Exhibit
4.10


 


 




	
  Crucell N.V.

  
	
  Confidential Materials Omitted and Filed Separately with the

  
	
  Securities and Exchange Commission.

  
	
  Confidential Portions denoted by [***].

  






 


 





 


18 June 2004


 


Berna Biotech Ltd

Rehhagstrasse 79

CH-3018 Bern

SWITZERLAND


 


Attention: Kuno Sommer, Chief
Executive Officer


 


Dear Kuno,


 


Letter of Amendment to Supply
Agreement


 


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


 


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


 


1.         Agreement to Supply


 


Under clause 1.7, the
Agreement pertains to the supply of Product for Northern Hemisphere influenza
vaccine manufacture by Berna. Supply of Product for Berna to manufacture
influenza vaccine for the Southern Hemisphere will be the subject of a separate
agreement if the parties agree to proceed.


 


2.         Term and Termination


 


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


 


3.         Supply of
Product(s) against Orders


 


a)        Under
Clause 3.1. Berna is to provide in November each year a five-year
indicative forecast to be discussed at a face to face meeting. At that meeting
CSL will confirm whether it expects to be able to supply the forecasted
quantity of Product and make adjustments to the indicative non-binding maximum
quantities for the five year forecast period.


 

















 


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


 


	
  Year

  	
   

  	
  Total GM HA

  	
   

  	
  25 mcgm doses

  	
   

  
	
  2005

  	
   

  	
  [***]

  	
   

  	
  [***]

  	
   

  
	
  2006

  	
   

  	
  [***]

  	
   

  	
  [***]

  	
   

  
	
  2007

  	
   

  	
  [***]

  	
   

  	
  [***]

  	
   

  
	
  2008

  	
   

  	
  [***]

  	
   

  	
  [***]

  	
   

  
	
  2009

  	
   

  	
  [***]

  	
   

  	
  [***]

  	
   

  



 


CSL
shall use its best efforts to be able to supply to Berna the quantities
outlined in the five-year indicative forecast and up to the maximum quantities
as follows:


 


	
  Year

  	
   

  	
  Total GM HA

  	
   

  	
  25 mcgm doses

  	
   

  
	
  2005

  	
   

  	
  [***]

  	
   

  	
  [***]

  	
   

  
	
  2006

  	
   

  	
  [***]

  	
   

  	
  [***]

  	
   

  
	
  2007

  	
   

  	
  [***]

  	
   

  	
  [***]

  	
   

  
	
  2008

  	
   

  	
  [***]

  	
   

  	
  [***]

  	
   

  
	
  2009

  	
   

  	
  [***]

  	
   

  	
  [***]

  	
   

  



 


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


 


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


 


	
  Year

  	
   

  	
  Total GM HA

  	
   

  	
  25 mcgm doses

  	
   

  
	
  2005

  	
   

  	
  [***]

  	
   

  	
  [***]

  	
   

  
	
  2006

  	
   

  	
  [***]

  	
   

  	
  [***]

  	
   

  
	
  2007

  	
   

  	
  [***]

  	
   

  	
  [***]

  	
   

  
	
  2008

  	
   

  	
  [***]

  	
   

  	
  [***]

  	
   

  
	
  2009

  	
   

  	
  [***]

  	
   

  	
  [***]

  	
   

  



 


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


 


c)        Under
clause 3.4, each of Berna’s orders for Product shall be in writing and shall
constitute a binding order upon CSL. Insofar as Berna requires quantities
exceeding those mentioned in Berna’s November best estimate CSL shall use
reasonable efforts to deliver such quantities.


 


4.         Price and Payment


 


a)        Under clause 4.1 the
Product(s) will be invoiced at the prices set out in Schedule 2. The price
will be based on the number of eggs used to manufacture the quantity of Product
ordered and delivered to Berna. The amount due per egg used will for the year
2005-2009 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

  



 


2

















 


b)        Under Schedule 2 the 2005 calendar year
price for a trivalent dose (25 mcgm of each strain) will be based on an amount
of A$ [***] 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 25 mcgm HA of each strain
is 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 price
per dose reduces because the processing cost is fixed, as shown in the table
below:


 


	
  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 are
indicative only. The actual yield could be greater or less than ±10% from the
five-year average.


 


5.         Product Recall


 


Under clause 19.1 Berna will
inform CSL immediately by telephone or facsimile transmission (immediately
confirmed in writing) in the event of any circumstances giving rise to a
possible or actual recall of Finished Influenza Vaccine containing the
Product(s) where the recall is alleged to be due to Product(s). CSL will
inform Berna immediately by telephone or facsimile transmission (immediately
confirmed in writing) in the event of any circumstances giving rise to a
possible or actual recall of any batches of the Product(s) delivered to
Berna.


 


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


 


6.         Adverse Drug Events


 


Clause 20.2 and 20.5 and Schedule 4 shall be deleted
without replacement. Clause 20.1, 20.3 and 20.4 are changed as follows and will
replace the previous provisions:


 


a)        Under
clause 20.1 CSL and Berna shall keep each other informed on all reports of
Adverse Drug Events (ADE) coming to either party’s knowledge with regard to the
Product(s) regardless of the origin of such reports. The term Reports
shall also include publications in journals and other media. If Berna receives
any ADE report which is both serious and unexpected and alleged to be caused by
the Product(s) Berna will report the matter to the Registration Authority
in compliance with the laws and regulations in the Territory.


 


b)        Under
clause 20.3 Berna will give immediate written notice to CSL of any alleged
manufacturing or other defect in the Products(s) of which Berna becomes
aware and of any possible expense, liability, cost, claim or proceeding arising
from the alleged defect.


 


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


 


Terms used in this letter shall have the same meaning
as defined in the Agreement unless the context requires otherwise. Except as
amended by this letter, the terms of the Agreement remain in full force and
effect.


 


	
  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

  



 


 


 


3

















 


Please confirm Berna’s formal agreement to the above
by 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 Biotech
Ltd 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 Australia

  June.McKay@csl.com.au

  	
   

  	
  Fax: +61 9389
  1076

  



 


4

















 


THIS SUPPLY AGREEMENT is
made 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 the
manufacture and distribution of human and veterinary pharmaceutical and
diagnostic products.


 


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


 


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


 


THE PARTIES AGREE


 


1.        Agreement to Supply


 


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


 


1.2       This
Agreement will oblige CSL to manufacture or (if it is not able to manufacture
by decisions  of the authority
concerned) to deliver the Product(s) as ordered by BERNA and accepted by
CSL.


 


1.3       Nothing
in this Agreement will restrict BERNA’s ability to deal in bulk influenza
vaccine (other than the Product) and Finished Influenza Vaccine formulated with
the Product or other vaccines utilising Virosome technology formulated with the
Product except that BERNA agrees not to sell such vaccines to any third party
where BERNA knows that same may be used within the Excluded Territory.


 


1.4       BERNA
will not use the Product(s) in any way other than as permitted under this
Agreement. In particular, BERNA will use the Product(s) only as a bulk
component in the formulation of Finished Influenza Vaccines and other vaccines
utilising Virosome technology.


 


1.5       Nothing
in this Agreement will restrict CSL’s ability to deal in bulk influenza vaccine
and Finished Influenza Vaccines except that CSL agrees not to sell Finished
Influenza Vaccines to any third party where CSL knows that same may be used
within the Exclusive Territory. BERNA may on or before 30 June 2002
request that the Exclusive Territory be expanded and CSL will notify BERNA of
its agreement or otherwise to such expansion on a country by country basis by
30 September 2002.


 


1.6       Regarding
new influenza products developed by BERNA, BERNA agrees to consider CSL as a
distributing partner for the Excluded Territory.


 


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


 


1

















 


3.        Supply of
Product(s) against Orders


 


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


 


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


 


3.3       Each
order will be for a minimum quantity of 100 gm HA per strain for the 2002
calendar year, 150 gm HA per strain for the 2003 calendar year and for each
subsequent calendar year a scaled up minimum quantity will be agreed between
CSL and Berna based on the agreed European SRID assay.


 


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


 


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


 


3.6       If
CSL delivers Product(s) in excess of BERNA’s firm order, BERNA must advise
CSL in writing of the quantity held in excess as soon as such excess is
determined. BERNA will process the excess quantity and store it for potential
use in the following Northern Hemisphere season. If the excess quantity is able
to be used in the following seasons, BERNA will pay CSL for the excess quantity
at the price applicable at the time of delivery within 30 days of the official
announcement of Northern Hemisphere strain selection. If the excess quantity is
unable to be used in the following season, BERNA will destroy the excess
quantity and notify CSL in writing that the excess quantity has been destroyed.


 


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


 


3.8       An
indicative timing program for ordering and price negotiations is set out in
Schedule 3.


 


4.        Price and Payment


 


4.1       The
Product(s) will be invoiced at the prices set out in Schedule 2. For the
2002 calendar year the price will be based on an amount of A$ [***] per egg
used to manufacture that quantity of product delivered to Berna. For the 2003
calendar year the price will be based on an amount of [***] and for 2004
calendar year the price will be based on an amount of [***]. The  parties will negotiate in good faith a
new price for the 2005 calendar year and the 2006 calendar year prior to 30
April 2004. The parties will take into account any change in CSL’s
manufacturing costs and the general influenza market conditions. If this
agreement is renewed, the


 


2

















 


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


 


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


 


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


 


5.        Packing, Delivery and Risk
in Transit


 


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


 


5.2       [Intentionally
Deleted]


 


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


 


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


 


6.        Quality Control


 


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


 


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


 


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


 


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


 


6.5       BERNA
will store the Product(s) in suitable storage facilities having regard to
both the Specification and Conditions of Registration and in a manner which
ensures proper rotation of stock.


 


6.6       BERNA
will test samples of delivered Product(s) and if it believes a particular
Product(s) (hereinafter referred to as “the Notified Product”) does not
comply with clause 6.1, it will notify CSL advising the batch number. CSL will
examine and test from that batch a sample retained by it (hereinafter referred
to as  “the Batch Sample”). If CSL
finds the Batch Sample does not comply with clause 6.1 then CSL will if
practicable replace the Notified Product in due time and after discussion with
BERNA.


 


3

















 


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


 


7.        BERNA’s and CSL’s Duties
and Obligations


 


7.1       BERNA
will:


 


(a)       only
distribute and sell Finished Influenza Vaccine and other vaccines utilising
Virosome technology containing the Product(s) as agreed under this
Agreement


 


(b)      comply
with all laws, ordinances, regulations, rules and administrative
directions applicable to or governing or controlling the importation of the
Product(s) into, and the sale and use of the Product(s) in, the
Territory


 


(c)       notify
CSL of any reason BERNA has to believe that a particular Product(s) does
not comply with clause 6.1 as soon as possible and preferably within fourteen
days of that reason coming to the attention of BERNA. The notification will
identify the particular Product’s batch number. BERNA will also notify CSL of
any Adverse Drug Events under clause 20.


 


7.2       BERNA
and CSL will ensure that their respective employees, agents and dealers are
acquainted with the obligations imposed by this Agreement to the extent
reasonably necessary to ensure compliance with the Agreement.


 


4

















 


8.        Promotion and Marketing


 


8.1       BERNA
will have the absolute unilateral right to determine its promotion and
marketing activities, and the prices at which it will sell the Finished
Influenza Vaccine containing the Product(s) and to determine payment
arrangements with purchasers of the same. CSL does not desire to participate
and will not participate in any price determinations.


 


9.        Provision of Technical
Information


 


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


 


9.2       BERNA may use any
technical information made available to it pursuant to this clause but only for
the proper discharge of its obligations. BERNA will not use any of the
technical information made available to it for any purpose after this Agreement
ends. For Confidential Material see clause 12.


 


10.      [Intentionally Deleted]


 


11.      Registration Requirements


 


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


 


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


 


12.      Confidentiality


 


12.1     Each
party will:


 


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


 


(b)      not
permit the other party’s Confidential Material to be disclosed other than in
confidence to its employees to the extent strictly necessary for the purposes
of this Agreement;


 


(c)       use
the other party’s Confidential Material only for the purpose of this Agreement
and not to use for any commercial purpose other than under a further agreement
with the other party;


 


(d)      not
copy or reduce to writing the other party’s Confidential Material except as
reasonably necessary for the purposes of this Agreement. Copies or reductions
to writing of Confidential Material of the other party shall be owned by that
party;


 


(e)       maintain
the other party’s Confidential Material in a way which provides adequate
protection from unauthorised disclosure, copying or use;


 


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


 


5

















 


(g)      return
promptly to the other  party all
documents and materials (and all copies thereof) containing the other party’s
Confidential Material at the end of this Agreement.


 


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


 


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


 


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


 


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


 


but excludes information
which the receiving party proves:


 


(d)      is
in or has come into the public domain in any way without it breaching this
Agreement;


 


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


 


(f)       it
has obtained or has available from a source other than the disclosing party
without breach of any obligation of confidentiality or non-use;


 


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


 


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


 


12.3     Either
party may disclose the other party’s Confidential Material in confidence to the
Registration Authority to the extent required to comply with the law and its
obligations under this Agreement.


 


13.      Product Liability


 


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


 


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


 


14.      Term and Termination


 


14.1     This
Agreement will begin on the Commencement Date and remain in effect during the
Initial Period. It will thereafter be renewed for successive two year periods
until terminated.


 


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


 


14.3     The party not
affected may terminate this Agreement by giving to the other party written
notice to terminate on the date specified in the notice if:


 


6
















 


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


 


(b)      if
a party becomes insolvent, is adjudged bankrupt, applies for judicial or
extra-judicial settlement with its creditors, makes an assignment for the
benefit of its creditors, voluntarily files for bankruptcy or has a receiver or
trustee (or the like) in bankruptcy appointed over its business, property or
assets, or becomes the subject of liquidation or dissolution (except for
reconstruction purposes such as mergers, etc) or involuntary bankruptcy
proceedings or otherwise discontinues business;


 


(c)       any
other right of termination in favour of the first party arises under this
Agreement; or


 


(d)      a
change in effective control of the other party.


 


14.4     If
an important parameter changes so materially that the continuation of this
agreement would lead to a material adverse financial effect for a party, that
party may by written notice request a negotiation in good faith to amend the terms
of this Agreement to address the change in that parameter. If the parties are
unable to agree on an appropriate amendment within three months of the date of
the notice, either party may terminate this Agreement by immediate written
notice. Such termination will not affect firm commitments made in connection
with the supply of Product(s) for the upcoming Northern Hemisphere
influenza season.


 


14.5     Termination
will not affect any other rights or obligations which may have accrued prior to
termination.


 


14.6     At
the end of this Agreement BERNA will promptly forward to CSL, at BERNA’s
expense, all technical information relating to this Agreement it received from
CSL BERNA will not keep any copies.


 


15.      General


 


15.1     No
waiver of any provision of this Agreement will be of any force or effect unless
confirmed in writing, signed by the parties. Then such waiver will be effective
only to the extent for which it is made.


 


15.2     The
invalidity or unenforceability of any provision of this Agreement will not
affect the validity and enforceability of all other provisions which are
self-sustaining and capable of separate enforcement.


 


15.3     This
Agreement constitutes the entire agreement and understanding between the
parties with respect to its subject matter. It replaces all previous agreements
between, or undertakings by either of, the parties with respect to its subject
matter.


 


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


 


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


 


15.6     The
laws of Victoria, Australia will govern this Agreement.


 


15.7     Clauses
11, 12,13,14.5 and 17.1 will continue to apply after this Agreement ends.


 


15.8     Neither
party will be liable for any failure or delay in the performance of its
obligations under this Agreement to the extent that such failure or delay
arises from any circumstance beyond its control including any Acts of Nature,
strikes, lock-outs, labour disputes or in the event of an influenza pandemic in
the Excluded Territory. Where such failure or delay continues for a continuous
period exceeding six months, the party not experiencing such failure or delay
may terminate this Agreement


 


7

















 


without penalty by written notice. The parties
acknowledge that manufacturing and formulation of the Product(s) and
Finished Influenza Vaccine is an extremely time sensitive business and
therefore agree to notify each other as early as possible of any failure or
delay under this clause 15.8.


 


15.9     Each
party will bear its own legal costs and expenses of and incidental to the
preparation of this Agreement.


 


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


 


16.      Notices


 


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


 


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


 


(b)      be
sent to the contact address or facsimile number given above (or any other point
previously advised in writing by the recipient), and


 


(c)       be
marked to the attention of a signatory to this Agreement (or any other person
previously advised in writing by the recipient).


 


16.2     No
written notice is to be effective until received, or deemed to be received by the
other party as follows:


 


(a)       in
the case of personal delivery, upon delivery;


 


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


 


(c)       in
the case of a facsimile transmission, on the business day on which it is
despatched, or, if despatched on a non-business day, or after 5 pm on a
business 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 of
the transmission will be evidence of transmission, unless proved to the
contrary.


 


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


 


17.      Arbitration


 


17.1     All
disputes arising under this Agreement will be finally settled under the
Rules of Conciliation and Arbitration of the International Chamber of
Commerce in Zurich, where CSL initiates the action, or in Melbourne, where
BERNA initiates the action, by one or more arbitrators appointed in accordance
with those Rules. All arbitrations will be conducted in the English language.


 


18.      Benefit of Indemnities


 


18.1     For
the avoidance of doubt, it is agreed that where a party agrees to indemnify the
other, the indemnified party will be or be deemed to be acting as agent for and
on behalf of and for the benefit of all persons who are or might be its
directors, officers, employees, consultants or agents from time to time and all
such persons will to this extent be or be deemed to be parties to this
Agreement.


 


19.      Product Recall


 


19.1     BERNA
will inform CSL immediately by telephone or facsimile transmission (immediately
confirmed in writing) in the event of any circumstances giving rise to a
possible or actual recall of any Finished Influenza Vaccine containing the
Product(s). CSL will inform BERNA immediately by telephone or


 


8

















 


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


 


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


 


19.3     Where
a product recall has been initiated whether by the Registration Authority or
other authority in the Territory or by BERNA or CSL under clause 19.2  BERNA will inform all purchasers of the
Product(s) so affected and shall require them to deliver or make available
for collection all such stocks of Finished Influenza Vaccine containing the
defective Product(s) in their possession. BERNA will ensure that all such
stocks of Finished Influenza Vaccine containing the defective Product(s) are
collected and stored in secure conditions on premises controlled by BERNA.


 


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


 


9

















 


20.      Adverse Drug Events


 


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


 


20.2     BERNA
will report to CSL by telephone or facsimile transmission (immediately
confirmed in writing) any other adverse experience occurring in the Territory
and 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 or
other defect in the Product(s) or Finished Influenza Vaccine containing the
Product(s) of which BERNA becomes aware and of any possible expense, liability,
cost, claim or proceedings arising from the alleged defect.


 


20.4     With
respect to any adverse experiences alleged to be caused by, and any alleged
manufacturing or other defects in, the Product (s) or Finished Influenza Vaccine
containing same BERNA will not make any admission of liability to any third
party with respect to claims either in the name of BERNA or on behalf of CSL
without CSL’s prior written consent.


 


20.5     For
the purpose of this clause 20, “serious” and “unexpected” will have the meaning
ascribed to it at the relevant time by the Registration Authority or as
otherwise notified by CSL from time to time.


 


21.      Definitions and
Interpretation


 


21.1     In
this 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 in
writing by CSL;


 


(e)       Exclusive Territory  means the territory set out in Item 1A of
Schedule 1;


 


(f)       Excluded Territory  means  the territory set out in Item IB
of Schedule 1;


 


(g)      Finished Influenza Vaccine  means product that is intended for the
prevention of influenza only and is formulated, filled in final container and
packed;


 


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


 


(i)        ha  means haemaglutinin


 


(i)        Initial Period  means the period set out in Item 2 of
Schedule 1;


 


(i)        Notified Product is  defined
in clause 6;


 


(j)        SRID  means the single radial immunodifusion;


 


10

















 


(k)       Territory  means  the
territory set out in Item IA of Schedule 1;


 


(l)        Product  means  the
product set out in Schedule 2;


 


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


 


(n)      Specification  means the Product Specification set out
in Schedule 2; and


 


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


 


21.2.    In this Agreement:


 


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


 


(b)      Words
denoting any gender include all genders;


 


(c)       References
to persons include bodies corporate and vice versa;


 


(d)      Words
defined in another part of this Agreement will have the meaning given in that
part;


 


(e)       References
to Recitals, clauses, sub-clauses, Schedules and Annexures are references to
Recitals, clauses, sub-clauses, Schedules and Annexures of or to this
Agreement;


 


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


 


(g)      Headings
are 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

  



 


11

















 


SIGNED
as 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

  	
   

  



 


 


 


12

















 


SCHEDULE 1

to 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.

  



 


13

















 


SCHEDULE 2

to the Supply Agreement between CSL and BERNA


 


Product(s), Prices
and 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 yield
could be greater or lower than ± 10%.


 


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


 


The quantity of Product(s) delivered
will be determined pursuant to the accepted SRID assay method using the agreed
SRID 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 variance
in 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 good
faith a resolution. If CSL and BERNA are unable to resolve the discrepancy,
then an independent testing agency tests the material. The accepted result will
be the average of the two closest results. The cost of the independent testing
agency 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 EuPharm
monography on influenza vaccines and Product testing requirements shall be sent
by BERNA to CSL or CSL to BERNA as soon as possible.


 


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


 


14

















 


SCHEDULE 3

to the Supply Agreement between CSL and BERNA


 


Timing of
Forecasts, 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

  



 


15

















 


SCHEDULE 4

to 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 correspond
basically to the European Union Directive (EU) 93/39 and the corresponding
regulations of each country of the Territories brought to knowledge of the
BERNA. The ADE shall preferably be forwarded using the format of the COMS-formulary.


 


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


 


3.         Reports
on such ADEs which according to the informing party’s careful professional
evaluation may negatively affect the benefit-risk-ratio of the Product or may
have consequences regarding the Product’s Information (eg. labelling, data
sheets, package inserts) or may require immediate safety measures or regulatory
authorities (such as special information/warnings to the medical profession,
patients, authorities or withdrawal of the Product) shall be forwarded to the other
party without delay after having become known.


 


4.         The
same immediate forwarding, without delay shall apply in cases of reports on
ADEs being both serious and unexpected (ie. hitherto not specified in the
Product’s Information).


 


5.         The
informing party is invited to give both the primary reporter’s and its own
professional evaluation of such reports, in particular with regard to suspected
causality, with reasoning, either together with such information or at a later
date.


 


Categories for determining relationship of ADE to the
Product:


 


•  Certain


 


•  Probable


 


•  Possible


 


•  Unlikely


 


•  Unrelated


 


•  Insufficient Evidence


 


6.         The
aforementioned 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 provided
by either party.


 


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


 


8.         All
reports to be provided hereunder shall be in English, using the MeDRA adverse
reaction terminology.


 


16