**Exhibit 10.33**

 

ConfidentialMaterials omitted and filed separately with the Securities and ExchangeCommission.  Asterisks denote omissions.

 

 

**MASTER PRODUCTIONAGREEMENT**

 

This Master Production Agreement (this “**Agreement**”) is made as of this 1stday of December, 1998 between Bio Science Contract ProductionCorp., a Maryland corporation (“**BSCP**”),and Transkaryotic Therapies Inc, a Delaware corporation (“**Client**”).

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**RECITALS**

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A.            BSCP operates a multi-client production facility,operated in accordance with the U.S. Food and Drug Administration’s (the “**FDA**”)current Good Manufacturing Practices, located at 5901 East Lombard Street,Baltimore, Maryland 21224 (the “**Facility**”).

 

B.            Clientis a development-stage biotechnology company active in research and developmentof drug products.

 

C.            From time to time, Client desires to have BSCP produce,and BSCP is willing to produce, one or more Products (as hereinafter defined)at the Facility.  Each Product shall bedescribed in a separate **Schedule A-( )**(each Product produced pursuant to this Agreement and the Schedules heretoshall be separately sequentially numbered and identified, beginning with “1”,and the blank spaces set forth within the parentheses to each Schedule shallcontain such number, for example, the Schedules for the first Product shall be **Schedule A-(1), Schedule B-(1)**,etc.).  Each Product shall be producedin accordance with the terms and subject to the conditions hereinafter setforth and contained in the Schedules hereto.

 

D.            BSCP shall produce each Product pursuant to theProduction Record for each Product and the Operating Documents.  Based on the information provided to BSCPpursuant to Paragraph 1 below, BSCP shall prepare, and Client shall approve,the Production Record for each Product in accordance with the terms of thisAgreement.

 

NOW, THEREFORE, in consideration of the foregoing andthe mutual promises and covenants hereinafter set forth, BSCP and Client,intending to be legally bound, hereby agree as follows:

 

 

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**DEFINITIONS**

 

 

The following capitalizedterms used in this Agreement shall have the following meanings:

 

“**BSCP Parties**”means BSCP, its employees, agents and affiliates.

 

“**Commencement Date**”with respect to each Product will be set forth on **Schedule B-(__)** attached hereto, relating to that Product.

 

“**Product**”shall mean each bulk substance that BSCP has agreed to produce pursuant to theProduction Record relating thereto.

 

“**Production Record**”shall mean the Client-specific batch production records required for BSCP toproduce each Product in the Facility.

 

“**Production Term**”shall mean, for each Product, that period commencing on the Commencement Dateand terminating on the Termination Date.

 

“**BSCP OperatingDocuments**” shall mean the standard operating procedures, standardmanufacturing.  procedures, protocols,validation documentation, and supporting documentation, such as environmentalmonitoring, for operation and maintenance of the Facility and BSCP equipment.

 

“**Client Operating Documents**”shall mean the standard operating procedures, standard manufacturingprocedures, protocols and validation documentation specific to the Client’sProduct and Client equipment.

 

“**Termination Date**”for each Product will be set forth on **ScheduleB-(__)** attached hereto, relating to that Product.

 

“**cGMP**”means FDA’s current good manufacturing practices as specified in 21 CFR Article210 and FDA’s guidance documents, and all successor regulations and guidancedocuments thereto.

 

[Intentionallyleft blank]

 

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# 1.             ProductionRecord.  The Production Record shallbe prepared by BSCP under Client’s direction pursuant to the informationprovided by Client.  Client shallprovide information and procedures required to create an approvable ProductionRecord and to produce the Product, and any intermediate or by-products thereof,including:

 

## (a)           Processinformation, SOPs, production records, development reports

 

## (b)           Qualitycontrol assays

 

## (c)           Rawmaterials and raw materials test specifications

 

## (d)           Productpacking and shipping instructions

 

## (e)           Productspecific cleaning and decontamination information

 

If Client is unable toprovide the items listed above, Client shall cooperate reasonably with BSCP toenable BSCP to write the Production Record. When BSCP finalizes the Production Record, it shall deliver it to Clientfor its approval and acceptance.  Clientshall notify BSCP in writing of any objections it has to the Production Record,and upon such notification, BSCP and Client shall work together promptly toresolve such objections.  Upon Client’swritten notification to BSCP that the Production Record is satisfactory, theProduction Record shall be deemed approved and accepted by Client.  The ownership of the Production Record shallremain with Client at all times.  Thecost of the preparation of the Production Record shall be as set forth on **Schedule B-(__)** attached hereto.

 

2.             [**]  Inconnection with the production of each Product hereunder in the ProductionArea, BSCP shall supply [**].  Clientshall be responsible for providing to BSCP, in a timely manner, [**], otherthan those to be supplied by BSCP required to produce each Product pursuant toits Production Record (unless BSCP otherwise agrees in writing, to provide suchitems).  Any Client-provided items withrespect to the production of a Product are as set forth in **Schedule C-(__)** attached hereto.  Client provided equipment, materials,consumables, or other Client provided items shall only be used for Client productionor testing.

 

3.             Production Term.

 

(a)           Each Product shall be produced in thesuite identified on Schedule B-(  ),such suite being called the “Production Area”. The Production Term is set forth in **ScheduleB-(__)** attached hereto relating to that Product.  The term of this Agreement shall continue infull force and effect for a period ending on the later of 10 years from thedate hereof or the Termination Date of the final Product to-be producedhereunder unless terminated earlier in accordance with the following provisionsof this Section 3.

(b)           Each party (the “Terminating Party”)shall have the right to terminate this Agreement upon six (6) months priorwritten notice (the “Termination Period”) to the other party in accordance withthe following:

 

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### (i)            IfClient is the Terminating Party, it shall have the option (if set forth inClient’s notice of termination to BSCP), in lieu of requiring BSCP to continueits performance under the Agreement during the Termination Period, to elect topay BSCP, within [**] of the delivery of the termination notice, immediatelyavailable funds equal to [**] production fee at the then current rate, togetherwith the costs of all materials and consumables purchased by BSCP through theend of the Termination Period.  Allmaterials and consumables purchased by BSCP through the end of the TerminationPeriod should be delivered to the Client or its subsidiaries/designees at theClient’s cost.

 

### (ii)           IfBSCP is the Terminating Party, then BSCP and Client shall continue to performtheir respective obligations under this Agreement throughout the TerminationPeriod unless otherwise agreed to in writing by the parties.

 

All materials and consumables purchased by BSCPthrough the end of the Termination Period should be delivered to the Client orits subsidiaries/designees at the Client’s cost.

 

(c)           BSCP shall have the right toterminate this Agreement [**].

 

(d)           Each party shall have the right toterminate this Agreement (i) following a material breach of this Agreement thatthe breaching party fails to remedy within [**] after written notice thereof bythe non-breaching party; and (ii) immediately upon the bankruptcy, insolvency,dissolution, or winding up of the other party.

##  

(e)           The expiration or earlier terminationof this Agreement shall not relieve the parties of any obligation accruingprior to such expiration or termination including, without limitation, allmonetary obligations for work, services, materials, and costs previouslyperformed or incurred by BSCP pursuant to this Agreement.  The confidentiality and indemnificationprovisions contained in the Agreement, the warranty provisions in Sections 5(f) and 5 (g) and the miscellaneous provisions in Section 9 shall survive theexpiration or earlier termination of this Agreement.

 

# 4.             Compensation.  Compensation for BSCP’s production of eachProduct under this Agreement shall be payable by Client to BSCP as follows:

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## (a)           Set-UpFee.  Simultaneously with itsexecution of the Schedules attached hereto for the production of each Product,Client shall pay to BSCP a non-refundable Set-Up fee per Production Term (a “**Set-Up Fee**”) as set forth on **Schedule B-(__)** attached hereto.  A Set-Up Fee shall compensate BSCP for thework performed prior to commencement of the per diem charge for each Product.

BSCP shall not commence preparation for the productionof the Product prior to its receipt of a Set-Up Fee and, if applicable, aseparate fee to write the Production Record, in connection with each Productproduction run.

 

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## (b)           [**]Production Fee.

 

### (i)            Foreach Product, Client shall pay to BSCP a [**] production fee (the “[**]**Production Fee**”) as set forth in **Schedule B-(__)** attached hereto.  The [**] Production Fee shall be due andpayable in advance of the Commencement Date and on the same calendar date ofeach subsequent [**] during the Production Term (if the Production Termincludes a period of time which [**], the [**] Production Fee [**] shall equalthe [**] multiplied by [**], which is the [**] Production Fee [**]).

 

### (ii)           Materialsand consumables [**] in the [**] Production Fee, but shall be paid for byClient at BSCP’s out-of-pocket cost for such materials and consumables uponreceipt of the invoice sent by BSCP to Client [**].

 

(c)           OtherCharges.  As required to produce theProduct, BSCP may provide [**] to Client (collectively the “**Other Production Requirements**”).  Client shall pay BSCP for the provision ofthe Other Production Requirements as agreed upon in advance by BSCP and Client,as set forth in **Schedule D-(__)**attached hereto.  Client shall pay forsuch Other Production Requirements upon receipt of the invoice sent by BSCP toClient, except if such charges are anticipated to exceed $[**], then Clientshall pay such charges in advance. Client shall provide, in **ScheduleD-(__)** attached hereto, a list of all hazardous wastes orsubstances, and the anticipated quantities, that will be used in the productionprocess for each Product.  BSCP shallnotify Client of those hazardous wastes or substances that cannot be disposedof through BSCP’s waste disposal system in the quantities that Client proposeswill be produced in connection with the production of each Product.  BSCP’s waste disposal system is both adecontamination and pH adjustment system. Client agrees to pay for the disposal by BSCP of such materials thatcannot be disposed of by BSCP in accordance with the rates set forth on **Schedule D-(__)** attached hereto.  To the extent that any incorrect informationprovided by Client on **Schedule D-(__)**attached hereto results in increased costs to BSCP to dispose of hazardouswastes or substances, Client shall pay those incremental costs.  The waste disposal charges shall be paidwithin [**] of receipt of the invoice sent by BSCP to Client.

 

(d)           Taxes.  Client agrees to pay for any sales and usetaxes or other (the “**Taxes**”)resulting from BSCP’s production of each Product hereunder (except for incomeor personal property taxes payable by BSCP). To the extent not paid by Client, Client shall indemnify and holdharmless the BSCP Parties from and against any and all penalties, fees,expenses and costs, whatsoever, in connection with the failure by Client to paythe Taxes.  BSCP shall not collect anysales and use taxes from Client in connection with the production of anyProduct hereunder if Client obtains an exemption therefrom.  In furtherance of the foregoing, BSCP shallnot collect sales and use taxes from Client in connection with the productionof any Product hereunder if (i)(A) Client provides a certificate to BSCP inwhich it states that such Product will be used or consumed outside of the Stateof Maryland and (B) Product is either shipped directly outside the State ofMaryland or stored in Maryland pending shipment to another State or (ii) Clientprovides a certificate to BSCP in which it states that such Product is forresale.

 

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(e)           LateCharge; Interest.  Any fee, chargeor other payment due to BSCP by Client hereunder (including, withoutlimitation, pursuant to a Schedule attached hereto) that is not paid within 30days after it is due shall accrue interest (except as is provided in the finalsentence of this section 4(e)), from the date when the same was due andpayable, at the rate of twelve percent (12%) per annum, payable on demand.  If unpaid for more than [**], Client [**]and simultaneously pay to BSCP the unpaid balance of the [**] Production Feesfor the Product that are payable during the remainder of the Production Termfor the Product, and any other Obligations (as defined in subparagraph (h)below) relating to the Product, all of which shall become immediately due andpayable.  Notwithstanding anythingcontained in this section 4(e) to the contrary, if there is a bona fide disputebetween Client and BSCP as to any fee, charge, or other payment due to BSCP byClient hereunder with respect to which Client has given BSCP prompt writtennotice, specifying in detail the facts and circumstances occasioning such bonafide dispute, interest shall not accrue on such unpaid fee, charge, or otherpayment, and Client shall not have to vacate the production area as describedabove in this paragraph 4 (e).

 

(f)            Payments.  All payments to BSCP hereunder by Clientshall be by check, wire transfer, money order, or other method of paymentapproved in writing by BSCP.

 

(g)           SecurityDeposit.  Client shall,simultaneously with the execution and delivery of the applicable Schedulesattached hereto relating to the production of each Product, remit to BSCP asecurity deposit (each, a “**Security Deposit**”)in an amount equal to $[**] for each Product; however, if Client has alreadyremitted to BSCP a reservation deposit in the amount of $[**] with respect to aProduct pursuant to the terms of a reservation deposit agreement with BSCP,then the amount of said reservation deposit (the “**Reservation Deposit**”) shall be withdrawn by BSCP and creditedtoward the Security Deposit payable with respect to a Product (Client shall beresponsible for remitting any deficiency between the amount of the ReservationDeposit and the Security Deposit required hereunder).  If BSCP is producing multiple products in the facility then Clientshall only pay one Security Deposit in which case such Security Deposit shallbe held by BSCP until completion of all Client’s Product Production Terms.  The Security Deposit shall be returned toClient within 30 days after the termination of the last Production Term for thelast Product if Client has paid all fees, charges, or other payments due inconnection with the production of each Product, including charges for lost,destroyed, stolen or damaged property of BSCP (all such fees, charges, or otherpayments being called “**Obligations**”).  If any Obligations with respect to a Productremain outstanding after the expiration of such 30-day period, then BSCP shallbe entitled to apply the Security Deposit against the payment of suchObligations, and the amount of the Security Deposit remaining, if any, afterthe application of such payments shall be returned to Client.  Client shall remain liable to BSCP for anydeficiencies remaining after the application of the Security Deposit againstthe Obligations.

 

(h)           Damageto Equipment.  Client shall beresponsible for the reasonable cost of repairing or replacing (to the extentthat BSCP determines, in its reasonable judgment that repairs cannot beadequately effected) any BSCP equipment damaged or destroyed by ClientPersonnel, as defined in Paragraph 5(b) hereof (ordinary wear and tearexcepted).

 

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# 5.             TheProduction Process.

 

## (a)           TheProduction Record.  BSCP shalladhere to the Production Record in producing each Product, except to the extentthat such Production Record conflicts with applicable law, in which event, BSCPwill discuss the conflict with Client and attempt to resolve the issues beforecomplying with applicable law.  BSCPwill maintain accurate records for the production of each Product and willprovide all batch records approved by BSCP’s QA department at Client’srequest.  Client shall own theProduction Records and Client Operating Documents relating to each Productproduced for Client.  BSCP shall own allBSCP Operating Documents, and shall make copies thereof available to Clientupon Client’s request and at Client’s expense. BSCP Operating Documents shall remain BSCP Confidential Information.

 

BSCP will provide to Client documentation regardingthe production of purified bulk product for the Chemistry, Manufacturing andControls (“CMC”) section required for a Biologics License Application (“CBLA”)or an analogous Marketing Authorization Application as required by the FDA orother authorized regulatory authority.

 

(b)           ClientPersonnel.  Client’s employees andagents (including its independent contractors) (collectively, “**Client Personnel**”) [**].  Client Personnel working at the Facilityshall be and remain employees of Client, which solely shall be responsible for(i) the payment of their compensation (including applicable Federal, state andlocal withholding, FICA and other payroll taxes, workers’ compensationinsurance, health insurance, and other similar statutory and fringe benefits)and (ii) the payment of any and all expenses, costs, claims and losses(including, but not limited to attorneys’ fees and related expenses) inconnection with injuries suffered by Client Personnel while at the Facility orelsewhere except as a result of BSCP’s willful misconduct or gross negligence(such expenses, costs, claims, losses, attorneys’ fees and related expensesbeing hereinafter collectively called, “**InjuryExpenses**”).  Client covenantsand agrees, with respect to Client Personnel working at the Facility, tomaintain workers’ compensation benefits and employers’ liability insurance asrequired by applicable Federal and Maryland laws.  In addition, Client covenants and agrees to indemnify and holdharmless the BSCP Parties from and against any and all Injury Expenses.

 

## (c)           Personnel.  BSCP and Client both agree not to employ orsolicit for employment (or for use as an independent contractor) either party’semployees during the term of this Agreement and for a period of two (2) yearsthereafter.

 

## (d)           NoProduct Development, No Representations or Warranties as to Safety of Product,Products Liability Insurance. Client acknowledges that neither BSCP nor its personnel will engage inany Product refinement or development (other than the production of eachProduct pursuant to the Production Record). BSCP makes no representation or warranty regarding each Product’s safetyor effectiveness, or otherwise, except that BSCP shall produce each Product inaccordance with all applicable cGMP guidelines to meet the description setforth in **Schedule A - (  )** or the specifications set forthin the Production Record.  Clientacknowledges and agrees that neither BSCP nor its personnel have participatedin the invention or testing of any Product, or have evaluated its safety or suitabilityfor use in humans or others.

 

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## Other than qualitycontrol testing of each Product by BSCP as required by the Production Record,BSCP shall not be in any way responsible for Product testing.  Client shall maintain at its sole cost andexpense, at all times during the term of this Agreement and for three yearsthereafter, a general liability insurance policy (the “**Insurance Policy**”) with bodily injury,death and property damage limits of two million U.S. dollars ($2,000,000) peroccurrence and five million U.S. dollars ($5,000,000) in the aggregate and product liability coverage ofthree million U.S. dollars ($3,000,000) per occurrence as of September 15,1998.  Promptly, following execution ofthe Master Production Agreement, Client shall provide a Certificate ofInsurance to BSCP signed by an authorized representative of Client’sunderwriter evidencing the insurance coverage required by the Agreement andproviding for at least thirty (30) day’s prior notice to BSCP of anycancellation, termination, material change or reduction of such coverage.

 

BSCP shall maintain at its sole cost and expense, atall times during the term of this Agreement and for three years thereafter, ageneral liability insurance policy with product liability coverage of onemillion U.S. dollars ($1,000,000) per occurrence and two million U.S. dollars($2,000,000) in the aggregate with an umbrella of ten million U.S. dollars($10,000,000).  BSCP shall give Clientthirty (30) days notice of any cancellation, termination, or material change orreduction of such coverage.

 

## (e)           Deliveryof Each Product; Other Shipping Charges. Upon completion of the Production Term for a Product (or sooner uponClient’s instructions), BSCP shall ship (i) the Product, and (ii) client suppliedequipment, unused materials and consumables, samples, or any other client owneditems (together with the Product being shipped, the “**Shipped Items**”).  Allsuch shipments shall be in accordance with Client’s packing and shippinginstructions and procedures supplied by Client as part of the Production Recordor, with respect to the items referenced in subparagraph (ii) above, asprovided by Client to BSCP, and shall be by common carrier unless otherwisespecified by Client.  Delivery shall beF.O.B. Shipping Point (the Facility). Client shall provide its preferred carrier’s account number and shallpay for all shipping costs in connection with the delivery of each ShippedItem.  BSCP’s responsibility, except asset forth herein, ceases and Client’s risk of loss arises, upon BSCP’s deliveryof each Shipped Item to the common carrier.

 

## (f)            BSCPLiability for Destroyed or Damaged Client Production Equipment and Materials;Dispute.

 

(i)(A) If during a Product production process,production equipment supplied by Client (“**ClientProduction Equipment**” as set forth in Schedule C) is destroyed ordamaged by BSCP Personnel and such damage or destruction resulted from BSCP’sfailure to execute such Product production process in conformity with theProduction Record, then, except as provided in subparagraph (i)(B) below, BSCPshall be responsible for repairing or replacing the destroyed or damaged ClientProduction Equipment or, at BSCP’s sole option, paying to Client thereplacement value of the damaged or destroyed Client Production Equipment atthe time of its damage or destruction. In no other event shall BSCP be liable to Client for damaged ordestroyed Client Production Equipment.

 

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(i)(B)Notwithstanding anything to the contrary set forth in subparagraph (i)(A)above, if Client Production Equipment is destroyed or damaged by BSCP Personnelwhile BSCP Personnel were acting at the direction of Client Personnel, thenBSCP shall not be liable to Client for damage or destruction occurring toClient Production Equipment.

 

(ii)(A)If during a Product production process, but prior to the delivery of suchProduct to Client in accordance with the terms of this Agreement, all or aportion of the Product and/or Materials supplied by Client (“Client Materials”)are destroyed or damaged by BSCP Personnel, and such damage or destructionresulted from BSCP’s failure to execute a Product production process inconformity with the Production Record, then, except as provided in subparagraph(ii)(B) below, BSCP shall use its best efforts to provide Client withadditional Product production time [**] in the applicable Production Area (oranother area at the facility suitable for a Product production process) withoutcharging Client a Set-Up Fee or [**] Production Fee, equal to the actual timelost because of the destruction or damage of the Product and/or ClientMaterials.

 

(ii)(B) Notwithstandinganything to the contrary set forth in subparagraph (ii)(A) above, if during aProduct production process, but prior to the delivery of such Product to Clientin accordance with the terms of this Agreement, Product and/or Client Materialsare destroyed or damaged by BSCP Personnel while BSCP Personnel were acting atthe direction of Client Personnel, then BSCP shall have no liability to Clientas the result of such destruction or damage.

 

(iii)BSCP and Client expeditiously shall attempt to resolve any dispute regardingthe liability of the parties under subparagraphs (i) and (ii) above, asapplicable, but if such dispute cannot be settled within [**] after theoccurrence of the applicable damage or destruction, then the dispute shall besubmitted to an arbitrator located in the State of the party not bringing theaction, with the requisite scientific background and training (the “**Paragraph 5(f) Arbitrator**”), selectedjointly by BSCP and Client.  TheParagraph 5(f) Arbitrator, employing the Commercial Arbitration Rules of theAmerican Arbitration Association, shall determine the cause of such failure, andthe Paragraph 5(f) Arbitrator’s findings, unless clearly erroneous, shall befinal.  The costs and expenses of theParagraph 5(f) Arbitrator shall be borne by the party which does not prevail inthe arbitration proceeding.

 

(iv)Client agrees that its sole remedy with respect to damaged or destroyedProduct, Client Materials (except for those circumstances covered by Paragraph5(g) hereof) and Client Production Equipment is as set forth in this Paragraph5(f), and in furtherance thereof, Client hereby waives all other remedies atlaw or in equity regarding the foregoing.

 

## (g)           BSCPLiability for Non-Conforming Product; Dispute.

 

### (i)            Clientshall have [**] after receipt of each Product and completed Production Record(including all manufacturing and QC testing) to deliver to BSCP, in accordancewith the notice provisions set forth in Paragraph 9(d) hereof, written noticeof disapproval (the “**Disapproval Notice**”)of such Product, after which time, if the Disapproval Notice is not sent toBSCP, Client shall be deemed to have provided its final approval of theProduct.  The Disapproval Notice shallstate with specificity the reason(s) for Client’s

 

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### disapproval of theProduct.  Any Disapproval Notice sent toBSCP in bad faith shall be null and void. If the Disapproval Notice shall be transmitted to BSCP in accordancewith the foregoing provisions within the time period therein set forth, then,to determine if the Product fails to conform to the description set forth in **Schedule A-(  )**or the specifications set forth in the Production Record and the Product cannot be used in clinical trials or for commercial use, BSCP shall have [**] toconduct Product testing, upon the completion of which it and Client shall provideone another with the results of their quality control tests and all relatedpaperwork and records relating to the production of the Product.  BSCP and Client expeditiously and in goodfaith shall attempt to resolve any dispute regarding the interpretation ofvarying quality control tests and related paperwork, but if such dispute cannotbe settled within [**] of the submission of such test results and relatedpaperwork, then the dispute shall be submitted to an arbitrator located in theState of the party not bringing the action with the requisite scientificbackground and training (the “**Paragraph 5(g)Arbitrator**”), selected jointly within 14 days by BSCP andClient.  The Paragraph 5(g) Arbitrator,employing the Commercial Arbitration rules of the American ArbitrationAssociation, shall determine the cause of such failure, and the Paragraph 5(g)Arbitrator’s findings, shall be final. Any additional testing or information that is generated as part of aninvestigation will be reported with the Production Record.

 

### (ii)           Ifit is (A) agreed by BSCP and Client or (B) determined by the Paragraph 5(g)Arbitrator, in accordance with the procedures set forth in subparagraph (i)above, that the Product produced by BSCP hereunder failed to conform to thedescription set forth in **Schedule A-(  )** or the specifications set forthin the Production Record due to the failure of (I) BSCP personnel properly toexecute the Production Record or (II) the utilities, then BSCP shall againproduce for Client the Product in accordance with the provisions of thisAgreement (the “**Production Rerun**”)that portion of the non-conforming Product when the Production Area (or anotherarea at the Facility suitable for the Production Rerun) next becomes available,without charging Client a Set-Up Fee or a [**] Production Fee for theProduction Rerun, but otherwise charging Client the fees and charges set forthin Paragraph 4 hereof (to be paid in accordance with such provisions).  BSCP shall use its best efforts to performthis production rerun with [**]. Notwithstanding the foregoing, BSCP shall have no liability to Client,whatsoever, if it is determined, in accordance with the procedures set forth inthis Paragraph 5(g), that (aa) the Production Record was materially defectiveand the non-conforming Product was the result thereof, (bb) Client Personnelexerted significant physical influence over the production of the Product, orwere responsible for the non-conformance, or (cc) the failure of the utilitiesor of BSCP personnel properly to execute the Production Record was not theproximate cause of the failure of the Product produced by BSCP to conform tothe description set forth in Schedule A-( ) or the specifications set forth in the Production Record.  Client agrees that its sole remedy withrespect to non-conforming Product is as set forth in this Paragraph 5(g), andin furtherance thereof, Client hereby waives all other remedies at law or inequity regarding the foregoing.

 

### (iii)          Thecosts and expenses of the Paragraph 5(g) Arbitrator shall be borne by BSCP ifit is required, in accordance with the provisions of this Paragraph 5(g), toeffect the Production Rerun.  In allother events, Client shall be responsible for the payment of such costs and expenses.

 

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## (h)           Indemnification.

 

### (i)            Clientshall indemnify and hold harmless the BSCP Parties from and against any and allthird-party claims, damages, costs and expenses of any kind (includingattorneys’ and experts’ fees) incurred by BSCP Parties in connection with orrelating to each Product, including, but not limited to, any third-partyinfringement claims.

 

### (ii)           BSCPshall indemnify and hold harmless Client and its employees, agents andaffiliates (collectively, “Client Parties”) from and against any and all thirdparty claims, damages, costs and expenses of any kind (including attorneys’ andexperts’ fees) incurred by Client Parties resulting from infringement claimsagainst BSCP in connection with BSCP’s equipment or facility, or a cause asdescribed in 8b(ii) below.

 

### (iii)          Ifeither party (the “Indemnified Parry”) promptly notifies the other party (the“Indemnifying Party”) in writing of any action brought against the IndemnifiedParty for which it is indemnified under (i) and (ii) of this Section 5 (i),then the Indemnifying Party shall defend, indemnify and hold the IndemnifiedParty harmless from and against all costs and damages incurred by theIndemnified Party or assessed against it which arise out of such action,provided that (i) the Indemnifying Party shall have sole control and authoritywith respect to the defense or settlement of any such action, and (ii) theIndemnified Party shall cooperate fully with the Indemnifying Party in thedefense of any such action.  Anysettlement of any such actions, which imposes any liability or limitation onthe Indemnified Party shall not be entered into without prior written consentof the Indemnified Party.

 

### (iv)          Inthe event a claim is based partially on an indemnified claim described in (i) or(ii) of this Section 5 or Section 8 (a) or 8 (b) and partially on anon-indemnified claim, any payments and reasonable attorney fees incurred inconnection with such claims are to be apportioned between the parties inaccordance with the degree of cause attributable to each party.

 

## (i)            Limitationof Liability.  Subject to theprovisions of Paragraph 5(b) hereof and except for third-party claims under5(h) and 8(b), Client hereby agrees that to the fullest extent permitted bylaw, BSCP’s liability to Client for any and all injuries, claims, losses,expenses, or damages, whatsoever, arising out of or in any way related toBSCP’s production of each Product hereunder from any cause or causes,including, but not limited to, negligence, errors, omissions, breach ofrepresentations or warranties, or strict liability, and including, but notlimited to, the events covered by Paragraph 5(f), (g) or any non-third partyclaims under 5(h) and Paragraph 8(b) hereof, shall not exceed the total chargespaid by Client to BSCP hereunder with respect to such Product.  To the extent that this clause conflictswith any other clause in this Agreement, this clause shall take precedence oversuch conflicting clause.  If applicablelaw prevents enforcement of this clause, then this clause shall be deemedmodified to provide the maximum protection to BSCP as is allowable underapplicable law.

 

## (j)            Storage.

 

### (i)            Priorto the Commencement Date.  Clientshall not deliver any Materials or other Client property to the Facility priorto [**] before each applicable

 

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Commencement Date.  Any suchMaterials, equipment or other property delivered to the Facility prior to suchdate may be accepted by BSCP for storage, in its sole discretion, and if soaccepted, shall be subject [**] from the period of acceptance until [**] priorto the applicable Commencement Date, in accordance with BSCP’s storage ratesand procedures, as set forth on **ScheduleE-(  )** attached hereto, asamended from time to time.

 

### (ii)           StorageAfter Completion of the Production Term. Any Product, Materials, Equipment or other Client property that remainsat the Facility after completion of the applicable Production Term (the date ofsuch completion being called, the “**CompletionDate**”) may be stored by BSCP at the Facility upon Client’s request,without cost, for up to 30 days after notice of disposition has been deliveredto Client.  If Client has not respondedprior to the expiration of such [**] period, BSCP may, in its sole discretion,continue to store such Product, Materials and other Client property at theFacility or elsewhere, in which event Client shall pay to BSCP a storagecharge, in accordance with BSCP’s storage rates and procedures as set forth on **Schedule E-(  )**attached hereto, as amended from time to time, for the period beginning on the[**] after the notice of disposition through the date that the storageterminates.

 

# 6.             ConfidentialInformation.  All informationcommunicated by Client to BSCP, including the Production Record (collectively,“**Client Confidential Information**”),shall remain the exclusive property of Client, and shall be held in confidenceby BSCP and shall not be used by BSCP except in connection with the dischargeof its obligations under this Agreement. Client shall not disclose to any third party confidential informationregarding the Facility or the identity of any other BSCP client using theFacility, or information regarding such other client’s product, processes oroperations at the Facility (collectively, “**BSCPConfidential Information**”).

 

Client Confidential Information shall be disclosed toBSCP personnel and consultants on a need to know basis only.  All consultants to BSCP are bound underexisting Non-Disclosure Agreements.  Theforegoing restrictions on use and disclosure shall not apply to any ClientConfidential Information or BSCP Confidential Information that:

 

(1)               wasknown to the receiving party prior to its disclosure to the receiving party bythe disclosing party as evidenced by written documents predating the receivingparty’s receipt of such information; or

 

(2)               ispublic knowledge at the time of its disclosure to the receiving party throughno act or omission or on its behalf; or

 

(3)               islawfully disclosed or made available to the receiving party by a third partyhaving no direct or indirect obligation to the disclosing party to maintain theconfidentiality of such Information; or

 

(4)               isindependently developed by the receiving party without the aid or benefit ofInformation disclosed to the receiving party by the disclosing party.

 

12

----

 

Information may bedisclosed by the receiving party pursuant to a document lawfully issued by acourt or governmental agency provided that the receiving party notifies thedisclosing party immediately upon receipt of any such document.

 

# 7.             SecurityProcedures.  Client Personnelauthorized to have access to the Facility shall abide by the securityprocedures established by BSCP from time to time and communicated toClient.  Client shall be liable for anybreaches of security by Client Personnel. In addition, Client shall reimburse BSCP for the cost of any lostsecurity cards issued to Client Personnel, [**].  All Client Personnel shall agree, in writing, to abide by BSCPpolicies and standard operating procedures established by BSCP from time totime.

 

# 8.             Representationsand Warranties.

 

## (a)           Clientrepresents and warrants to BSCP that, to the best of its knowledge, (i) it hasthe requisite intellectual property rights to each Product and the methodsrequired to produce it in accordance with the Production Record, and ii) theproduction by BSCP of each Product, employing the materials, the productionequipment and in accordance with the procedures set forth in the ProductionRecord and the Operating Documents, will not give rise to a potential cause ofaction by a third party against BSCP for infringement or another violation ofintellectual property rights.  Suchrepresentation and warranty shall not apply to the production equipmentsupplied by BSCP.

 

## (b)           BSCPrepresents and warrants to Client that, to the best of its knowledge, (i) ithas the requisite intellectual property rights in its equipment and facility tobe able to perform its obligations hereunder, (ii) that BSCP’s use of itsequipment and facility as contemplated in this Agreement will not give rise toa potential cause of action by a third party against Client for infringement oranother violation of intellectual property rights and (iii) that Productdelivered to Client pursuant to this Agreement shall be produced in accordancewith the Production Record and shall be in compliance with all applicable cGMPguidelines.

 

# 9.             Miscellaneous.

 

## (a)           NoAgency.  Neither party hereto isauthorized, nor shall undertake, to bind the other party in any way as agent,partner, joint venturer or otherwise, whether in the name of BSCP or Client orotherwise.  Neither party hereto shallrefer to, display or use the other’s name, corporate style, trademarks or tradenames confusingly similar thereto, alone or in conjunction with any other wordsor names, in any manner or connection whatsoever, including any publication,article, or any form of advertising or publicity, except with the prior writtenconsent provided by the other party. BSCP is an independent contractor of Client, and neither BSCP nor anyperson or entity employed, contracted, or otherwise utilized by BSCP for anypurposes shall be deemed to be an employee, representative or agent of Client.

 

## (b)           ForceMajeure.  In the event of a delaycaused by inclement weather, fire, flood, strike or other labor dispute, actsof God, acts of governmental officials or agencies, or any other cause beyondthe control of BSCP, BSCP shall be excused from performance hereunder for theperiod or periods of time attributable to such delay.  There shall be no increase in compensation as a result of anyevent of delay under this Paragraph 9(b) or otherwise.

 

13

----

 

## (c)           EminentDomain.  If the Facility is taken asa result of the exercise of the power of eminent domain or shall be conveyed toa governmental agency having power of eminent domain under the threat of theexercise of such power (any of the foregoing being called “Eminent Domain”),then this Agreement shall terminate as of the date on which title to theFacility vests in the authority so exercising or threatening to exercise suchpower and Client shall not have any right to the Eminent Domain proceeds.

 

## (d)           Notices.  All notices, consents, waivers, and othercommunications under this Agreement must be in writing and will be deemed tohave been given when (i) delivered by hand (with written confirmation ofreceipt), (ii) sent by fax (with written confirmation of receipt), providedthat a copy is mailed by U.S. registered mail, return receipt requested, (iii)when received by the addressee, if sent by a nationally recognized overnightdelivery service (receipt requested), in each case to the appropriate addressand fax numbers set forth below (or to such other addresses and fax numbers asa party may designate by notice to the other party):

 

If to BSCP, to:

 

Bio Science Contract Production Corp.  

5901 East Lombard Street

Baltimore, Maryland 21224 

Fax (410) 563-9206 

Attention: Jacques R.  Rubin, Chairman &CEO

and

If to Client, to:

 

Transkaryotic Therapies Inc.  

195 Albany Street

Cambridge, MA 02139

Tel (617) 349 0200 

Fax (617) 491-7903 

Attention: President and CEO

 

with a copy to

 

Hale and Dorr LLP 

60 State Street 

Boston, MA 02109 

Tel (617) 526 6000 

Fax (617) 526 5000 

Attention: Steven D. Singer

 

Any party hereto maychange his or its address for notice by giving notice thereof in the mannerhereinabove provided.

 

14

----

 

## (e)           EntireAgreement.  This Agreement,including the Schedules hereto, constitutes the entire agreement of the partieshereto with respect to the subject matter hereof and supersedes all prioragreements and understandings, oral and written, among the parties hereto withrespect to the subject matter hereof. The “RECITALS”, “DEFINITIONS”, and Schedules hereto are incorporatedherein by reference.

 

## (f)            GoverningLaw.  This Agreement shall begoverned by and construed in accordance with the internal laws of the State ofMaryland, without giving effect to its conflicts of laws provisions.  Except as provided in Paragraph 5(f) and (g)hereof, all suits, disputes, actions, and other legal proceedings(collectively, “**Suits**”) related toor arising out of this Agreement, shall be brought in the Federal DistrictCourt of the District of Maryland, which shall have the exclusive jurisdictionover such Suits, and to the personal jurisdiction of which BSCP and Clientirrevocably submit.  Process in any Suitmay be served on any party anywhere in the world.

 

## (g)           Counterparts.  This Agreement and any Schedule hereto maybe executed in counterparts, each of which shall be deemed an original, but allof which together shall constitute one and the same instrument.

 

## (h)           Amendments.  This Agreement (including any Schedulehereto) may not be amended or modified, and no provisions hereof may be waived,without the prior written consent of the parties hereto.

 

## (i)            Severability.  Each provision of this Agreement (and eachSchedule hereto) shall be treated as a separate and independent clause, and theunenforceability of any one clause shall in no way impair the enforceability ofany of the other clauses herein.                Ifone or more of the provisions contained in this Agreement (or any Schedulehereto) shall for any reason be held to be excessively broad as to scope,activity, subject or otherwise so as to be unenforceable at law, such provisionor provisions shall be construed by the appropriate judicial body by limitingor reducing it or them so as to be enforceable to the maximum extent compatiblewith the applicable law as it shall then appear.

 

## (j)            Titlesand Subtitles.  The titles andsubtitles used in this Agreement (including any Schedule hereto) are forconvenience only and are not to be considered in construing or interpreting anyterm or provision of this Agreement (or any Schedule hereto).

 

## (k)           Pronouns.  Where the context requires, (i) all pronounsused herein shall be deemed to refer to the masculine, feminine or neutergender as the context requires, and (ii) the singular context shall include theplural and vice versa.

 

## (l)            Assignment.  BSCP shall not assign this Agreement (or anySchedule hereto) without the prior written consent of Client, except that BSCPshall be permitted to assign its rights and obligations hereunder without suchconsent to (i) one or more of its affiliates or (ii) the purchasers of all orsubstantially all of its assets, through merger, consolidation orotherwise.  Client may assign thisAgreement upon: (x) providing prior written notice to BSCP; and (y) causing theassignee to acknowledge that it will be bound by the terms and conditions ofthis

 

15

----

 

Agreement; and (z) agreeing that Client itself will continue to bebound by all the terms of this Agreement even in the event of such anassignment.

 

## (m)          NoLease.  BSCP and Client agree thatthis Agreement (including any Schedule hereto) is not a lease and therelationship between them is not that of landlord and tenant and that BSCPretains all rights of control and possession of the Facility, including eachapplicable Production Area.

 

## (n)           NoWaiver.  The failure of any partyhereto at any time or times to require performance of any provision of thisAgreement (including any Schedule hereto) shall in no manner affect its rightsat a later, time to enforce the same. No waiver by any party hereto of the breach of any term contained inthis Agreement (including any Schedule hereto), whether by conduct or otherwise,in any one or more instances, shall be deemed to be or construed as a furtheror continuing waiver of any such breach or the breach of any other term of thisAgreement (including any Schedule hereto).

 

## (o)           Waiverof Jury Trial.  BSCP and Clienthereby waive trial by jury in any suit brought by either of the parties heretoagainst the other or on any counterclaim in respect thereof on any matters,whatsoever, arising out of, or in any way in connection with, this Agreement(including any Schedule hereto).

 

## (p)           NoPresumption Against Drafter.  Forpurposes of this Agreement, Client hereby waives any rule of construction thatrequires that ambiguities in this Agreement (including any Schedule hereto) beconstrued against the drafter.

 

## (q)           Expenses.  Except as otherwise provided in thisAgreement, each party to this Agreement will bear its respective expensesincurred in connection with the preparation, execution, and performance of thisAgreement (including any Schedule hereto).

 

## (r)            Disclosureof Client, Product and Agreement. Except as Client may be required by law or regulation, neither partyshall disclose the name of the other party, the identity of the Product or anyinformation with respect thereto, the existence of this Agreement or the termsand provisions of this Agreement without the prior written approval of theother party.  Neither party shall usethe name of the other party in any publicity or advertising without the otherparty’s prior written consent.

 

If BSCP is required in accordance with SEC or otherrelevant governmental regulations to disclose Client’s name, the identity ofthe Product or any information with respect thereto, the existence of thisAgreement or the terms and provisions of this Agreement, BSCP shall: (I) giveClient prior written notice of such disclosure; and (ii) assist Client in anyefforts to prevent or limit such disclosure (including without limitationseeking confidential treatment of such information).

 

16

----

 

## (s)           Accessto Facility.  Upon execution of aconfidentiality agreement acceptable to BSCP and substantially the same as thatsigned by Client, BSCP shall permit Client’s marketing partners access duringbusiness hours to those areas of BSCP’s facility where Product is manufactured,stored and handled and to manufacturing records of Product produced by BSCP sothat Client’s marketing partners may perform a quality assurance audit of suchfacilities and activities.

 

 

{signatures appearon following page}

 

17

----

 

IN WITNESS WHEREOF, the parties have executed thisAgreement as of the day and year first above written.

 

 
| WITNESS:  |                | TRANSKARYOTIC THERAPIES  INC      |
|----------------|---------------------|----------------------------------------|
|           |                |                                   |
| By:            | /s/ Kelly A. Gladle |                                   |   | By: | /s/ Richard F.  Selden                        (SEAL) |   |
|           |                |                                   | Richard F. Selden |
|           |                |                                   | President and Chief  Executive Officer |
|           |                |                                   |
|           |                |                                   |
| WITNESS:       |                | BIO SCIENCE CONTRACT  PRODUCTION CORP. |
|           |                |                                   |
| By:            | /s/ Debra G. Sydnor |                                   |   | By: | /s/ Jacques R.  Rubin                        (SEAL) |   |
|           |                |                                   | Jacques R. Rubin |
|           |                |                                   | Chief Executive Officer |

 

18

----

 

**SCHEDULE A-( 1 )**

**TO PRODUCTIONAGREEMENT**

** **

**PRODUCTDESCRIPTION**

 

**α-GalactosidaseA**

 

α-Galactosidase A isan acid hydrolase which specifically cleaves terminal α-linked galactoseresidues from the glycosphingolipid trihexoside (CTH).  The enzyme is a glycoprotein which consistsof a homodimer of two identical approximately 50,000 molecular weight subunits.

 

α-Galactosidase A ispost-translationally modified by the cleavage of a signal sequences of 31residues and by glycosylation. α-Galactosidase A consists of approximately 398 amino acids.

 

The following are theproposed specifications for purified bulk α-Galactosidase A.  These specifications will be reviewed whensufficient information is available from the pilot and/or GMP manufacturingruns performed at Bio Science Contract Production Corp.  Until that time these specifications are forinformational purposes only.

 
|   |   | **Proposed Specification** |
|--------|--------|----------------------------|
| [**]   |   | [**]                       |

 

******************************************

 

----

 

The content of this **Schedule A-(1)** is agreed to by theparties listed below to that certain Master Production Agreement dated as of12/1, 1998.

 

 
| TRANSKARYOTIC THERAPIES  INC. | BIO SCIENCE CONTRACT  PRODUCTION CORP. |
|-------------------------------|----------------------------------------|
|                          |                                   |   |
|                          |                                   |   |
| By:                           | /s/Richard Seldon                      | (SEAL) | By: | /s/Louise  Campbell-Blair | (SEAL) |
|                          | Name: Richard Selden                   |   | Name:  Louise Campbell-Blair |
|                          | Title: President &  CEO            |   | Title:  VP Business Development |
|                          |                                   |   |
| Date:  12/1, 1998        |
|                               |                                        |  |  |  |  |

 

----

 

**SCHEDULE B-( 1a)**

**TO**

**PRODUCTIONAGREEMENT**

** **

**PRODUCTION TERM,SUITE AND FEES**

** **

**PRODUCTION TERM**

** **

| Commencement Date (the  “**Commencement Date**”): | August 1, 1998    |
|-------------------------------------------------------------|-------------------|
| Termination Date (the “**Termination Date**”):    | December 31, 1998 |

 

**SUITE**

**(markbelow with an “X”)**

 

| SUITE 1 |   |   | SUITE 3 |   |   |
|---------|--------|--------|---------|--------|--------|
| SUITE 2 |   |   | SUITE 4 | X      |   |

 

**FEES**

 

| Production Record Fee:                       |   | $ | [**] |   |
|----------------------------------------------|--------|---|------|--------|
| Set-Up Fee per Product  per Production Term: |   | $ | [**] |   |   |

 

| [**] Production Fee: |   | [**] |   |
|----------------------|--------|------|--------|
|                 |   | [**] |   |
|                 |   | [**] |   |

 

($[**] paid on August 12th;$[**])

 

*****************************************

 

The content of this **Schedule B-(1a)** is agreed to by theparties listed below to that certain Master Production Agreement dated as of12/1, 1998.

 

 
| TRANSKARYOTIC THERAPIES  INC. | BIO SCIENCE CONTRACT  PRODUCTION CORP. |
|-------------------------------|----------------------------------------|
|                          |                                   |   |
|                          |                                   |   |
| By:                           | /s/Richard Seldon                      | (SEAL) | By: | /s/Louise  Campbell-Blair | (SEAL) |
|                          | Name: Richard Selden                   |   | Name:  Louise Campbell-Blair |
|                          | Title: President &  CEO            |   | Title:  VP Business Development |
|                          |                                   |   |
| Date:  12/1, 1998        |
|                               |                                        |  |  |  |  |

 

----

 

**SCHEDULE B-(1b)**

**TOPRODUCTION AGREEMENT**

** **

**PRODUCTION TERM,SUITE AND FEES**

** **

**PRODUCTION TERM**

** **

| Commencement Date (the  “**Commencement Date**”): | January 1, 1999      |
|-------------------------------------------------------------|----------------------|
| Termination Date (the “**Termination Date**”):    | October 31st  , 1999 |

 

*(TheProduction Term may be extended with written approval by both parties)*

 

**SUITE**

**(Mark below with an “X”)**

 

| SUITE 1 |   |   | SUITE 3 |   |   |
|---------|--------|--------|---------|--------|--------|
| SUITE 2 |   |   | SUITE 4 | X      |   |

 

FEES

 

| Production Record Fee:                       |   | $      | [**]   |   |
|----------------------------------------------|--------|--------|--------|--------|
| Set-Up Fee per Product  per Production Term: |   | $      | [**]   |   |   |
|                                         |   |   |   |   |   |
| [**] Production Fee:                         |   | $      | [**]   |   |   |

 

 

*($*[**]*payable by January 1st, 1999 then*[**]*payments of $*[**]*due*[**]*starting March, 1999)*

 

*****************************************

 

The content of this **Schedule B-(1b)** is agreed to by theparties listed below to that certain Master Production Agreement dated as of12/1, 1998.

 

 
| TRANSKARYOTIC THERAPIES  INC. | BIO SCIENCE CONTRACT  PRODUCTION CORP. |
|-------------------------------|----------------------------------------|
|                          |                                   |   |
|                          |                                   |   |
| By:                           | /s/Richard Seldon                      | (SEAL) | By: | /s/Louise  Campbell-Blair | (SEAL) |
|                          | Name: Richard Selden                   |   | Name:  Louise Campbell-Blair |
|                          | Title: President &  CEO            |   | Title:  VP Business Development |
|                          |                                   |   |
| Date:  12/1, 1998        |
|                               |                                        |  |  |  |  |

** **

----

** **

**SCHEDULE C-(1)**

**TO**

**PRODUCTIONAGREEMENT**

** **

**CLIENT-PROVIDEDITEMS**

** **

| [**] |   | [**] |
|------|--------|------|

 

***Other Client-Provided Items, if any, to be mutually agreedupon.***

 

****************************************

 

The content of this **Schedule C-(1)** is agreed to by theparties listed below to that certain Master Production Agreement dated as of12/1                , 1998.

 

 
| TRANSKARYOTIC THERAPIES  INC. | BIO SCIENCE CONTRACT  PRODUCTION CORP. |
|-------------------------------|----------------------------------------|
|                          |                                   |   |
|                          |                                   |   |
| By:                           | /s/Richard Seldon                      | (SEAL) | By: | /s/Louise  Campbell-Blair | (SEAL) |
|                          | Name: Richard Selden                   |   | Name:  Louise Campbell-Blair |
|                          | Title: President &  CEO            |   | Title:  VP Business Development |
|                          |                                   |   |
| Date:  12/1, 1998        |
|                               |                                        |  |  |  |  |

** **

----

 

**SCHEDULE D-(1)**

**TO**

**PRODUCTIONAGREEMENT**

** **

**OTHER PRODUCTIONREQUIREMENTS**

PERSONNEL:                BSCP MAY PROVIDE ADDITIONALPERSONNEL AT THE RATE OF $[**] PER HOUR.

 

HAZARDOUS WASTES ANDSUBSTANCES:

 
| **Type** |   | **Amount** |   | **Charge for Disposal** |   |
|----------|--------|------------|--------|-------------------------|--------|

 

Such rates shall besubject to change from time to time in accordance with written notice providedby BSCP to Client.

 

****************************************

 

The content of this **Schedule D-(1)** is agreed to by theparties listed below to that certain Master Production Agreement dated as of12/1, 1998.

 

 
| TRANSKARYOTIC THERAPIES  INC. | BIO SCIENCE CONTRACT  PRODUCTION CORP. |
|-------------------------------|----------------------------------------|
|                          |                                   |   |
|                          |                                   |   |
| By:                           | /s/Richard Seldon                      | (SEAL) | By: | /s/Louise Campbell-Blair | (SEAL) |
|                          | Name: Richard Selden                   |   | Name:  Louise Campbell-Blair |
|                          | Title: President &  CEO            |   | Title:  VP Business Development |
|                          |                                   |   |
| Date:  12/1, 1998        |
|                               |                                        |  |  |  |  |

** **

----

** **

**SCHEDULE E-(1)**

**TO**

**PRODUCTIONAGREEMENT**

** **

**[**] STORAGE RATESAND PROCEDURES**

[**] Storage Charge:

 

$[**] per square foot for Room Temperature Storage

 

$[**] per cubic foot for Refrigerated Storage

 

$[**] per cubic foot for Freezer Storage

 

Minimum Storage Charge:

 

$[**] for Room Temperature Storage

 

$[**] for Refrigerated Storage

 

$[**] for Freezer Storage

 

Procedure:

 

Client will not ship anymaterials, equipment or supplies to BSCP without the prior written approval ofBSCP.  The storage charges during theSet-Up period for the Product described in Schedule A-(1) are included in the[**] production fee shown in Schedule B-(la).

 

***********************************

 

The content of this **Schedule E-(1)** is agreed to by theparties listed below to that certain Master Production Agreement dated as of12/1                , 1998.

 

 
| TRANSKARYOTIC THERAPIES  INC. | BIO SCIENCE CONTRACT  PRODUCTION CORP. |
|-------------------------------|----------------------------------------|
|                          |                                   |   |
|                          |                                   |   |
| By:                           | /s/Richard Seldon                      | (SEAL) | By: | /s/Louise  Campbell-Blair | (SEAL) |
|                          | Name: Richard Selden                   |   | Name:  Louise Campbell-Blair |
|                          | Title: President &  CEO            |   | Title:  VP Business Development |
|                          |                                   |   |
| Date:  12/1, 1998        |
|                               |                                        |  |  |  |  |

 

----

 

**Bio Science Contract Production Corp.**

** **

**AMENDMENT TOMASTER PRODUCTION AGREEMENT**

** **

Bio Science was informedat the November 19, 1998, telephone conference with Transkaryotic TherapiesInc. (TKT) that it may be necessary [**]. Based on TKT’s written approval, Bio Science can process TKT’s GMPproduction runs [**], however, Bio Science’s review of the batch record cannotbe completed until all testing associated with the batch is completed andreported.

 

TKT understands that [**]Bio Science will label all the batches and the associated batch records thatwere processed [**] TKT retains the right [**].

 

TKT further understandsthat it will be responsible for payment for any batch rejected under thesecircumstances.

 

 
| TRANSKARYOTIC THERAPIES  INC. | BIO SCIENCE CONTRACT  PRODUCTION CORP. |
|-------------------------------|----------------------------------------|
|                          |                                   |   |
|                          |                                   |   |
| By:                           | /s/Richard Seldon                      | (SEAL) | By: | /s/Louise  Campbell-Blair | (SEAL) |
|                          | Name: Richard Selden                   |   | Name:  Louise Campbell-Blair |
|                          |                                   | Title: President &  CEO |   |   | Title:  VP Business Development |
|                          |                                   |   |
| 01/05/99                      |                                   | 1/7/99 |   |
| Date                          | Date                                   |
|                               |                                        |  |  |  |  |  |  |  |  |

 

----

 

**SCHEDULE B-(1b)REVISED**

**TO**

**PRODUCTIONAGREEMENT**

** **

**PRODUCTION TERM,SUITE AND FEES**

** **

**PRODUCTION TERM**

** **

 

**SCHEDULE B-(1b)**

**TOPRODUCTION AGREEMENT**

** **

**PRODUCTION TERM,SUITE AND FEES**

** **

**PRODUCTION TERM**

** **

| Commencement Date (the  “**Commencement Date**”): | January 1, 1999      |
|-------------------------------------------------------------|----------------------|
| Termination Date (the “**Termination Date**”):    | December 25th,  1999 |

 

*(TheProduction Term may be extended with written approval by both parties)*

 

**SUITE**

**(Mark below with an “X”)**

 

| SUITE 1 |   |   | SUITE 3 |   |   |
|---------|--------|--------|---------|--------|--------|
| SUITE 2 |   |   | SUITE 4 | X      |   |

 

FEES

 

| Production Record Fee:                       |   | $      | [**]   |   |
|----------------------------------------------|--------|--------|--------|--------|
| Set-Up Fee per Product  per Production Term: |   | $      | [**]   |   |   |
|                                         |   |   |   |   |   |
| [**] Production Fee:                         |   | $      | [**]   |   |   |

 

 

*($*[**]*payable by January 1st, 1999 then*[**]*payments of $*[**]*due by*[**]*starting March, 1999)*

 

*****************************************

 

The content of this **Schedule B-(1b) REVISED** is agreed to bythe parties listed below to that certain Master Production Agreement dated asof 12/1, 1998.

 

 
| TRANSKARYOTIC THERAPIES  INC. | BIO SCIENCE CONTRACT  PRODUCTION CORP. |
|-------------------------------|----------------------------------------|
|                          |                                   |   |
|                          |                                   |   |
| By:                           | /s/Richard Seldon                      | (SEAL) | By: | /s/Louise  Campbell-Blair | (SEAL) |
|                          | Name: Richard Selden                   |   | Name:  Louise Campbell-Blair |
|                          | Title: President &  CEO            |   | Title:  VP Business Development |
|                          |                                   |   |
| Date:  2/25, 1999        |
|                               |                                        |  |  |  |  |

 

----

 

**Agreement for BLA Preparation**

** **

Transkaryotic TherapiesInc (“TKT”) agrees that Bio Science Contract Production Corp. (“Bio Science”)will have review and approval of those aspects of TKT’s BLA submission thatdescribe or refer to Bio Science’s facility or operation.  Further, a copy of the final version ofthese sections as submitted to the FDA will be provided to Bio Science.

 

For TranskaryoticTherapies Inc.

 

 
| AME:   | /s/Kurt C. Gunter, M.D.   |   |
|--------|---------------------------|--------|
| TITLE: | VP, Clin & RegAffairs |   |
| DATE:  | 20 Apr 99                 |   |

 

----

 

**SCHEDULE A-(2)**

**TO**

**PRODUCTIONAGREEMENT**

** **

**PRODUCTDESCRIPTION**

** **

***a-*GalactosidaseA**

*a*-GalactosidaseA is an acid hydrolase which specifically cleaves terminal *a*-linked galactose residues from theglycosphingolipid trihexoside (CTH). The enzyme is a glycoprotein which consists of a homodimer of twoidentical approximately 50,000 molecular weight subunits.

 

*a*-GalactosidaseA is post-translationally modified by the cleavage of a signal sequences of 31residues and by glycosylation.  *a*-Galactosidase A consists ofapproximately 398 amino acids.

 

The following are theproposed specifications for purified bulk *a*-GalactosidaseA.  These specifications will bereviewed when sufficient information is available from the pilot and/or GMPmanufacturing runs performed at Bio Science Contract Production Corp.  Until that time these specifications are forinformational purposes only.

 
|   |   | **Proposed Specification** |   |
|--------|--------|----------------------------|--------|
| [**]   |   | [**]                       |   |

 

******************************

 

----

 

The content of this **Schedule A-(2)** is agreed to by theparties listed below to that certain Master Production Agreement dated as ofDecember 1, 1998.

 

 
| TRANSKARYOTIC THERAPIES  INC. | BIO SCIENCE CONTRACT  PRODUCTION CORP. |
|-------------------------------|----------------------------------------|
|                          |                                   |   |
|                          |                                   |   |
| By:                           | /s/Richard Seldon                      | (SEAL) | By: | /s/Louise  Campbell-Blair | (SEAL) |
|                          | Name: Richard Selden                   |   | Name:  Louise Campbell-Blair |
|                          | Title: President &  CEO            |   | Title:  VP Business Development |
|                          |                                   |   |
| Date:  12.10, 1999       |
|                               |                                        |  |  |  |  |

 

----

 

**SCHEDULE B-(2)**

**TO**

**PRODUCTIONAGREEMENT**

** **

**PRODUCTION TERM,SUITE AND FEES**

** **

**PRODUCTION TERM**

** **

| Commencement Date (the  “**Commencement Date**”): | January 1, 2000   |
|-------------------------------------------------------------|-------------------|
| Termination Date (the “**Termination Date**”):    | December 31, 2000 |

** **

**FEES**

1.               [**] Production Fee: $[**]

 

2.               PaymentTerms:

 

(a)                                  $[**] has been paid on November 15,1999; then $[**] each [**] in advance starting with January2000.  Advance payments due by the [**].

 

(b)                                 Torecover the $[**] owed by BSCPto TKT, the [**] payments willbe reduced by $[**] for January2000 through and including July 2000 and by $[**].

 

(c)                                  Upontermination or expiration of this agreement BSCP shall pay to TKT within [**] after such termination thebalance of any reductions, prepayments, production delay damages, and advanceswhich have not been recovered through reductions in the [**] Production Fees.  Latepayments will accrue interest from the date when the same became due at therate of 12% per annum.  The deposit willbe refunded [**] after a finalreconciliation is completed.

 

3.               RenewalPeriods:

 

This production term maybe renewed for an additional term of no more than [**] on the same terms and conditions contained herein.  Client must provide notice of renewalincluding the length of such extension no later than.  September 1st 2000.

 

12/07/99

 

----

 

4.               Milestones& Penalties:

 

(a)                                  CultureInitiation - The production campaign shall be initiated on or before January 17th,2000.  There shall be no more than a [**] lag between the initiation ofsubsequent campaigns ([**]).  If there is a delay in Cell Culture, notcaused by either the Client or the contract testing labs (as defined below),the following penalties will apply;

 

1.             It is the responsibility of BSCP to[**] testing at the contracttesting labs.

 

2.                                       IfBSCP encounters a problem with obtaining results from a contract testing lab,they will notify Client in a timely manner, whereupon Client will assist BSCPin gaining resolution to the issue.

 

3.                                       Aslong as BSCP is working in good faith with Client and testing laboratory toresolve issues so that they will not impact Culture Initiation dates, theapplicable penalties will not apply.

 
| **Duration of Delay** |   | **Penalty** |   |
|-----------------------|--------|-------------|--------|
| Up to [**]            |   | $           | [**]   |   |
| Between [**]          |   | $           | [**]   |   |
| Up to [**]            |   | $           | [**]   |   |
| Up to [**]            |   | $           | [**]   |   |

 

(b)                                 Releaseof batch records Parts A & B - The Part A and Part B batch records for alllots produced in a campaign (Slots/campaign x 2 batch records/lot = 10 batchrecords/campaign) shall be signed off by BSCP and released to Client no laterthan one week after the receipt and acceptance (by both Client and BSCP) of thefinal QC data and associated QC documentation (e.g.  deviations, ICARS) required to complete the batch records.

 
| **Duration of Delay**      |   | **Penalty**                              |   |
|----------------------------|--------|------------------------------------------|--------|
| [**] days – [**] days |   | $                                        | [**]   |   |
| [**] days – [**] days |   | $                                        | [**]   |   |
| [**] days – [**] days |   | $                                        | [**]   |   |
| Thereafter                 |   | Additional $[**] for each [**] day delay |   |

 

----

 

** **

(c)                                  Releaseof batch records Part C - The Part C batch records for each lot shall be signedoff by BSCP and released to Client no later than [**] after the receipt and acceptance (by both Client and BSCP) ofthe final QC data and associated QC documentation (e.g. deviations, ICARS)required to complete the batch records.

 
| **Duration of Delay**      |   | **Penalty**                              |   |
|----------------------------|--------|------------------------------------------|--------|
| [**] days – [**] days |   | $                                        | [**]   |   |
| [**] days – [**] days |   | $                                        | [**]   |   |
| [**] days – [**] days |   | $                                        | [**]   |   |
| Thereafter                 |   | Additional $[**] for each [**] day delay |   |

 

**REGULATORY INSPECTIONS**

 

Concerning FDA or anyother Regulatory Authority Inspection or teleconferences;

 

a)                                      Clientwill not be permitted to participate directly in general GMP inspections ornon-          Client related inspectionsor teleconferences.

b)                                     One QARepresentative from Client will be permitted to participate as part of theinspection team or participate in teleconferences (Client must beat BSCP’sfacility to participate in teleconferences) related to or as part of,Pre-Approval inspection requirements for its products that are manufactured atBSCP facilities.

c)                                      Inthe case of responses to inspections pertaining to part b) above, Client willbe allowed one business day to review responses to questions related to itsproduct, prior to submission by BSCP. The wording and submission of the final response is the responsibilityof BSCP.

 

***********************************

 

The content of this **Schedule B-(2)** is agreed to by theparties listed below to that certain Master Production Agreement dated as ofDecember 1, 1998.

 

 
| TRANSKARYOTIC THERAPIES  INC. | BIO SCIENCE CONTRACT  PRODUCTION CORP. |
|-------------------------------|----------------------------------------|
|                          |                                   |   |
|                          |                                   |   |
| By:                           | /s/Daniel Geffken                      | (SEAL) | By: | /s/Jacques Rubin | (SEAL) |
|                          | Name: Daniel Geffken                   |   | Name:  Jacques Rubin |
|                          | Title:                                 |   | Title:  CEO & Chairman |
|                          |                                   |   |
| Date:  12.10, 1999       |
|                               |                                        |  |  |  |  |

 

 

----

 

**SCHEDULE C0-(2)**

**TO**

**PRODUCTIONAGREEMENT**

 

**CLIENT-PROVIDEDITEMS**

 
| [**] |   | [**] |   |
|------|--------|------|--------|

 

***Other Client-Provided Items, if any, to be mutually agreedupon.***

 

****************************************

 

The content of this **Schedule C-(2)** is agreed to by theparties listed below to that certain Master Production Agreement dated as ofDecember 1, 1998

 

 
| TRANSKARYOTIC THERAPIES  INC. | BIO SCIENCE CONTRACT  PRODUCTION CORP. |
|-------------------------------|----------------------------------------|
|                          |                                   |   |
|                          |                                   |   |
| By:                           | /s/Daniel Geffken                      | (SEAL) | By: | /s/Jacques Rubin | (SEAL) |
|                          | Name: Daniel Geffken                   |   | Name:  Jacques Rubin |
|                          | Title:                                 |   | Title:  CEO & Chairman |
|                          |                                   |   |
| Date:  12.10, 1999       |
|                               |                                        |  |  |  |  |

 

----

 

**SCHEDULE D-(2)**

**TO**

**PRODUCTIONAGREEMENT**

 

**OTHER PRODUCTIONREQUIREMENTS**

 

PERSONNEL:                                          [**] staff (including one QA person)are provided in the [**]Production Fee.  This is equivalent to [**] hours.  BSCP may provide additional personnel hours at the rate of $[**] per hour.  A budget for labor hours will be submittedprior to December 15th, 1999. Any variance greater than [**]%of budget will be accompanied by a written explanation to Client.  [**]chargeable to the Client.

 

HAZARDOUS WASTES ANDSUBSTANCES:

 
| **Type** |   | **Amount** |   | **Charge for Disposal** |   |
|----------|--------|------------|--------|-------------------------|--------|

 

Such rates shall besubject to change from time to time in accordance with written notice providedby BSCP to Client.

 

***********************************

 

The content of this **Schedule D-(2)** is agreed to by theparties listed below to that certain Master Production Agreement dated as ofDecember 1, 1998.

 

 

 
| By:                     | /s/Daniel Geffken    | (SEAL) | By:                             | /s/Jacques Rubin | (SEAL) |
|-------------------------|----------------------|--------|---------------------------------|------------------|--------|
|                    | Name: Daniel Geffken |   | Name:  Jacques Rubin       |
|                    | Title:               |   | Title:  CEO & Chairman |
|                    |                 |   |
| Date:  12.10, 1999 |

 

----

 

**SCHEDULE E-(2)**

**TO**

**PRODUCTIONAGREEMENT**

 

**[**]**STORAGE RATES AND PROCEDURES

 

[**]Storage Charge:

 

$[**]per square foot for Room Temperature Storage$[**] per cubic foot forRefrigerated Storage$[**] per cubic foot for FreezerStorage

 

Minimum Monthly StorageCharge:

 

$[**]for Room Temperature Storage$[**] for Refrigerated Storage$[**] for Freezer Storage

 

Procedure:

 

Client will hot ship anymaterials, equipment or supplies to BSCP without the prior written approval ofBSCP.

 

*********************************

 

| **Schedule  E-(2)** |   | The content of this is agreed to by the parties  listed below to that certain Master Production Agreement dated as of December  l, 1998. |
|---------------------|--------|------------------------------------------------------------------------------------------------------------------------------------------|
|                |   |                                                                                                                                     |
|                |   | By:                                                                                                                                      | /s/Daniel   Geffken | (SEAL) |
|                |   |                                                                                                                                     | By:/s/Jacques Rubin | (SEAL) |
|                |   |                                                                                                                                     | Name: Daniel Geffken |
|                |   |                                                                                                                                     | Name: Jacques Rubin |
|                |   |                                                                                                                                     | Title: | Title: |
|                |   | CEO & Chairman                                                                                                                       |
|                |   |                                                                                                                                     |
|                |   |                                                                                                                                     | Date:  12.10,  1999 |
|                     |        |                                                                                                                                          |  |  |  |  |  |

 

----

 

**SCHEDULE B-(2)-(AMENDED)**

**TO**

**PRODUCTION AGREEMENT**

 

**PRODUCTION TERM, SUITE AND FEES**

 

Client has decidedto exercise its renewal option under Schedule B-(2), signed by both parties onDecember 10, 1999.  Client has decidedto renew the production term for four (4) years on the same terms and conditionsstated in the Master Production Agreement, dated December 1, 1998 and theappended Schedules signed on December 10, 1999.

 

This means thatthe Production Term Termination Date shall now be extended to December 31,2004.

 

The MonthlyProduction Fee of $[**] shallremain unchanged for the length of the renewal period.

 

The hourly laborrate of $[**] stated in ScheduleD-(2) (signed on December 10,1999) shall be subject to a [**]% percent increase on  January 1st of each year,beginning January 1st, 2001.

 

**********************************************

 

The content ofthis **ScheduleB-(2)-(AMENDED)** is agreed to by the parties listed below to thatcertain Master Production Agreement dated as of December 1, 1998.

 

TRANSKARYOTICTHERAPIES, INC.           BIO SCIENCECONTRACT

            PRODUCTION CORP.

 

 
| TRANSKARYOTIC THERAPIES  INC. | BIO SCIENCE CONTRACT  PRODUCTION CORP. |
|-------------------------------|----------------------------------------|
|                          |                                   |   |
|                          |                                   |   |
| By:                           | /s/ Daniel Geffken                     |   | By: | /s/ Jacques R. Rubin |   |
|                          | Name: Daniel Geffken                   |   | Name: Jacques R. Rubin |
|                          | Title: VP, CFO                         |   | Title: CEO |
|                          |                                   |   |
|                          | Date:                                  | September 21, 2002 |
|                               |                                        |  |  |  |  |  |  |

 

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