Dissolution Apparatus 1 and 2 Performance Qualification Protocol Dissolution Apparatus Serial Number,_ 1-4 394-1297 PIN 70-8900 Revision J ‘August 2010 Pa ‘This dot fs Copyright protected. therefore reproduction Is prohibited. aS ‘hie uaeaion proteome oo ons ope one ot pret neato VARIANDissotuton Apparatus Performance Qualification Protocol Varian, nc. ~ Serving Industries Worldwide Biosciences, Pharmaceuticals Clinical Research and Forensics Food and Agricuiture (Chemical Analysis Environmental Fucls and Energy Material Sciences Contact Details Varian, ine, 113000 Weston Parkway Cary, North Carolina 27613-2250 (800.229.1108 919.677.1108 Fax: 919.677.1138 Varian, Inc. Web Site ‘wow. varianine.com ata, nis the owner of copyright en this docunen and any associated sofware. Under ‘aw, the writen permission of Varian, Inc. must be ablainad betore the dacumentaion or software is copied, reproduced, lranslated or converted to electronic ov othr machines Feadable form in whole, orn pat. First published August 2010. Varian and the Varian logo are trademarks orregistared trademarks of Varian In. inthe US. ‘and other countries. (© 2010 Varian Ine The following terms are trademarks of Varian, nc. + Benchsavor™ + Rand aani™™ + BIO-DIS II? + TruAlign™ + Enhancer Cet? + TruCenier™ + Full Flow Fiters™ + Vanker® + Peak Vessel™ VK * Practical Solutions® Allother trademarks are the properly oftheir respective owners. “This documents copyright potted terete reproduction i prohibited > ‘This uaifeaton protocol is iva the log onthe pape dost nat spat in ler aN RI Page 20158 Pn 70800, Reson J. Aust 2010 VAIDissolution Apparatus Performance Qualification Protocol a mS VARIAN 72 Revision History. Protocol Approval. Protocol Acceptance User License Agreement 9 Qualification Representative and Reviewer Details... Qualification Representative Details Reviewer Detai Abbreviations. a Protocol Abbreviations. 8 General Abbreviations 13 Qualification Guidelines. 15 ‘Qualification Summary 15 Qualification Guidelines 15 Page Numbering of Appendices 16 Exception Reports 7 Performance Qualification USP Dissolution PVT Setup 19 7AA Procedure Objective 19 74.2 Procedure Overview 19 7.1.3. Materials Needed 20 7.44 Site information 20 7.1.5. Apparatus Identification and Configuration a 7.6 Accessory Identification 23 7A.7 Calibrated Test Equipment Required 23 7.4.8 Chemicals Required 27 7.1.9 Test Procedure Selection a 7.1.10 Protocol Deviations 29 USP PVT - Prednisone Procedure 30 7.2.1 Prednisone Medium Preparation 30 7.22 Prednisone Standard Preparation a” 7.23. Filler Validation - Prednisone 32 7.24 System Setup and Operation - Prednisone 34 7.25 Analysis Procedure - Prednisone 39 “This document i copyright protected, therefore reproduction is prohibited ‘This quatiteation protocols invaté if the logo on this page does not appear in coer. ‘PIN 704000, Revision J Avgust 2010, Page 30156Dissolution Apparatus Performance Qualification Protocol ‘This documents copyright protected, therefore reproduction fe prohibited. ‘This qualiteationprotocel is lnvalld if the logo on this page doesnot appear in color. Page 4056 73 74 Result Interpretation 7.3.1. Single Stage Test (Prednisone) 7.32 Optional Two-Stage Test (Prednisone) Final Evalustion Qualification Acceptance. Appendices. an S 2 2 > 2 Pn 70.6000, Revision J August 2010 VAIDissolution Apparatus Performance Qualifation Protocol Revision History a b mS VARIAN ‘This qualification protocol is updated as necessary, which includes the event of any regulatory changes to Title 21 of the Code of Federal Regulations (21 CFR) Parts 11, 210 and 211 (if applicable), any software or hardware changes, or ‘updates that may impact regulatory compliance. Revision | Date Comments A 10100 ‘Newly created Performance Qualification Guide to be Used only by a qualified VanKel chemist for all manial dissolution testers Editorial and technical changes twoughaul Adapted ‘document for use asthe standard Performance Qualification Guide for essolution testrs ‘Add serial number boxes for vessels, paddle shafs, basket shafts end baskets. Added note box indicating a linearity testis necessary ithe absorbance reading is iteater than 1.5 AU. ° ows Minor format changes to template, Editorial and technical changes throughout, Reforma to new sive: remove VanKel logo and name, ‘Changed statement regarding drying of standard Corrected calculations. Added information for Salicylic ‘Acid Lot P to Saliyic Acid Medium Preparation and Saliofic Acd Data Sheet. Added Socium Hysroxise to ‘Chemical Required table ‘Added stalement to use leading standard value, Changed ‘example caleulation formula to use leading standard value. Removed ‘Non-confermance Checkl” section (willbe availabe in separate stand-alone document). ‘Added information about PIN 70-6915 “Apparatus 1 ‘Apparatus 2 PQ Addendum Guide’. Added Appendix B, “Attachments” 4 omo ‘Revised tempiate. Added option to perform single sage ‘or optional two-stage PVT with Prechisone, 4 osito ‘Removed Salicic Acid test procedure. Removed feferences to "Tradiiona" PVT (Prednisone Lot 'POE203), Added items ta conform to USP Cerificate for Prednisone Lot P11300, Minor text edits. ‘This documents copyright protected therefore reproduction i prohibited. This qualiteation protocols invaldif the logo on this page does not appear incor. Pv 70.4000, Revision J, Avgust 2010 Page sot 58DDissoluton Apparatus Performance Quailiation Protocal This page was intentionally left blank, except for this message. ‘This documents copyright protected, therfore reproduction le prohibited. ‘This quatiteation protocols Invalid it the logo on this page does net sppear in coor Popa 6ot55 PN 70-6000, Revision J August 2010_Dissolution Apparatus Performance Qualification Protocol 2. Protocol Approval ‘Varian has prepared this qualification protocol and it has been approved for Publishing by the following representatives: Prepared by Name (pint) Fisctae “Yc ie, Valipynos CHE nist a ot ZA, pe. tf. lic Approved by Name (print) “Dan Seisae Title Naumann Sore enisor, Signature DSS Date Oe ADE 10 a > ‘Ta documents copyright rotate, tesoreeproducton rch aS hie quacaton protocol svat Whe logo oni pape dons not eppenr in ear VARIAN PN 70.6000, Rovisen J August 2010 Page 7056This page was intentionally left blank, except for this message. “This qualitation protocol i invalid the logo on this page does ot appear In coor. Pape sot 6 IN 70-8000, Revision J, Aust 2010 ye < > as > x Ar_Dissoluion Apparatus Performance Qualification Protocol Protocol Acceptance 34 a, & Bd VARIAN User License Agreement ‘By choosing to use the Protocol alter reading this User License Agreement, you indicate acceptance of these terms. If you do nat accept the terms ofthe User License Agreement promplly return the Protocol fora refund, This Protocol and the medium on which itis contained (the Licensed Manual’) are licensed to you, the end user for your own use, You do not obtain title to the Licensed Manual or any copyrights or proprietary rights in the Licensed ‘Manual. You may not transfer, sub-license, rent, lease, convey, copy, modity, translate or in any way alter the Licensed Manual for any purpose without the approval of Varian, Inc The ‘Licensed Manuals provided ‘as is’ All warranties and representations of ‘any kind with regard to the Licensed Manual are hereby disclaimed, including the implied warranties of merchantablity and fitness for a particular purpose, Under no circumstances will the manufacturer or developer of the Licensed ‘Manual be liable for any consequential, incidental, special or exemplary damages even if apprised of the likelinood of such damages occurring, Some States do not allow the limitation of exclusion of lability for incidental or Consequential damages, so the above imitation or exclusion may not apply to you. Varian, inc. declares that the instrument shall be properly qualified as of the date on which successful testing was performed in accordance with the procedures outined in this protocol. Varian, Inc. shall not be responsible for loss of qualification that may occur thereafter. Itis the user's responsibilty to verity that this qualification document is, ‘consistent and compliant with their internal policies, The signature below verifies agreement, Accepted by Name (Print) Signature Tite Organization Organization Address “This documents copyigh protected, therefore reproduction is prohibited ‘Tis ualieaton protocols vai the ogo on thls page does not appear olor PIN 70.6000, Revision J, August 2010 Poze a 8Dissolution Apparatus Performance Qualification Protocol This page was intentionally left blank, except for this message. This document is copyright protected, therefore reproduction ie prohibited, This quaication protocols invalid fhe logo on this page doesnot appear In ctor. Pope toot Pv 70.6000, Revision J, Avgust 2010, @ ave = 5° 5 A z4. Qualification Representative and Reviewer Details 441 Qualification Representative Details Each person responsible for executing any part of this Protocol must complete the table below, providing a sample oftheir signature and initials, and recording the date the Qualification was performed. uaiication representatives are nominated to execute and verify the Completeness of the test protocol and correctness of all entves, All testing must be performed in accordance with procedures outlined in this ‘manual. The representative must be trained and qualified to perform the procedures outlined in this document, ‘A copy oftheir appropriate qualifications may be inserted into Appendix A: Attachments Name (Pan) Pala frosla Ayue Tile lee Qamica Signature a eee nals ea Date Iz] se (eoie [name ent ula "Tia: Nia : : Signature ae i via via - a & aS VARIAN PIN 704000, Rovson J, August 2010 Pape 1156This documents copyright protected therefore reproduction le prohibited. ‘This qualifeation protocols invalid the logo on this page doesnot appear in coor. Papo 12156 Reviewer Details Each representative responsible for reviewing any part ofthis protocol must ‘record their details in the following tables, providing a sample oftheir signature ‘and initials, and recording the date the qualification was performed. ‘An employee or designee of the company that owns the instrument must ‘review these qualification procedures, Al calculations and data will be ‘checked by the reviewer, Data review must be performed in accordance with the qualification guidelines (see Section 6) and in compliance with current ‘Good Manufacturing Practice (CGMP) as specified by 21 CFR Parts 210 and 2m ‘Documentation supporting training in the area of data review and cGMP must be carefully maintained and reviewed by the instrument owner. Reviewer representatives are responsible for reviewing the completeness of the qualification protocol and accuracy ofall entries Name Pin) WEAGSa Rdacio Nitledg, Tile Quinic formacohvs, Signature Coneader = Intals an _ Date GATOR G0 ae ‘Name (Print) wR Title RIA Signature NIA Initiats NIA | Date KIA zm ave = iv > A 2 Pv 70.5800, Revision J August 2010, VA5. Abbreviations ‘The following abbreviations are used throughout this qualification protocol 5.1 Protocol Abbreviations ‘AlQ: Analytical Instrument Qualification CV: Coofficient of Variation DM: Dosage Delivery Module GM: Geometric Mean PVT: Performance Verification Test RS: Reference Standard USP: United States Pharmacoposlia 5.2 General Abbreviations CCE: Conformité Européenne’ (European Conformity) CFR: Code of Federal Regulations NIA: Not applicable NNT: Not More Than No: Number a +), ‘i mnt ih pn tn ri mS ‘it quate ants eattnctge sham epee crane VARIAN PN 70.6500, Roision J August 2010, Poge 13.056Dissolution Apparatus Performance Qualiiation Protocol This page was intentionally lef blank, except for this message. ‘This document copyright protectod, therefore reproduction is prohibited, “This qualification protocal is invalid the logo on this page does no apnea color Page 140158 PI 70.6600, Revision J August 2010, @ ave 2 ar >” zDissolution Apparatus Performance Qualification Protocol 6. Qualification Guidelines 6.1 Qualification Summary Atthe end of qualification execution, all tables and data entry fields must be ‘completed and ail test results, where specified, must be printed and attached to the protocol ‘The Qualification Representative and the Reviewer must sign (signature or initials) and date each page that has a signature field. This represents ‘agreement and acceptance ofall data and information on the signed page. Varian does not provide instructions for ful qualification of the personal ‘computer (PC) used to operate the Varian instrumentation, If further qualification of the PC is required the end-user must contact the PC manufacturer. Varian does not provide fll qualification instructions for non-Varian ‘manufactured accessories. Limited instructions may be supplied. If qualification of a non-Varian accessory is required, the end user must contact the accessory manufacturer. 6.2 Qualification Guidelines ay The following are general guidelines for performing the qualification tests in ‘accordance with cGMP for the Manufacturing, Processing, Packaging, or Holding of Drugs per 21 CFR Parts 210 and 211. Additional local requirements may also apply. ‘+ Read the guidelines before starting the qualification, + Perform all tests exactly as writen ‘Use a pen with permanent blue or black ink unless otherwise specified by ‘company policy. * Neatly stke out any incorrect words or numbers, made while writing ‘comments or recording results, information or data within this protocol, with a single line. The word(s) crossed out must remain legible. Write the correction as close as possible tothe original entry. Write a brief description Of the error. For example, write "Transcription error’ or ‘Re-written for clarity’. initial and date the change. ‘+ Entering initials where a signature is requested, and vice versa is permitled. The exception to this is in Section 4, where examples of each person's signature and initials are required, “This document I copyright protected, therefore reproduction Is prohibited. ae ‘his uailenton protcl tei og on hs page en not appar near. VARI AN PIN 706000, Revision J, Avg 2010 Page 15.056‘+ The preferred date format is dd mon yy (e.g. 05 Jan 08), Altemate formats are acceptable, especially if specified by company policy. * Complete all tables and data fields to comply with this protocol. Blank fields : {are not permitted. For items that are not applicable, draw a line through the field, and write 'N/A' (Not Applicable). If entire tables or sections of tables ‘are not applicable, strike a line ether through the entire table or the specific ‘area and enter ‘N/A. Complete the signature fields on the page. ‘Write ‘Pass’, ‘Fai or N/A’ as applicable tothe test requirement or outcome. * Ensure that results andor specific documents are printed and attached to the specified appendix. ‘+ The Qualification Representative and Reviewer must both sign (signature oF initials) and date the signature field on each page. This represents ‘agreement and acceptance of all data and information on the page. 6.3 Page Numbering of Appendices Each page that is inserted after the appendix is numbered withthe letter of the ‘appendix and a sequential number. The appendix page number must be intialed and dated by both the Quaiication Representative and the Reviewer. For example, pages inserted after Appendix A are numbered A-1, A-2, ‘A;3...et¢ along withthe initials and date. lt the reverse of each appendix page is left blank it should be marked 'N/A’ and signed and dated When the PQ is complete the total number of pages inserted after each ‘appendix is written on the front page of the respective appendix sheet ay ~ ‘ect eh ci ar rpreteton pate. + ‘hs aatcnon protest ag nt oer apps cl as ae tae Pn eo, Ret. Ait 210 VARIAN6.4 a *, mS VARIAN Dissolution Apparatus Performance Qualification Protocol Exception Reports ‘An exception to the protocol occurs when the observed result differs from the acceptance criteria or expected result All exceptions to the protocol must be documented in the Exception Report The Exception Report includes a detailed description ofthe exception and resolution by the Qualification Representative Each Exception Report shall be issued with a unique identification number in the form of ERID-XX-X. This number is generated by the page number on Which the exception occurred followed by a sequential number indicating each ‘exception found on the page. For example, if an exception occurs on page 34, it shall be identified as Exception Report ‘ERID-34-1'. If another exception occurs on page 34, the ‘second exception shall be identified as ‘ERID-34-2’. This identification number ‘should be recorded in the ‘Pass / Fail / NA’ field after each test. Each Exception Report must be signed by the Qualification Representative ‘and the Reviewer as evidence of approval ‘The Exception Report is inserted in the appropriately named appendix and ‘humerated as per 6.3 of this protocol. ‘This documents copyright protected, therafore reproduction Is prohibited ‘This qualiteationprotocl ls Invalid fe logo on tis page does not appear in cole. [PIN 70.6000, Revcon J, August 2010 Page 17 of 58Dissoluton Apparatus Perfomance Qualification Protocol This page was intentionally of blank, except for this message. ab ‘rt douman copy prota, ttre rpeducon pron the ‘hs quinoprotein ite og on epg sat eos Incl, mS on tats 70400 Ren J Apt 2010 VARIANDissolution Apparatus Performance Qualification Protocol Performance Qualification Procedure Objective ‘The Performance Qualifcation (PQ) procedure is intended to assist in ensuring that your dissolution apparatus performs in accordance with current USP requirements. The following USP Dissolution Performance Verification Tests are performed as outlined in the current USP General Chapters, Dissolution <711> and Drug Release <724> in accordance with current Good Manufacturing Practices, For a complete understanding of how to use the apparatus, use this PQ protocol in conjunction with the Operator's Manual or any other operating instructions supplied with the instrument. Procedure Overview ‘The USP Dissolution PVT is a standardized test protocol provided by the United States Pharmacopoeia to assure that the dissolution apparatus functions to an acceptable level for USP Apparatus 1 (Baskel) and 2 (Paddle) {1 the instrument is dedicated for use with only one apparatus (basket or paddle), then testing of only that apparatus is required. The recommended {frequency of the PQ procedure is every six months, Qualification Representative: __P. A pate__t2} sep hors Dat “This document is copyright protected, thrafore reproditin le prohibited ‘This qualiaton protocols Invalid the ogo on this page does not appear in clos, PN 70.6800, Revision J, August 2010 Page 19.056Dissolution Apparatus Performance Qualiation Protocol 7.1. Materials Needed ‘The following Is alist of addtional miscellaneous supplies that may be necessary to complete the Performance Qualification, + Cannula extenders (for use Pipette bulb with optional autosampler) « Pipettes (Class A), various sizes + Cannula fiters + Sampling syringes + Cannulas + Silica get + Cuvettes + Small beakers + Desiccator + Spatulas, + Drying trays + TD volumetric flasks, 500 mL, or + Filter for degassing, Class A 500 mL graduated cylinder 0.45 yim or loss * Volumetric flasks (Class A), various + Filtering apparatus sizes + Kimwipes: + Weigh boats / papers TAA Site Information ‘Complete the folowing table to record all applicable information for the instalation ste CompanyName | Laboradanos Pinein SAS Address Camera 44 No 4q-32 Department Medellin — Antioquia Location foarrol de Cahdad Contact wa Ada Palaco ‘Qualincation Representative: BA Date__\el sep |zo16 Reviewer: Date ab ‘hie document cop pretend, hrfore reproduction le prehited > "Wis aiicatonpretocel einai he log ont page doe et appar nel aS Pace 20088, PI 706500, Reveon J. nut 040 VARIANDissolution Apparatus Performance Quelification Protocol 715 Apparatus Identification and Configuration Complete the folowing tables to record all applicable information forthe apparatus being qualified: ec Dissolution | Mode! Number VERIO ‘Apraratts | serel Number 4-439 - 1249 tdenttcation Number Device Configuration rent? | NA Baskets Y_ [= USP apparatus Petes i= om s = Dissolution apparatus ‘AwtoTemp a options features Me 7 la ‘Qualico Represeniave: __b- & pate:_ietsep leo Reviower: Date: +. a < This document is copyright protected, therefore reproduction is prohibited. 7 ‘This qualification protocol is invalid ifthe logo on this page does not appear in coor VARIAN ‘PIN 70.6900, Revision J, August 2010 Page 21 of 58automated equipment is used to perform the qualification, complete the following table, Manufacturer —_ | ‘Mode! Number = ‘Autosampler emer Te ofel Nvibor Identification Number Manufacturer Model Number ‘Type (Peristali, Syringe) ‘Serial Number Pump ‘identification Number Manufacturer Model Number Filter is ua Changer ‘Serial Number Identification Number ‘Qualification Representative: __P-® pae._(2 |sep lot Reviewer: Date: a Ts eed ese seal ioe pal 4h alumna SCNT NES lea as x * ron 288 nT, Reson 4. tt 2010 VARIANDissolution Apparatus Performance Qualfiation Protocol 7.16 Accessory Identification ‘Complete the following table to record the serial numbers ofthe dissolution ‘apparatus accessories used to complete the Dissolution Apparatus 1 and 2 PQ. Mark N/A in the box of any items or positions not being used. Postion | Vesset_ | &egBtor Sta | agate shan | Basket Shan | Basket vessel | 1 R394 wis |Ao3zaqoz | 03ss39 o4 vessei2 | 4 9943 wis [a0gaq03 vass3r 92 [ vessais | 48 996 via |aoss 817 oass3q 03 Vessel4 | [42553 Rha AUBS BF oass40 oq Vessel | 4 2439 ma AvaS 819 o3sss44 os vessels | 4P 9S 5 Nia |Aoss 820 | Oassaz 06 vessel7 | 1849 6 vin [aosss2e* | 0assaq 0 vessels | 18994 Kia AOSSB22 oass4qs Or TAT Calibrated Test Eq ‘Complete the folowing table to record all applicable information for the equipment used to complete the Dissolution Apparatus 1 and 2 PQ: ment Required Manufacturer Vanae Model Number | Cary SO aged Caliration Date | V31 sep |eors Spectrophotometer Gatoraton ove |afsep 12016 Identiicati Nope EL060S34q CQuattcaton Representative: PA ate:_1z Lsep hot & Reviewer Date a aS “This documant i copycight protected therefore reproduction i prohibited aS “Ths quaiation protools vali the too on his pag dos not appear n color VARIAN Pi 70-6500, Revision J, August 2010 Page 23 of 6 $F se leon exett be Set AvasaztBalance (Medium) | Calibration Date Calibration Due Date Identification Number Manufacturer Metter Toledo Mode! Number | AB 20 4-5 Balance (Standard) | Calibration Date | 21 / Mov | 2016 Cattration D gateraton due | yaar | 2013 Harionson: W2915 2802 Manufacturer Varian, Inc. os eal ‘QA Station Calibration Date Calibration Due Date Identification Number ae Varian, ne, Model Number VK 5010 Calibration Date Calibration Due Date Identification Number Quaifcation Representative; B® pate:__t2t sep 2016 Reviewer: Date: ve TAT 2s > z ‘This documents copyright protected, therefore reproduction le prohibited Page 240156 Pv 70.6500, Revision J August 2010, VAIDissolution Apparatus Performance Qualification Protocol Manutactror Model Number (oven Thermometer | Cabraton Date Be Calibration Due Date ‘Identification ia Number Manufacturer Control Company Model Number S000) Calibrated Timer | Catoraton Date | 30 {sep hous Due gagrine | sep hod Identiti nee 2ao2zz1 FZ 'no QA Station Is available, record the following information: Calibrated Tachometer Manufacturer Modet Number Identification Number Calibration Date Calibration Due Bate Calibrated Runout Gauge Manufacturer ‘Mode! Number Calibration Date Calibration Due Date ‘dentification Number Qualification Representative: __p- A Date: Reviewer a b aS VARIAN “This documents copyright protected, therefore reproduction is probitited “This qualitaton protocols Invalid the logo onthe page does not appear in color. Date: [PIN 706000, Revslon J, August 2010 12) sep )zer6Dissolution Apparatus Performance Qualifcation Protocol Manufacturer Mode! Number Other: Calibration Date Ms pis 7 Calibration Due B: Identification Number Manufacturer Mode! Number Other: Identification pla. Number Calibration Date Calibration Due Date Manutacturer a Model Number Other: Identification pla Number Calibration Date Qualfcaton Representative: PA ae, ep 2016 Reviewer: Date: ‘The document is copyright protected therefore reproduction fe probed > ‘This qualiteation protocol inv the logo on this poge dees net appecr In color. ” Page 26058 70-6900, Revson J August 2010 VAI- Dissolution Apparatus Performance Qualification Protocol 71.8 Chemicals Required ‘Complete the following table to record all applicable information for the ‘chemicals required to perform the Dissolution Apparatus 1 and 2 PQ: Soure Chemical or Reagent | yaretacturer von | Pas | Gea Water Minerodin | i2tsep hove | ahep ko} ~— USP alcoho! ee zoreodre Balmer fest] 961 Prednisone RS use coaase | — | aas/ Prednisone Tablets usp R08144 bokn/zon 719 Test Procedure Selection ‘Stop 1 Review the PVT procedure options listed in the table beneath Step 2. Stop 2 Based on the Product Owner's decision or laboratory's internal procedure, place an "X* in the appropriate box indicating what test(s) will be performed and the criteria that the results are subject to: ‘Test Description Selection ‘Single-Stage Test: Perform testing based on mean and variation results according to the defined acceptance ranges for GM and S6CV (on the appropriate USP certificate provided. This option requires a ae ‘minimum of 12 individual results. This selection applies to Prednisone Lot P11300 or later. Optional Two-Stage Test: Perform tasting based on mean and Variation results according to the defined acceptance criteria for GM and %CV on the appropriate USP certificate provided. Acceptance x ranges are more stringent with this option but provide the possiblity to pperform only one test. This selection applies to Prednisone Lot P11300 orate. ‘Qualiication Representative: _P- A vate,_tzlsep]zore Reviewer: Date: + ye This document copyright protected theelore reproduction prohtid air ‘he qultoon protects tram ope on bs pape ewe nt eon eaa VARIAN PN 70.6900, Revision J August 2010 Page 27 of 58Dissolution Apparatus Performance Qualification Protocol ‘Stop 3, Ensure the Product Owner (or appropriate designee) signs the following table to record the Test Procedure selection before beginning any testing, Alternatively, reference an officially approved internal procedure that explicitly defines the procedure to be used, Test Procedure Verification NA The information below cerifes thal the appropriate Test Procedure Selection indicated beneath Step 2 was made prior to the beginning of testing Printed Name Title Signature Date Time | List below the information of the approved internal procedure that defines the type of| testing to be performed forthe periodic calibration(s) of dissolution Apparatus 1 and 2. Document Title Document Reference No. / Revision ‘Approval Date Pass (indeate Pass Flt WA) ‘Qualification Representative: PA iz lseplzore Reviewer: Date: ay 2 This documents copyright protected, therefore reproduction fe profited, NA ‘Tis qualiaton protocol is invalid Ifthe logo onthe page does not apps in color, 5 | Page 28056 PN 7.6800, Revision J August 2010, VARIANDissolution Apparatus Performance Qualification Protocol 7.1.10 This section is present to allow for alternate procedures to be completed as part Of this protoco's execution. The deviations listed below must be approved by the Product Owner (or appropriate designee) and agreed upon by the uaiifcation representative performing the sarvice. ‘Deviations should only be necessary in order to conform to updated regulatory agency criteria or specific internal procedures not reflected in this protocol. | applicable, document inthe following space provided any deviations from ‘the Performance Qualification protocol required by the Product Owner (or appropriate designee): pla Step 2 Obtain the signature of the Product Owner (or appropriate designee) in the following table to indicate approval of any necessary protocol deviations. Protocol Deviation Verification NA The information below certifies thatthe PO protocol deviations listed beneath Step 1 have been approved prior tothe beginning of testing, wie wa x Printed Name Tite wha bin rors ‘Signature Date Time Nia (indiate Pass Ft WA) Qualification Representative: P-A ate: _tz Sep] ole Reviewer Date: ay aS This document is copyright protected, therefore reproduction Is prohibited. “The quaication protocols mai te tgo on hs page des ot appear nel VARIAN PN 70-8900, Revision J, August 2010, Pape 29 6Dissoluton Apparatus Performance Qualification Protocol 7.2 USP PVT - Prednisone Procedure ‘The following sections describe the procedure for execution of the USP PVT with Prednisone Reference Standard (RS) Tablets, 7.21 Prednisone Medium Preparation ‘Stop 1 Heat an adequate amount of water to about 45 °C while stirring gently Step 2 Filer under vacuum using a filer with a porosity of 0.45 pm or less into an appropriate container equipped with a stirring device. Step 3. Continue sting the fitrate under vacuum for five addtional minutes Step 4 another validated deaeration technique is used, describe the method in the folowing bo« la piWoae> se reales con A Was -dipereatey a] fs mencionidss te el paso bs. 2. Step 5. Record the fiter information inthe following table Filter Manufacturer Advantec ined) [pore sie/type | 0,32 m9 per cwcle Ouattcaton Representa: _P-¥ pue,_izisep]eore Reviewer: Date ab {Wis acon i opi rote, rf reproducon poh > Thi qunaadon rowel strane ie ogo nb pron cmne atone eae 5 A z Al Page 300156 PA 70.6500, Revision J August 2010, VAR7.2.2 Prednisone Standard Preparation 7.2.2.1 Prednisone Stock Standard Solution (30 mg/L) Stop 1 applicable, dry the USP Prednisone RS according to the instructions on the bottle. Store the standard in a desiccator until coo! or ready for preparation. Step 2 Weigh an appropriate amount of reference standard for a 30 mg/L. solution ‘The standard should be prepared on the day of use. Step 3 Record the standard weight, standard volume, and date /time of preparation in the folowing table: Prep. | Standard Wt.(mg) | Standard Vol. (mL) Date Time 1 30,2 2.00 felsep /2ow) 10: 30. 2 a = = = Step 4. ‘Add 1 mL of alcohol per 100 mL of standard volume to the standard solution For example, add 10 ml. of alcohol for a 1000 mL. standard preparation, ‘Additional alcohol may be added to bring the Prednisone standard into solution prior to dilution (not to exceed 5% of the total volume). Step 5. necessary, sonicate the standard until completely dissolved (not to exceed 16 minutes) Step 6. Dilute to volume with the medium prepared in Section 7.2.1, Prednisone ‘Medium Preparation. Pass (indleate Pass Fat NIA) Qualitcation Representative: __P-& pate_(2fsep lore Reviewer: Date. ap Bg This docamen copyright prota, hrefoereprdutin pei ‘This qualieaton protocols Invalid the loge on ths page does not appear in color. VARIAN PN 70.6500, Revision J, August 2010, Page 31 of 56em Apert PRETENSE FIN _ EEE 7.2.2.2 Prednisone Working Standard - Apparatus 1 Step 1 Prepare an appropriate dition ofthe stock standard solution in dissolution medium to provide @ working standard saution with a concontration of 6.016 moi. Example(s): 30 mg > 1000 mL. (Stock), then 50 mL > 100 mt; or, 30 mg > 200 mi. (Stock), then 10 mL. > 100 ml, ‘Stop 2. Record this dilution scheme in the example % Labeled calculation in Section 7251 Pas $ (indicate Pas Fat NA) 7.2.2.3 Prednisone Working Standard - Apparatus 2 Stop 1 Prepare an appropriate dilution of the stock standard solution in dissolution ‘medium to provide a working standard solution with a concentration of 0.0075 mg/ml. ‘Example(s): 30 mg > 1000 mL (Stock), then 25 mL > 100 mL; of, 30 mg > 200 mil. (Stock), then § mL > 100 mL. Step 2. Record this dilution scheme in the example % Labeled calculation in Section 7282, 7.2.3 Filter Validation - Prednisone Stop 1 Record the fiter information in the table beneath Step 6 Step 2. ‘Withdraw and fiter three separate 10 ml aliquots of a Prednisone working standard solution through separate syringes and cannulas, Step 3 Collect the fitrate. | nore | tfmembrane fiters are used, discard the fist 2 ml. of solution Qualification Representative: _P date_tz sep }eote Reviewer Date: a This document is copyright protected, therefore reproduction e prohibited. > ‘This qualifation protocol ls invalid the logo on this page does nt appear incor a = a pw” Pages20ts PIN 70.6000, Revision J, August 2010 VAIDissolution Apparatus Performance Quelificaton Protocol Step 4 ‘Set the spectrophotometer to scan mode and perform a scan of the blank dissolution medium (recommended wavelength range: 260 - 220 nm). ‘Step 5 ‘Scan the unfitered standard solution to locate the maximum absorbance ‘wavelength (approximately 242 nm). ‘Step 6 Record the observed maximum wavelength and cell pathlength in the following table: Filter manufacturer Agilent Te chawlogid Pore size /type qo Wavelength maximum from scan | 242 om Pathlength of flow cell/ cuvette | 4¢”~ Step 7. Measure each absorbance of the filered and unfltered standard solutions, Step 6 Record the standard absorbances in the table beneath Step 9, ‘Stop 9. Use the equation below and indicate the results in the folowing table: 1% Recovered = 100 ‘Uniliered Std Standard | Abs at~242nm | %Recovered | Pass | Fail untitered | 9.3235 100 a Fitered 1 | 0.3204 984 = Fitered2 | 9, 3224 as 7 a Fiteed3 | 9.3225 94,9 = ‘Acceptance Criteria: % Recovered of each of the three fitered aliquots is between 98% - 102%. Step 10. Show an example calculation of the % Recovered value for tho Fired 1 aliquot inthe folowing space provides: % Recovered =_ 0-320! x 499 = BF 0.3235 Pass (indieate Pass Fall WA) Qualfcation Representative: pate_1z sep lees Reviewer: Date: ro ‘Te cocumenti copyright protected, tharear reproduction protied aS ‘This qualification protecol Is invalid Hf the logo on this page does not appear in color. VARIAN PIN 70-6900, Revision J, August 2010 Page 33 of 86Dissolution Apporatus Performance Qualification Protocol 7.2.4 System Setup and Operation - Prednisone 7.2.4.1 Physical Parameters - Prednisone Apparatus 1 Stop 1 Prior to performing the Prednisone USP Apparatus 1 PVT, ensure the following physical parameters comply with USP criteria. Indicate the results in the following table: Spindle Speed - RPM 24% Basho Rim Wobnie | #1. mm ie Vessel Gontring | WNT 2mm romoeneraxs| 7 | — | = Vessel Temperature | 37.0°C 205°C Vj -—|= BastetHoght | 35mma2 mm “{—To Vessel TeioLovel | Wihinbobbieorzas | | — | = Record all physical parameter measurements in Appendix A: Attachments or attach the printout from the QA Station on the Report Center Printout pages. provided. Alternatively, cite the location ofthe raw data, Pass odicte Pas Feil NA) 7.2.4.2 PVT - Prednisone Apparatus 1 ‘Stop 1 Program the dissolution apparatus spindle speed to 60 RPM (or the designated RPM on the USP technical data sheet for the lo of tablets to be tested), ‘Stop 2 Fill each vessel with 500 mL of water (or the designated volume of media on the USP technical data sheet for the lot of tablets to be tested), Stop 3, {f applicable, program an appropriate bath temperature to achieve a vessel temperature of 37.0 °C + 0.5°C. Allow the vessel temperatures to equilibrate. Where possible the media should not be stirred prior to initiation of the test ‘Stop 4 Prepare the Prednisone calibrator tablets by inspecting for chips and cracks, Remove any powder residue with a soft rush. Qualicaton Represeniatve: __B& date:_re sep hoe Reviewer Date: ab ‘hl docamor a opi poet, orp roi, Ot Ths guanclon pectin te opoee ape tnt ri cler as oe tetso PN Tota, Ron Ait 2010 VARIANDissolution Apparatus Performanco Qualification Protocol Stop 5, ‘Measure the initial temperature ofthe dissolution media in each vessel and ‘ecord the values in the table beneath Step 10. ‘Step 6 Indicate the method of sampling to be used and the sample volume inthe table beneath Step 10. ‘Stop 7. Drop a single Prednisone tablet in each dry basket and attach to the shaft. Step 8. Use a timer to record times as the baskets are lowered and as samples are pilled. Times may be staggered to allow for sampling at 30 minutes # 2%. Record the times in the table beneath Step 10. ‘Step 9 Remove an aliquot of the test solution from each dissolution vessel at 30 ‘minutes + 2% (# 36 seconds). Fiter each sample aliquot immediately, Stop 10. ‘Upon completion ofthe test, measure the final temperature of each vessel and record in the following table: Serping |_er vw samp | 40 ‘Automated — Postion | rempt'c) | thnwtmarse) | “imeos"® | tent) ‘Vessel 1 320 00:60, 30:00 SHO Vessel 2 aa 00 3004 3hO vess's | 24.1 00 3: 08 300 Vesela | 341 0:00 BOAZ 320 Vessel 5 sno wood 30.16 SAO esse | 280 D0 3d e0 320) [ Vesserz | 36" we 324 | ano vessis | 3 06:00 30:28 330 step 14 Properly label and cover samples unt analysis. Proceed to Section 72.5 for ‘analysis instructions. ‘Qualification Representative: Ppa pate _\2}sephore Reviewer: Date a aS ‘his document copra protected, haror reproduction prohiis ‘This qualieaton protocols Invalid the logo on this page does not appear in color VARIAN PIN 70-8000, Revision J. August 2010 Page 350156Dissolution Apparatus Performance Qualification Protocol Step 12 Repeat Steps 1 - 11 ifa second Prednisone testis required based on the PVT procedure seleced in Secton 7.1.9. Use the following table to record all applicable tost data: a 7 Sampling |_Mansal Sample Volume | sla, 108 | Automated nla ee toitiat | Introduction | Sample Time | _ Final Position | yemp(rc) | Timetmmiss) | —(mmiss)" | Temp(’c) Vessel 1 Vessel 2 Vessel 3 Vessel 4 v = é Vessel 5 Vessel 6 Vessel 7 Vessel 8 Qualication Representative: Reviewer: “This documents copyright protecod, therefore reproduction fe prohibited ‘This quatifteation protocol i invalid if the logo on this page dows net appear in color “4 PN 70.6800, Revision J August 2010 VARIAN Page 260156 Pass Aieat ass /FatWA)Dissolution Apparatus Performance Qualification Protocol 7.2.4.3 Physical Parameters - Prednisone Apparatus 2 Step 1. Prior to performing the Prednisone USP Apparatus 2 PVT, ensure the following physical parameters comply with USP criteria. Indicate results in the following table: Spindle Speed ‘Set RPM + 4% : ‘Shaft Wobble: 'No significant wobble Vessel Centering NMT 2 mm from center axis Vessel Temperature | 370°C +0.5°C Paddle Height 25 mm £2 mm NNNANA \ Vessel Table Level | Within bubble or + 0.5* Record all physical parameter measurements in Appendix A: Attachments or attach the printout from the QA Station on the Report Center Printout pages provided. Altematively, cite the location ofthe raw data, Pass (indicate Pass Fall WA) 7.2.4.4 PVT~-Prednisone Apparatus 2 ‘Step 1 Program the dissolution apparatus spindle speed to 50 RPM (or the designated RPM on the USP technical data sheet for the lot of tablets to be tested), ‘Step 2 Fill each vessel with $00 mL of water (or the designated volume of media on the USP technical data sheet for the lot of tablets to be tested). Step 3 | applicable, program an appropriate bath temperature to achieve a vessel ‘temperature of 37.0 °C + 0.5 °C. Allow the vessel temperatures to equilibrate. ‘Where possible the media should not be stirred prior to initiation ofthe test Stop 4. Prepare the Prednisone calibrator tablets by inspecting for chips and cracks, Remove any powder residue with a soft brush, Gpuenteee fA ee hcl aep colt Reviewer: ate, ay aS “is dna a copy protec hore repredton pried, ‘This qualitestion protocol ls Invalid i to logo on this page does not appear in calor. VARIAN PN 7.6900, Revision J, August 2010 Pape 37 of 86Step 5. ‘Stop 6 Step 7. Step & Stop 9. Measure the initial temperature of the dissolution media in each vessel and record inthe table beneath Step 9. Indicate the method of sampling to be used and the sample volume in the table beneath Step 9. Use a timer to record times as tablets are dropped and as samples are pulled, ‘Times may be staggered to allow for sampling at 30 minutes # 2%. Record drop times in the table beneath Step 9. ‘Remove an aliquot ofthe test solution from each dissolution vessel at 30 minutes + 2% ( 36 seconds). Fiter each sample aliquot immediately. ‘Upon completion of the test, measure the final temperature of each vessel and record in the folowing table: Sampting |Manual a RSE? Toma | nar | a0 Postion | remptcy | timetmmss) | Strmesa™® | tafe) vessi1 | 3x0 | to:00 30:00 aa [Weds | an. Con 30:10 340 vessei3 | 34! wee | a0 340 Sedo So eG sl eiass [aos teeals [> 380 O40 30:40 320 Vous | 30 00:50 30:50 3n0 vessei7 | 30 01:00 54 320 wee et [et sar [Lone ae aal Step 10 Property label and cover samples untl analysis. Proceed to Seetlon 72.5 for analysis instructions. Quaticaton Represeniatve: B® pote_I2 sep) zeus Reviewer Date: an cont protec, trl rprducon pried a oct wai teagan page doe nat peat in cle Ss % PIN 70-6900, Revision J, August 2010, VARIANDissolution Apparatus Performance Qualification Protocol Step 11. Repeat Steps 1 - 10 if a second Prednisone test is required based on the PVT procedure selected in Section 7.19, Use the folowing table to record all applicable test data: Sarat | Mere} sepnagine | ta ‘Automated Postion | remptc) |_timetmmes) | ““tnmias)"® | tempttc) Vessel 1 Z| Vessel 2 . Vessel 3_| 7 Vessel 4 Vessel 5 | Vessel 6 Vessel 7 Vessel 8 Pass (indicate Pass Fall NA) 7.2.5 Analysis Procedure - Prednisone 7.2.5.1 Sample Analysis - Prednisone Apparatus 1 ‘Stop 1 ‘Set the UV-Vis spectrophotometer to read at the maximum absorbance ‘wavelength (approximately 242 nm) as previously determined during the Prednisone fier validation (Section 7.2.3). ‘Step 2. ‘Measure the absorbance of the appropriate working standard solution and record the value in the table beneath Step 9 (Std, Absorbance). ‘Stop 3 ‘Measure the absorbance of each sample solution and record the values in the table beneath Step 9 (Vessel 1 Absorbance, Vessel 2 Absorbance, etc) ‘Queltication Representative: pa pate 12 Isep Leo Revi Date: ab, aS This donumant apy protein rors repre poh This quatiteation protocols invalid ifthe loge on tis page does not appee in color. VARIAN [PIN 70.6000, Revson J, August 2010 Pago 39 0t55Dissolution Apparatus Performance Qualifeatin Protocol Stop 4 ‘Measure the absorbance of the appropriate working standard solution and record the value in the table beneath Step 9 (Std, Absorbance). Step 5. ‘Verify thatthe relative difference between the two standard absorbance values {is nol more than 2.0%. Use the following equation to complete the example calculation: ‘Std % Relative Difference = (Sidi x 100 \Absorbance - StdAbsorbance)_ {Std Absorbance + Std,Absorbance) 814% Relative Diference = 0.665% _. 9.6630 _ 499 0.6058 + O 6610 Std % Relative Difference v.04 /. Stop 6. Record the Std % Relative Difference result inthe table beneath Step 8 Step 7 Uso the formula beneath Step 8 to calculate the quay of Prednisone ‘expressed as a percentage of the labeled amount. Record the results in he table beneath Step 8. For each set of samples, use the standard absorbance value immediately preceding the sample readings for quantitation. If sample or standard dilutions are required due to the pathlength ofthe flow cell, the dilutions must be ‘accounted for in the equations. Qualitication Representative: __-P#® pate: _\2Isep 2006 Reviewer: ete an Tie document i copra protec, hrtoe reproduction prohibie. > ‘This qualiieatlon protocol is Invalid he logo on tis page doesnot appear In coor | Page 40056 IN 70.8000, Revision J Avg 2010 VARIANDissolution Apparatus Performance Qualification Protocal Step 8. Use the folowing equation to fil in the example calculation below for the ‘% Labeled Prednisone for Vessol 1, Test 1: Dion factor = Volume of tandard pinned (in) folume of volumetric flask (mL) Dilution factors AO me = __O-d door Fe X_ Dilution factor x x 100 ‘Soak Sandord VOL TAL) capelenen RS Os Fe. x x (i) x 100= 2-3 mg 200 ces 40 (mg) % Labeled Pred.= Sampig Abs x Standard Wt. (mg) x St, Puy (as decimal) x F 6462 y 2 gy ON9T 2.5 0.6683 a2 ‘% Labeled Prednisone (for Vessel 1)= _ 42s Qualification Representative: @°* ates, tse pero Reviewer: Date: ab ae Ths docu capi rota hrs ropreducton poh “as “The quatention protocols nv te ogo om hs page oust eppern esr VARIAN ‘PIN 70-6900, Revision J, August 2010 Page 41 of 86sep, Record the values of the analysis forthe Prednisone Apparatus 1 PVT in he folowing table. Mark NIA for eny vessel postions not used Test 1 Description Sid/Sample | % Labeled Absorbance | Prednisone thm oot aT ‘Vessel 1 Absorbance: 04462 az. ‘Vessel 2 Absorbance: 0 6506 33,403 Vessel 3 Absorbance 0.460! 74.499 Vessel 4 Absorbance o.¢3a2 | 72,008 Vessel 5 Absorbance oesae | Vhzaq Vessel 6 Absorbance 0.684q | 33.2 he Vessel 7 Absorbance o62s0 | aos ‘Vessel 6 Absorbance o.sea2 | c6.zsq Sid, Absorbance 6.660 Sates cay ‘Step 10. Use the values in the above: ee results of the PVT for Prednisone Apparatus 1 in Section 7.3, Result Interpretation, Pass (indicate Pass Flt 1A) Qualification Representative: fh pate_i2lsepleore Reviewer: Date: ab Tis dom copy prolate reproduction pros NA ‘Wis quaiteton protocols inva he og ont page ds net pperin lr ae age sot 870.60, Revie, ug 2010 VARIANDissolution Apparatus Performanco Qualification Protocol 7.2.5.2 Sample Analysis - Prednisone Apparatus 2 ‘Step 1. ‘Set the UV-Vis spectrophotometer to read at the maximum absorbance ‘wavelength (approximately 242 nm) as previously determined during the Prednisone filter validation (Section 7.2.3). Step 2. ‘Measure the absorbance of the appropriate working standard solution and record the value in the table beneath Step 9 (Std, Absorbance). Stop 3. ‘Measure the absorbance of each sample solution and record the values in the table beneath Step 9 (Vessel 1 Absorbance, Vessel 2 Absorbance, etc). Step 4 ‘Measure the absorbance of the appropriate working standard solution and record the value in the table beneath Step 9 (Std Absorbance). ‘Stop 5. Verify that the relative difference between the two standard absorbance values 's not more than 2.0%. Use the following equation to complete the example calculation: Std % Relative Difference = (Sid \Absorbance -SidpAbsorbance). x 100 (6td;,Absorbance + StdaAbsorbance) Std % Relative Ditference=__©- 3246 ___©- 3234 409 o.32de + 0.3234 Std % Relative Ditterence = AVA Step 6. Record the Std % Relative Difference result in the table beneath Step 9 Step 7. Use the formula beneath Step 8 to calculate the quantity of Prednisone expressed as a percentage of the laboled amount. Record the results in the table beneath Step 9 For each set of samples, use the standard absorbance value immediately preceding the sample readings for quantitation. If sample or standard dilutions {are required due to the pathlength ofthe flow cell the dilutions must be ‘accounted for in the equations, Quoliicaton Representative: = pate,_iztsep 1201 6 Reviewer: Date: an ac ‘hls document copy roti herr reproduction probed. “a8 ‘iis questo protests te loge on te poe ees not eppern ele VARIAN PN 70-6000, Revision J, August 2010 Page 43 of 8Dissolution Apparatus Performance Qualification Protocol Step 8 Use the following equation to fil in the example calculation below forthe % Labeled Prednisone for Vessel 1 Dilution factor = Ditton facto Ss mt 9.08 405 me Fs Scaceandavermy | Ditlontactorx _Vasselvol ims x 100 ‘Sock Standard Var. ml) bel Content (rg) Fe 4 % 09S 255, % x 500 fy 40 (mg) % Labeled Pred. = Sample Abs x Standard Wt. (mg) x Std Puy (as decimal) x F % Labeled Pred. = __O.2394 B82 mg x OAS x_ 175 ng! 0.3296 % Labeled Prednisone (for Vessel 1)= __ 33.453 °¢. Qualification Representative: pA pate,_12 | dep 12016 Reviewer: 2 ay “Tne document i copy protec, hrefoe reproduction prohibite : “is ealifeation protocol isin te loge oni page dae et appear clo Page 44086 PN 70.6000, Revision J, August 2010,Dissolution Apparatus Performance Qualification Protoco! Step 9 Record the values of the analysis forthe Prednisone Apparatus 2 PVT in the {ollowing table. Mark NIA for any vessel positions not used. Test t Test 2 Description ‘Std7Sample | %Labeled | Std/Sample | % Labeled Absorbance | Prednisone | Absorbance | Prednisoné ‘3a; Absorbance 0.3246 Vessel 1 Absorbance oz | 23,483 jd ‘Vessel 4 Absorbance 0.298 32,26) ‘Vessel 5 Absorbance 0.298) | 32,120 ye Vessel 8 Absorbance: O.2954 31 86F ‘Std2 Absorbance 0.3234 ‘Step 10. Use the values in the above table to indicate the results of the PVT for Prednisone Apparatus 2 in Section 7.3, Result Interpretation, Pass Coden Pea Wn 7.3 Result Interpretation For addtional information on result interpretation, refer to Chapter <711> of the current USP. Refer to the certificate supplied with the specific lot of calibrator tablets used for this procedure and record the specified ranges below. Compare these ranges to the values calculated for each apparatus tested. The dissolution apparatus is considered suitable for use i ll calculated values fall within the specified ranges, Refer to USP or Varian-provided resources to determine GM and %CV values. Include copies of any references used where applicable. (Qualfcation Representative: __P- A pote_t2bsep lore Reviewer: Date: a aS ‘This document is copyright protected, therefore reproduction is prohibited. ‘This quatiteation protocl fs Invall f the logo on this page dove not appear in color. VARIAN ‘PIN 70.6900, Revision J, August 2010 Pago 45 of 8Dissolution Apparatus Performance Qualification Protocol 7.3.41 Single Stage Test (Prednisone) Apparatus | om, | SMenor | seve | %cvnmty | Pass | Fall NA taney | — |---| _ a a ae Wa 2 (Paddles) --> ~ =] 1-Goometric Mean Coefficient of Variation 3 - not more than 7.3.2 Optional Two-Stage Test (Prednisone) foot om, | SManor | seve | sscvnmts| pass | Fai | wa 1(askets)-tststge| FS |s2-20] so | a2) 7) —] — 2(Paddies)-tststage| 32 | 24-36| 3.4] 4.3 |4%] —] — 1 (Bagkots)- 2nd : a ial il case —| —|-|-|~4 2 (Paddles) -2nd = Petal lp oe sehactes ‘Sage 1*GoometricMean Coefficient of Variation 3 -not more than 7.4 Final Evaluation Upon final evaluation: Step 1. Ensure all equipment has been restored to normal operating condition Step 2. Ensure all requirements ofthe PQ have been completed Stop 3 Ensure any exceptions to the acceptabilty, and appropriate resolutions, are noted in Appendix B. Pass (indicate Pass Fall WA) Caitcaton Representative: __°°# oae_ lai sepJeo! 6 Reviewer: Date ab This acon is opi procter repodicton roe. NA ‘his uamenton rowenta tea ne pe ee at open eae mS age tte Pn 70400 Reon Aust 2010 VARIAN__ Dissolution Apparatus Performance Qualification Protoco! Qualification Acceptance ‘The Varian instrumentation identified in this PQ Protocol is certified: Dissolution Apparatus Serial Number | 4-4334-429) ‘Apparatus Qualified (e., Tand/or2)| > 4 Certification ‘Suceessflly Qualified without Exceptions ‘Successfully Qualified with Exceptions (Appendix B) = Failed i Qualification Representative Name (ry Foula hola aque Tile Le Gama Signature PA Aeat— Date Te lsep Feove ‘This completed Performance Qualification Protocol is accepted, Reviewer 1 ‘Name (print) ‘Signature Date Reviewer 2 ‘Name (print) Date a Thi decomet scopy peau preucn a poh aS “Ths qusitcstion rtecelle vate ge onthe page dove not appear neler VARIAN Pv 70.6600, Revision J August 2010, Page 47 0158Dissolution Apparatus Performance Qualification Protocol This page was intentionally left blank, excopt for this message. This documents copyright protected, therefore reproduction ie prohibited ‘This qualiteation protocel i invalid the logo on this page doesnot appecr In color Pago 48 0158 Pn 70-0800, Revision J August 2010, @avh 2 ar > zDissolution Apparatus Performance Qualification Protocol Appendices Each page that is inserted after the appendix is numbered with the letter of the ‘appendix and a sequential number. The appendix page number must be initialed and dated by both the Qualification Representative and the Reviewer. For example, pages inserted after Appendix A are numbered A-1, A-2, ‘A-3...ete. along with the initials and date. It the reverse of each appendix page i lft blank it should be marked NIA’ and signed and dated. When the PQ is compiete the total number of pages inserted after each ‘appendix is written on the front page of the respective appendix sheet Cusmaitin Récreseitome © tk me _ te sep zat Reviewer Date: ah ae This document is copyright protected, therefore reproduction is prohibited. VARIAN “his qualifcation protocol fs oval f the logo on is page does not appear in eloe PN 70.6900, Revision J August 2010 Page 49 0f56Dissolution Apparatus Performance Qualiiaton Protocol Appendix A: Attachments ‘Attach any necessary documents after this page. Complete the following table: for all atachments (indicate page number as A-1, A-2, A-3, ec.) No. of Pages Inserted 4S Attachment Title Page Nanaere Bardo Espectal ] A-l Vekdacs de fio oS lectures Aparats | y Il lee Reswilacs sp Aparah | y UI Taes 4 AWG Cert frado table tas one usp [AF A-w Cerripcacd — Erkdndor Predauora UIP fariz q Aad Cer peed — Crommetro 7 ' A a4 AAW) [ale ‘ bla This area was Inna of blank valicaton Representative: _ pate_12i sep lee! halen Dae tment is copyright protected, therefore reproduction is prohibited. ‘This quatiteation protocol invalid i the logo on this page dose not appear In color Page S056 ‘PIN 70.8000, Revision J, August 2010 ve < Be = Rr 5 A zA-! 9/20/2016 5:41:52 PM Page 1 of 1 1.0 Ugappioa ESPECrRAL 0.8 0.6 ® 2 % g 0.4 2 0.2 0.0 200 220 240 260 280 300 Wavelength (nm) Scan Analysis Report Report Tine : Tue 20 Sep 05:40:36 PY 2016 Batch: C:\Documents and Settings \adinistrator\My Documents \HUMAX PHARHACEUTICAL\2026\VAL wWew Folder\PV?. 294 Software version: 02.50(156) Operator: HUNAX\dubanhigui ta Sample Name: PREDNISONA\ Eeitection Tine 9/20/2016 $:40:44 PM po eee lelsep hos Al Sep ]o16pla Ke yl te ea9/20/2016 :04:57 PM Page 1 of 1 Varian 21-CER-i1 package active Simple Reads Report Collection Time: 9/20/2016 Software Version: 02.50(156) NYALIDAGON DE Instruments Cary 50 Read \° aes gm TOS ED sw Fre 2 013201 42.0 pueteoy 5 013223 2a2'0 Pitreoe 4 013228 242.0 Exures 3 A-2 Fura " Je Acst— (2) Sep Jeoreple pele fiat— J wl HP ieee9/20/2016 6:45:34 PM Page 1 of 1 Varian 21-CER-11 package active Simple Reads Report Collection Time: Software Version: Instrument Read abs 5658 6462 6506 6601 6382 6846 6849 6250 5872 6670 9/20/2016 6:41:25 PM 02.50(156) ? Cary 50 PET St Iwiciat 242.0 Uasot 242.0 Yaxod 242.0 Yasos 242/0 Vaso 242.0 Vases 242.0 Vaso 6 24210 Yao 242.0 Yasoy 242.0 SO PNA L "“LEccuRAS aes APARATO TL" CANMASTILLAS ee feels (2| sep hotDele Ve tege lee9/20/2016 6:02:42 PM Page 1 of 1 Varian 21-CFR-11 package active Simple Reads Report Collection Time: 9/20/2016 5:56:02 PM Software Version: 02.50(156) Instrunent 3 Cary 50 Read = Absa TOS TET ae Micra 2 0.2891 242.0 yasor 3 0.2632 242.0 vaso 4 0.2695 242.0 yasoaz 5 0.2788 2420 arog 5). couavait $242) egaaey 7! <0)23199- 242.0. nag 8 0.2800 242.0 Yasog 9 012754 24210 yor 10 013234 24210 St FINAL A-4 LECTORAS APARATO ID" PALE TA pl S ae A cea te rz lsep [oreNIA pe [— fret \ il sep frorsPerformance Verification Test Calculation Tool Laboratory Information (optional) Date performed Stage 1: 9/12/2016 Operator: AMERICAN FARMAGRUP S.A. ‘Assembly ID: 4-4371-1207 Note book: PVT APARATO | (CANASTILLAS) ‘Notes: | EQUIPO DE DISOLUCION MARCA VANKEL MODELO VK7010 PROPIEDAD DE LABORATORIOS MINERALIN Apparatus 1 -- 2-stage test for equipment with 8 positions Acceptance eriteia for USP Prednisone Tablets RS, RO21Y% ‘Stage 1 | Stage 2 Geottean, lower | 68 54 GeoMean,upper| 80 84 wevjupper| 8.2 " Stage 1 (Run 1) data Vessels 7901 Vessel? 73407 Vessel Taare Vessels 72008 Vessel 772k Vessel 6 Tare Vessel 70st Vessel 254 Test Resse ‘st Stage Geotfeon 3 Moots ‘st Stage XV 50 Moots PASSES Signature: ese dele Pvt. loulation Tool V2. JerreAD \ le fete yet sep erePerformance Verification Test Calculation Tool Laboratory Information (optional) Date performed Stage 1: | 09/12/2016 Operator: | AMERICAN FARMAGRUP S.A S. Assembly 1D: | 1-4371-1207 Note book: | PVT APARATO II (PALE TAS) DE LABORATORIOS MINERALIN ‘Notes: | EQUIPO DE DISOLUCION MARCA VANKEL MODELO VK7010 PROPIEDAD. Apparatus 2 ~ 2-stage test for equipment with 8 positions Acceptance criteria for USP Prednisone Tablets RS, ROSY ‘Staget | Stage2 Geotiean, lower] 29 7 Geottean, upper] 36 0 wcviupper| 4a | 62 Stage 1 (Run 1) data Vessel 1 a8 Vessel? 30488 Vessels 31.188 Vessel é 32261 Vessels 32.180 Vessel6 td Vessel? 32400 Vessel 31.868 ‘Test Results ‘st Stage Geotlean 2 Meets Ast Stage CV 34 ects PASSES oe Signature: PVT Calculation Toot — v2.0 ‘Copy 2016 Tha United States PharmssopsialCanreton le / se A-6pla Oe : C vl veal te _A-3 “Comerica Certificate PREDNISONE TABLETS USP Catalog No. 1559505 USP Lot No.: _ RO31Y1 (20 mg nominal prednisone content per tablet) FOR DISSOLUTION PERFORMANCE VERIFICATION TEST (PVT) Period of validity: This certificate of USP Prednisone Tablets Lot RO31Y1 is valid through Sune 30°, 2017. The USP Prednisone Tablets RS is provided for use in the Performance Verification Test for USP Apparatus | and 2 with 1 liter vessels in the USP General Test Chapter on DISSOLUTION <711> and DRUG RELEASE <724>, APPARATUS SUITABILITY, Store in a dry place. Store the tablets at controlled room temperature not exceeding 25° Dissolution Medium: We recommend preparing the medium as follows: Heat a suitable amount of water, while stirring gently, to about 41-45°, Filter under vacuum through a 0.45-;umeporosity filter into a suitable filtering flask equipped with a stirring device, Seal the flask and continue to apply vacuum while stirring for an additional five minutes. Measured vacuum should be less than 100 mbar. The temperature of the Dissolution ‘medium should not fall below 37° prior tothe initiation ofthe test Procedure [See DISSOLUTION <711> in the current USP}: Determine the quantity of prednisone, CaiHasOs, dissolved at 30 minutes, in each vessel, expressed as percent of the labeled amount. Use 499 g of Dissolution Medium: (which corresponds to 500 mi), where possible the medium should not be stirred prior to the initiation ofthe test forthe purpose of cquiliration, and conduct the test at 37°. Operate each apparatus at $0- ypm speed, Withdraw an aliquot of sample solution at 30 minutes and filter immediately. Measure the amount of prednisone dissolved from filtered portions of the sample aliquots at 242 nm in comparison with a solution of known concentration of USP Prednisone Reference Standard. ‘Notes: An amount of alcohol not to exceed 5% of the total volume of the standard solution may be used to bring the prednisone reference standard into solution. The filtering method must not cause adsonptive loss of drug, Bias introdoced by automated methods is to be avoided. LF equipment is dedicated for use with only one apparatus (basket or paddle), then performance verification is only required for that apparatus, At the time of use, peel back the paper-backed lidding to remove the tables from the blister card ‘Test Interpretation: Laboratory can choose cither ofthe test schemes listed below. Single-Stage Test The following are step-by-step instructions for the Single-Stage test 1. For each positon in the assembly, test one USP Prednisone Tablets RS, and record the percent dissolved at the sampling ‘time point specified. Transform the percent dissolved results to the natural log scale, determine the mean and variance. For assemblies with 12 or 14 positions (12 or 14 dissolution vessels), no further testing is required 2, For assemblies with fewer than 12 positions, repeat Step 1 with an additional set of tablets, Again after transforming the percent dissolved results to the natural log scale, determine the mean and variance. 3. Calculate the average of the two means and of the two variances obtained in Steps | and 2. (Use the results from Step 1 lone for assemblies that have 12 of 14 positions.) Copyright 2016 The United States Pharmacopei! Convention Allright reserved USP Certificate Certificate Date: 12May2016 Page 1 of 5 USP Template No. CERT1_4-04 Effective 21Jan2016 p-A— Ast~— {ye sep foreAv use US Pharmacopeit A2C8HFE the results of Step 3 to a geometric mean (GM) and pervent coefficient of variation (%CV). See calculation ‘example below for more detail 5. Compare the results of Step 4 to the Single-Stage acceptance ranges in Table 1. The GM mast not fall outside the limits, and the %CV must not be greater than the limit. If both meet the criteria, the assembly has passed the PVT. Optional Two-Stage Test A laboratory may choose to implement the PVT as a Two-Stage test in case of assemblies with less than 12 positions. The ‘Two-Stage testi a statistically valid means of allowing the possibility of stopping the test at the first stage with a penalty ‘The following are step-by-step instructions for the two-stage test. 1. For each position in the assembly, test one USP Prednisone Tablets RS, and record the percent dissolved atthe sampling time point specified. After transforming the percent dissolved results to the natural tog scale, determine the mean and 2. Convert the results of Step | to a GM and %CV, and compare to the I" Stage of Two Stages acceptance ranges in Table 1. The GM must not fall outside the limits, and the %CV must not be greater than the limit. For calculation of the GM and ‘%CV. see calculation example for more detail 3. results of Step 2 satisfy both acceptance criteria, the assembly has passed the PVT. Otherwise continue to Step 4, (see note 1, 4. Repeat Step 1 with an additional set of tablets and after transforming the percent dissolved results to the natural log scale determine the mean and variance for the data obtained at this step. 5. Average the two means and two variances obtained in Steps land 4 66. Convert the results of Step 5 to a geometric mean (GM) and percent coefficient of vatiation (CV). For calculation of the GM and %4CY, see calculation example for more detail 7. Compare the results of Step 6 to the 2"!Stage of Two Stages acceptance ranges in Table 1. The GM must not fall onside the limits, and the %@CV must not be greater than the limit. If both meet the acceptance criteria, the assembly has passed the PVT, In order to comply withthe requirements of ASTM E29, all limit values in Table 1 are expressed with two significant figures. Table J, Performance Verification Test (PVT) limits (values apply only to Lot RO31Y 1) _ Two-Stage Apparatus | # of vessels spain 2" Stage of Two Stages GM" | “ev GM* %CV_| GM*_ | %CV é 7 58-80 82 54-84 in 1 3 54-84 u 12 Ta 14 na 6 64 =z 3 7 63 29-36 ne 27-40 6 2 3 27-40 62. a8 62 2 63 a 14 62 na * Percent ofthe labeled amount of prednisone dissolved at 30 minutes at S0-rpm Copyright 2016 The United states Pharmacopeial Convention. Alighs reserved. USP Certificate Certificate Date: 12May2016 USP Template No. CERT1_4-04 Effective 214an2016A-4 Calculation example (expressed as Microsoft Excel® worksheet functions): Run 1: Xo vim natural log scale: Ln xj, Lax», Lay Run 2: Xess Syn, wn Yann natural log seale: Ln xy, Ln Zp, LO st Stage of Two-Stage for n=6, 7, 8 and Single-Stage forn=12, 14 OMI = explaverage (Ln x1Ln x3) CVI = 100*sqr(exp(var(Ln x)-Ln x) -1) ‘Single Stage or 2nd Stage of Two-Stage for n= 6, 7, 8: GM = exp(average((average (Ln x:Ln x)), (average (Ln xqu1:Ln x3). = expaverage (La x):Ln x4)) %CV= 100° sqrt explaverage( (var(Ln x :Ln x,))var{Lm Xpe:Ln X29) -1) exp: exponeatial (@") yar: variance sqrt: square root _*: multiply 100: conversion factor to percentage Note 1: ‘There ae circumstances when the MCV after the first stage equals r exceeds the value inthe Futility Faetor table (without ounding), ‘hen itis impossible to meet the 96CV criterion after the second stage. The lab can stop after the frst stage (run). However after any adjustments to equipment, test procedure, and soon, the PVT must be restarted with a new first un, Futility Factor (CV at or above value given, second stage testing will not produce passing result) [Apparatus | ‘No. of Vessels 1 leas 7 eel feet 6 is 6 [2 89 89 a ‘oyriht 2016 The United states Pharmacopeisl Convention Al ighsraserved, USP Certificate Certificate Date: 12May2016 Page 3 of 5 USP Template No. CERT1_4-04 Effective 21/an2016 pA— fewt— : Tip henA use “Sern eo] REFERENCE STANDARD PREDNISONE TABLETS 30 Tablets ‘The nominal weight of prdrisona in each tbe is 107g. Do nt push ibis cugh ot beckng. To remove tabats fo biter, pe! fol Use ony hese abet Sex he certicate fr adlionat information. ‘Store 8 dry pace, Storm a controled room ‘ompereture no exceeding 25°C. Unused ar unopened stor snp shoul be hep Be sovondary package Dengert Causes eye tation. Suspactad of damaging fet or the luton chi Ceuses daraga organ (endain syst) trough rolonged o rapes exposure bien social instutons bore use. Oo not hand nt a sat precautions have ban ‘at an undersiood. Wash thorough afar handing. Wear preitte ghwssprtec, ‘otingieye protactonTacepreactan if in ayer: Rinsacautously wah wot Io svar minutes. Remave contact ances, preset an easy odo. Conus cnsng eye ‘ison persists: Gat medial aancatatenton I exposed o concemed Gt eet lon. Store locked up. Disposa of conketsconeaer m accorsance wih locarogionanatnanornatonal egustons ere amcor es wan Ritorute asa, See SOS prio ue tenia oie suc_t_ doth ‘Quality Assurance Forune wh oscied SP compe se ‘Copyright 2016 The United States Pharmacopelal Convention, Al rghts reserved USP Certificate Certificate Date: 12May2016 Page 4of 5 USP Template No. CERTI_4-04 Del Nert Effective 2Uan2016 iz Sep)jeotsCalculation Value '¥ value snot provided onthe label or accompanying documentation and the Reference Standard has a quantitative USP compendial application, a value of 100.0% s used. The purity value fs not applicable for qualitative uses, Please refer tothe speciic Reference Standard label for further information, Expiration Current lots are identified in the current USP Catalog. n some cases, the previous lot may stil be considered valid for use. fo, itis fdentfed inthe column marked "Previous Lot/Valid Use Date.” tis the responsibility of each user to determine that this loti curent or valid when used, For the most up-to-date information, please refer to the USP Store t wovwusp org Instructions for Use Follow the instructions on the label of the USP Reference Standard and in the appropriate USP documentary standard) "Non-Monograph Use ‘The suitably ofthis Reference Standard for use in non-compendil applications is solely the responsibilty of the user. Lesat noTice USP WARRANTS GOOD TITLE TO USP REFERENCE STANDARDS ON DISPATCH FROM USP. THE FOREGOING WARRANTY ISIN LIEU OF ANY OTHER WARRANTIES, EXPRESS OR IMPLIED, INCLUDING WITHOUT LIMITATION ANY WARRANTY OF MERCHANTABILITY OR FITNESS FOR AA PARTICULAR PURPOSE, OR ANY WARRANTY THAT THE PRODUCTS, INCLUDING THIS CERTIFICATE, ARE OF MERCHANTASLE QUALITY, USP'S LABILITY ARISING OUT OF OR RELATING TO THE SUPPLY OF USP REFERENCE STANDAROS AND THIS CERTIFICATE SHALL INNO EVENT INCLUDE LOSS OF PROFITS, COST OF PROCURING SUBSTITUTE GOODS OR SERVICES, OR ANY INCIDENTAL, INDIRECT, OR CONSEQUENTIAL DAMAGES OF ANY KIND, EVEN IF USP IS AWARE OF THE POSSIBILITY OF SUCH DAMAGES. WITHOUT LIMITING THE GENERALITY OF THE FOREGOING, USP DOES NOT WARRANT THAT THE USE OR RESALE OF USP REFERENCE STANDARDS, INCLUDING THEIR USE TO PERFORM TESTS AND ASSAYS PUBLISHED BY USP, WILL NOT INFRINGE UNITED STATES OR ANY OTHER PATENTS. USP Reference Standards are not intended for use as drugs, dietary supplements, or as medical devices This certificate may not be reproduced without the express written permission of USP. ‘copyright 2016 The United States Pharmacoeil Convention. Alright ceserved USP Certificate Certificate Date: 12May2016 Page 5 of 5 UsP Template No. CERT1_4-04 Effective 21/an2016 A-4 0 Rent tel stp Jewisi USP Certificate US. Fharmacopeio The Slondord of Qual Prednisone LOT 006356 ° Molecular Formula Hc HO on aero Molecular ae CAS Number 53-03-2 it tw REFERENCE STANDARD USP certifies that the USP Reference Standards Committee, in accordance with their rules and procedures, determined that this USP Reference Standard lot is suitable to assess compliance with the monograph standards for \Which itis specified. The critical characteristics ofthis lot are usually determined independently in three or more laboratories, including USP, government, academic, and industrial collaborators QA Director 17-Jun-2008 poe fot repsep eee Page | of 2A-13 5 Calculation Value Unless otherwise stated on the Reference Standard label, a value of 100.0% should be used in USP or NF compendial applications for which the use ofthis Reference Standard is intended. Please refer to the specific Reference Standard label for further information, Expiration (Current Iots are identified in the Official USP Reference Standards catalog. In some cases, the previous lot may still bbe considered official. If so, itis identified in the column marked “Previous LovValid Use Date.” Ordinarily, the previous lot is carried in official status for about one year after the current lot enters distribution Is the responsibility of each user to determine that this lot is current when used. To ensure up-to-date information, USP publishes the Official USP Reference Standards Catalog, which contains official lot designations, This information is also available on the USP web site at www.usp.org, as well as inthe bimonthly subscription publication, Pharmacopeial Forum. Instructions for Use Follow the instructions in the appropriate USP or NF Monographs and General Requirements for Tests and Assays of the current USP-NF. In the event that instructions on the label ofthis lot differ from those found in the current USP-NF, those on the label supersede any instructions listed in Chapter <11>. Non-Monograph Use ‘The suitability ofthis Reference Standard for use in non-compendial applications is solely the responsibilty ofthe user. LEGAL NOTICE USP MAKES NO REPRESENTATION OR WARRANTY WITH RESPECT TO THE ACCURACY, COMPLETENESS, OR CURRENTNESS OF THIS CERTIFICATE; AND USP SPECIFICALLY DISCLAIMS ANY OTHER WARRANTY, EXPRESS, IMPLIED, OR STATUTORY, INCLUDING BUT NOT LIMITED TO, THE IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE. USP_DOES NOT WARRANT THAT THE INFORMATION CONTAINED HEREIN MEETS THE CUSTOMER'S REQUIREMENTS. USP SHALL NOT BE LIABLE ON ACCOUNT OF ANY SUCH ERRORS ‘OR OMISSIONS. USP Reference Standards are not intended for use as drugs, dietary supplements, or as medical devices. This document is not a Material Safety Data Sheet. ‘This certificate may not be reproduced without the express written permission of USP. (Copyright 2007 The United States Phanmacopial Convention Inc Al sights reserved. Page 2 of 2 17-Jun-2008 ee tebsep feoreFLPTOIOI Edicion: 19(2012- LABORATORIO DE CALIBRACION COLMETRIK LIDA.® CERTIFICADO DE CALIBRACION (CAUBRATION CERTIFICATE CMK-TFA- 15178 09-14) iictante: eine AMERICAN FARMAGRUP S.A.S. Ghecclénc Carrera 31 No. 25 A - 42. Bogota D.C. Insttumento Calibrade: Three-Channel Alarm Timer Calibrated insiument —_Fabricanter CONTROL COMPANY Modelo: 5000 ser 200221683 Dispositivo indicador: tco Inlervato de Medici 00h 00 min 00 s «99 h 59 min 595 Mélodo de Caiibracién: Resolucién : Especiticacién de exactitud: Praclice Guide 960-12 Slopwaich and Timer Calloralions Gel NIST Enero de Is 0,001 Calibration method 2009, Trazabilided: Las mediciones reaizadas son Wazables ol ssfema inlemaconal de unidades Trazebitity segiin se evidencia en ios cerfificados referidos a continuacién: ~ Contador de Frecuencia Agilent 53132A. ID: CMK-010223, Certiicado dle Catibrackin CMK-TFK-14026 del 2014/11/14 por faboratorio de metrologi Comet LIDA.® Acrecitado ONAC ~ Oscilacor de Rubialo SYMMETRICOM ET 6500, 1D: CMK-010102 Certiicado de Catibracién No. 0353 del 2014/01/14 por Instituto Nacional de ‘Metrologia de Colombia. Fecha de recepelén: 2015/09/28 Fecha de catibracién: 2015/09/20 Date of reception Date of calibration Fecha de emisién: 2015/10/02 Dale of emission Callbré: Calibrated by Avtoriza este cerliicado: Authorized by ‘or raitodos corespandn inicamente ais caltvootn Ge equiaa Gevalia Crlicada io Gaba ar epoGuaGo We jodorcorespar Iron Ge fo. i caicads oa ro he Sergio Soir Vitotoa Técnico de laboratorio i Tuan Sebastian Soto Gomer Coorcinacier de Laboratorio Revisado por - Checked by ‘sctta de Colette Lda ers Soa Rect ceamyA-13| FLPTOIO1 Edicion: 11(2012-09-14) ce | onac | colmetriii 7 LABORATORIO DE CALIBRACION COLMETRIK LTDA. Cerliicado de Calibracién No. CMK-TFA- 15178 “+ Incerlidumbre de medicién: La estimacién de Ia incertidumbre es basada en la "GUIA PARA LA EXPRESION DE INCERTIDUMBRE EN LAS MEDICIONES" GTC §1-1997 y en 6 procedimiento interno LPT-06. La incerlidumbre de medicién reportada fue esfimada teniendo en cuenta las contribuciones debidos a fa resolucién del patrén, trazabilidad del patrén y por Ia dispersién de los datos al medi. Esta Incertidumbre fue tratada como una distibucion normal, y esta expandida con el factor de cobertura reportado como ke 2.3 con el cual se aleanza un nivel de confianza del 95.45 %. “+ Condiciones ambientales: Temperatura maxima: 25,6 °C Temperatura minima: 252 °C 2% Humedad maxima: 35% Humedad minim: + Resultados de calibracién: Se reaiizaron mediciones del instrumento, se determiné el error al medit respecto al instrumenio Patrén, encontiande los siguientes resultados expresados como error + incerlidumbre: En valor absoluto: Eloscilador de 82 768 Hz tiene un error de 1.2556-01 Hz t= 2.6603 He En valor relative: 1 oscilador de 32 768 Hz tiene un error de 3830608 Ha/Hz + — 80F-08 Hafiz Ele err equate aun: ADSANO de 1 segundo cada 3 os, Oho 3 minus 3401 segundos um ABELANTO Se O55 cots po soon ese Conecclon: ty = Lectura a [= Bearers £8 am, Sees Lectura iy = Loctra del crondmetroen segundos Error, irror relative U iaeyy,) = Incertidumbre relativa “+ Observaciones: Para la ullzacién de esto nsrumento deben tenerse en cuenta los resuitados de ettacaltxacion, 6 Uwatio determina de acuerdo la folerancia eslablecida para | proceso de medcion con l instumento, este le es Ui con los resullados emlidos en este certticade, El uivatio es responsible de recalorar en un intervaloapropiado de lem sus nerumentos. Los resutadosreportados coresponden al momento y 0 ls condiciones en los cuales se realzaron lax pruebas mencionacles. COLMETRIE L'OA® no se resporscbilea por ios perhicion ses ve poocon Droduck por uso Inadecvado de este rsrumento Se aslgné y se achiié ol nsiumento la estampila de coliracion nimero: CMK-IFA 15178 _-, FIN DE CERTIFICADO Poe Nextt peg Poe een Rees goin)— : __Dissolution Apparatus Performance Qualification Protocol Report Center Printouts Attach any applicable Report Center printouts below: Goiemvedal Rrwseonishw: 2 nom iz sep lel’ Reviewer: ee ay aS ‘ie document i copia protected, tereore reproduction i proied ‘This quatitaton protocols Invalid Ifthe loge on tis page does not appear incor. VARIAN ‘PIN 70-6000, Revision J, August 2010 Page 51 of 56Dissolution Apparatus Performance Qualification Protocol Report Center Printouts ‘Atlach any applicable Report Center printouts below: ‘Qualification Representative: _P = Reviewer: 's copyright protected, therefore reproduction i prohibited. ‘This quatiteaion protects invalid ithe logo on this page doesnot eppeer In cooe. Page 520158 Pn 70.6800, Revision J August 2010,Appendix B: Dissolution Apparatus Performance Quelifcation Protocol Exceptions Each Exception Report shall be issued with a unique identification number in the form of ERID-XX-X. This number is generated by the page number on which the exception occurred followed by a sequential number indicating each ‘exception found on the page. For example, if an exception occurs on page 34, it shall be identified as Exception Report ‘ERID-34-1' f another exception occurs on page 34, the ‘second exception shall be identified as 'ERID-34-2'. Ths identification number ‘should be recorded in the passifall field ter each t Insert Exception Reports (i any) after this page. No. of Pages Inserted ° Exception Report Exceplion Report 1D. Date: ‘AIQ Protocol Name: ‘AIQ Protocol PIN: ‘AlQ Test Reference: Instrument Serial No Description of exception: wis Resolution to the exception: via ‘Qualincation Representative: Reviewer: a as VARIAN er paw_1zhsep }20r8 Date ‘This docamentis copyright protected therefore reproduction fs prohibited This qualieation protocols invalid the logo on this page does not appear in color [PIN 70.6900, Revision J, August 2010 Page 53056Dissolution Apparatus Performance Qualification Protocol Exception Report Exceplion Report 10: Date: "AIG Protocal Name: ‘AIG Protocol PIN: ‘AIG Test Reference! instrument Serial No Description of exception: via Resolution to the exception: 7 wie Exception Report aR Bat TG Peis Nara: ‘AQ Protocol PN —— TN Test Reerence inane! Sorat No: Description of exception: bie Resolution to the exception: via Cuaitston Representawve: _P- bate,_(2/sep 2016 Reviewer: Date: ‘dear nth pac nec a pea + : ‘Ths qulitestion protocol is invalid the lego on this age dows not appear in color. ae Page 54ot86 PIN 70-6000, Revision J, August 2010 VARIANDissolution Apparatus Performance Qualification Protocol End of Document 4 oe {Wis acon ony peat fore reproduction preibed mS Thi qutneton punliteehav be ope ships atop ent VARIAN PN 70-8900, Revision J. August 2010 Page 55.0156This page was intentionally left blank, except for this message. ‘This documents copyright protected, therefore reproduction Is prohibited. ‘This quaication protocols iavala i he loge on this page doesnot appear in ctor, Page 580156 Pv 70.6800, Revision J, August 2010 ap s 2 > 2