EXHIBIT 10.1
Confidential Materials omitted and filed separately with the Securities and
Exchange Commission. Asterisks denote omissions.
1ST ADDENDUM TO THE SUPPLY AGREEMENT
(GRAPHIC OMITTED) DATED 25TH JANUARY, 1995 - HOVIONE/COLLAGENEX
1ST ADDENDUM TO THE SUPPLY AGREEMENT
DATED 25TH JANUARY, 1995
between
Hovione International Limited
00 Xxxxx, Xxxxx Xxxxx
000 Xxxxxxxxxx Xxxx
Xxxxxxx, Xxxx Xxxx
Hereinafter referred to as Hovione, duly represented by its Chief Executive, Xxx
Xxxxxx, and
CollaGenex, Inc.
00 Xxxxxxxxxx Xxxxx, Xxxxx 000
Xxxxxx, XX 00000
XXX
Hereinafter referred to as CollaGenex, duly represented by Vice President Xxxxxx
X. Xxxxxx
Recitals
--------
Whereas the original supply agreement was entered into on 25th January 1995, and
was subsequently extended through 25th January 2002 by CollaGenex's letter dated
24th April 1996.
Whereas Parties are satisfied with their business under this contract and wish
to extend the life of the contract, adjust prices and to update Annex 1 (The
Territory) and Annex 2 (The Specifications)
Now therefore, the parties agree to both reconfirm the existing agreement and to
amend it as follows:
1. Definitions - one annex is substituted
-----------------------------------------------
1.2. The Territory: as defined in Annex 1
2. Quality of the Product - one annex is substituted and one clause amended
--------------------------------------------------------------------------------
2.1 The Quality of the product will conform both to reference samples sent
by Hovione to CollaGenex, to the most recent monograph of the United
States Pharmacopeia and of the European Pharmacopeia and to the
specifications in Annex 2. The Product will be manufactured, packaged
and stored in accordance with the current Good Manufacturing Practices
of the Food and Drug Administration (USA) and of the European Union,
in an inspected and ISO9000 certified facility and in strict
compliance with Hovione's Drug Master Files.
4. Price and payments - two new clauses are added:
4.3 Parties agree that the price of the product set previously at $[**]/kg
is revised to $[**]/kg as from 1st January 2000 (fax n(0)SO000056 dated
of 20th January 2000).
1ST ADDENDUM TO THE SUPPLY AGREEMENT
(GRAPHIC OMITTED) DATED 25TH JANUARY, 1995 - HOVIONE/COLLAGENEX
4.4 For all sales that occur after the 25th January 2002, and during the
validity of this Agreement, the price of the Product shall depend on the
total quantity bought within the calendar year:
---------------------------------------- ---------------------
THE PO PLACED IN ANY CALENDAR THEN THE PRICE
YEAR CORRESPONDS TO A PER KILO FOR
SHIPMENT(S) THAT IS (ARE) WITHIN: THAT PO IS:
---------------------------------------- ---------------------
The first [**]kg that year USD[**]/kg
---------------------------------------- ---------------------
The second [**]kg that year USD[**]/kg
---------------------------------------- ---------------------
The third [**]kg that year USD[**]/kg
---------------------------------------- ---------------------
For the additional quantities that
make the total for that year greater
than [**]kg USD[**]/kg
---------------------------------------- ---------------------
The prices are CIF Air any continental USA airport.
11. Duration - one clause is amended
11.1 This agreement commenced on the 25th January 1995, and on 15th May 2001
was extended for a period of 5 years to expire on 14th May 2006. On
expiry this agreement shall be automatically renewed for successive
periods of two (2) years unless either party gives the other party
written notice of termination ninety (90) days prior to the expiration
of the commercial term.
All the other terms of the Supply Agreement remain unchanged.
Accepted:
CollaGenex, Inc. Hovione International Limited
Name: /s/ Xxxxxx X. Xxxxxx Name: /s/ Xxx Xxxxxx
--------------------------- -----------------------------
Title: Vice President Title: C.E.O.
Date: December 10, 2001 Date: 9 Nov 2001
--------------------------- -----------------------------
1ST ADDENDUM TO THE SUPPLY AGREEMENT
(GRAPHIC OMITTED) DATED 25TH JANUARY, 1995 - HOVIONE/COLLAGENEX
ANNEX 1 TO THE
SUPPLY AGREEMENT
DATED 25TH JANUARY, 1995
between
Hovione International Limited
00 Xxxxx, Xxxxx Xxxxx
000 Xxxxxxxxxx Xxxx
Xxxxxxx, Xxxx Xxxx
Hereinafter referred to as Hovione, duly represented by its Chief Executive, Xxx
Xxxxxx, and
CollaGenex, Inc.
00 Xxxxxxxxxx Xxxxx, Xxxxx 000
Xxxxxx, XX 00000
XXX
Hereinafter referred to as CollaGenex, duly represented by Vice President Xxxxxx
X. Xxxxxx
The Territory:
U.S.A.
European Union
(to include: Austria, Belgium, Denmark, Finland, France, Germany,
Greece, Ireland, Italy, Luxembourg, Netherlands, Norway, Portugal,
Spain, Sweden, United Kingdom).
Accepted:
CollaGenex, Inc. Hovione International Limited
Name: Xxxxxx X. Xxxxxx Name: /s/ Xxx Xxxxxx
---------------------------- ----------------------------
Title: Vice President Title: C.E.O.
Date: December 10, 2001 Date: 9 Nov 2001
---------------------------- ----------------------------
1ST ADDENDUM TO THE SUPPLY AGREEMENT
[GRAPHIC OMITTED] DATED 25TH JANUARY, 1995 - HOVIONE/COLLAGENEX
ANNEX 2 TO THE
SUPPLY AGREEMENT
DATED 25TH JANUARY, 1995
between
Hovione International Limited
00 Xxxxx, Xxxxx Xxxxx
000 Xxxxxxxxxx Xxxx
Xxxxxxx, Xxxx Xxxx
Hereinafter referred to as Hovione, duly represented by its Chief Executive, Xxx
Xxxxxx, and
CollaGenex, Inc.
00 Xxxxxxxxxx Xxxxx, Xxxxx 000
Xxxxxx, XX 00000
XXX
Hereinafter referred to as CollaGenex, duly represented by Vice President Xxxxxx
X. Xxxxxx
The Specifications of the product are found in the Hovione PharmaScience Limited
(formerly Hovione Macau Sociedade Quimica Limitada) Quality Control test methods
and specification sheets - herewith attached:
Product Code: 5/MA51U/E
Effective date: 2001.11.19
Revision: 01
Accepted:
CollaGenex, Inc. Hovione International Limited
Name: /s/ Xxxxxx X. Xxxxxx Name: /s/ Xxx Xxxxxx
---------------------------- ---------------------------
Title: Vice President Title: C.E.O.
Date: December 10, 2001 Date: 9 Nov 2001
---------------------------- ---------------------------
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QUALITY CONTROL
----------------------------------------------------
Prepared By Check By
Xiao Jun Ng Xxxx Xxxx
(GRAPHIC OMITTED) ----------------------------------------------------
Approved By Effective Date
Xxxxxxx Xxxxxxxx 2001.11.19
--------------------------------------------------------------------------------
PRODUCT NAME CODE No.
Doxycycline Hyclate 5/MA51U/E
--------------------------------------------------------------------------------
OTHER NAME PRODUCT GROUP
FINISHED PRODUCTS
--------------------------------------------------------------------------------
STRUCTURE FORMULA
C22H24N2O8.CH5ClO
------------------------------
(GRAPHIC OMITTED) MOLECULAR WEIGHT
512.94
------------------------------
VALIDITY
60 months
------------------------------
Revision: 01 Page: 1/2
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TEST Specification
Description Yellow to light yellow powder.
Crystallinity The product is crystalline.
Solubilities Freely soluble in water and in methanol;
sparingly soluble in alcohol; practically
insoluble in chloroform and in ether. It
dissolves in aqueous solutions of alkali
hydroxides and carbonates.
Identification (by TLC) In the chromatogram obtained with the
sample solution, the principal spot should
have the same Rf, colour and size as the
principal spot in the chromatogram
obtained with the reference solution.
Identification (by reaction with
sulphuric acid) A yellow colour develops in sulphuric acid.
Identification (of chlorides) It gives reaction A of chlorides.
Identification (by IR) Conforms to the spectrum of the United
States Pharmacopeia Reference Standard.
Ultraviolet absorption Not less than 300 and not more than 335 at
the maximum at about 349 nm (in methanol 1%
1M HCl), calculated with reference to the
anhydrous and ethanol-free substance.
Light absorbing impurities Not more than 0.07 at 490 nm (in methanol
1% 1M HCl), calculated with reference to
the anhydrous and ethanol-free substance.
Specific optical rotation Not less than -120(Degree) and not more
than -105(Degree) (c=1, in methanol 1% 1M
HCl), t=25 (Degree) C and 589.3 nm),
calculated with reference to the anhydrous
and ethanol-free substance.
pH Not less than 2.0 and not more than 3.0 (1%
w/v solution in water).
Sulphated ash Not more than 0.4% w/w.
Heavy metals Not more than 50 ppm.
-------------------------------------
STORAGE CONDITIONS: Well-closed and light resistant containers: below 27
(Degree)c and 65% RH
----------------------------------------------------
QUALITY CONTROL
----------------------------------------------------
Prepared By Check By
Xiao Jun Ng Xxxx Xxxx
(GRAPHIC OMITTED) ----------------------------------------------------
Approved By Effective Date
Xxxxxxx Xxxxxxxx 2001.11.19
--------------------------------------------------------------------------------
PRODUCT NAME CODE No.
Doxycycline Hyclate 5/MA51U/E
--------------------------------------------------------------------------------
OTHER NAME PRODUCT GROUP
FINISHED PRODUCTS
--------------------------------------------------------------------------------
STRUCTURE FORMULA
C22H24N2O8.CH5ClO
------------------------------
(GRAPHIC OMITTED) MOLECULAR WEIGHT
512.94
------------------------------
VALIDITY
60 months
------------------------------
Revision: 01 Page: 2/2
--------------------------------------------------------------------------------
Water (by Xxxx Xxxxxxx) Not less than 1.40% w/w and not more
than 2.75% w/w.
Content of ethanol (by GC) Not less than 4.3% w/w and not more
than 6.0% w/w.
Related substances 6-epidoxycycline Not more than 0.8% w/w.
Methacycline Not more than 0.3% w/w.
Other impurities Not more than 0.2% w/w, individually.
Total impurities Not more than 1.3% w/w.
Assay (by HPLC) Not less than 849ug/mg and not more
than 884 ug/mg, expressed as
doxycycline.
Not less than 90.0% w/w and not more
than 94.0% w/w as doxycycline,
calculated with reference to the
anhydrous and ethanol-free substance.
INFORMATION TESTS
Particle Size Not less than 10% below 12 um.
Not less than 50% and not more than
90% below 100 um.
Not less than 90% below 250 um.
Bulk density: before compacting Not less than 0.5 g/cm3.
after compacting Not less than 0.7 g/cm3.
Residual solvents Methanol Not more than 2000ppm.
(by GC):
Acetone Not more than 500ppm.
-------------------------------------------
STORAGE CONDITIONS: Well-closed and light resistant containers: below 27
(Degree)c and 65% RH.
----------------------------------------------------
QUALITY CONTROL
----------------------------------------------------
Prepared By Check By
(GRAPHIC OMITTED) Xiao Jun Ng Xxxx Xxxx
----------------------------------------------------
Approved By Effective Date
Xxxxxxx Xxxxxxxx 2001.11.19
--------------------------------------------------------------------------------
PRODUCT NAME CODE No.
Doxycycline Hyclate 5/MA51U/E
--------------------------------------------------------------------------------
TEST METHODS
Description LAB004A/GT013
Crystallinity CFR, 436.203 (a)
Solubilities LAB004A/GT030
Identification (by TLC) EP, Monograph
Identification (by reaction with sulphuric acid) EP, Monograph
Identification (of chlorides) EP, Monograph
Identification (by IR) USP, Monograph
Ultraviolet absorption EP, Monograph
Light absorbing impurities EP, Monograph
Specific optical rotation EP, Monograph
pH EP, Monograph
Sulphated ash EP, Monograph
Heavy metals EP, Monograph
Water (by Xxxx Xxxxxxx) EP, Monograph
Content of ethanol (by GC) EP, Monograph
Related substances (by HPLC) EP, Monograph
EP, Monograph
EP, Monograph
Assay (by HPLC) USP, Monograph
EP, Monograph
INFORMATION TESTS
Particle Size LAB004A/GT067
LAB004A/GT067
LAB004A/GT067
Bulk density LAB004A/GT012
LAB004A/GT012
Residual solvents (by GC) LAB004C/CR066
LAB004C/CR066
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