BVL公司（美国注射剂生产商）FDA检查缺陷

DEPARTMENT OF HEALTH AND HUMAN SERVICES FOOD AND DRUG ADMJNISTRAilON DATE(S) OF INSPECTIONDISTRICT OFFICE ADDRESS AND PHONE NUMBER 6751 Steger Drive Cincinnati, Ohio 4523 7 FEI NUMBER 1519257 NAME AND TITLE OF INDIVIDUAL TO WHOM REPORT IS ISSUED TO: Thomas J. Murphy, President & CEO l_:_:~=:=.~=l-~-~-~-u-~-N-~-~-:_z~-~~~6-~a~:-;~~=·e_"_s_~·-··I_.-n~c~.=~--~·- ... _·_·-·_·--_-.-~..·--··-[i];~~~~=~;•o ... ~=·~-~-"'-~~--~-~--·_ --~-=~~- -~·- -_ DURING AN INSPECTrON OF YOUR FIRM {I) (liVE} OBSERVED: This document lists observations made by the FDA representative{s) durjng the inspection. ofyour facility. They are inspectiona1 observations, and do not represent a final Agency detem1ination regarding your compliance. If you have an objection regarding an observation, or have implemented, or plan to implement, corrective action in response to an observation~ you may discuss the objection or ac.,iion with the FDA representative(s) during the inspection or submit this information to FDA at the address above. Ifyou have any questions, please contact FDA at the telephone number and address above, During an Inspection ofyour facility we observed. 1. The "Quality Manual", document #030-SOP-OP-01340, dated 28 Feb 2011, '~describes the pharmaceutical quality system (PQS) as implemented at BVL. The Quality Manual identifies the elements of the PQS and the sequences, linkages, and interdependencies of related processes, and the responsibilities of Management to ensure effective implementation." The ..Quality Manual includes the principles and responsibilities for implementation of BVL's PQS and pertains to all BVL departments involved in performing and/or supporting the development, manufacturing, testing, holding, distribUtion, and marketing of phannaceutical products." However, the following observations document a lack of adequate oversight by the Quality Unit to approve or reject the products manufactured and processed, as well as, approve or reject the established procedures and/or specifications impacting the quality of the drug product. 2. Failure to identify the root cause of foreign material, identified as stainless steel particles in two products, and which are contract manufactured by your firm. These products were all manufactured in the BVL south complex. All of the rots were released and distributed. Your firm has received 9 complaints from 08/16/06 to 02/09110. In 7 of the 9 c9mplaints, the foreign material was analyzed by a third party laboratory that identified the particles as stainless steel or elementally consistent with stainless steel. In the two other complaints, TRK 46061, the third party analysis identified that the particle appeared to be metallic and TRK 87006, the third party analysis identified the particle to be an iron particle, probably rust Neither a definitive root cause nor a corrective/preventative action has been identified or implemented to address the foreign particle issue. Also, for each of the complaints there are no samples retained to evaluate the foreign particle issue. received - Prod~ct(s) L BVLiot # I v;:~r rAnalyt. ica.f results oali~ T0o77:po~9o2o~~3,_,__._I_391J comeJaiQL'!.~ide~ ·;;:;A,.~<--A­ (b) (4) (b) (4) (b) (4) DEPARTMENT OF HEALTH AND HUMAN - •• ·~-: FOOD AND DRUG ADMINISTRATION ~---------~---~--------·~··~~W.--~-· DISTRICT OFFICE ADDRESS AND PHONE NUMBER 6751 Steger Drive Cincinnati, Ohio 45237 (513) 679-2700 M-­ DATE(S) OF INSPECTION 5/2-25/11 FE! NUMBER 1519257 !---'-~----------·~~-~--~-------.,--•••••--'"'"-'" ''""'"""'"""''_.,.,.,,.,..,.,,,,"'""''w"•--·"'"""·~·w- NAME AND TITLE OF INDIVIDUAL TO WHOM REPORT IS ISSUED TO: Thomas J. Murphy, President & CEO ~-------..-·--~--~·"------·------......,_•....~--~""'"....,...~,,... __............,, ·-"~-~----~ •Fl STREET ADDRESS Ben Venue Laboratories, Inc. 300 Northfield Road --···-~·•·•m•.w~w.. " -··=··~·'"=·•·•=m•.'•'·"'"·"'mm.•.-·•--"'~"·---+-------··•••• ,,.~•••·•--·~··----~~'"'" CITY, STATE AND ZIP CODE TYPE OF ESTAI3USHME:NT INSPECTED Bedford, Ohio 44146 Pharmaceutical Manufacturer DURING AN INSPECTION OF YOUR FIRM (I) {WE} OBSERVED: This document lists observations made by the FDA representative(s) during the inspection ofyour facility. They are inspectional observations, and do not represent a final Agency detennination regarding your compliance. Ifyou have an objection regarding an observation, or have implemented, or plan to implement, corrective action in response to an observation, you may discuss the objection or action with the FDA representative(s) during the inspection or submit this information to FDA at the address above. Ifyou have any questions, please contact FDA at the telephone number and addre ~rove.-t>\cming-atHtlspeetieJ t-ef..yew"-faeiJi.ty we--ebservecl. r--------1 ~~~~ces- Investigation Report (QIR) 30887 ~~~~-)7~·~-+-0-9/-06-/0_6_'"'1,_.... ~:-~-~:....,.~--~i-:-~-=-::-,---+-~::--~-::=-~:-----l--:::~~i~:~~;- r -~·~ -"622s":oa:·1acfo847=~rs1"o4'""'-'"~·· -3rd. party 0229-00-604280, 5093J #3885J indicates 0077-00-902093, 3911 J the particle 0077-00-874585, 3888J characteristics 0077-00-604240, 3839J suggest metal 0230-40-715940 5584J flakes I stainless steel ....36169-----·--04/1B/07-- ··· 0229-00-1000847 510~ 3ra. party 1 c______ analytical report, 05/9/07 lists metallic flakes I stainless steel variety 46061 03/07/oa I 0077-00-1007259 3920 3rd. party - analytical report, 02/06/08, identifies, main body of the particle appears to be metallic. -482"5"1'~~~-J""'~o-5712toif~" analytical report, - 04/07/08,I DATE ISSUED S/2r/u FORM FDA 483 (8/00) PRt;VIOUS EDITION OBSOLETE PAGE 2. OF']J PAGES (b) (4) (b) (4) (b) (4) (b) (4) DEPARTMENT OF HEALTH AND HUMAN SERVICES FOOD AND DRUG ADMINISTRATION 679-2700 adare~&i~ev~~~~tJfff\~a~rtasp,~tlem~ye,irt.~1t~~ve~~~~~d~----~r----,-~·---G-~~-----~-~---·, indicates particle 87006 94475 95173 95083 09/01/09 01/28/10 02/10/10 02/09/10 0077~00 ..1715034 0229-00-1739828 0229-00-1739828 0077-00-1793765 0229-00-1739828 3989 5123 5123 3996 5123 is likely a form of stainless steel party analysis performed on or about 08/27/09 identifies the particle to be an iron particle, rust. . party analytical report, 01/27/10, indicates the particle was a piece of stainless DISTRICT OFFICE ADDRESS AND PHONE NUMBER 6751 Steger Drive Cincinnati, Ohio 45237 WHOM REPORT IS ISSUED TO: Thomas J. Murphy, President & CEO FIRM NAM•r---~--~--------~ -- ---~---·-·---··-rsmEErADoREss--- ----·---··----------- ~-----,.-----·----w~--~---"--··------~- Ben Venue Laboratories, Inc. 300 Northfield Road ---~.•.....,.........,.-..-.,,.,._...,_._H.I.W.WW<.'Uu.-.•••"•'',..W.w."•''""""'.,_.,,.,,,..,_,,,,_,,,., ..-,.,.,, •···-... ,.,,,,_.,,_.,.,,,,,,.,,,,..,..... ,. ........,_,_,.,___,,,, .. ,, .. ,.,.,....,___ --.......-.--•..•--•••••"••••••••....,....,...~"·""-''·-~···w,·,·,·, ,'''•"''''...,.,.,.....,.,.____,_..........,.,. CITY, STATE AND ZIP CODE TYPE OF ESTABUSHMENT INSPECTED Bedford, Ohio 44146 Pharmaceutical Manufacturer ---··-· --·-·----~---~-----·------..·--·-----····-----~--! DURING AN INSPECTION OF YOUR FIRM {I) (WE) OBSERVED: This document lists observations made by the FDA representative(s) during the inspection ofyour facility. They are inspectional observations, and do not represent a final Agency detennination regarding your compliance. Ifyou have an objection regarding an observation, or have implemented, or plan to implement, corrective action in response to an observation, you may discuss the objection or action with the FDA representative(s) during the inspection or submit this information to FDA at the address above. Ifyou have any questions) please contact FDA at the telephone number and steel most steel, elementally ent with d party cal report, 02/05/10 (b) (4) (b) (4) (b) (4) (b)(4) (b) (4) (b) (4) DEPARTMENT OF HEALTH AND HUMAN SERVICES FOOD AND DRUG ADMINISTRAiiON DISTRICT OFFICE ADDRESS AND PHONE NUMBER 6751 Steger Drive OF INSPECTION 5/2-25/11 Cincinnati, Ohio 45237 FEI NUMBER (5132 679-2700 1519257 NAME AND TFfLE OF INDIVIDUAL TO WHOM REPORT IS ISSUED TO~ Thomas J. Murphy, President & CEO 'FIRM NAME__,,._..w,--,··-···-·-···--·-·-·--·"''.......- ...-...........-·--···--..- ........----····-·--..····--·-··--"·M·STREETADDRE·ss··.................--.----,..------,--.w--···---..·----.w-,-~ .......,, ___, Ben Venue Laboratories, Inc. 300 Northfield Road -·--·._...,,......__,.,,. .,.., ••w .... •_.,,,,,,,,,,,,,,_._,..,,..,.....,.,..,,,,.,,,,....._.,_.,,,,_.,,,,,,,,,,,,_,,_,,,__,.......,...,_....,,.,.,.,.,..,,,., .. ,,.....,.......,.,.,..........,..,.,. • .....,.,-,..,,,,.,._.......,""---..,,......., __,.....,._,..___,..,,,.....,.,..,.,,.,,..,., ..............__,........_.,__..,,.,·.·,·,·.•J•...,.........-..•.,.,,,,,_,.....,.._.~""'......,..,__.........,~.,.~,.......,. CITY, STATE AND ZIP CODE lYPE OF ESTA8USHMeNT INSPECTED Bedford, Ohio 44146 Pharmaceutical Manufacturer ~_,...,_~,,.. -•· ' . ... . ' '"'"' • . . "' • . ' . . """ •·w.·.·'~"""~--_ _,._...~.~ DURING AN INSPECTION OF YOUR FIRM (I) (WE) OBSERVED: This document lists obsetVations made by the FDA representative(s) during the inspection ofyour facility. They are inspectional observations, and do not represent a final Agency determination regarding your compliance. Ifyou have an objection regarding an observation, or have implemented, or plan to implement, corrective action in response to an observation, you may discuss the objection or action with the FDA representative(s) during the inspection or submit this infonnation to FDA at the address above. Ifyou have any questions, please contact FDA at the telephone number and indicates particle from fot#3996 predominantly a piece of stainless steel most li of In addition, SEE Rl:iVERSE OF THIS PAGE a. Complaint Report TRK # 95083, date received 02/09/10, contains two, third party analyticallabs, dated 4/9/10 and 4/15/10 which identify stainless steel particles in two lots {3996 and 40061). Lot 3996 was identified in complaint report TRK#95 ver, per your Supervisor, Quality System, there was no complaint investigation conducted for the stainless steel particles found in lot 40061. b. We observed the metal access doors {e.g., 9-10 doors in buildi used to transfer various pi~ces of equipment, and/or production related materials, into and out of the manufacturing areas. The metal access doors and door window frames appear to be severely dented with deep scratches/scoring on the metal surface areas. The damaged door conditions provide a source for metal particle contamination within the manufacturing areas; c. On 5/6/11, we observed tray racks which were located behind your facility. Your Supervisor Equipment and Component Prep, South Facility stated that these tray racks had been e south facility to this area that morning. The underside of tray rac ained an area that appeared to be rust-like material. We obsetved appare tches on two sides of the f he bottom shelf and on the outside face of two legs of rack num EMPJ.OYEE{S} SIGNATURE FORM FDA 463 (8/00) (b) (4) (b)(4) (b)(4) (b) (4) ( (b) (4) (b) (4) (b) (4) ----------~~------ DISTRICT OFFICE ADDRESS AND PHONE NUMBER 6751 Steger Drive Cincinnati, Ohio 45237 679k2700 NAME AND TITLE OF INDIVIDUAL TO TO: Thomas J. Murphy, President & CEO FIRM NAME Ben Venue Laboratories, Inc. ~-4+o~M.~'.WHNH.'............'A~'•~">NMW.".'•W·'·"••<«S NUMBER 6751 Steger Drive Cincinnati, Ohio 4523 7 679-2700 REPORT IS ISSUED TO: Thomas J. Murphy, President & CEO ~~e L:oratories, Inc .. ~·~ ·-·-._--·----··--------1$~~~~~~R:~~------- -----~--- cl;d~~~~~~~:~4~~~E ~-········ ··-~--~···-~----~~~~-,,~h":~~;~~~=:ro --·-=----.~ DURING AN INSPECTION OF YOUR FIRM (I) (WE) OBSERVED: This document lists observations made by the FDA representative(s) during the inspection ofyour facility. They are inspectional observatisms, and do not represent a final Agency detennination regarding your compliance. Ifyou have an objection regarding an observation, or have implemented, or plan to implement, corrective action in response to an observation, you may discuss the objection or action with the FDA representative(s) during the inspection or submit this infonnation to FDA at the address above. Ifyou have any questions, please contact FDA at the telephone number and address above._Du~n JJ..ection_Qf..¥our facilitv w~ observed. . e. The t-'roaua \5peclffc meata fill manufactunng batch record #1105-08-2125730, dated 9/19/10, document process simulations with manual interventions of the lyophilization pre-chilled vial steps, whic