EX-10 3 form8k_exh10-1dec2001.txt EXH 10.1 1ST ADDENDUM TO SUPPLY AGMT DTD 1_25_95 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 11 Floor, Aubin House 171 Gloucester Road Wanchai, Hong Kong Hereinafter referred to as Hovione, duly represented by its Chief Executive, Guy Villax, and CollaGenex, Inc. 41 University Drive, Suite 200 Newton, PA 18940 USA Hereinafter referred to as CollaGenex, duly represented by Vice President Robert A. Ashley 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/ Robert A. Ashley Name: /s/ Guy Villax --------------------------- ----------------------------- 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 11 Floor, Aubin House 171 Gloucester Road Wanchai, Hong Kong Hereinafter referred to as Hovione, duly represented by its Chief Executive, Guy Villax, and CollaGenex, Inc. 41 University Drive, Suite 200 Newton, PA 18940 USA Hereinafter referred to as CollaGenex, duly represented by Vice President Robert A. Ashley 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: Robert A. Ashley Name: /s/ Guy Villax ---------------------------- ---------------------------- 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 11 Floor, Aubin House 171 Gloucester Road Wanchai, Hong Kong Hereinafter referred to as Hovione, duly represented by its Chief Executive, Guy Villax, and CollaGenex, Inc. 41 University Drive, Suite 200 Newton, PA 18940 USA Hereinafter referred to as CollaGenex, duly represented by Vice President Robert A. Ashley 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/ Robert A. Ashley Name: /s/ Guy Villax ---------------------------- --------------------------- Title: Vice President Title: C.E.O. Date: December 10, 2001 Date: 9 Nov 2001 ---------------------------- --------------------------- ---------------------------------------------------- QUALITY CONTROL ---------------------------------------------------- Prepared By Check By Xiao Jun Ng Wang Chon (GRAPHIC OMITTED) ---------------------------------------------------- Approved By Effective Date Claudia Ferreira 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 -------------------------------------------------------------------------------- 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 Wang Chon (GRAPHIC OMITTED) ---------------------------------------------------- Approved By Effective Date Claudia Ferreira 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 Karl Fischer) 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 Wang Chon ---------------------------------------------------- Approved By Effective Date Claudia Ferreira 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 Karl Fischer) 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 Page: 1/1