1

FDA Inspection and FDA Inspection and ManagementManagementgg

Fran Rabe, MSFran Rabe, MS

Director of QADirector of QA

University of Minnesota, MCTUniversity of Minnesota, MCT

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Hosting a FDA InspectionHosting a FDA Inspection

Preparing for an inspectionPreparing for an inspection

Management of the FDA inspection processManagement of the FDA inspection process

Inspection responseInspection response

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2

Assignment ProcessAssignment Process

District or headquarters will send District or headquarters will send assignment to field inspectorsassignment to field inspectors

-- will include pertinent documents (e.g.:IND, will include pertinent documents (e.g.:IND, Drug Master File, copy of complaint, Drug Master File, copy of complaint, adverse event reports)adverse event reports)

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Types of FDA InspectionsTypes of FDA Inspections

Compliance Audit Compliance Audit –– Unlicensed ProductUnlicensed Product-- 361 product361 product-- Manufacturer of devices (e.g.: infectious disease Manufacturer of devices (e.g.: infectious disease test kits Isolex)test kits Isolex)test kits, Isolex)test kits, Isolex)-- Testing laboratory (e.g.: donor screening, Testing laboratory (e.g.: donor screening, microbiological cultures)microbiological cultures)-- licensed productlicensed product

Biomedical Monitoring (BioMo)Biomedical Monitoring (BioMo)

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-- Clinical trials Clinical trials -- IND or IDEIND or IDE

Biologics License Application (BLA) preBiologics License Application (BLA) pre--licensurelicensure-- review data used to support the applicationreview data used to support the application

3

Categories of InspectionsCategories of Inspections For Cause = DirectedFor Cause = Directed

-- Not a routine inspectionNot a routine inspection-- May be based on;May be based on;a) product complaint/problem reported by the PI or other a) product complaint/problem reported by the PI or other entityentityentityentityb) adverse events too many or too few (as compared to b) adverse events too many or too few (as compared to other investigational sites)other investigational sites)c) patient complaintc) patient complaintd) sponsor reports concerns about investigatord) sponsor reports concerns about investigatore) too may research subjects enrolled (as compared to e) too may research subjects enrolled (as compared to other investigational sites)other investigational sites)

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f) employee notification of “problems”f) employee notification of “problems”

Routine = SurveillanceRoutine = Surveillance

FDA Inspections of Facilities*FDA Inspections of Facilities*

20082008 20092009

Cord Blood and 19 42Cord Blood and 19 42Peripheral BloodPeripheral Blood

Trends show approximately 30% of inspections resulted in Trends show approximately 30% of inspections resulted in the issuance of a 483the issuance of a 483

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*Mary Malarkey, Director OCBQ, CBER*Mary Malarkey, Director OCBQ, CBER66thth Annual FDA and the Changing Paradigm for HCT/P RegulationAnnual FDA and the Changing Paradigm for HCT/P Regulation

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Inspection ClassificationInspection Classification

(NOI): No Action Indicated. Most (NOI): No Action Indicated. Most observations fall into this category.observations fall into this category.

-- Favorable outcomeFavorable outcome

-- No objectionable practices were identifiedNo objectionable practices were identified

(VAI): Voluntary Action Indicated(VAI): Voluntary Action Indicated

-- Objectionable conditions were identifiedObjectionable conditions were identified

-- Regulatory actions not requiredRegulatory actions not required

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Regulatory actions not requiredRegulatory actions not required

(OAI): Official Action Indicated(OAI): Official Action Indicated

-- Warning letterWarning letter

FDA Inspection ResultsFDA Inspection ResultsCord Blood and Peripheral BloodCord Blood and Peripheral Blood

NAINAI VAIVAI 0AI0AI

20082008 1515 44 00

20092009 2828 1010 44

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**Mary Malarkey, Director OCBQ, CBERMary Malarkey, Director OCBQ, CBER6th Annual FDA and the Changing Paradigm for HCT/P Regulation6th Annual FDA and the Changing Paradigm for HCT/P Regulation

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A FDA Form 482 versus a 483A FDA Form 482 versus a 483

FDA Form 482FDA Form 482

Notice of InspectionNotice of Inspection

-- FDA has the authority to inspect your facilityFDA has the authority to inspect your facility

FDA Form 483FDA Form 483

The report of inspection findingsThe report of inspection findings

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The report of inspection findings The report of inspection findings

-- Presented to person of most authorityPresented to person of most authority

-- Not a final determination regarding complianceNot a final determination regarding compliance

Be PreparedBe Prepared

Successful inspections are a result Successful inspections are a result comprehensive preparationcomprehensive preparation

-- Ensure you facility is compliant with Ensure you facility is compliant with regulatory requirementsregulatory requirements

-- Have procedures that define the process Have procedures that define the process for hosting the inspectionfor hosting the inspection

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for hosting the inspectionfor hosting the inspection

-- Have procedures for responding to Have procedures for responding to inspection reportinspection report

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Prepare in AdvancePrepare in Advance(BIOMO advanced notice)(BIOMO advanced notice)

Notify all pertinent staff (and others)Notify all pertinent staff (and others) Reserve dedicated roomReserve dedicated room

P t i lP t i l Prepare materials:Prepare materials:-- ProtocolProtocol-- Investigator brochure and consent formInvestigator brochure and consent form-- FDA Form(s) 1572 and CV(s)FDA Form(s) 1572 and CV(s)-- IRB approvalIRB approval-- SOPsSOPs

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-- SOPsSOPs-- Case report formsCase report forms-- Study related correspondenceStudy related correspondence-- Table of organizationTable of organization

FDA Methods of InspectionFDA Methods of Inspection ObservationObservation Interviewing staffInterviewing staff Reviewing documents (SOPs, records)Reviewing documents (SOPs, records) Examining facility equipment raw materialsExamining facility equipment raw materials Examining facility, equipment, raw materials, Examining facility, equipment, raw materials,

labels, packaging, final productlabels, packaging, final product Collecting Samples (obtain receipt) Collecting Samples (obtain receipt)

-- Finished productFinished product-- InIn--process or intermediate productprocess or intermediate product

Raw materialsRaw materials

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-- Raw materialsRaw materials-- LabelingLabeling-- PackagingPackaging

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FDA Methods of InspectionFDA Methods of Inspection

Ensure SOPs meet FDA regulationsEnsure SOPs meet FDA regulations

Establishment follows SOPsEstablishment follows SOPs

-- If it isn’t in a SOP, you don’t have to do itIf it isn’t in a SOP, you don’t have to do it

Documentation/records collaborate Documentation/records collaborate procedures are being followedprocedures are being followed

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-- If you didn’t document it, you didn’t do itIf you didn’t document it, you didn’t do it

Off Limits to FDAOff Limits to FDA

Internal audit reportsInternal audit reports Financial dataFinancial data Personnel personal data (other than Personnel personal data (other than

qualifications)qualifications) NonNon--IND research dataIND research data

May not breach sterility or impedeMay not breach sterility or impede

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May not breach sterility or impede May not breach sterility or impede productionproduction

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Audit ManagementAudit Management

Follow your internal SOPs on audit Follow your internal SOPs on audit managementmanagement

Review inspector credentialsReview inspector credentials

Relegate inspectors to dedicate Relegate inspectors to dedicate roomroom

Understand scope and potential length of Understand scope and potential length of auditaudit

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Example Procedure1. Upon arrival of a FDA inspector, the first contact person will:- Greet the investigator and get his or her name and ask the purpose of the visit.-Escort him to an open meeting room Page the PI or whoever the FDA wants to see (insert your site’s language re how to find the PI)FDA wants to see (insert your site s language re how to find the PI)and notify him/her of the2. Contact the Facility Director, Medical/Scientific Director and Director of Quality Assurance. Where applicable, the PI should be contacted.

3. The Principal Investigator and/or most senior member greets the inspector and:- review their credentials.

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review their credentials.4. Determine the purpose of the visit-For cause or routine inspection5. Notify all staff of the FDA’s presence in the facility6. For management of audit refer to SOP #234

SOP# 123, version C Effective 00/00/2010

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Inspection ProcessInspection Process

Opening meeting. Provided/request from the Opening meeting. Provided/request from the agency:agency:g yg y

-- FDA Form 482FDA Form 482

-- Scope of inspection (Directed versus For Cause)Scope of inspection (Directed versus For Cause)

-- Anticipated lengthAnticipated length

-- Staff expected to be needed Staff expected to be needed

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-- Facilities that will be involvedFacilities that will be involved

-- Review process: will they do summary at end of Review process: will they do summary at end of each day?each day?

Control the InspectionControl the Inspection

Ensure Ensure allall staff know the FDA is in your facilitystaff know the FDA is in your facility

Limit idle business conversation by Limit idle business conversation by allall staffstaff

-- Do not want FDA to overhear any information Do not want FDA to overhear any information that is not pertinent to the inspectionthat is not pertinent to the inspection

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Accompany inspector at all times when they are in Accompany inspector at all times when they are in your facility your facility

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How to Answer QuestionsHow to Answer Questions

TruthfullyTruthfully

Don’t elaborate beyond direct questionDon’t elaborate beyond direct questionDon t elaborate beyond direct questionDon t elaborate beyond direct question

OK to say “I don’t know”, but I’ll get you the OK to say “I don’t know”, but I’ll get you the answeranswer

OK to ask for clarity related to questionOK to ask for clarity related to question

OK to disagree and provide a clarification or OK to disagree and provide a clarification or example (provide documentation whereexample (provide documentation where

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example (provide documentation, where example (provide documentation, where applicable)applicable)

PolitePolite

Audit ManagementAudit Management Maintain a copy of all documents providedMaintain a copy of all documents provided Keep notesKeep notes Maintain a list of documents provided to the agency, Maintain a list of documents provided to the agency,

hi h th t k ith thhi h th t k ith thwhich they take with themwhich they take with them Obtain a receipt for products, materials, Obtain a receipt for products, materials,

packing/labeling taken by the FDApacking/labeling taken by the FDA End each day with a synopsis with the FDA of End each day with a synopsis with the FDA of

findings/concernsfindings/concerns Meet with staff to see what corrections/clarity canMeet with staff to see what corrections/clarity can

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Meet with staff to see what corrections/clarity can Meet with staff to see what corrections/clarity can help with remaining audit timehelp with remaining audit time

Generate potential corrective action immediately to Generate potential corrective action immediately to present to FDA the following daypresent to FDA the following day

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Handling 483Handling 483

Response not “required”Response not “required”

-- But, lack of response is viewed as a lack of But, lack of response is viewed as a lack of concernconcern

Immediately respond to reportImmediately respond to report

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-- Response within 15 days can result in Response within 15 days can result in revised 483s (to your benefit)revised 483s (to your benefit)

483 Response483 Response FactualFactual

-- do not speculatedo not speculate Describe interim controlsDescribe interim controls

D t t l ti f t dD t t l ti f t d Demonstrate evaluation of root cause and Demonstrate evaluation of root cause and systems that may have contributed to problemsystems that may have contributed to problem

Provide comprehensive description of corrected Provide comprehensive description of corrected system controlssystem controls

Address impact to past previously distribute Address impact to past previously distribute productproductAdd i t t ti d t i tAdd i t t ti d t i t

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Address impact to quarantine product inventoryAddress impact to quarantine product inventory Address prevention of future problemsAddress prevention of future problems Provide dates for completion of all corrective Provide dates for completion of all corrective

actionaction

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Inaccurate Observation FindingsInaccurate Observation Findings

Demonstrate where finding is incorrectDemonstrate where finding is incorrect

-- provide documents and/or referencesprovide documents and/or references

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Establishment Inspection ReportEstablishment Inspection Report(EIR)(EIR)

A detailed narrative of the inspection. Includes A detailed narrative of the inspection. Includes lists of all records reviewed what aspect oflists of all records reviewed what aspect oflists of all records reviewed, what aspect of lists of all records reviewed, what aspect of the facility was audited. A detailed summary the facility was audited. A detailed summary of the inspection. Includes identification of of the inspection. Includes identification of specific records reviewed, identification of specific records reviewed, identification of participating staff, staff commentsparticipating staff, staff comments Available to inspected establishment afterAvailable to inspected establishment after

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Available to inspected establishment after Available to inspected establishment after inspection process is inspection process is closedclosed Available to pubic through Available to pubic through Freedom of Freedom of

Information Act Information Act

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Example EIRExample EIR

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FOIFOI The Freedom of Information Act (FOIA) and FDA's The Freedom of Information Act (FOIA) and FDA's

regulations governing disclosures require release regulations governing disclosures require release of inspection information to the publicof inspection information to the public

List of inspectional observations (FDAList of inspectional observations (FDA 483)483)-- List of inspectional observations (FDAList of inspectional observations (FDA--483)483)-- EIR (attachments and exhibits are excluded from EIR (attachments and exhibits are excluded from requirement)requirement)-- Warning letters communication with the Warning letters communication with the regulated establishment must be disclosed upon regulated establishment must be disclosed upon request by any member of the publicrequest by any member of the public

Mandate publicly accessible "electronic readingMandate publicly accessible "electronic reading

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Mandate publicly accessible electronic reading Mandate publicly accessible electronic reading rooms" with electronic search and indexing rooms" with electronic search and indexing featuresfeatures

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FOIFOI-- RequestsRequests

Requests must be in writing (do not accept eRequests must be in writing (do not accept e--mail)mail) AA. Requestor's name, address, and telephone number.. Requestor's name, address, and telephone number. BB. A description of the records being sought. The records . A description of the records being sought. The records

should be identified as specifically as possible A requestshould be identified as specifically as possible A requestshould be identified as specifically as possible. A request should be identified as specifically as possible. A request for specific records that are releasable to the public can be for specific records that are releasable to the public can be processed much more quickly than a request for "all processed much more quickly than a request for "all information" on a particular subject. Also fees for a more information" on a particular subject. Also fees for a more specific and limited request will generally be less.specific and limited request will generally be less.

CC. Separate requests should be submitted for each firm or . Separate requests should be submitted for each firm or product involved.product involved.

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DD. A statement concerning willingness to pay fees, . A statement concerning willingness to pay fees, including any limitations.including any limitations.

FDA web: FDA web: http://www.fda.gov/RegulatoryInformation/FOI/HowtoMakeaFOIARequest/default.htmhttp://www.fda.gov/RegulatoryInformation/FOI/HowtoMakeaFOIARequest/default.htm

FDA LettersFDA LettersUntitled versus WarningUntitled versus Warning-- Both Intend to Notify of Both Intend to Notify of

Practices that Need to be AmendedPractices that Need to be Amended

Warning Letter:Warning Letter:gg Expresses FDA’s stance (based on statue or Expresses FDA’s stance (based on statue or

rules)rules) Not a commitment to enforcement, but a prelude Not a commitment to enforcement, but a prelude

to to possiblepossible enforcement enforcement Serious stuff (call your lawyer)Serious stuff (call your lawyer)Untitled Letter:Untitled Letter:

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Untitled Letter:Untitled Letter: Intended to induce voluntary compliance with Intended to induce voluntary compliance with

regulationsregulations Does not include a statement about potential Does not include a statement about potential

enforcement actionenforcement action

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Warning LettersWarning Letters

Letter states requirement timeLetter states requirement time--line for line for response (usually 15 days)response (usually 15 days)

Letter of closure issued after corrective Letter of closure issued after corrective actions have been satisfactorily addressedactions have been satisfactorily addressed

li bl t i l tt i d ftli bl t i l tt i d ft

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-- applicable to warning letters issued after applicable to warning letters issued after 9/1/20099/1/2009

FDA LettersFDA Letters

FDA posts warning letters on their web site:FDA posts warning letters on their web site:

http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/default.htmhttp://www.fda.gov/ICECI/EnforcementActions/WarningLetters/default.htm

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CSL Biotherapies Untitled LetterBrian McNameeChief Executive Officer (CEO)CSL Biotherapies

[Example of Actual Untitled Letter]

p45 Poplar RoadParkville, Victoria 3052Australia

Dear Mr. McNamee:

The Food and Drug Administration (FDA) conducted an inspection of CSL Biotherapies, located at 45 Poplar Road, Parkville, Victoria 3052, Australia, between April 19 and April 28 2010 During the inspection FDA investigators documented

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April 19 and April 28, 2010. During the inspection, FDA investigators documented deviations from current good manufacturing practice (CGMP) requirements in the manufacture of licensed biological vaccine products and monovalent influenza bulks.

We would like to meet with you and other senior management at CSL Biotherapies to further discuss the issues cited in this letter and how you will address them going forward..

Regenerative Sciences, IncJuly 25, 2008CERTIFIED MAILRETURN RECEIPT REQUESTEDChristopher J. Centeno, M.D.Medical DirectorRegenerative Sciences, Inc.11080 Circle Point Road

[Example of Actual Untitled Letter]

Building 2, Suite 140Westminster, Colorado 80020

Dear Dr. Centeno:

The Food and Drug Administration (FDA) has reviewed your website at Internet address: http://www.regenexx.com and has determined that you are promoting your use of mesenchymal stem cells under conditions that cause these cells to be drugs under section 201(g) of the Federal Food, Drug, and Cosmetic Act (the Act) [21

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(g) g ( ) [U.S.C. 321(g)] and biological products, as defined in section 351(i) of the Public Health Service Act (PHS Act) [42 U.S.C. 262].

We request that you notify this office, in writing, of the steps you have taken or will take to address the violations noted above and to prevent their recurrence. Your response should be sent to me at the following address: U.S. Food and Drug Administration, Center for Biologics Evaluation and Research, HFM-600, 1401 Rockville Pike, Suite 200 N, Rockville Maryland 20852-1448.

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FDA NEWS RELEASEFor Immediate Release: August 6, 2010Media Inquiries: Shelly Burgess, 301-796-4651, shelly.burgess@fda.hhs.govConsumer Inquiries: 888-INFO-FDAFDA Seeks Injunction Against Colorado Manufacturer of Cultured Cell Product

Example of Actual FDA News Release Regarding Action

The U.S. Food and Drug Administration is seeking an injunction in federal court against Regenerative Sciences LLC, of Broomfield, Colo., citing violations of current good manufacturing practice (cGMP) that cause its cultured cell product to be adulterated. The product is also misbranded due

3333http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm221656.htm

p pto the lack of adequate directions for use and the failure to bear the “Rx only” symbol.

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EnforcementEnforcement RecallsRecalls InjunctionInjunction

-- a civil action to prevent cease production and/or a civil action to prevent cease production and/or distributiondistributionS i f fi l d tS i f fi l d t Seizure of final productSeizure of final product

FinesFines Consent decreeConsent decree

-- an legal agreement to correct. Details exact an legal agreement to correct. Details exact requirements.requirements.

Criminal investigationsCriminal investigations-- allows FDA to hold employees legally liable for theirallows FDA to hold employees legally liable for their

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allows FDA to hold employees legally liable for their allows FDA to hold employees legally liable for their actionsactions

http://www.fda.gov/Safety/Recalls/EnforcementReports/default.htmhttp://www.fda.gov/Safety/Recalls/EnforcementReports/default.htm

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Dr. Cook Warning LetterDr. Cook Warning Letter

We acknowledge your July 2009 response and commitment to develop We acknowledge your July 2009 response and commitment to develop a a (b)(4)(b)(4). Please provide a copy of your . Please provide a copy of your (b)(4)(b)(4). . ΧΧ In addition, if not included in theIn addition, if not included in the (b)(4)(b)(4) provide corrective actions to provide corrective actions to prevent similar deviations from recurring. prevent similar deviations from recurring. p gp gΧΧ Note that failure to have an adequate number of qualified personnel Note that failure to have an adequate number of qualified personnel is not justification to circumvent your adherence to CGMP is not justification to circumvent your adherence to CGMP requirements.requirements.

We acknowledge your July 2009 response that indicates the We acknowledge your July 2009 response that indicates the (b)(4)(b)(4) in in the completion of your APRs and your commitment to the completion of your APRs and your commitment to (b)(4)(b)(4) to to complete APRs. complete APRs. ΧΧ Please provide timeframes for the completion of the Please provide timeframes for the completion of the (b)(4)(b)(4). In . In additionaddition

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addition, addition, ΧΧ please provide corrective actions to prevent similar deviations please provide corrective actions to prevent similar deviations regarding your failure to follow your APR procedure. regarding your failure to follow your APR procedure. ΧΧ Note that failure to have an adequate number of qualified personnel Note that failure to have an adequate number of qualified personnel is not justification to circumvent your adherence to CGMP is not justification to circumvent your adherence to CGMP requirements.requirements.

Gibson LaboratoriesGibson Laboratories Your firm rejected 14 lots of product in 2008 due to Your firm rejected 14 lots of product in 2008 due to

contamination and the corrective action was to retrain contamination and the corrective action was to retrain employees on aseptic technique.employees on aseptic technique.ΧΧ This corrective action was not effective. In 2009, your This corrective action was not effective. In 2009, your film received 23 complaints on contaminated product andfilm received 23 complaints on contaminated product andfilm received 23 complaints on contaminated product and film received 23 complaints on contaminated product and rejected 13 lots of product due to contamination. rejected 13 lots of product due to contamination. ΧΧ Additionally, your firm's failure investigations into Additionally, your firm's failure investigations into nonconforming products do not include reviewing the nonconforming products do not include reviewing the results of environmental testing of the fill room for the days results of environmental testing of the fill room for the days in which contaminated product has been produced. in which contaminated product has been produced.

ΧΧ You have failed to conduct a failure investigationYou have failed to conduct a failure investigation

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ΧΧ You have failed to conduct a failure investigation You have failed to conduct a failure investigation that identifies the root cause of contaminationthat identifies the root cause of contaminationΧΧ You have not taken a corrective action that reduces You have not taken a corrective action that reduces the trend of contaminated product.the trend of contaminated product.

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Washington Homeopathic Products, Inc.Washington Homeopathic Products, Inc.

Broken glass was identified in filled 15 cc glass bottles of TBroken glass was identified in filled 15 cc glass bottles of T--Gone Gone Remedies Type 4 (lot Remedies Type 4 (lot (b)(4)(b)(4)) on January 20, 2009, during product filling ) on January 20, 2009, during product filling operations. This lot was rejected and destroyed on January 29, 2009. operations. This lot was rejected and destroyed on January 29, 2009. "Deviation Report," dated January 22, 2009, stated: "Broken glass was "Deviation Report," dated January 22, 2009, stated: "Broken glass was in the prepackaged and sealed bottles from the distributor. No risks in the prepackaged and sealed bottles from the distributor. No risks

i l d P d t ll d d d t d J 29 2009i l d P d t ll d d d t d J 29 2009were involved. Product was pulled and destroyed on January 29,2009. were involved. Product was pulled and destroyed on January 29,2009. The broken glass inside the bottles accrued at the distributor's The broken glass inside the bottles accrued at the distributor's operation. The drug product with the broken glass was destroyed and operation. The drug product with the broken glass was destroyed and all other products that were used with that component was rechecked all other products that were used with that component was rechecked and all were all were clear." and all were all were clear." ΧΧ The investigation failed to identify other related products and The investigation failed to identify other related products and lots manufactured with the implicated glass vials to assure no lots manufactured with the implicated glass vials to assure no additional broken glass was present. additional broken glass was present. ΧΧ Finally, the specific lot number of the problematic glass bottles Finally, the specific lot number of the problematic glass bottles

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(components) used to fill T(components) used to fill T--Gone Remedies Type 4 (lot (b)(4)) on Gone Remedies Type 4 (lot (b)(4)) on January 20, 2009 was not documented in the investigation.January 20, 2009 was not documented in the investigation.

Dr. Cook Warning LetterDr. Cook Warning Letter

We acknowledge your July 2009 response and We acknowledge your July 2009 response and commitment to complete stability testing, commitment to complete stability testing, (b)(4)(b)(4) to ensure to ensure adherence to the stability procedureadherence to the stability procedureadherence to the stability procedure. adherence to the stability procedure. ΧΧ However, we believe your response does not provide However, we believe your response does not provide adequate preventive actions becauseadequate preventive actions because (b)(4)(b)(4) do not address do not address the failure of the QCD to ensure your procedures are the failure of the QCD to ensure your procedures are followed and training is effective. Please provide corrective followed and training is effective. Please provide corrective action to prevent recurrence of similar deviations. For action to prevent recurrence of similar deviations. For example, you may develop a contingency plan to send example, you may develop a contingency plan to send your stability samples for testing to a qualified contractyour stability samples for testing to a qualified contract

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your stability samples for testing to a qualified contract your stability samples for testing to a qualified contract laboratory, or you may reduce your product line to reduce laboratory, or you may reduce your product line to reduce the laboratory workload.the laboratory workload.

21

483 Response483 ResponseEnsure safety of this product/lot # identified. Ensure safety of this product/lot # identified.

Determine dispositionDetermine disposition

Evaluate status of product collected and remaining in Evaluate status of product collected and remaining in establishment quarantine/released inventoryestablishment quarantine/released inventory

Evaluate status of product (same type and/or lot #) Evaluate status of product (same type and/or lot #) that has been release and may be in (hospital) that has been release and may be in (hospital) inventoryinventory

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yy

Ensure future products are problem freeEnsure future products are problem free

483 Response Approach483 Response Approach

Root Cause Analysis Root Cause Analysis Exact CauseExact Cause

Prevent reoccurrence through application of Prevent reoccurrence through application of quality systems. E.G.:quality systems. E.G.:-- design controldesign control-- quality controlquality control

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quality controlquality control-- quality review (trending, etc.)quality review (trending, etc.)-- early detection of problems (through audit)early detection of problems (through audit)

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Lessons LearnedLessons Learned A good relationship with headquarters does not impact the inspection A good relationship with headquarters does not impact the inspection

processprocess-- the inspectors are from “the field”the inspectors are from “the field”

Cellular Therapy area is new for FDACellular Therapy area is new for FDA-- Not always very familiar with processes or application of regulationsNot always very familiar with processes or application of regulations

Every inspection is unique:Every inspection is unique:-- Focus variesFocus varies-- Adverse findings will vary and/or conflicts with previous inspectionsAdverse findings will vary and/or conflicts with previous inspections

Respond to 483 promptly and appropriatelyRespond to 483 promptly and appropriately

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QuestionsQuestions

Fran RabeFran Rabe

rabex022@umn.edurabex022@umn.edu

612612--625625--56325632

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