Document:

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                                                                    EXHIBIT 10.8

WHEREVER CONFIDENTIAL INFORMATION IS OMITTED HEREIN (SUCH OMISSIONS ARE DENOTED
BY AN ASTERISK), SUCH CONFIDENTIAL INFORMATION HAS BEEN SUBMITTED SEPARATELY TO
THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO A REQUEST FOR CONFIDENTIAL
TREATMENT.

                 AMENDMENT TO MANUFACTURING AND SUPPLY AGREEMENT

      THIS AMENDMENT (the "Amendment") is made and entered into as of December
22, 2003 to the Manufacturing and Supply Agreement entered into as of August 6,
1997 by and between JPI PHARMACEUTICA INTERNATIONAL, a division of Cilag AG
International Zug ("JPI"), JANSSEN PHARMACEUTICA INC. ("JANSSEN US") and
ALKERMES CONTROLLED THERAPEUTICS INC. II ("ACT II"), as amended (the
"Agreement") (any terms used but not defined herein shall have the meaning set
forth in the Agreement).

                                    RECITALS:

       WHEREAS, JPI, JANSSEN US and ACT II have entered into the Agreement; and

       WHEREAS, the parties now wish to enter into this Amendment to clarify the
terms for payment of the Manufacturing Fee as set forth in the Agreement by
amending the terms and conditions of the Agreement as set forth below;

       NOW, THEREFORE, in consideration of the mutual promises contained herein
and other good and valuable consideration, the receipt and sufficiency of which
is hereby acknowledged, the parties agree as follows:

1.     Article 1.3 of the Agreement shall be deleted in its entirety and
replaced with a new Article 1.3 which shall read as follows:

1.3    "Final Product" shall mean a Presentation Form approved and marketed by
       JANSSEN, their Affiliates and licensees, ready for sale to the final
       customer.

2.     Article 1.5 of the Agreement shall be deleted in its entirety and
replaced with Article 1.5(a) and Article 1.5(b) which shall read as follows:

1.5(a) "U.S. Licensed Net Selling Price" shall mean the * offered by JANSSEN,
       its Affiliates or licensees in a given calendar year (or such shorter
       period as may be applicable) to independent third parties for each
       Presentation Form of the Final Product for sale in the United States, its
       territories and possession, less deductions for (i) trade, cash and
       ordinary business discounts allowed; (ii) allowances or credits to
       customers on account of rejection or return of Final Product; and (iii)
       managed care rebates or allowances and mandatory price allowances imposed
       by governments.

       If JANSSEN, its Affiliates or licensees sell any Presentation Form of the
       Final Product in the United States in such a manner that the * of the
       same is not readily identifiable then the * shall be whichever is the
       higher of (i) the fair market value of such Final Product or (ii) the
       proportion of the bundled price attributed to such Final Product by
       JANSSEN, its Affiliates or licensees whenever the Final Product is sold
       as o part of a package of products or services. For the purpose hereof
       "fair market

<PAGE>

       value" shall mean, without limitation, the value of such Final Product
       sold to similar third parties in similar quantities in the United States.
       If the fair market value cannot be determined in the United States, the
       fair market value will be negotiated by the parties in good faith.

1.5(b) "ROW Licensed Net Selling Price" shall mean the * offered by JANSSEN, its
       Affiliates or licensees in a given calendar year (or such shorter period
       as may be applicable) to independent third parties for each Presentation
       Form of the Final Product for sale in the Territory (other than the
       United States, its territories and possessions), less deductions for (i)
       trade, cash and ordinary business discounts allowed; (ii) allowances or
       credits to customers on account of rejection or return of Final Product;
       and (iii) managed care rebates or allowances and mandatory price
       allowances imposed by governments.

       If JANSSEN, its Affiliates or licensees sell any Presentation Form of the
       Final Product in a country in the Territory (other than the United
       States, its territories and possessions) in such a manner that the * of
       the same is not readily identifiable then the * for that country shall be
       whichever is the higher of (i) the fair market value of such Final
       Product or (ii) the proportion of the bundled price attributed to such
       Final Product by JANSSEN, its Affiliates or licensees whenever the Final
       Product is sold as part of a package of products or services. For the
       purpose hereof "fair market value" shall mean, without limitation, the
       value of such Final Product sold to similar third parties in similar
       quantities. If the fair market value cannot be determined in any given
       country, the fair market value will be determined by the value of such
       Final Product sold to similar customers in countries with similar pricing
       and reimbursement structures and for similar quantities.

3.     Article 1.7 of the Agreement shall be deleted in its entirety and
replaced with a new Article 1.7 which shall read as follows:

1.7    "Manufacturing Fee" shall mean the fee to be paid by JPI and JANSSEN US
       to ACT II for each Presentation Form of the Product in consideration for
       the Manufacture of Products supplied to each of them in accordance with
       the terms hereof and which fee will be calculated as a percentage of the
       U.S. Licensed Net Selling Price and/or the ROW Licensed Net Selling
       Price, as applicable, for each Presentation Form of the Final Product in
       accordance with the mechanism set forth in Article 6.

4.    A new Article 1.13 shall be added to the Agreement which shall read as
follows:

1.13  "Presentation Form" shall mean a form of the Product or the Final Product
      determined by the amount of the single dose (either 25 mg., 37.5 mg. or 50
      mg.) of the depot formulation of Risperidone contained therein.

<PAGE>

5.    Article 6 of the Agreement shall be deleted in its entirety and replaced
with a new Article 6 which shall read as follows:

6.1   In consideration of the manufacturing activities to be performed by ACT II
      hereunder, JPI and JANSSEN US will pay the Manufacturing Fee for the
      Products supplied to each of them.

      The Manufacturing Fee will be calculated as a certain percentage of the
      U.S. Licensed Net Selling Price and/or ROW Licensed Net Selling Price, as
      applicable. Subject to the terms and conditions set forth in this
      Agreement, the actual percentage that shall apply with respect to a given
      calendar year will be determined in accordance with the mechanisms set
      forth in this Article 6 and Exhibit D attached hereto.

      6.1.1 The Manufacturing Fee for calendar year 2002 has been established
      pursuant to Exhibit I hereto.

      6.1.2 (a) Determination of Manufacturing Fee. Subject to the terms and
      conditions set forth in this Article 6.1.2, the Manufacturing Fees for
      calendar year 2003 and any subsequent calendar year will be calculated on
      the basis of the (i) U.S. Licensed Net Selling Prices and/or ROW Licensed
      Net Selling Prices for such calendar year (expressed in USD at the
      exchange rates then applied by JANSSEN in accordance with its normal
      accounting procedures), as applicable, for each Presentation Form of the
      Final Product and (ii) the total amount of Product expressed in units that
      has been Manufactured and shipped pursuant to Article 4 by ACT II for such
      calendar year.

      (b)   Determination of a Provisional Manufacturing Fee. For the sake of
      administrative ease, by *, JANSSEN and ACT II will agree in good faith on
      the "U.S. Provisional Manufacturing Fee" and the "ROW Provisional
      Manufacturing Fee" for each Presentation Form of the Product for the
      upcoming calendar year. The "U.S. Provisional Manufacturing Fee" for each
      such Presentation Form of the Product shall be calculated by taking the
      forecast submitted by JANSSEN in * for the upcoming calendar year in
      accordance with Exhibit E (the "* Forecast"), to determine an estimated
      total amount of Product to be ordered, then determining the applicable
      percentage from Exhibit D to the Agreement (based on the such estimated
      total amount of Product) (the "Applicable Percentage") and adding * to
      facilitate cash flow (the "Additional Percentage") to such Applicable
      Percentage to determine the "Provisional Manufacturing Fee Percentage."
      The Provisional Manufacturing Fee Percentage shall then be applied to
      JANSSEN's estimated U.S. Licensed Net Selling Price for the upcoming
      calendar year (which shall be determined by JANSSEN in good faith and
      submitted to ACT II by * of the prior calendar year) to determine the U.S.
      Provisional Manufacturing Fee. "ROW Provisional Manufacturing Fee " for
      each such Presentation Form of

<PAGE>

      the Product shall be calculated by taking (i) the * Forecast; and
      (ii) JANSSEN's estimated ROW Licensed Net Selling Price for the upcoming
      calendar year (which shall be determined by JANSSEN in good faith and
      submitted to ACT II by * of the prior calendar year) and
      applying the Provisional Manufacturing Fee Percentage to the estimated ROW
      Licensed Selling Price to determine the ROW Provisional Manufacturing
      Fee. Subject to the other provisions of this Article 6.1.2, ACT II shall
      invoice JANSSEN US for all Product to be shipped to JANSSEN US in the
      subsequent calendar year at the U.S. Provisional Manufacturing Fee and
      shall invoice JPI for all Product to be shipped to JPI in the subsequent
      calendar year at the ROW Provisional Manufacturing Fee. Either the "U.S.
      Provisional Manufacturing Fee" and/or the "ROW Provisional Manufacturing
      Fee" may also be referred to as the "Provisional Manufacturing Fee."

      (c)   Recalculation of the Provisional Manufacturing Fee. Within *
      business days after the end of each calendar quarter JANSSEN shall send to
      ACT II a report setting forth for each Presentation Form of the Final
      Product (i) its actual U.S. Licensed Net Selling Price for the calendar
      year to date; (ii) its actual ROW Licensed Net Selling Price for the
      calendar year to date; and (iii) the actual number of units of Product
      ordered by JANSSEN pursuant to Exhibit E for the calendar year to date
      plus the number of units of Product forecast to be ordered by JANSSEN
      during the balance of the calendar year as set forth in the most recent
      forecast submitted in accordance with Exhibit E (specifying such units by
      Presentation Form and by geographical area (US - ROW)) ("Revised Annual
      Total Products"). The parties shall use such Revised Annual Total Products
      to recalculate the Applicable Percentage from Exhibit D by substituting
      such number for the comparable estimated number used to determine the then
      current Provisional Manufacturing Fee Percentage. The parties shall add an
      Additional Percentage to this Applicable Percentage to create a new
      Provisional Manufacturing Fee Percentage. The parties shall also apply the
      Applicable Percentage to the actual year-to-date US Licensed Net Selling
      Price and ROW Licensed Net Selling Price to determine an interim US
      Provisional Manufacturing Fee and an interim ROW Provisional Manufacturing
      Fee to be used for calculation purposes. The parties shall next use such
      newly calculated interim Provisional Manufacturing Fees to recalculate the
      total amount payable for Product shipped to JANSSEN during the current
      calendar year to date to determine if such recalculation would result in
      an underpayment or overpayment for such Product (a "Payment Differential")
      of more than *. The parties shall also calculate the total amount payable
      for Revised Annual Total Products using the newly calculated interim
      Provisional Manufacturing Fees as well as the prior Provisional
      Manufacturing Fees to determine if these amounts represent more than a *
      potential overpayment or underpayment for such Product. In the event that
      there is either a underpayment or overpayment of more than * or * as
      described above, then the party who has overpaid or who has been underpaid
      may request the other party to pay the Payment Differential within * of
      the end of such calendar quarter (such payment a "True Up"). In addition,
      in the event that there is a

<PAGE>

      True Up, the parties shall apply the newly calculated Provisional
      Manufacturing Fee Percentage to the actual year-to-date US Licensed Net
      Selling Price and ROW Licensed Net Selling Price to determine a revised US
      Provisional Manufacturing Fee and ROW Provisional Manufacturing Fee which
      shall become the Provisional Manufacturing Fees to be used during the
      balance of the calendar year, unless replaced by subsequently recalculated
      Provisional Manufacturing Fees in accordance with this paragraph.

      (d)   Annual Reconciliation. Within * days after the end of each calendar
      year, JANSSEN shall send to ACT II a report stating for each Presentation
      Form of the Final Product (i) its U.S. Licensed Net Selling Price for such
      calendar year; (ii) its ROW Licensed Net Selling Price for such calendar
      year; and (iii) the total number of units of Product shipped to JANSSEN
      during such calendar year (on a country-by-country basis). Any payment
      required by JANSSEN to ACT II or vice versa to compensate for any
      difference between the U.S. Provisional Manufacturing Fee and/or the ROW
      Provisional Manufacturing Fee (calculated in accordance with paragraphs
      (b) and (c) above) and the applicable Manufacturing Fees as determined by
      such actual prices and total number of units of Product shipped shall be
      made to the appropriate Party no later than * of the year in which the
      report is delivered and in accordance with the provisions of Article 6.4.

      (e)   Calculation of Units During Calendar Years *. In calculating the
      total number of units of Product shipped to JANSSEN for each of calendar
      years *, whether or not such units of Product are actually shipped, the
      parties will deem as shipped (i) all Product ordered by JANSSEN prior to
      the end of * of each such calendar year and (ii) all Product ordered
      by JANSSEN in the * forecast for each such calendar year (the "*
      Forecast") submitted in accordance with the ordering procedures set forth
      in Exhibit E. Any Product ordered by JANSSEN other than as set forth
      above, even if such Product is shipped, will not, however, be deemed to be
      shipped when making such calculation, and will also not be deemed to be
      shipped when calculating the total number of units of Product shipped
      during any subsequent calendar year. Any units of Product ordered by
      JANSSEN as set forth above, but not shipped, shall be invoiced to JANSSEN
      when shipped at the Manufacturing Fee for the applicable calendar year,
      rather than at the then current Provisional Manufacturing Fee. From the
      calendar year * onwards, the Manufacturing Fee will be calculated based on
      the total number of units of Product actually shipped to JANSSEN for such
      calendar year.

      (f)   *
<PAGE>

            (g)   *

            (h)   Illustrative Examples. Exhibit J hereto provides examples for
            illustrative purposes only of calculations made pursuant to
            paragraphs (b), (c), (d) and (e) hereof. In the event of any
            conflict between Exhibit J and this Agreement, the provisions of
            this Agreement shall control.

      6.2   JANSSEN shall keep or cause to be kept accurate records in
            sufficient detail to enable the Manufacturing Fees for Products sold
            hereunder to be determined. JANSSEN, upon the written request
            (including reasonable notice) and at the expense of ACT II, and in
            any event not more frequently than once in any calendar year, shall
            permit an independent public accountant of national prominence
            selected by ACT II, and approved by JANSSEN (with approval not
            unreasonably to be withheld), to have access during normal business
            hours to those records as may be reasonably necessary to verify the
            accuracy of the Manufacturing Fees for Products sold for any
            calendar year ending not more man three (3) years prior to the date
            of the aforementioned written request. If such accountant determines
            that the Manufacturing Fees have been overstated or understated,
            then one party shall make a payment to the other party as necessary
            to correct the amount of the Manufacturing Fees paid for Product
            supplied hereunder, which payment shall be based on the difference
            between the actual and the misstated Manufacturing Fees. In
            addition, if such accountant reasonably determines that the
            Manufacturing Fees have been understated for the audited period by
            more than *, then JANSSEN shall pay the reasonable costs of such
            audit. ACT II agrees that all information subject to review under
            this Article 6.2 shall be deemed JANSSEN's Confidential Information
            subject to the terms and conditions of Article 7. ACT II shall
            retain and cause its independent accountant to retain all such
            information in confidence in accordance with Article 7 and such
            information may only be used for purposes germane to this Article
            6.2.

      6.3   ACT II shall invoice JPI or JANSSEN US for the Provisional
            Manufacturing Fee due with respect to each batch of Product supplied
            to each of them or their

<PAGE>
            respective designee when shipped pursuant to Article 4. JPI and
            JANSSEN US shall pay such, invoice within * after the date of the
            invoice.

      6.4   All payments required to be paid hereunder shall be made in United
            States Dollars by wire transfer of immediately available funds to
            the financial institution, account number, account party's name and
            wire transfer information designated in writing by ACT II to JPI and
            JANSSEN US as the place of payment.

      6.5   No party shall have the right to reduce, by set off, counterclaim,
            adjustment or otherwise, any amount owed by it to the other party
            pursuant to this Agreement, unless explicitly provided for
            otherwise.

      6.6   JANSSEN shall bear all applicable national, federal, provincial,
            municipal and other governmental taxes (such as sale, use or similar
            taxes), duties, or import charges, except for any tax on profits or
            income of ACT II, that ACT II may be required to pay or collect as a
            result of the payments of the Manufacturing Fee or the Provisional
            Manufacturing Fee.

      6.7   Within * after the end of each month, JANSSEN shall deliver to ACT
            II a report setting forth the dollar amount and the units of each
            Presentation Form of the Final Product sold during the prior month
            on a country-by-country basis. In addition, each month JANSSEN shall
            provide to ACT II the foreign currency exchange rates used to
            calculate the Final Product sales for each country.

      6.    Exhibit D shall be amended by deleting the words "Licensed Net
      Selling Price" and substituting the words "U.S. Licensed Net Selling Price
      and/or ROW Licensed Net Selling Price."

      7.    This Amendment and the Agreement shall be governed by and construed
      in accordance with the laws of the State of New York without regard to its
      conflict of law provisions.

      8.    Except as expressly provided in this Amendment, all other terms,
      conditions and provisions of the Agreement shall continue in full force
      and effect as provided therein. This Amendment and the Agreement
      constitute the entire agreement between the parties hereto relating to the
      subject matter hereof and thereof and supersede all prior and
      contemporaneous negotiations, agreements, representations, understandings
      and commitments with respect thereto.

                            [signature page follows]

<PAGE>

      IN WITNESS WHEREOF, JPI, JANSSEN US and ACT II have executed and
delivered this Amendment effective as of the date first set forth above.

      ALKERMES CONTROLLED                      JPI PHARMACEUTICA
       THERAPEUTICS INC. II              INTERNATIONAL represented by
                                          CILAG AG INTERNATIONAL ZUG

By:    /s/ Michael Landine              By:  /s/  Erik Rombouts
       ---------------------                 ----------------------------------
Name:  Michael Landine                  Name: ERIK ROMBOUTS
Title: Vice President                   Title: VP ALLIANCE MGMT

                                        By:   /s/ Heinz Schmid
                                             ----------------------------------
                                        Name:  HEINZ SCHMID
                                        Title: GENERAL MANAGER

                                        JANSSEN PHARMACEUTICA INC.

                                        By: /s/ Peter Miller
                                            ------------------------------------
                                        Name: Peter Miller
                                        Title: President
<PAGE>

                                   EXHIBIT I

                                     [***]

THIS EXHIBIT HAS BEEN REDACTED AND IS THE SUBJECT OF A CONFIDENTIAL TREATMENT
REQUEST. REDACTED MATERIAL IS MARKED WITH "*" AND HAS BEEN FILED SEPARATELY
WITH THE SECURITIES AND EXCHANGE COMMISSION.
<PAGE>

                                   EXHIBIT J

                                     [***]

THIS EXHIBIT HAS BEEN REDACTED AND IS THE SUBJECT OF A CONFIDENTIAL TREATMENT
REQUEST. REDACTED MATERIAL IS MARKED WITH "*" AND HAS BEEN FILED SEPARATELY
WITH THE SECURITIES AND EXCHANGE COMMISSION.<PAGE>

                                                                    EXHIBIT 10.9

WHEREVER CONFIDENTIAL INFORMATION IS OMITTED HEREIN (SUCH OMISSIONS ARE DENOTED
BY AN ASTERISK), SUCH CONFIDENTIAL INFORMATION HAS BEEN SUBMITTED SEPARATELY TO
THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO A REQUEST FOR CONFIDENTIAL
TREATMENT.

             FOURTH AMENDMENT TO MANUFACTURING AND SUPPLY AGREEMENT

THIS FOURTH AMENDMENT (the "Amendment") is made and entered into as of January
10, 2005 (the "Amendment Effective Date") to the Manufacturing and Supply
Agreement entered into as of August 6, 1997, as amended, by and between JPI
PHARMACEUTICA INTERNATIONAL, a division of Cilag AG International Zug ("JPI"),
JANSSEN PHARMACEUTICA INC. ("JANSSEN US" and, together with JPI, "JANSSEN"), on
the one hand, and ALKERMES CONTROLLED THERAPEUTICS INC. II ("ACT II"), on the
other hand (the "Agreement").

                                    RECITALS:

WHEREAS, JANSSEN and ACT II have entered into the Agreement; and

WHEREAS, JANSSEN and ACT II have also entered into an Addendum to the Agreement,
dated as of August 1, 2001 (the "Addendum"), regarding the expansion of ACT II's
manufacturing facilities; and

WHEREAS, the parties now wish to enter into this Amendment regarding the further
expansion of ACT II's manufacturing facilities, and the financial responsibility
of each of the parties in connection with such expansion;

NOW, THEREFORE, in consideration of the mutual promises contained herein and
other good and valuable consideration, the receipt and sufficiency of which is
hereby acknowledged, the parties agree as follows:

1.    DEFINITIONS. Unless provided otherwise, any capitalized terms used in this
Amendment that are not defined herein will have the meaning set forth in the
Agreement or the Addendum. The following terms will have the following meanings:

"Depreciation Credit" means an amount calculated by dividing the Total Third
Line Cost by the divisor of *, representing * for depreciation multiplied by *
of Product per year.

"FTE" means a full-time technical person dedicated by ACT II to perform
technical work on or directly related to the Third Line Plan, or in the case of
less than a full-time dedicated technical person, a full-time equivalent
technical person year, based upon a total of * (i.e., * of technical work on or
directly related to the Third Line Plan.

"FTE Hourly Rate" means the amount of *.

"Total Third Line Cost" means the total amount of the costs incurred by ACT II,
calculated as of the date of Validation Completion, for activities performed
pursuant to the Third Line Plan, including without limitation the purchase of
equipment and the design, engineering, construction and validation activities so
performed. In no event, shall the Total Third Line Cost exceed the overall
budget set forth in the Third Line Plan, unless such excess costs have been
approved by JANSSEN.

2.    THIRD LINE. ACT II will design, engineer, construct and validate a third
wet process line at its manufacturing facility located in Wilmington, Ohio (the
"Third Line"). A description of the design, engineering, construction and
validation activities for the Third

<PAGE>

Line, including the equipment to be installed therein and the timeline and
budget for such design, engineering, construction and validation activities
(the "Third Line Plan") will be established by the parties. A draft Third Line
Plan including a project budget and project timeline is set forth in Exhibit A
to this Amendment.

3.    APPROVAL OF THIRD LINE PLAN. Within * of the Amendment Effective Date, the
parties will meet to review and finalize the draft Third Line Plan. Any
modifications to the draft Third Line Plan affecting the anticipated timelines,
scope or budget thereof shall only become effective with the consent of both ACT
II and JANSSEN, which consent shall not be unreasonably withheld or delayed. The
final Third Line Plan will be attached to this Amendment as Exhibit A 1.

4.    PERFORMANCE OF ACTIVITIES. Upon finalization of the Third Line Plan, ACT
II will begin to perform, and to have performed, the activities set forth
therein. ACT II will be responsible for the management of the design,
engineering, construction and validation of the Third Line. The Global Supply
Team, or a designated Sub-Team thereof, may, however, recommend actions to ACT
II following periodic reviews of the design, engineering, construction and
validation of the Third Line. Periodically ACT II may also notify the Global
Supply Team of proposed amendments to the Third Line Plan. Within * of receipt
of any proposed amendment to the Third Line Plan, the Global Supply Team, or the
designated Sub-Team, will meet to evaluate the amendment to the Third Line Plan
and to recommend actions; provided, however, that the scope, timelines or budget
set forth in the Third Line Plan may only be amended with the consent of both
ACT II and JANSSEN, which consent shall not be unreasonably withheld or delayed.
ACT II will keep the Global Supply Team, or any designated Sub-Team, regularly
informed, and at least on a quarterly basis, of issues and decisions affecting
the design, engineering, construction and validation of the Third Line and will
consult with the Global Supply Team, or any designated Sub-Team, before making
any decisions with respect thereto whenever possible.

5.    PAYMENT. JANSSEN US will reimburse ACT II at the * for design,
engineering, construction and validation activities performed by * pursuant to
the Third Line Plan and will also reimburse ACT II for any for any out-of-pocket
costs incurred by ACT II in connection with such activities, including without
limitation costs incurred for equipment, and third-party design, engineering,
construction and validation services. Any costs for design, engineering,
construction and validation activities that exceed the overall budget set forth
in the Third Line Plan will be borne by and will be the responsibility of ACT II
unless such excess costs have been approved by JANSSEN. The parties will
regularly review the status of the budget in the Third Line Plan, in accordance
with the anticipated spending schedule provided for in the Third Line Plan.

Notwithstanding the foregoing, the costs of manufacturing any necessary
development and validation batches of the Product in connection with the
validation of the Third Line will be borne by ACT II, it being understood that
if any such Product is supplied to JANSSEN in accordance with the terms of the
Agreement, ACT II will be paid the Manufacturing Fee for such Product. JANSSEN
will provide Compound for the manufacture of such development and validation
batches of the Product free of charge, and no Compound so supplied will be a
factor in any yield variance calculation, including without limitation any
calculation made pursuant to Section 2.7 of the Agreement.

6.    PAYMENT PROCESS. ACT II will invoice JANSSEN US, or such other entity as
JANSSEN US shall direct, on a * for design, engineering and construction
activities based on the payment schedule set forth in Exhibit A.1, and JANSSEN
US, or such

                                        2
<PAGE>
other designated entity, will pay ACT II within *. Upon approval of the process
validation reports for the Third Line ("Validation Completion"), ACT II will
invoice JANSSEN US, or such other entity as JANSSEN US shall direct, for the
costs of all validation activities set forth in the Third Line Plan, and JANSSEN
US, or such other designated entity, will pay ACT II within *. All payments
required to be made hereunder will be made in United States dollars by wire
transfer of immediately available funds to the financial institution, account
number, and account party's name designated in writing from time to time by ACT
II to JANSSEN US as the place of payment.

7.    OWNERSHIP OF EQUIPMENT. JANSSEN US will own the pieces of equipment
described in the Third Line Plan (the "Equipment"). To the extent that the
provisions of this Amendment are in conflict with Section 2.2 of the Agreement,
Section 2.2 will be deemed to be amended with respect to the Equipment. To
perfect JANSSEN US's ownership interest in the Equipment, ACT II, at JANSSEN's
request, will file appropriate Uniform Commercial Code financing statements with
respect to the Equipment. ACT II will keep the Equipment free and clear of all
liens and encumbrances, other than those which may result from acts of JANSSEN.
JANSSEN US will be responsible for paying any taxes, including without
limitation personal property and sales taxes, that may accrue with respect to
the Equipment.

8.    USE OF EQUIPMENT. ACT II will have the right to use the Equipment during
the term of the Agreement in accordance with the provisions of the Agreement and
this Amendment, without obligation to make any payments to JANSSEN US with
respect to such right of use other than as provided for in Section 11 hereof.
ACT II will maintain each piece of Equipment in good operating order and repair,
normal wear and tear excepted. ACT II agrees, at its own expense, to keep all
Equipment insured in appropriate amounts for damage or loss.

9.    DELIVERY OF EQUIPMENT UPON TERMINATION. Subject to ACT II's purchase
rights as set forth in Section 11, upon termination or expiration of the
Agreement, JANSSEN US may request that ACT II deliver to any destination in the
United States any Equipment that is not permanently fixed to ACT II's facilities
in Wilmington, Ohio and that can be removed from such facilities without
destroying any portion thereof or significantly disrupting the operation
thereof, as reasonably determined by ACT II. ACT II will promptly crate and ship
such Equipment to such destination at JANSSEN US's cost and expense.

10.   USE OF THIRD LINE. The parties agree that after the first and second wet
process lines at ACT II's Wilmington, Ohio facility have been utilized to their
appropriate capacity for the manufacture of the Product, as determined by the
Global Supply Team taking into account the forecasts for the Product provided by
JANSSEN in good faith pursuant to the Agreement, manufacture of the Product will
be given priority on the Third Line. Subject to the foregoing limitation, ACT II
will have the right at any time to manufacture products other than the Product
using the Third Line, provided that (i) ACT II has provided * prior notice of
such intended manufacturing activities to JANSSEN (the "Manufacturing Notice")
and discussed such intended manufacturing activities with the Global Supply
Team, and (ii) the Global Supply Team, using its reasonable judgment in good
faith, has approved such use following review of a facility master plan to be
provided by ACT II specifying the proposed production campaigns on the Third
Line. Any such discussion with the Global Supply Team will be subject to ACT
II's obligations of confidentiality (if any) to its collaborative partner for
the products to be manufactured using the Third Line. Unless the Global Supply
Team notifies ACT II within * of

                                        3
<PAGE>

receipt of the Manufacturing Notice that it does not approve the intended
manufacturing activities, ACT II will have the right to manufacture products
other than the Product using the Third Line, and ACT II will purchase the
Equipment in accordance with the provisions of Section 11 hereof at the latest *
prior to the date of manufacturing the first commercial batch of any such
product on the Third Line.

11.   PURCHASE OF EQUIPMENT. In addition to its purchase obligations under
Section 10 above, at any time, upon thirty (30) days prior written notice to
JANSSEN, ACT II will have the right to purchase the Equipment. Any purchase by
ACT II of the Equipment will be made at its then current book value, as set
forth in JANSSEN US's financial statements, which book value will be determined
by depreciating the Equipment and the related installation and validation costs
set forth in the Third Line Plan in accordance with United States generally
accepted accounting principles (US GAAP) consistently applied; provided,
however, that if ACT II exercises its purchase right following the receipt of
notice from JANSSEN of termination of the Agreement pursuant to Section 10.2.4
thereof, then ACT II will have the right to purchase the Equipment for
consideration of Ten U.S. Dollars (US $10.00). JANSSEN US will depreciate the
Equipment and the related costs on a straight- line basis over a period of *.
Within * of receipt of the Manufacturing Notice or a notice from ACT II of
intended purchase of the Equipment, JANSSEN will provide ACT II with notice of
the Equipment's then current book value. ACT II will have the right to request
an audit of JANSSEN US' determination of book value of the Equipment, which
shall be conducted by an independent public accountant of national prominence at
ACT II's expense. Such accountant will treat all information subject to audit
under this Section 11 as confidential and will provide a report to ACT II and
JANSSEN US regarding only the accuracy or inaccuracy of the book value
determination. Following receipt of JANSSEN's notice regarding the book value of
the Equipment (and any audit conducted by ACT II), JANSSEN US and ACT II will
promptly execute and deliver appropriate bills of sale and other documents for
the purchase of the Equipment. Upon the execution and delivery of such
documents, this Amendment will be automatically amended to delete Sections 7
through 10 hereof, and JANSSEN will promptly file amendments terminating any
Uniform Commercial Code financing statements that have been filed with respect
to the Equipment.

12.   DEPRECIATION CREDIT. If ACT II manufactures more than * of the Product on
the Third Line during any calendar year, then ACT II will give JANSSEN a
Depreciation Credit in accordance with the terms of this Section 12 for each
batch of Product in excess of * that are so manufactured. For any calendar year
in which more than * of the Product were manufactured on the Third Line, ACT II
will grant to JANSSEN within * of the end of such calendar year a credit in the
amount of: (i) the Depreciation Credit per batch of the Product, multiplied by
(ii) the number of batches of the Product in excess of * manufactured on the
Third Line in such calendar year. JANSSEN shall have the right to apply this
credit until it is exhausted against Manufacturing Fees payable for the Product
supplied by ACT II during the subsequent calendar year.

13.   LONG TERM CAPACITY. ACT II and JANSSEN agree that if, and only if, the
Global Supply Team agrees in good faith, taking into account the forecasts for
the Product provided by JANSSEN in good faith pursuant to the Agreement, that
the volumes of the Product so ordered by JANSSEN will exceed the combined
capacity of the first, second and third wet process lines and the existing
filling lines at ACT II's Wilmington, Ohio facilities, then JANSSEN will have
the option to establish its own manufacturing facility for the

                                        4
<PAGE>

manufacture of the Product by JANSSEN or any of its Affiliates. If the Global
Supply Team so agrees, both parties will discuss in good faith the timing and
specific conditions for the establishment of any such additional manufacturing
facility with a view to maximizing the chances for an expedient and successful
validation of such facility. Among other conditions to be negotiated by the
parties in good faith and agreed upon in writing, ACT II will provide, if
necessary and at the expense of JANSSEN, commercially reasonable training and
support including the transfer of all necessary data and instructions to achieve
such objectives. The parties agree that commercial manufacturing at such
facility will not begin unless and until ACT II and JANSSEN have negotiated in
good faith and agreed in writing upon appropriate economic mechanisms to
preserve ACT II's net economic benefit under the current agreements between the
parties with respect to the Product, including without limitation the Agreement,
the Addendum, and the Agreement between the parties dated December 21, 2002, as
amended. For the purpose of determining the net economic benefit referred to
above, the parties will also consider a reasonable utilization percentage of the
first, second and third wet process lines and the existing filling lines at ACT
II's Wilmington, Ohio facilities. At the Effective Date of this Amendment, the
parties contemplate such reasonable percentage to be * of the capacity thereof,
unless the parties agree otherwise when negotiating such economic mechanisms
referred to above. The parties furthermore agree that such percentage may vary
as a result of *. The terms and conditions of this Section 13 will supersede the
terms and conditions of Section 9 of the Agreement between the parties dated
December 21, 2002, as amended.

14.   OPERATING COSTS. Following the Validation Completion, ACT II will be
responsible for the ongoing operating costs of the Third Line in accordance with
the provisions of the Agreement.

15.   PRESS RELEASE. Neither party will originate any written publicity, news
release or public announcement, written or oral, relating to this Amendment,
other than such announcements or filings that are required to be made by
applicable law, rules or regulations (or the applicable rules of any securities
exchange or market on which a party's or its affiliates' securities are listed
or traded) or that are otherwise agreed by the parties or expressly permitted
under this Amendment. An approved press release announcing this Amendment is
attached hereto as Exhibit B. If in the reasonable opinion of a party's legal
counsel, a public announcement is required to be made by applicable laws, rules
or regulations (or the applicable rules of any securities exchange or market on
which a party's or its affiliates' securities are listed or traded), then the
disclosing party will provide the other party notice reasonable under the
circumstances of such intended announcement and, to the extent feasible under
circumstances, will consult with the other party with respect to the nature and
scope of such intended announcement. Routine references to this Amendment and
the arrangements hereunder will be allowed in the usual course of a party's
business. Once information has been approved for disclosure or publication under
this Section 15, either party may use such approved information in written
publicity, news releases, public announcements and other future communications
with third parties.

16.   GOVERNING LAW. This Amendment will be governed by and construed in
accordance with the laws of the State of New York without regard to its conflict
of law provisions.

                                        5

<PAGE>

17.   INTEGRATION. Except as expressly provided in this Amendment, all other
terms, conditions and provisions of the Agreement will continue in full force
and effect as provided therein. This Amendment, the Agreement and the Addendum
constitute the entire agreement between the parties hereto relating to the
subject matter hereof and thereof and supersede all prior and contemporaneous
negotiations, agreements, representations, understandings and commitments with
respect thereto. In the event of a conflict between the terms and conditions of
the Agreement or the Addendum and the terms and conditions of this Amendment,
the terms and conditions of this Amendment shall control.

                            [signature page follows]

                                        6

<PAGE>

IN WITNESS WHEREOF, JPI, JANSSEN US and ACT II have executed and delivered this
Amendment effective as of the date first set forth above.

        ALKERMES CONTROLLED                   JPI PHARMACEUTICA
        THERAPEUTICS INC. II            INTERNATIONAL represented by
                                         CILAG AG INTERNATIONAL ZUG

By: /s/ Michael Landine                By: /s/ Heinz Schmid
   ___________________________            _____________________________
Name: Michael Landine                  Name: Heinz Schmid
     _________________________              ___________________________
Title: Vice President                  Title: General Manager
      ________________________               __________________________

                                       By: /s/ Gilber Eyer
                                          _____________________________
                                       Name: Gilber Eyer
                                            ___________________________
                                       Title: Finance Director
                                             __________________________

                                         JANSSEN PHARMACEUTICA INC.

                                       By: /s/ Janet Vergis
                                          ____________________________
                                       Name: Janet Vergis
                                            __________________________
                                       Title: President
                                             _________________________

                                        7

<PAGE>

                                    EXHIBIT A

                                     [***]

THIS EXHIBIT HAS BEEN REDACTED AND IS THE SUBJECT OF A CONFIDENTIAL TREATMENT
REQUEST. REDACTED MATERIAL IS MARKED WITH "*" AND HAS BEEN FILED SEPARATELY
WITH THE SECURITIES AND EXCHANGE COMMISSION.
<PAGE>

                                    EXHIBIT B
                                  PRESS RELEASE
                         [To be approved by the parties]

                                                   Contact:
                                                   Barbara Yates
                                                   Alkermes, Inc.
                                                   (617)583-6321

DRAFT - NOT FOR RELEASE

ALKERMES TO EXPAND PRODUCTION CAPACITY FOR
RISPERDAL(R) CONSTA(R)

CAMBRIDGE, MA, JANUARY 11, 2005 -- Alkermes, Inc. (Nasdaq: ALKS) today announced
that the Company will expand production capacity for Risperdal(R) Consta(R)
[(risperidone) long-acting injection], an atypical antipsychotic medication
approved for the treatment of schizophrenia. This expansion at Alkermes'
Wilmington, Ohio, facility is designed to meet anticipated future demand for
Risperdal Consta. Alkermes' partner, Janssen-Cilag, a wholly owned division of
Johnson & Johnson, will help fund the building of the new manufacturing line.
Under the terms of the agreement, Alkermes will be responsible for managing the
design, engineering, construction, validation and all other aspects of the
project based upon a mutually-developed project plan.

"The decision to expand our manufacturing capabilities highlights the success of
Risperdal Consta," commented Richard Pops, Chief Executive Officer of Alkermes.
"We are excited to build this third manufacturing line to support the plans to
continue to meet the market needs for Risperdal Consta as an important product
for patients."

About Alkermes, Inc.

Alkermes, Inc. is a pharmaceutical company that develops products based on
sophisticated drug delivery technologies to enhance therapeutic outcomes in
major diseases. The Company's lead commercial product, Risperdal Consta
[(risperidone) long-acting injection], is the first and only long-acting
atypical antipsychotic medication approved for use in schizophrenia, and is
marketed worldwide by Janssen-Cilag ("Janssen"), a wholly owned subsidiary of
Johnson & Johnson. The Company's lead proprietary product candidate, Vivitrex(R)
[(naltrexone) long-acting injection], is a once-a-month injection for the
treatment

                                       12
<PAGE>

of alcohol dependence. The Company has a pipeline of extended-release injectable
products and pulmonary drug products based on its proprietary technology and
expertise. Alkermes' product development strategy is twofold: the Company
partners its proprietary technology systems and drug delivery expertise with
several of the world's finest pharmaceutical companies and it also develops
novel, proprietary drug candidates for its own account. The Company's
headquarters are in Cambridge, Massachusetts, and it operates research and
manufacturing facilities in Massachusetts and Ohio.

This press release may contain forward-looking statements within the meaning of
the Private Securities Litigation Reform Act. There can be no assurance that
actual results will not differ materially from the forward-looking statements
discussed in this press release. These forward-looking statements include risks
and uncertainties that the third manufacturing line will be built on budget or
will be validated on time, risks and uncertainties inherent in the collaboration
with and dependence upon Johnson & Johnson, and risks and uncertainties
regarding the drug discovery and development process. These statements reflect
Alkermes' current beliefs; however, as with any pharmaceutical product, there
remain substantial risks and uncertainties related to market acceptance. There
are no guarantees regarding what the actual demand for Risperdal Consta may be
nor whether Alkermes can manufacture Risperdal Consta on a commercial scale or
economically. These and additional risks and uncertainties are described more
fully in Alkermes' filings with the Securities and Exchange Commission under the
Securities Exchange Act of 1934, such as its Annual Report on Form 10-K for the
fiscal year ended December 31, 2003 under the heading "Risk Factors Related to
Our Business" and its subsequently filed Quarterly Reports on Form 10-Q.
Alkermes undertakes no duty to update forward-looking statements.

                                       13

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