Product Safety/Pharmacovigliance Services
Agreement dated February 25, 2003, as amended by Amendment No. 1 dated January
15, 2004 and Amendment No. 2 dated March 30, 2004 (collectively, the
“Agreement”) pursuant to which PPD provides certain medical information
services to CLIENT; and


 


WHEREAS,
CLIENT and PPD wish to further amend the Agreement as set forth herein.


 


NOW,
THEREFORE, in consideration of the premises and mutual
covenants contained herein, the receipt and sufficiency of which are hereby acknowledged, the parties
agree as follows:


 


1.             The
last sentence of Section 1C(i) of the Agreement shall be deleted in its
entirety and replaced with the following:


 


“Completed case files and source documents will be
retained for a period of time determined by mutual agreement and in accordance
with applicable laws and regulations. All non-serious AEs shall be processed,
archived, and analyzed through utilization of a validated safety platform.”


 


2.             The
last sentence of Section 1C(ii) of the Agreement shall be deleted in its
entirety and replaced with the following:


 


“Completed case files and source documents will be
retained for a period of time determined by mutual agreement and in admittance
with applicable laws and regulations. All SAEs shall be processed, archived,
and analyzed through utilization of a validated safety platform.”


 


3.             Section
1C(iv) of the Agreement shall be deleted in its entirety and replaced with the
following:


 


“(iv)
Periodic Scientific Literature Surveillance. PPD will process all AEs/SAEs
identified as a result of regularly scheduled systematic scientific literature
surveillance. Unless otherwise specified by CLIENT, scientific literature
surveillance will he performed at least [***] using [***] bibliographic
databases (EMBASE, Medline, Reactions Weekly). If requested, CLIENT will be
provided with photocopies of scientific literature which cite safety issues,
for which CLIENT will be charged article processing and/or procurement fees and
applicable copyright clearance fees. In addition, upon CLIENT request, PPD will
make provision for language translation, and translation fees for non-English
articles will be charged on a pass-through basis. Should CLIENT not request
translation service, PPD will send photocopies of non-English articles to
CLIENT and CLIENT will assume full responsibility for their further
processing.”


 






[***]:  Certain information on this
page has been omitted and filed
separately with the Commission. Confidential treatment hasbeen requested with
respect to the omitted portions. 


 

















 


4.             In
Section 1D of the Agreement “Safety Coordination Specialist(s)” shall be
deleted and replaced by “Product Safety Specialist(s)”.


 


5.             Pursuant
to Section 5A of the Agreement, Services Provided by PPD the 2005 PPD Fee
Structure attached to this Amendment No. 3 as Attachment A shall be effective
beginning January 1, 2005 and shall remain in effect until December 31, 2005.


 


6.             In
Section 5C of the Agreement ‘56-2203444’ shall be deleted and replaced by
“22-2734293”.


 


7.             The
Appendix to the Agreement shall be deleted in its entirety and replaced by the
Appendix attached hereto.


 


8.             In
the event of any inconsistency or conflict of terms between the Agreement and
this Amendment, the terms of this Amendment shall control.


 


9.             Except
as provided herein, all other terms and conditions of the Agreement shall
remain in full force and effect.


 


IN WITNESS
WHEREOF, the parties hereto have caused this Amendment
to be executed as of the date first above written.


 


	
  RELIANT
  PHARMACEUTICALS, INC.

  	
  ATP, LLC

  
	
   

  	
   

  
	
   

  	
   

  
	
  By:

  	
  /s/ Keith
  Rotenberg

  	
   

  	
  By:

  	
  /s/ Lori
  Eberhardt

  	
   

  
	
   

  	
   

  
	
  Name:

  	
  Keith S.
  Rotenberg, Ph.D.

  	
   

  	
  Name:

  	
  Lori
  Eberhardt

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Title:

  	
  Sr. VP,
  Research & Development

  	
   

  	
  Title:

  	
  VP,
  Operations

  	
   

  
								



 

















ATTACHMENT A

Revised 2005 PPD FEE STRUCTURE

01/01/2005 - 12/31/2005

Page 1 of 1


	
  TECHNOLOGY COSTS (as indicated)

  	
   

  	
   

  	
   

  
	
  Information Systems Support, Database and
  Report Programming, Videoconferencing and Telephone Programming Rate (per
  hour):

  	
   

  	
  $

  	
  144.50

  	
   

  
	
  Bibliographic Database Access (MedLine,
  EMBASE, REACTIONS) (per month):

  	
   

  	
  $

  	
  500.00

  	
   

  
	
  Validated Safety Database
  (maintenance/year)

  	
   

  	
  $

  	
  3,000.00

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
  RESOURCE COSTS (hourly unless otherwise
  indicated)

  	
   

  	
   

  	
   

  
	
  Management Rate

  	
   

  	
   

  	
   

  
	
  Supervisor, Product Safety Manager,
  Trainer, Quality Assurance:

  	
   

  	
  $

  	
  123.00

  	
   

  
	
  Product Safety Specialist:

  	
   

  	
  $

  	
  109.00

  	
   

  
	
  Associate Director:

  	
   

  	
  $

  	
  154.75

  	
   

  
	
  Director, Executive Director/Vice
  President:

  	
   

  	
  $

  	
  182.25

  	
   

  
	
  Periodic Safety Literature Searches

  	
   

  	
   

  	
   

  
	
  Execute Monthly Search Strategy (per
  Chemical Entity)(per search)

  	
   

  	
  $

  	
  80.25

  	
   

  
	
  Review abstract/title for reportability
  (per abstract)

  	
   

  	
  $

  	
  9.75

  	
   

  
	
  Article Management (per article)

  	
   

  	
  $

  	
  13.50

  	
   

  
	
  Full text article review & analysis
  (per article)

  	
   

  	
  $

  	
  80.25

  	
   

  
	
  Adverse Event Report Management Rate (per
  event)

  	
   

  	
   

  	
   

  
	
  Non-Serious Adverse Event:

  	
   

  	
  $

  	
  471.50

  	
   

  
	
  Serious Adverse Event (SAE):

  	
   

  	
  $

  	
  996.50

  	
   

  
	
  Literature Adverse Event Report:

  	
   

  	
  $

  	
  883.00

  	
   

  
	
  Periodic Safety Reports*

  	
   

  	
   

  	
   

  
	
  Annual NDA Report (per 21CFR 314.81)**

  	
   

  	
  $

  	
  9,500.00

  	
   

  
	
  Quarterly NDA Report (per 21CFR 314.80)**

  	
   

  	
  $

  	
  5,800.00

  	
   

  
	
  Quarterly NDA Report (with no AE/SAE reports)**

  	
   

  	
  $

  	
  1,000.00

  	
   

  
	
  Monthly Product Safety/Pharmacovigilance
  (PSPV) Management Fee:

  	
   

  	
  $

  	
  5,200.00

  	
   

  
	
  Staff Rate for Travel or Specified Hourly
  Services

  	
   

  	
   

  	
   

  
	
  Product Safety Specialist:

  	
   

  	
  $

  	
  109.00

  	
   

  
	
  Senior Product Safety Specialist:

  	
   

  	
  $

  	
  118.00

  	
   

  
	
  PSM:

  	
   

  	
  $

  	
  123.00

  	
   

  
	
  Medical Director:

  	
   

  	
  $

  	
  255.00

  	
   

  
	
  Research Assistant/Data Entry:

  	
   

  	
  $

  	
  79.50

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
  ADDITIONAL COSTS (as indicated)

  	
   

  	
   

  	
   

  
	
  Telephone/Pager/Cell Phone Charges, Faxing,
  Outsourced Photocopying, Translation Services, Travel, Meals, Copyright
  Clearance, External Document Retrieval, Supplies, Postage and Fulfillment,
  Off-Site Storage:

  	
   

  	
  $

  	
  Cost

  	
   

  
	
  Internal Photocopying:

  	
   

  	
  $

  	
  0.09/copy

  	
   

  







*Refer to
Appendix for listing or drug products subject to annual or quarterly NDA
periodic reports.


**Annual
report charge is based on a base cost of $8,500 per report plus a surcharge
that depends on AE/SAE volume.  The
surcharge is $1,000 if there are no more than 100 reported events (80 AEs and
20 SAEs) per product during the reporting interval.  Should the volume of AE/SAEs exceed this
threshold, additional charges would be calculated on a prorated basis.


Quarterly report is based on
a base cost of $5,300 per report plus a surcharge that depends on AE/SAE
volume.  The surcharge is $500 if there
are no more than 50 reported events (40 AEs and 10 SAEs) per product during the
reporting interval.  Should the volume of
AE/SAEs exceed this threshold, additional charges would be calculated on a
prorated basis. If there are no reported events, then the charge for the
quarterly report is $1,000.


 


 


1

















 


APPENDIX


 


Periodic NDA Reporting Obligations


 


Annual
Reports


 


[***]


[***]


[***]


[***]


[***]


 


Quarterly Reports  


[***]


[***]


 






[***]:                Certain
information on this page has been omitted and filed separately with the
Commission. Confidential treatment has been requested with respect to the
omitted portions


 

















 


 


AMENDMENT
NO. 4


 


THIS
AMENDMENT NO. 4 (“Amendment”) is made this 7th
day of November, 2005 (“Effective Date”) by and between Reliant Pharmaceuticals,
Inc. (“Reliant” or “CLIENT”) and ATP, LLC d/b/a PPD Medical Communications (“PPD”).


 


WHEREAS,
CLIENT and PPD entered into a certain Product Safety/Pharmacovigilance Services
Agreement dated February 25, 2003, as amended by Amendment No. 1 dated January
15, 2004, Amendment No. 2 dated March 30, 2004 and Amendment No. 3 dated
November 29, 2004 (collectively, the “Agreement”) pursuant to which PPD
provides certain medical information services to CLIENT; and


 


WHEREAS,
CLIENT and PPD wish to further amend the Agreement as set forth herein.


 


NOW,
THEREFORE, in consideration of the premises and mutual
covenants contained herein, the receipt and sufficiency of which are hereby
acknowledged, the parties agree as follows:


 


1.                                       Section 1C(i):  The
second sentence shall be deleted in its entirety and replaced with the
following:


 


“PPD will send to CLIENT,
via email, a [***] summary report
of all AEs received for that [***], unless otherwise specified by CLIENT.”


 


2.                                       Section 1C(ii):  The
second sentence shall be deleted in its entirety and replaced with the
following:


 


“PPD will notify CLIENT
immediately via telephone or email, but no later than [***], of all SAE reports
received by PSPV. These reports will also be included in the [***] summary report.”


 


3.                                       Attachment A to the Agreement shall be deleted in its
entirety and replaced by the revised Attachment A attached hereto.


 


4.                                       Attachment A to this Amendment shall be effective beginning
January 1, 2006 and shall remain in effect through December 31, 2006.


 


5.                                       In the event of any inconsistency or conflict of terms
between the Agreement and this Amendment, the terms of this Amendment shall
control.


 


6.                                       Except as provided herein, all other terms and conditions of
the Agreement shall remain in full force and effect.


 






[***]:  Certain information on this
page has been omitted and filed separately with the Commission. Confidential
treatment has been requested with respect to the omitted portions.


 





















 


IN WITNESS
WHEREOF, the parties hereto have caused this Amendment
to be executed as of the date first above written.


 


	
  RELIANT
  PHARMACEUTICALS, INC.

  	
  ATP, LLC

  
	
   

  	
   

  
	
   

  	
   

  
	
  By:

  	
  /s/ Steve
  Ketchum

  	
   

  	
  By:

  	
  /s/ Vivian
  Broach

  	
   

  
	
   

  	
   

  
	
  Name:

  	
  Steve
  Ketchum, Ph.D.

  	
   

  	
  Name:

  	
  Vivian
  Broach, Pharm D

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Title:

  	
  Sr. VP,
  R&D

  	
   

  	
  Title:

  	
  Executive
  Director, Ops.

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Date:

  	
  November 7,
  2005

  	
   

  	
  Date:

  	
  November 10,
  2005

  	
   

  
								



 

















 


ATTACHMENT
A

2006 PPD FEE STRUCTURE


 


	
   

  	
   

  	
  01/01/2006 - 

  	
   

  
	
  HOURLY RATES (unless otherwise indicated)

  	
   

  	
  12/31/2006

  	
   

  
	
  PRODUCT SAFETY/PHARMACOVIGILANCE (PSPV)
  RATES

  	
   

  	
   

  	
   

  
	
  Monthly PSPV Management Fee

  	
   

  	
  [***]

  	
   

  
	
  Program Management

  	
   

  	
   

  	
   

  
	
  PSPV Medical Director

  	
   

  	
  [***]

  	
   

  
	
  PSPV Director

  	
   

  	
  [***]

  	
   

  
	
  PSPV Associate Director

  	
   

  	
  [***]

  	
   

  
	
  Product Safety Manager

  	
   

  	
  [***]

  	
   

  
	
  Product Safety Specialist

  	
   

  	
  [***]

  	
   

  
	
  Product Safety Assistant

  	
   

  	
  [***]

  	
   

  
	
  Adverse Event Report Management (per event)

  	
   

  	
   

  	
   

  
	
  Non-Serious Adverse Event

  	
   

  	
  [***]

  	
   

  
	
  Serious Adverse Event

  	
   

  	
  [***]

  	
   

  
	
  Literature Adverse Event Report

  	
   

  	
  [***]

  	
   

  
	
  Periodic Safety Literature Searches

  	
   

  	
   

  	
   

  
	
  Execute Monthly Search Strategy (per
  chemical entity)(per search)

  	
   

  	
  [***]

  	
   

  
	
  Review abstract/title for reportability
  (per abstract)

  	
   

  	
  [***]

  	
   

  
	
  Full text article review & analysis
  (per article)

  	
   

  	
  [***]

  	
   

  
	
  Periodic Safety Reports(1)

  	
   

  	
   

  	
   

  
	
  Annual NDA Report (per 21CFR 314.81)(2)

  	
   

  	
  [***]

  	
   

  
	
  Quarterly NDA Report (per 21CFR 314.80)(2)

  	
   

  	
  [***]

  	
   

  
	
  Quarterly NDA Report (with no AE/SAE
  reports)(2)

  	
   

  	
  [***]

  	
   

  
	
  INFORMATION TECHNOLOGY (IT) RATES

  	
   

  	
   

  	
   

  
	
  Information Systems Support, Database &
  Report Programming, Telephone Programming, and Workstation

  Set-up

  	
   

  	
  [***]

  	
   

  
	
  Bibliographic Database Access -
  MEDLINE, EMBASE, REACTIONS (per month)

  	
   

  	
  [***]

  	
   

  
	
  Validated Safety Database Access (per
  month)

  	
   

  	
  [***]

  	
   

  



 


	
   

  	
   

  	
  01/01/2006 - 

  	
   

  
	
  ADDITIONAL COSTS (as indicated)

  	
   

  	
  12/31/2006

  	
   

  
	
  External Document Procurement, Language
  Translation, Copyright Clearance, Telephone, Pager & Fax Usage, Postage
  & In-house Fulfillment, Wide Area Network Access, Travel, Meals,
  Supplies, Off-site Storage and Outsourced Copying, Literature Searches

  	
   

  	
  [***]

  	
   

  
	
  Internal Document Procurement (per
  document)

  	
   

  	
  [***]

  	
   

  
	
  Internal Copying (per page)

  	
   

  	
  [***]

  	
   

  
	
  Videoconferencing (per hour)

  	
   

  	
  [***]

  	
   

  



 






	
  [***]:
  

  	
  Certain
  information on this page has been omitted and filed separately with the
  Commission. Confidential treatment has been  requested with respect to the omitted
  portions. 

  



 

















 


Note 1:  Refer to Appendix for
listing of drug products subject to annual or quarterly NDA periodic reports.


Note 2:  The annual and quarterly
report charges are invoiced on a per report basis. If there are five or fewer
reported events for the reporting Interval, then the charge for the quarterly
report is [***] .


 


PPD invoices on a monthly basis according to the rates shown above.


 


 






	
  [***]:
  

  	
  Certain
  information on this page has been omitted and filed separately with the
  Commission. Confidential treatment has been  requested with respect to the omitted
  portions. 

  



 

















 


AMENDMENT
NO. 5


 


THIS
AMENDMENT NO. 5 (“Amendment”) is made this 28th
day of June, 2006 (“Effective Date”) by and between Reliant Pharmaceuticals,
Inc (“Reliant” or “CLIENT”) and ATP, LLC d/b/a PPD Medical Communications (“PPD”).


 


WHEREAS,
CLIENT and PPD entered into a certain Product Safety/Pharmacovigilance Services
Agreement dated February 25, 2003, as amended by Amendment No. 1 dated January
15, 2004, Amendment No. 2 dated March 30, 2004, Amendment No. 3 dated November
29, 2004 and Amendment No. 4 dated November 7, 2005 (collectively, the “Agreement”)
pursuant to which PPD provides certain medical information services to CLIENT;
and


 


WHEREAS,
CLIENT and PPD wish to further amend the Agreement as set forth herein.


 


NOW,
THEREFORE, in consideration of the premises and mutual
covenants contained herein, the receipt and sufficiency of which are hereby
acknowledged, the parties agree as follows:


 


1.                                       Attachment A to the Agreement shall be deleted in its
entirety and replaced by the revised Attachment A attached hereto.


 


2.                                       The Appendix attached to the Agreement shall be deleted in
its entirety and replaced by the revised Appendix attached hereto.


 


3.                                       In the event of any inconsistency or conflict of terms
between the Agreement and this Amendment, the terms of this Amendment shall
control.


 


4.                                       Except as provided herein, all other terms and conditions of
the Agreement shall remain in full force and effect.


 


IN WITNESS
WHEREOF, the parties hereto have caused this Amendment
to be executed as of the date first above written.


 


	
  RELIANT
  PHARMACEUTICALS, INC.

  	
  ATP, LLC

  
	
   

  	
   

  
	
   

  	
   

  
	
  By:

  	
  /s/ Steve
  Ketchum

  	
   

  	
  By:

  	
  /s/ Lori
  Eberhardt

  	
   

  
	
   

  	
   

  
	
  Name:

  	
  Steve
  Ketchum, Ph.D.

  	
   

  	
  Name:

  	
  Lori
  Eberhardt

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Title:

  	
  Sr. VP,
  R&D and Medical Affairs

  	
   

  	
  Title:

  	
  VP,
  Operations

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Date:

  	
  June 28, 2006

  	
   

  	
  Date:

  	
  July 13,
  2006

  	
   

  
								



 

















 


ATTACHMENT
A


2006
PPD FEE STRUCTURE


 


	
   

  	
   

  	
  01/01/2006 -

  	
   

  
	
  HOURLY RATES (unless otherwise indicated)

  	
   

  	
  12/31/2006

  	
   

  
	
  PRODUCT SAFETY/PHARMACOVIGILANCE (PSPV)
  RATES

  	
   

  	
   

  	
   

  
	
  Monthly PSPV Management Fee

  	
   

  	
  [***]

  	
   

  
	
  Program Management

  	
   

  	
   

  	
   

  
	
  PSPV Medical Director

  	
   

  	
  [***]

  	
   

  
	
  PSPV Director

  	
   

  	
  [***]

  	
   

  
	
  PSPV Associate Director

  	
   

  	
  [***]

  	
   

  
	
  Product Safety Manager

  	
   

  	
  [***]

  	
   

  
	
  Product Safety Specialist

  	
   

  	
  [***]

  	
   

  
	
  Product Safety Assistant

  	
   

  	
  [***]

  	
   

  
	
  Adverse Event Report Management (per event)

  	
   

  	
   

  	
   

  
	
  Non-Serious Adverse Event

  	
   

  	
  [***]

  	
   

  
	
  Serious Adverse Event

  	
   

  	
  [***]

  	
   

  
	
  Literature Adverse Event Report

  	
   

  	
  [***]

  	
   

  
	
  Periodic Safety Literature Searches

  	
   

  	
   

  	
   

  
	
  Execute Monthly Search Strategy (per
  chemical entity)(per search)

  	
   

  	
  [***]

  	
   

  
	
  Review abstract/title for reportability (per
  abstract)

  	
   

  	
  [***]

  	
   

  
	
  Full text article review & analysis
  (per article)

  	
   

  	
  [***]

  	
   

  
	
  Periodic Safety Reports(1)

  	
   

  	
   

  	
   

  
	
  Annual NDA Report (per 21CFR 314.81)(2)

  	
   

  	
  [***]

  	
   

  
	
  Annual NDA Report (per 21CFR 314.80)(2)

  	
   

  	
  [***]

  	
   

  
	
  Quarterly NDA Report (per 21CFR 314.80)(2)

  	
   

  	
  [***]

  	
   

  
	
  Quarterly NDA Report (with no AE/SAE
  reports)(2)

  	
   

  	
  [***]

  	
   

  
	
  INFORMATION TECHNOLOGY (IT) RATES

  	
   

  	
   

  	
   

  
	
  Information Systems Support, Database &
  Report Programming, Telephone Programming, and Workstation Set-up

  	
   

  	
  [***]

  	
   

  
	
  Bibliographic Database Access -
  MEDLINE, EMBASE, REACTIONS (per month)

  	
   

  	
  [***]

  	
   

  
	
  Validated Safety Database Access (per
  month)

  	
   

  	
  [***]

  	
   

  



 


	
   

  	
   

  	
  01/01/2006 - 

  	
   

  
	
  ADDITIONAL COSTS (as indicated)

  	
   

  	
  12/31/2006

  	
   

  
	
  External Document Procurement, Language
  Translation, Copyright Clearance, Telephone, Pager & Fax Usage, Postage
  & In-house Fulfillment, Wide Area Network Access, Travel, Meals,
  Supplies, Off-site Storage and Outsourced Copying, Literature Searches

  	
   

  	
  [***]

  	
   

  
	
  Internal Document Procurement (per
  document)

  	
   

  	
  [***]

  	
   

  
	
  Internal Copying (per page)

  	
   

  	
  [***]

  	
   

  
	
  Videoconferencing (per hour)

  	
   

  	
  [***]

  	
   

  



 


Note 1:  Refer to Appendix for
listing of drug products subject to annual or quarterly NDA periodic reports.


Note 2:  The annual and quarterly
report charges are invoiced on a per report basis. If there are five or fewer
reported events for the reporting Interval, then the charge for the quarterly
report is $[***].


 






	
  [***]:
  

  	
  Certain
  information on this page has been omitted and filed separately with the
  Commission. Confidential treatment has been requested with respect to the
  omitted portions. 

  



 

















 


PPD invoices on a monthly basis according to the rates shown above.


 

















 


APPENDIX


 


Annual
Reports


 


[***]


[***]

[***]

[***]

[***]


 


Quarterly
Reports


 


[***]

[***]

[***]


 






	
  [***]: 

  	
  Certain information on
  this page has been omitted and filed separately with the Commission.
  Confidential treatment has been  requested with respect to the omitted
  portions. 

  



 

















 


AMENDMENT
NO. 6


 


THIS
AMENDMENT NO. 6 (“Amendment”) is made this 15th
day of December, 2006 (“Effective Date”) by and between Reliant
Pharmaceuticals, Inc (“Reliant” or “CLIENT”) and ATP, LLC d/b/a PPD Medical
Communications (“PPD”).


 


WHEREAS,
CLIENT and PPD entered into a certain Product Safety/Pharmacovigilance Services
Agreement dated February 25, 2003, as amended by Amendment No. 1 dated January
15, 2004, Amendment No. 2 dated March 30, 2004, Amendment No. 3 dated November
29, 2004, Amendment No. 4 dated November 7, 2005, and Amendment No. 5 dated
June 28, 2006 (collectively, the “Agreement”) pursuant to which PPD provides
certain post-approval safety services to CLIENT; and


 


WHEREAS,
CLIENT and PPD wish to further amend the Agreement as set forth herein.


 


NOW,
THEREFORE, in consideration of the premises and mutual
covenants contained herein, the receipt and sufficiency of which are hereby
acknowledged, the parties agree as follows:


 


1              Section
1.C(iv) of the Agreement shall be deleted in its entirety and replaced with the
following:


 


“(iv) Periodic Scientific
Literature Surveillance. PPD will process all SAEs identified as a result of
regularly scheduled systematic scientific literature surveillance. Unless
otherwise specified by CLIENT, scientific literature surveillance will be
performed at least[***] using [***] bibliographic databases (EMBASE, Medline,
Reactions Weekly). If requested, CLIENT will be provided with photocopies of
scientific literature which cite safety issues, for which CLIENT will be
charged article processing and/or procurement fees and applicable copyright
clearance fees. In addition, upon CLIENT request, PPD will make provision for
language translation, and translation fees for non-English articles will be
charged on a pass-through basis.”


 


2              A
new Section 1.N. shall be added to the Agreement, to read:


 


“N. “MedDRA and WHODrug Dictionary License. The parties
acknowledge that MedDRA and Uppsala Monitoring Centre product licenses are
required by all parties who wish to distribute or receive MedDRA or WHODrug
dictionary terminology. Each party represents and warrants that it possesses a
current MedDRA and/or Uppsala Monitoring Centre product license. In the event
CLIENT requests that PPD perform services which require PPD to distribute
MedDRA terminology or WHODrug dictionary to third parties, CLIENT shall be
responsible for ensuring that all such third parties possess the necessary
MedDRA and/or Uppsala Monitoring Centre product licenses.”


 






[***]:  Certain information on this
page has been omitted and filed separately with the Commission. Confidential
treatment has been requested with respect to the omitted portions.


 

















 


3              Section
5.B. of the Agreement shall be deleted in its entirety and replaced with the
following:


 


“CLIENT shall compensate PPD
for Start-up, Technology, Resource Costs, Project Management, and Additional
Costs as set forth in Attachment A. PPD’s Fee Schedule will include a Monthly
IT Support Fee which has been calculated based on program-specific technology
requirements and which covers the scope of services outlined below. Should IT
support outside of this scope be requested, PPD will provide a budget estimate
to cover the required services. Out of scope IT support services will not be
performed unless mutually agreed upon in writing.


 


The Monthly IT Support Fee
includes support and management of the following, based upon CLIENT program-specific
requirements:


 


a.                                       PPD-provided hardware, operating systems and applications


b.                                      PPD shared network resources


c.                                       PPD telephony and call-recording systems


i.                                          Quarterly updates to telephone message scripting and/or
programming


ii.                                       Ten (10) pre-defined holiday script changes per year


 


d.                                      General troubleshooting of client-provided hardware and/or
applications


e.                                       PPD-Company network connectivity


i.                                          Support/Configuration of inter-company VPN over the internet


ii.                                       Support assistance of client-owned or-managed WAN


iii.                                    Administration of PPD firewall for either connection type


 


4              The Appendix attached to the
Agreement shall be deleted in its entirety and replaced by the revised Appendix
attached hereto.


 


5              Attachment A to the Agreement
shall be deleted in its entirety and replaced by the revised Attachment A
attached hereto.


 


6              Attachment A to the Agreement
shall be effective beginning January 1, 2007, and shall remain in effect
through December 31, 2007.


 


7              Capitalized terms used herein and
not otherwise defined herein shall have the meaning ascribed to them in the
Agreement.


 


8              In the event of any inconsistency
or conflict of terms between the Agreement and this Amendment, the terms of
this Amendment shall control.


 


9              Except
as provided herein, all other terms and conditions of the Agreement shall
remain in full force and effect.


 

















 


IN WITNESS WHEREOF,
the parties hereto have caused this Amendment to be executed as of the date
first above written.


 


 


	
  RELIANT
  PHARMACEUTICALS, INC.

  	
  ATP, LLC

  
	
   

  	
   

  
	
   

  	
   

  
	
  By:

  	
  /s/ Steve Ketchum

  	
   

  	
  By:

  	
  /s/ Vivian
  Broach

  	
   

  
	
   

  	
   

  
	
  Name:

  	
  Steve
  Ketchum, Ph.D.

  	
   

  	
  Name:

  	
  Vivian
  Broach

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Title:

  	
  Sr. VP,
  R&D and Medical Affairs

  	
   

  	
  Title:

  	
  Executive
  Director, Operations

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Date:

  	
  December 15,
  2006

  	
   

  	
  Date:

  	
  January 2,
  2007

  	
   

  
								



 

















 


APPENDIX


 


	
  Annual
  Reports

  
	
   

  
	
  [***]

  [***]

  [***]

  [***]

  [***]

  [***]

  
	
   

  
	
  Quarterly
  Reports

  
	
   

  
	
  [***]

  



 


 






[***]:  Certain information on this page has been
omitted and filed separately with the Commission. Confidential treatment has
been requested with respect to the omitted portions.


 

















 


ATTACHMENT
A

2007 PPD FEE STRUCTURE


 


	
  PRODUCT SAFETY/PHARMACOVIGILANCE (PSPV) RATES

  	
   

  	
  Unit

  	
   

  	
  2007

  	
   

  
	
  PSPV Management Fee

  	
   

  	
  Per month

  	
   

  	
  [***]

  	
   

  
	
  Program Management

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  PSPV Medical Director

  	
   

  	
  Per hour

  	
   

  	
  [***]

  	
   

  
	
  PSPV Director

  	
   

  	
  Per hour

  	
   

  	
  [***]

  	
   

  
	
  PSPV Associate Director

  	
   

  	
  Per hour

  	
   

  	
  [***]

  	
   

  
	
  Product Safety Manager

  	
   

  	
  Per hour

  	
   

  	
  [***]

  	
   

  
	
  Product Safety Specialist

  	
   

  	
  Per hour

  	
   

  	
  [***]

  	
   

  
	
  Product Safety Assistant

  	
   

  	
  Per hour

  	
   

  	
  [***]

  	
   

  
	
  Adverse Event Report Management

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Non-Serious Adverse Event

  	
   

  	
  Per report

  	
   

  	
  [***]

  	
   

  
	
  Serious Event

  	
   

  	
  Per report

  	
   

  	
  [***]

  	
   

  
	
  Literature Adverse Event Report

  	
   

  	
  Per report

  	
   

  	
  [***]

  	
   

  
	
  Periodic Safety Literature Searches

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Execute Monthly Search Strategy (per
  chemical entity)

  	
   

  	
  Per search

  	
   

  	
  [***]

  	
   

  
	
  Review abstract/title for reportability

  	
   

  	
  Per abstract

  	
   

  	
  [***]

  	
   

  
	
  Full text article review & analysis

  	
   

  	
  Per article

  	
   

  	
  [***]

  	
   

  
	
  Periodic Safety Reports(1)

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Annual NDA Report (per 21CFR 314.81)

  	
   

  	
  Per report

  	
   

  	
  [***]

  	
   

  
	
  Annual NDA ADE Report (per 21CFR 314.80)

  	
   

  	
  Per report

  	
   

  	
  [***]

  	
   

  
	
  Quarterly NDA ADE Report (per 21CFR 314.80)

  	
   

  	
  Per report

  	
   

  	
  [***]

  	
   

  
	
  Quarterly NDA ADE Report (per 21CFR 314.80
  with 5 or fewer AE/SAE reports)

  	
   

  	
  Per report

  	
   

  	
  [***]

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  IT Support Fee

  	
   

  	
  Per month

  	
   

  	
  [***]

  	
   

  



 


	
  ADDITIONAL COSTS

  	
   

  	
  Unit

  	
   

  	
  2007

  	
   

  
	
  External Document Procurement, Language
  Translation, Copyright Clearance, Telephone, Pager & Fax Usage, Postage
  & In-house Fulfillment, Wide Area Network Access, Travel, Meals,
  Supplies, Off-site Storage and Outsourced Copying

  	
   

  	
  As needed

  	
   

  	
  [***]

  	
   

  
	
  Bibliographic Database Access

  	
   

  	
  Per month

  	
   

  	
  [***]

  	
   

  
	
  Validated Safety Database Access

  	
   

  	
  Per month

  	
   

  	
  [***]

  	
   

  
	
  Internal Document Procurement

  	
   

  	
  Per document

  	
   

  	
  [***]

  	
   

  



 


Note 1:  Refer to Appendix for listing of drug
products subject to annual or quarterly NDA periodic reports.


 






[***]:  Certain information on this page has been
omitted and filed separately with the Commission. Confidential treatment has
been requested with respect to the omitted portions.