**Exhibit4.10**

 

 

| Crucell N.V.                                                 |
|--------------------------------------------------------------|
| Confidential Materials Omitted and Filed Separately with the |
| Securities and Exchange Commission.                          |
| Confidential Portions denoted by [***].                      |

 

 

 

18 June 2004

 

Berna Biotech LtdRehhagstrasse 79CH-3018 BernSWITZERLAND

 

Attention: Kuno Sommer, ChiefExecutive Officer

 

Dear Kuno,

 

**Letter of Amendment to SupplyAgreement**

 

We refer to the SupplyAgreement dated 12 November 2001 (the ***Agreement****)*****between CSL Limited ***(CSL*)**and BernaBiotech Ltd (***Berna****)*for the supply of Product on a worldwidenon-exclusive basis subject to specified Exclusive and Excluded Territories.

 

As discussed, it is proposedthat the Agreement be amended as follows:

 

1.         Agreement to Supply

 

Under clause 1.7, theAgreement pertains to the supply of Product for Northern Hemisphere influenzavaccine manufacture by Berna. Supply of Product for Berna to manufactureinfluenza vaccine for the Southern Hemisphere will be the subject of a separateagreement if the parties agree to proceed.

 

2.         Term and Termination

 

Under Schedule 1 item 2, theInitial Period of the contract is extended by two years to end on 31December 2009.

 

3.         Supply ofProduct(s) against Orders

 

a)        UnderClause 3.1. Berna is to provide in November each year a five-yearindicative forecast to be discussed at a face to face meeting. At that meetingCSL will confirm whether it expects to be able to supply the forecastedquantity of Product and make adjustments to the indicative non-binding maximumquantities for the five year forecast period.

 

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As at the date of thisletter, the quantities outlined in the five-year indicative forecast and up tothe maximum quantities are as follows:

 
| **Year** | ** ** | **Total GM HA** | ** ** | **25 mcgm doses** | ** ** |
|----------|------------|---------------------------|------------|-----------------------------|------------|
| 2005     |       | [***]                     |       | [***]                       |       |
| 2006     |       | [***]                     |       | [***]                       |       |
| 2007     |       | [***]                     |       | [***]                       |       |
| 2008     |       | [***]                     |       | [***]                       |       |
| 2009     |       | [***]                     |       | [***]                       |       |

 

CSLshall use its best efforts to be able to supply to Berna the quantitiesoutlined in the five-year indicative forecast and up to the maximum quantitiesas follows:

 
| **Year** | ** ** | **Total GM HA** | ** ** | **25 mcgm doses** | ** ** |
|----------|------------|---------------------------|------------|-----------------------------|------------|
| 2005     |       | [***]                     |       | [***]                       |       |
| 2006     |       | [***]                     |       | [***]                       |       |
| 2007     |       | [***]                     |       | [***]                       |       |
| 2008     |       | [***]                     |       | [***]                       |       |
| 2009     |       | [***]                     |       | [***]                       |       |

 

Berna will, before 30June each calendar year provide CSL with a written best estimate of itssupply requirements for the Product for the subsequent year. Within 8 weeks CSLis to notify Berna whether CSL will be able to supply the forecasted quantityof Product for the following season based on expected strains and yields. Bernamay, before 30 November each year, submit to CSL a revised best estimateof its supply requirements.

 

b)        Under clause 3.3, eachorder placed by Berna will be for a minimum quantity of HA for each calendaryear as follows:

 
| **Year** | ** ** | **Total GM HA** | ** ** | **25 mcgm doses** | ** ** |
|----------|------------|---------------------------|------------|-----------------------------|------------|
| 2005     |       | [***]                     |       | [***]                       |       |
| 2006     |       | [***]                     |       | [***]                       |       |
| 2007     |       | [***]                     |       | [***]                       |       |
| 2008     |       | [***]                     |       | [***]                       |       |
| 2009     |       | [***]                     |       | [***]                       |       |

 

CSL confirms and Bernaunderstands and accepts that payment in full is required for the minimumquantity, regardless of whether the minimum quantity is ordered/purchased.

 

c)        Underclause 3.4, each of Berna’s orders for Product shall be in writing and shallconstitute a binding order upon CSL. Insofar as Berna requires quantitiesexceeding those mentioned in Berna’s November best estimate CSL shall usereasonable efforts to deliver such quantities.

 

4.         Price and Payment

 

a)        Under clause 4.1 theProduct(s) will be invoiced at the prices set out in Schedule 2. The pricewill be based on the number of eggs used to manufacture the quantity of Productordered and delivered to Berna. The amount due per egg used will for the year2005-2009 be as follows:

 
| 2005 |   | A$ | [***] per egg |   |
|------|--------|----|--------------------|--------|
| 2006 |   | A$ | [***] per egg |   |
| 2007 |   | A$ | [***] per egg |   |
| 2008 |   | A$ | [***] per egg |   |
| 2009 |   | A$ | [***] per egg |   |

 
| Phone: +61 3 9389 1769 |   | CSL Limited ABN  99 051 588 348  45 Poplar Road Parkville Victoria 3052 Australia  June.McKay@csl.com.au |   | Fax: +61  9389 1076 |
|------------------------|--------|----------------------------------------------------------------------------------------------------------|--------|--------------------------|

 

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b)        Under Schedule 2 the 2005 calendar yearprice for a trivalent dose (25 mcgm of each strain) will be based on an amountof A$ [***] per egg used to manufacture the quantity ofProduct(s) delivered to Berna. The relationship between price per egg usedto manufacture the Product and actual price paid per 25 mcgm HA of each strainis dependant upon the egg yield. Using the five year average yield the price of A$ [***] per egg used relates to A$ [***] per 25 mcgm trivalent dose. With better than average yields the priceper dose reduces because the processing cost is fixed, as shown in the tablebelow:

 
| **Yield**         | ** ** | **Yield Per Egg  (mcgm/egg)** | ** ** | **Price / Egg** | ** ** | **Price per  25mcgm dose** | ** ** |
|-------------------|------------|-----------------------------------------|------------|---------------------------|------------|--------------------------------------|------------|
| 10% above average |       | [***]                                   |       | [***]                     |       | [***]                                |       |
| 5 year average    |       | [***]                                   |       | [***]                     |       | [***]                                |       |
| 10% below average |       | [***]                                   |       | [***]                     |       | [***]                                |       |

 

Note: the above yields areindicative only. The actual yield could be greater or less than ±10% from thefive-year average.

 

5.         Product Recall

 

Under clause 19.1 Berna willinform CSL immediately by telephone or facsimile transmission (immediatelyconfirmed in writing) in the event of any circumstances giving rise to apossible or actual recall of Finished Influenza Vaccine containing theProduct(s) where the recall is alleged to be due to Product(s). CSL willinform Berna immediately by telephone or facsimile transmission (immediatelyconfirmed in writing) in the event of any circumstances giving rise to apossible or actual recall of any batches of the Product(s) delivered toBerna.

 

Clauses 19.2, 19.3 and 19.4will continue in full force and effect.

 

6.         Adverse Drug Events

 

Clause 20.2 and 20.5 and Schedule 4 shall be deletedwithout replacement. Clause 20.1, 20.3 and 20.4 are changed as follows and willreplace the previous provisions:

 

a)        Underclause 20.1 CSL and Berna shall keep each other informed on all reports ofAdverse Drug Events (ADE) coming to either party’s knowledge with regard to theProduct(s) regardless of the origin of such reports. The term Reportsshall also include publications in journals and other media. If Berna receivesany ADE report which is both serious and unexpected and alleged to be caused bythe Product(s) Berna will report the matter to the Registration Authorityin compliance with the laws and regulations in the Territory.

 

b)        Underclause 20.3 Berna will give immediate written notice to CSL of any allegedmanufacturing or other defect in the Products(s) of which Berna becomesaware and of any possible expense, liability, cost, claim or proceeding arisingfrom the alleged defect.

 

c)        Underclause 20.4 Berna will not make any admission of liability to any third partywith respect to claims either in the name of Berna or on behalf of CSL withrespect to any adverse experiences alleged to be caused by, and any alleged manufacturingor other defects in the Product(s) without CSL’s prior written consent.

 

Terms used in this letter shall have the same meaningas defined in the Agreement unless the context requires otherwise. Except asamended by this letter, the terms of the Agreement remain in full force andeffect.

 
| Phone: +61 3 9389 1769 |   | CSL Limited ABN  99 051 588 348  45 Poplar Road Parkville Victoria 3052 Australia  June.McKay@csl.com.au |   | Fax: +61  9389 1076 |
|------------------------|--------|----------------------------------------------------------------------------------------------------------|--------|--------------------------|

 

 

 

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Please confirm Berna’s formal agreement to the aboveby signing and returning the enclosed copy of this letter.

 

Yours sincerely

 
| /s/ Zita Cunningham |   |   |
|---------------------|--------|--------|
|                |   |   |

 

**Zita Cunningham**Business Development Director, Pharmaceuticals Group

 

Accepted and agreed for and on behalf of Berna BiotechLtd by its duly authorised representative(s):

 
| Illegible, 24 June 2004 |   | /s/ Jorg von Manger-Koenig           |
|------------------------------|--------|--------------------------------------|
| Place, date                  |   | Name:                                | Jörg  von Manger-Koenig |
|                         |   | Function:                            | Executive Vice President Legal,  Regulatory Affairs & IP |
|                         |   |                                 |   |
| Illegible,  24.06.04         |   | /s/ Dr. Alexandra Fischer-Hauck |
| Place, date                  |   | Name:                                | Dr. Alexandra Fischer-Hauck |
|                         |   | Function:                            | Director, Global Product Management |

 
| Phone: +61 3 9389 1769 |   | CSL Limited ABN  99 051 588 348  45 Poplar Road Parkville Victoria 3052 AustraliaJune.McKay@csl.com.au |   | Fax: +61 9389  1076 |
|------------------------|--------|--------------------------------------------------------------------------------------------------------|--------|---------------------|

 

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THIS SUPPLY AGREEMENT ismade on the date last signed

 
| BETWEEN: |   | CSL LIMITED ACN 051 588 348  45 Poplar Road, Parkville, Victoria, Australia 3052  Facsimile: (+613) 9389 1434 | * * | *(CSL)*   |
|----------|--------|---------------------------------------------------------------------------------------------------------------|----------|-----------|
|     |   |                                                                                                          |     |      |
| AND:     |   | BERNA BIOTECH LTD  Rehhagstrasse 79, CH-3018 Berne, Switzerland  Facsimile: (+41) 31 980 62 29                | * * | *(BERNA)* |

 

WHEREAS:

 

A.       CSL is engaged in themanufacture and distribution of human and veterinary pharmaceutical anddiagnostic products.

 

B.        BERNA is active in themanufacturing, distribution and marketing of similar products.

 

C.        BERNA wishes to obtain fromCSL and CSL wishes to supply to BERNA Bulk Inactivated Whole Virus InfluenzaConcentrate — Monovalent Pooled Harvest as set out in this Agreement.

 

THE PARTIES AGREE

 

**1.****        Agreement to Supply**

** **

1.1       CSLagrees to supply, and BERNA agrees to purchase, Product(s) on the termsand conditions set out in this Agreement.

 

1.2       ThisAgreement will oblige CSL to manufacture or (if it is not able to manufactureby decisions**of the authorityconcerned) to deliver the Product(s) as ordered by BERNA and accepted byCSL.

 

1.3       Nothingin this Agreement will restrict BERNA’s ability to deal in bulk influenzavaccine (other than the Product) and Finished Influenza Vaccine formulated withthe Product or other vaccines utilising Virosome technology formulated with theProduct except that BERNA agrees not to sell such vaccines to any third partywhere BERNA knows that same may be used within the Excluded Territory.

 

1.4       BERNAwill not use the Product(s) in any way other than as permitted under thisAgreement. In particular, BERNA will use the Product(s) only as a bulkcomponent in the formulation of Finished Influenza Vaccines and other vaccinesutilising Virosome technology.

 

1.5       Nothingin this Agreement will restrict CSL’s ability to deal in bulk influenza vaccineand Finished Influenza Vaccines except that CSL agrees not to sell FinishedInfluenza Vaccines to any third party where CSL knows that same may be usedwithin the Exclusive Territory. BERNA may on or before 30 June 2002request that the Exclusive Territory be expanded and CSL will notify BERNA ofits agreement or otherwise to such expansion on a country by country basis by30 September 2002.

 

1.6       Regardingnew influenza products developed by BERNA, BERNA agrees to consider CSL as adistributing partner for the Excluded Territory.

 

1.7       BERNAis interested to purchase Product(s) for the Southern Hemisphere and CSLagrees to consider BERNA’s request prior to 21 December 2001. If CSLnotifies BERNA that CSL is willing to supply such Product(s), CSL and BERNAwill negotiate in good faith an amendment to this Agreement to provide for thesupply of such Product(s).

 

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**3.****        Supply ofProduct(s) against Orders**

 

3.1       BERNAwill, as soon as practicable after the Commencement Date, provide CSL with awritten best estimate of its supply requirements for each of the Product(s) forthe 2002 calendar year. BERNA will, before 30 June each calendar year,provide CSL with a written best estimate of its supply requirements for each ofthe Product(s) for the subsequent calendar year. BERNA may, before 30November each year, submit a revised written best estimate of its supplyrequirements for each of the Product(s) for the subsequent calendar year.

 

3.2       On**or before 28 February, BERNA will place afirm written order with CSL for BERNA’s requirement for Product(s) for theupcoming season. BERNA’s order must be for at least 75% of its 30June written best estimate provided under clause 3.1.

 

3.3       Eachorder will be for a minimum quantity of 100 gm HA per strain for the 2002calendar year, 150 gm HA per strain for the 2003 calendar year and for eachsubsequent calendar year a scaled up minimum quantity will be agreed betweenCSL and Berna based on the agreed European SRID assay.

 

3.4       Eachorder will be binding upon CSL unless within 14 days of receipt of an order CSLnotifies BERNA that it does not accept the order in excess of the minimumquantity determined under clause 3.3.

 

3.5       Deliverydates for the Product(s) for the Northern Hemisphere will be based onyield and CSL will use its best endeavours to advise BERNA of estimateddelivery dates by 15 March. CSL will provide written confirmation of deliverydates by 30 April, which will include any delivery date after 15 July. CSL willuse reasonable endeavours to deliver at least 11.5gmHA of each strain by 30April for regulatory requirements. If BERNA require a commercial deliveryprior to 15 June 2002, CSL will only commit to deliver 75% of the quantityordered by Berna and accepted by CSL. CSL will use reasonable endeavours todeliver the balance of the accepted order by July 15.

 

3.6       IfCSL delivers Product(s) in excess of BERNA’s firm order, BERNA must adviseCSL in writing of the quantity held in excess as soon as such excess isdetermined. BERNA will process the excess quantity and store it for potentialuse in the following Northern Hemisphere season. If the excess quantity is ableto be used in the following seasons, BERNA will pay CSL for the excess quantityat the price applicable at the time of delivery within 30 days of the officialannouncement of Northern Hemisphere strain selection. If the excess quantity isunable to be used in the following season, BERNA will destroy the excessquantity and notify CSL in writing that the excess quantity has been destroyed.

 

3.7       CSLwill use its reasonable endeavours to supply the Product(s) in accordancewith BERNA’s orders. However, CSL’s liability for any loss or damage whichBERNA may suffer or incur as a result of CSL’s failure to supply theProduct(s) in accordance with accepted BERNA orders will be limited to thevalue of the accepted order (or part thereof) which CSL fails to supply. If CSLdelivers Product(s) for the Northern hemisphere to another customer andfails to deliver the accepted Berna order (or part thereof), CSL is liable forany loss or damage Berna may suffer as a result of unfilled Berna customerorders.

 

3.8       Anindicative timing program for ordering and price negotiations is set out inSchedule 3.

 

**4.****        Price and Payment**

 

4.1       TheProduct(s) will be invoiced at the prices set out in Schedule 2. For the2002 calendar year the price will be based on an amount of A$ [***] per eggused to manufacture that quantity of product delivered to Berna. For the 2003calendar year the price will be based on an amount of [***] and for 2004calendar year the price will be based on an amount of [***]. The**parties will negotiate in good faith anew price for the 2005 calendar year and the 2006 calendar year prior to 30April 2004. The parties will take into account any change in CSL’smanufacturing costs and the general influenza market conditions. If thisagreement is renewed, the

 

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parties will negotiate ingood faith a new price for the renewal period prior to 30 April of thecalendar year immediately prior to the initial year of the renewal term. Theparties will take into account any change in CSL’s manufacturing costs and thegeneral influenza market conditions.

 

4.2       Unlessotherwise agreed in writing all payments will be made under the terms and inthe currency set out in Schedule 2.

 

4.3*      *If the closing price ofthe whole market spot rate for the Australian Dollar relative to the SwissFranc as reported in The Australian Financial Review deviates by more than 10%from the closing price for the wholesale market spot rate reported in TheAustralian Financial Review on the Commencement Date, the parties agree toadjust any amounts due under this Agreement so as to ensure that each partybears 50% of the exposure created by the deviation. Any further deviation ofmore than 10% following any adjustment will result in a further adjustment onthe same terms.

 

**5.****        Packing, Delivery and Riskin Transit**

 

5.1       CSLwill sell the Product(s) ExWorks (lncoterms 2000), CSL’s Premises. CSLwill pack the Product(s) suitable for delivery to BERNA’s site in Berne,Switzerland.

 

5.2       [IntentionallyDeleted]

 

5.3       IfCSL agrees to arrange delivery on behalf of BERNA (beyond CSL’s obligationsunder clause 5.1) then the cost of freight and insurance arranged by CSL willbe to BERNA’s account, and CSL will be acting as BERNA’s forwarder. BERNA willindemnify and keep indemnified CSL against all actions, claims, demands,losses, damages, costs (including legal costs on a full indemnity basis) andexpenses for which CSL may become liable which relate directly or indirectly toCSL’s acting as BERNA’s forwarder under this clause.

 

5.4       Subjectto product liability under clause 13, CSL’s obligations under clause 5.1 andthe quality control and acceptance procedures, risk in the Product(s) willpass to BERNA upon ExWorks delivery. Property and ownership of theProduct(s) will pass to BERNA upon payment.

 

**6.****        Quality Control**

 

6.1       CSLwill supply Product(s) free of defects in materials and manufacture, andin compliance with the Specification and any Conditions of Registration(including protocols to EU-regulations) set by the Registration Authority ofwhich BERNA has given CSL reasonable prior written notice.

 

6.2       CSL and BERNA will enterinto a GMP Agreement, which is to be reviewed annually on or before 30November, that is to be consistent with terms of this Agreement.

 

6.3       CSLwill keep proper records and reference samples of all of its manufacturing andquality control activities performed under this Agreement. CSL will provide, onrequest, to Berna a copy of CSL’s current TGA certificate. BERNA may audit suchrecords and the production facilites at reasonable intervals, on reasonablenotice during normal business hours.

 

6.4       CSLwill notify BERNA of any special storage requirements for the Product(s).

 

6.5       BERNAwill store the Product(s) in suitable storage facilities having regard toboth the Specification and Conditions of Registration and in a manner whichensures proper rotation of stock.

 

6.6       BERNAwill test samples of delivered Product(s) and if it believes a particularProduct(s) (hereinafter referred to as “the Notified Product”) does notcomply with clause 6.1, it will notify CSL advising the batch number. CSL willexamine and test from that batch a sample retained by it (hereinafter referredto as**“the Batch Sample”). If CSLfinds the Batch Sample does not comply with clause 6.1 then CSL will ifpracticable replace the Notified Product in due time and after discussion withBERNA.

 

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6.7       IfCSL finds the Batch Sample does comply with clause 6.1 and BERNA, based on itsown results, does not accept CSL’s findings, then a mutually agreed independenttesting agency will make a final decision with regard to the releasespecification of the Notified Product, and that finding will be**conclusive for the two parties. If itsupports CSL findings it is evidence for all purposes that the Notified Productcomplied with in clause 6.1 when loaded for delivery at CSL’s premises. CSLwill not be liable to replace or allow a credit in respect of the NotifiedProduct. The alleged failure of the Notified Product to comply with clause 6.1will be deemed to have arisen or been caused by reason of an act or default ofa person (not being CSL or an employee or agent of CSL) or a cause independentof human control occurring after the Notified Product was loaded for deliveryat CSL’s premises. If the releasing authority’s findings do not support CSL’sfindings the Product(s) CSL will if practicable replace the NotifiedProduct in due time and after discussion with BERNA. The cost of theindependent testing agency will be shared equally by CSL and BERNA regardlessof the outcome.

 

**7.****        BERNA’s and CSL’s Dutiesand Obligations**

 

7.1       BERNAwill:

 

(a)       onlydistribute and sell Finished Influenza Vaccine and other vaccines utilisingVirosome technology containing the Product(s) as agreed under thisAgreement

 

(b)      complywith all laws, ordinances, regulations, rules and administrativedirections applicable to or governing or controlling the importation of theProduct(s) into, and the sale and use of the Product(s) in, theTerritory

 

(c)       notifyCSL of any reason BERNA has to believe that a particular Product(s) doesnot comply with clause 6.1 as soon as possible and preferably within fourteendays of that reason coming to the attention of BERNA. The notification willidentify the particular Product’s batch number. BERNA will also notify CSL ofany Adverse Drug Events under clause 20.

 

7.2       BERNAand CSL will ensure that their respective employees, agents and dealers areacquainted with the obligations imposed by this Agreement to the extentreasonably necessary to ensure compliance with the Agreement.

 

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**8.****        Promotion and Marketing**

 

8.1       BERNAwill have the absolute unilateral right to determine its promotion andmarketing activities, and the prices at which it will sell the FinishedInfluenza Vaccine containing the Product(s) and to determine paymentarrangements with purchasers of the same. CSL does not desire to participateand will not participate in any price determinations.

 

**9.****        Provision of TechnicalInformation**

 

9.1       CSL,at its expense, and as soon as practicable after the Commencement Date, willmake available to BERNA all technical information relating to theProduct(s) which CSL considers relevant to the reasonable needs of BERNAunder this Agreement and to the extent CSL has the right to divulge theinformation. Nothing in this Agreement other than the required responses to theRegistration Authority will oblige CSL to make available to BERNA anyinformation, technical or otherwise, which is in any way referable to themanufacture, formulation, production or processing of the Product(s).

 

9.2*      *BERNA may use anytechnical information made available to it pursuant to this clause but only forthe proper discharge of its obligations. BERNA will not use any of thetechnical information made available to it for any purpose after this Agreementends. For Confidential Material *see* clause 12.

 

**10.****      [Intentionally Deleted]**

 

**11.****      Registration Requirements**

 

11.1     BERNAwill effect, in its own name and at its expense, any necessary registrations ofthe Product(s) in the Territory. BERNA will provide CSL with all data andinformation and copies of all documentation to enable CSL to comply with itsobligations under this Agreement.

 

11.2     CSLwill assist BERNA with dossier preparation, at BERNA’s cost. CSL and BERNA willconsult and agree on all dossier requirements (updates) and CSL’s costs by 30November each year for the following calendar year.

 

**12.****      Confidentiality**

 

12.1     Eachparty will:

 

(a)       keepall Confidential Material disclosed to it by the other party confidential;

 

(b)      notpermit the other party’s Confidential Material to be disclosed other than inconfidence to its employees to the extent strictly necessary for the purposesof this Agreement;

 

(c)       usethe other party’s Confidential Material only for the purpose of this Agreementand not to use for any commercial purpose other than under a further agreementwith the other party;

 

(d)      notcopy or reduce to writing the other party’s Confidential Material except asreasonably necessary for the purposes of this Agreement. Copies or reductionsto writing of Confidential Material of the other party shall be owned by thatparty;

 

(e)       maintainthe other party’s Confidential Material in a way which provides adequateprotection from unauthorised disclosure, copying or use;

 

(f)       indemnifyand keep indemnified the other party against all actions, claims, demands,losses, damages, costs and expenses for which the other party may become liablewhich arise as a result of an unauthorised disclosure of the other party’sConfidential Material; and

 

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(g)      returnpromptly to the other**party alldocuments and materials (and all copies thereof) containing the other party’sConfidential Material at the end of this Agreement.

 

12.2     “ConfidentialMaterial” means all proprietary information disclosed by, or on behalf of, oneparty to the other party relating to this Agreement and includes:

 

(a)       informationdisclosed in writing, verbally or by any other means,

 

(b)      informationdisclosed before, after or on the Commencement Date; and

 

(c)       informationrelating to the other party’s operations, processes, plans, intentions,production information, know-how, data, formulae, expertise, methodology,drawings, specifications, design rights, trade secrets, market opportunitiesand business affairs, and any new and novel combinations thereof.

 

but excludes informationwhich the receiving party proves:

 

(d)      isin or has come into the public domain in any way without it breaching thisAgreement;

 

(e)       ithas developed independently as a result of its operations and activities;

 

(f)       ithas obtained or has available from a source other than the disclosing partywithout breach of any obligation of confidentiality or non-use;

 

(g)      itknew prior to being disclosed by the disclosing party; or

 

(h)      ithas disclosed with the prior written approval of the disclosing party.

 

12.3     Eitherparty may disclose the other party’s Confidential Material in confidence to theRegistration Authority to the extent required to comply with the law and itsobligations under this Agreement.

 

**13.****      Product Liability**

 

13.1     CSLwill indemnify and keep indemnified BERNA against all actions, claims, demands,losses, damages, costs (including legal costs on a full indemnity basis) andexpenses for which BERNA may become liable which relate directly or indirectlyto the Products, their uses or effects but only to the extent arising from abreach of this Agreement (including failure of Product(s) to comply withthe Specifications) by, or the negligence or wilful default of, CSL.

 

13.2     BERNAwill indemnify and keep indemnified CSL against all actions, claims, demands,losses, damages, costs (including legal costs on a full indemnity basis) andexpenses for which CSL may become liable which relate directly or indirectly toBERNA’s altered Product in any form, whether bulk, finished or otherwise, theiruses or effects except to the extent arising from any breach of this Agreementby, or the negligence or wilful default of, CSL.

 

**14.****      Term and Termination**

 

14.1     ThisAgreement will begin on the Commencement Date and remain in effect during theInitial Period. It will thereafter be renewed for successive two year periodsuntil terminated.

 

14.2     Eitherparty may terminate this Agreement on 12 months notice to end at the end of theInitial Period or any successive two year period thereafter.

 

14.3     The party notaffected may terminate this Agreement by giving to the other party writtennotice to terminate on the date specified in the notice if:

 

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(a)       aparty fails to rectify any breach of its obligations within 30 days ofreceiving a written notice requiring it to do so;

 

(b)      ifa party becomes insolvent, is adjudged bankrupt, applies for judicial orextra-judicial settlement with its creditors, makes an assignment for thebenefit of its creditors, voluntarily files for bankruptcy or has a receiver ortrustee (or the like) in bankruptcy appointed over its business, property orassets, or becomes the subject of liquidation or dissolution (except forreconstruction purposes such as mergers, etc) or involuntary bankruptcyproceedings or otherwise discontinues business;

 

(c)       anyother right of termination in favour of the first party arises under thisAgreement; or

 

(d)      achange in effective control of the other party.

 

14.4     Ifan important parameter changes so materially that the continuation of thisagreement would lead to a material adverse financial effect for a party, thatparty may by written notice request a negotiation in good faith to amend the termsof this Agreement to address the change in that parameter. If the parties areunable to agree on an appropriate amendment within three months of the date ofthe notice, either party may terminate this Agreement by immediate writtennotice. Such termination will not affect firm commitments made in connectionwith the supply of Product(s) for the upcoming Northern Hemisphereinfluenza season.

 

14.5     Terminationwill not affect any other rights or obligations which may have accrued prior totermination.

 

14.6     Atthe end of this Agreement BERNA will promptly forward to CSL, at BERNA’sexpense, all technical information relating to this Agreement it received fromCSL BERNA will not keep any copies.

 

**15.****      General**

 

15.1     Nowaiver of any provision of this Agreement will be of any force or effect unlessconfirmed in writing, signed by the parties. Then such waiver will be effectiveonly to the extent for which it is made.

 

15.2     Theinvalidity or unenforceability of any provision of this Agreement will notaffect the validity and enforceability of all other provisions which areself-sustaining and capable of separate enforcement.

 

15.3     ThisAgreement constitutes the entire agreement and understanding between theparties with respect to its subject matter. It replaces all previous agreementsbetween, or undertakings by either of, the parties with respect to its subjectmatter.

 

15.4     ThisAgreement can only be changed by written agreement of the parties.

 

15.5     Unlessexpressly provided elsewhere in this Agreement, the relationship between theparties is that of independent parties and will not be deemed to be that ofprincipal/agent, joint venture, partnership or otherwise.

 

15.6     Thelaws of Victoria, Australia will govern this Agreement.

 

15.7     Clauses11, 12,13,14.5 and 17.1 will continue to apply after this Agreement ends.

 

15.8     Neitherparty will be liable for any failure or delay in the performance of itsobligations under this Agreement to the extent that such failure or delayarises from any circumstance beyond its control including any Acts of Nature,strikes, lock-outs, labour disputes or in the event of an influenza pandemic inthe Excluded Territory. Where such failure or delay continues for a continuousperiod exceeding six months, the party not experiencing such failure or delaymay terminate this Agreement

 

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without penalty by written notice. The partiesacknowledge that manufacturing and formulation of the Product(s) andFinished Influenza Vaccine is an extremely time sensitive business andtherefore agree to notify each other as early as possible of any failure ordelay under this clause 15.8.

 

15.9     Eachparty will bear its own legal costs and expenses of and incidental to thepreparation of this Agreement.

 

15.10   This Agreement will bind and enure for the benefitof the parties and their respective successors in title. Neither party mayassign any of its rights and obligations without the prior written consent ofthe other party.

 

**16.****      Notices**

 

16.1     Anywritten notice required under this Agreement must meet all of the following

 

(a)       begiven by pre-paid post, personal delivery or facsimile transmission;

 

(b)      besent to the contact address or facsimile number given above (or any other pointpreviously advised in writing by the recipient), and

 

(c)       bemarked to the attention of a signatory to this Agreement (or any other personpreviously advised in writing by the recipient).

 

16.2     Nowritten notice is to be effective until received, or deemed to be received by theother party as follows:

 

(a)       inthe case of personal delivery, upon delivery;

 

(b)      inthe case of a letter, on the fifth business day after posting; and

 

(c)       inthe case of a facsimile transmission, on the business day on which it isdespatched, or, if despatched on a non-business day, or after 5 pm on abusiness day then on the next business day after day on which it is despatched.A record from the despatching facsimile machine detailing the time and date ofthe transmission will be evidence of transmission, unless proved to thecontrary.

 

Times and business days will be determined accordingto the place of receipt.

 

**17.****      Arbitration**

 

17.1     Alldisputes arising under this Agreement will be finally settled under theRules of Conciliation and Arbitration of the International Chamber ofCommerce in Zurich, where CSL initiates the action, or in Melbourne, whereBERNA initiates the action, by one or more arbitrators appointed in accordancewith those Rules. All arbitrations will be conducted in the English language.

 

**18.****      Benefit of Indemnities**

 

18.1     Forthe avoidance of doubt, it is agreed that where a party agrees to indemnify theother, the indemnified party will be or be deemed to be acting as agent for andon behalf of and for the benefit of all persons who are or might be itsdirectors, officers, employees, consultants or agents from time to time and allsuch persons will to this extent be or be deemed to be parties to thisAgreement.

 

**19.****      Product Recall**

 

19.1     BERNAwill inform CSL immediately by telephone or facsimile transmission (immediatelyconfirmed in writing) in the event of any circumstances giving rise to apossible or actual recall of any Finished Influenza Vaccine containing theProduct(s). CSL will inform BERNA immediately by telephone or

 

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facsimile transmission (immediately confirmed inwriting) in the event of any circumstances giving rise to a possible or actualrecall of any batches of the Product(s) delivered to BERNA.

 

19.2     CSLhas the right (irrespective of any power granted by law to the RegistrationAuthority or other authority in the Territory) on the grounds of public healthand safety to require BERNA to evaluate and in case to discontinue sale of andrecover some or all batches of Finished Influenza Vaccine containing theProduct(s) specified by CSL. If BERNA does not so discontinue sale, anysales made after the date of CSL’s request under this clause 19.2 will be madesolely at BERNA’s own risk and the indemnity in clause 13.1 will not apply.

 

19.3     Wherea product recall has been initiated whether by the Registration Authority orother authority in the Territory or by BERNA or CSL under clause 19.2**BERNA will inform all purchasers of theProduct(s) so affected and shall require them to deliver or make availablefor collection all such stocks of Finished Influenza Vaccine containing thedefective Product(s) in their possession. BERNA will ensure that all suchstocks of Finished Influenza Vaccine containing the defective Product(s) arecollected and stored in secure conditions on premises controlled by BERNA.

 

19.4     Costsof any action taken under this clause 19 will be borne by BERNA unless thecosts are caused by the breach of this Agreement, (including failure ofProduct(s) to comply with the Specifications) by, or negligence or wilfuldefault of, CSL, in which case CSL will indemnify BERNA against any and allactions, claims, demands, losses, damages, costs and expenses for which BERNAmay become liable which arise from such breach, negligence or wilful default.

 

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**20.****      Adverse Drug Events**

** **

20.1     IfBERNA receives any Adverse Drag Event (ADE) report which is both serious andunexpected and alleged to be caused by Finished Influenza Vaccine containingthe Product(s) BERNA will report the matter according to Schedule 4 to theRegistration Authority in compliance with the laws and regulations of theTerritory, and inform CSL without delay by telephone or facsimile transmission(immediately confirmed in writing). CSL will acknowledge receipt within 24hours by facsimile transmission.

 

20.2     BERNAwill report to CSL by telephone or facsimile transmission (immediatelyconfirmed in writing) any other adverse experience occurring in the Territoryand alleged to be caused by Finished Influenza Vaccine containing the Product(s)every three months.

 

20.3     BERNA will give immediate written notice to CSL of any alleged manufacturing orother defect in the Product(s) or Finished Influenza Vaccine containing theProduct(s) of which BERNA becomes aware and of any possible expense, liability,cost, claim or proceedings arising from the alleged defect.

 

20.4     Withrespect to any adverse experiences alleged to be caused by, and any allegedmanufacturing or other defects in, the Product (s) or Finished Influenza Vaccinecontaining same BERNA will not make any admission of liability to any thirdparty with respect to claims either in the name of BERNA or on behalf of CSLwithout CSL’s prior written consent.

 

20.5     Forthe purpose of this clause 20, “serious” and “unexpected” will have the meaningascribed to it at the relevant time by the Registration Authority or asotherwise notified by CSL from time to time.

 

**21.****      Definitions andInterpretation**

** **

21.1     Inthis Agreement:

 

(a)       ***Batch Sample*****is defined in clause 6;

 

(b)      ***Commencement Date*****means 1 November 2001;

 

(c)       ***Confidential Material***is defined in clause 12;

 

(d)      ***CSL’s Premises*****means CSL’s premises at 45 Poplar Road,Parkville, Victoria, Australia, 3052 or suet other address notified to BERNA inwriting by CSL;

 

(e)       ***Exclusive Territory*****means the territory set out in Item 1A ofSchedule 1;

 

(f)       ***Excluded Territory*****means**the territory set out in Item IBof Schedule 1;

 

(g)      ***Finished Influenza Vaccine*****means product that is intended for theprevention of influenza only and is formulated, filled in final container andpacked;

 

(h)      ***GMP Agreement*****means an agreement which specifies theAustralian Code of Good Manufacturing responsibilities relating to themanufacture of the Product(s);

 

(i)*        **ha***means haemaglutinin

 

(i)        ***Initial Period*****means the period set out in Item 2 ofSchedule 1;

 

(i)        ***Notified Product***is**definedin clause 6;

 

(j)        ***SRID*****means the single radial immunodifusion;

 

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(k)       ***Territory*****means**theterritory set out in Item IA of Schedule 1;

 

(l)        ***Product*****means**theproduct set out in Schedule 2;

 

(m)      ***Registration Authority*****means**SwissFederal Office of Public Health or any other body responsible for theregistration of the Product(s) in the Territory from time to time;

 

(n)      ***Specification*****means the Product Specification set outin Schedule 2; and

 

(o)      ***Virosome*****means virus-like particles consisting ofartificial bilayer liposomes with integrated viral surface antigens imitating avirus as developed and used by BERNA;

 

21.2.    In this Agreement:

 

(a)       Wordsdenoting the singular number include the plural number and vice versa;

 

(b)      Wordsdenoting any gender include all genders;

 

(c)       Referencesto persons include bodies corporate and vice versa;

 

(d)      Wordsdefined in another part of this Agreement will have the meaning given in thatpart;

 

(e)       Referencesto Recitals, clauses, sub-clauses, Schedules and Annexures are references toRecitals, clauses, sub-clauses, Schedules and Annexures of or to thisAgreement;

 

(f)       Referencesto the parties include references to respective directors, officers, employeesand agents of the parties; and

 

(g)      Headingsare inserted for convenience only and will not affect interpretation.

 

**22.****      Enclosures**

 
| Schedule 1: | Territory and Duration                        |
|-------------|-----------------------------------------------|
| Schedule 2: | Product(s), Prices and Payment Terms          |
| Schedule 3: | Timings                                       |
| Schedule 4: | Adverse Drug Event (ADE) reporting Guidelines |

 

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SIGNEDas an Agreement by the parties

 
| Signed for and on behalf of  | )      |                      |       |
|------------------------------|--------|---------------------------|------------|
| CSL Limited ACN  051 588 348 | )      | /s/ Colin Armit           | 12/11/01   |
| by its duly  authorised      | )      | Colin Armit               | (date)     |
| representatives              | )      | President Pharmaceuticals |       |
|                         | )      |                      |       |
|                         | )      | /s/ Peter Turvey          | 11/11/01   |
|                         | )      | Peter Turvey              | (date)     |
|                         | )      | Company Secretary         |       |
|                         |   |                      |       |
|                         | )      | /s/ Patrik Richard        | 02/11/2001 |
| Signed for and  on behalf of | )      | Patrik Richard            | (date)     |
| Berna Biotech  Ltd           |   | Secretary General         |       |
| by its duly  authorised      |   |                      |       |
| representatives              |   | /s/ Robert Mischler       | 02/11/2001 |
|                         |   | Robert Mischler           | (date)     |
|                         |   | Head of Production        |       |

 

 

 

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SCHEDULE 1to the Supply Agreement between CSL and BERNA

 

Territory and Duration

 
| 1:  | Territory:           | Worldwide non-exclusive subject to 1A and 1B below.                                            |
|-----|----------------------|------------------------------------------------------------------------------------------------|
| 1A: | Exclusive Territory: | Switzerland, Italy, Spain and Portugal.                                                        |
| 1B: | Excluded Territory:  | Australia and New Zealand.                                                                     |
| 2.  | Duration:            | The Initial Period commencing from the Commencement  Date and ending on 31 December 2006. |

 

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SCHEDULE 2to the Supply Agreement between CSL and BERNA

 

Product(s), Pricesand Payment Terms

 
| Product(s): | Bulk Inactivated Whole Virus Influenza Concentrate —  Monovalent Pooled Harvest.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             |
|-------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Price:      | The 2002 calendar year price for a trivalent dose  (25mcgm of each strain) will be based on an amount of [***] per egg used to  manufacture the quantity of Product(s) delivered to BERNA. The  relationship between price per egg used to manufacture the product and actual  price paid per 25mcgm HA of each strain is dependant upon the egg yield.  Using the average yield for the period l990-2000 the price of [***] per  egg used relates to [***] per 25mcgm trivalent dose. With better than average yields the  price per dose reduces because the processing cost price is fixed, as shown  in the table below. |

 
| Yield              | ** ** | **Yield Per Egg  (mcgm/egg)** | ** ** | **Price/Egg** | ** ** | **Price Per  25mcgm Dose** |
|--------------------|------------|-------------------------------|------------|---------------|------------|----------------------------|
| 10% above  average |       | [***]                         |       | [***]         |       | [***]                      |
| 10 Year  Average   |       | [***]                         |       | [***]         |       | [***]                      |
| 10% below  average |       | [***]                         |       | [***]         |       | [***]                      |

 

Note: • the yield is indicative only, the actual yieldcould be greater or lower than ± 10%.

 

CSL will notify BERNA ofindicative total cost of total order after one month of processing, ieindicative yields will be communicated but accurate costs (total numbers ofeggs used) will not be finalised until completion of the total order. CSL willnotify BERNA with each delivery the total number of inoculated eggs used.

 

The quantity of Product(s) deliveredwill be determined pursuant to the accepted SRID assay method using the agreedSRID standard and the volume measured by CSL and BERNA. Any difference of 10%or less between the CSL and BERNA test will result in a sharing of the variancein terms of price on a 50:50 basis. If there is a difference of more than 10%discrepancy between the CSL and BERNA test, CSL and BERNA will discuss in goodfaith a resolution. If CSL and BERNA are unable to resolve the discrepancy,then an independent testing agency tests the material. The accepted result willbe the average of the two closest results. The cost of the independent testingagency will be shared equally by CSL and BERNA regardless of the outcome.

 
| Payment Terms:         |   | If not otherwise specified, payment is due 60 days  from date of invoice. Prices in Australian Dollars Ex Works, Parkville,  Victoria 3052 (Incoterms 2000). |
|------------------------|--------|--------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Product Specification: |   | General Specifications according to Specifications  of European Pharmacopoeia already delivered to CSL.                                                      |

 

 

 

Any change of the EuPharmmonography on influenza vaccines and Product testing requirements shall be sentby BERNA to CSL or CSL to BERNA as soon as possible.

 

The Specifications for thestrains for the coming season shall be fixed according to the recommendationsof WHO and EU respectively and set out in BERNA’s order to CSL.

 

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SCHEDULE 3to the Supply Agreement between CSL and BERNA

 

Timing ofForecasts, Orders, etc

 
| Written best estimate from  BERNA for following calendar year.             |   | 30 June     |
|----------------------------------------------------------------------------|--------|-------------|
|                                                                       |   |        |
| Update of  written best estimate from BERNA for following calendar year.   |   | 30 November |
|                                                                       |   |        |
| Written  notification from BERNA of packaging requirements.                |   | 30 November |
|                                                                       |   |        |
| GMP Agreement  review and agreement regarding dossier preparation/updates. |   | 30 November |
|                                                                       |   |        |
| Notification of  Price Increase by CSL.                                    |   | 31 January  |
|                                                                       |   |        |
| Firm order by  BERNA.                                                      |   | 28 February |
|                                                                       |   |        |
| Notification of  Indicative Delivery Date by CSL.                          |   | 15 March    |
|                                                                       |   |        |
| Confirmation of  Delivery Dates by CSL.                                    |   | 30 April    |

 

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SCHEDULE 4to the Supply Agreement between CSL and BERNA

 

Adverse Drug Event(ADE) Reporting Guidelines(Clause 20)

 

1.         Principle:The Adverse Drug Event (hereinafter ADE) reporting system shall correspondbasically to the European Union Directive (EU) 93/39 and the correspondingregulations of each country of the Territories brought to knowledge of theBERNA. The ADE shall preferably be forwarded using the format of the COMS-formulary.

 

2.         CSLand the BERNA shall keep one another informed on all reports of ADEs coming toeither party’s knowledge with regard to the Product(s), regardless of theorigin of such reports. The term “Reports” shall also include publications injournals and other media.

 

3.         Reportson such ADEs which according to the informing party’s careful professionalevaluation may negatively affect the benefit-risk-ratio of the Product or mayhave consequences regarding the Product’s Information (eg. labelling, datasheets, package inserts) or may require immediate safety measures or regulatoryauthorities (such as special information/warnings to the medical profession,patients, authorities or withdrawal of the Product) shall be forwarded to the otherparty without delay after having become known.

 

4.         Thesame immediate forwarding, without delay shall apply in cases of reports onADEs being both serious and unexpected (ie. hitherto not specified in theProduct’s Information).

 

5.         Theinforming party is invited to give both the primary reporter’s and its ownprofessional evaluation of such reports, in particular with regard to suspectedcausality, with reasoning, either together with such information or at a laterdate.

 

Categories for determining relationship of ADE to theProduct:

 

•  Certain

 

•  Probable

 

•  Possible

 

•  Unlikely

 

•  Unrelated

 

•  Insufficient Evidence

 

6.         Theaforementioned Information shall be addressed to

 

in case of CSL:  CSL LIMITED ACN 051 588 348

 
| Attention:                                          | Head Medical Department |
|-----------------------------------------------------|-------------------------|
| 45 Poplar Road, Parkville, Victoria, Australia 3052 |
| Telephone:                                          | +61 3 9389 1911         |
| Facsimile:                                          | +61 3 9389 1434         |
|                                                |                    |
| BERNA BIOTECH LTD                                   |
| Attention:                                          | Head Medical Department |
| Rehhagstrasse 79, CH-3018 Berne, Switzerland        |
| Telephone:                                          | +41 31 980 67 37        |
| Facsimile:                                          | +41 31 980 67 75        |

 

or to such other address as may thereafter be providedby either party.

 

7.         Reportsshall be established by BERNA and delivered according to clause 20 andmeetings, if necessary, shall be held at mutually convenient times and places,for the purpose of discussing ADE issues.

 

8.         Allreports to be provided hereunder shall be in English, using the MeDRA adversereaction terminology.

 

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