INSPEC PECTIONS W S WORKSH SHOP October ber 23, 23, 2013 2013 - - PowerPoint PPT Presentation

Eight ghth h An Annual al F FDA A Inspect spections

• ns

Summi mmit Be Bethesda esda, , MD MD Sept eptember er 23 23-25 25, 2013 2013

Presented by:

Freder derick H.

• H. Br

Brandin ing R.

• R. Ph

Ph., JD JD Pr Prin incip ipal, , OFW Law Law Washi hingt ngton,

• n, D

D.C.; Chi hicago ago

INSPEC PECTIONS W S WORKSH SHOP October ber 23, 23, 2013 2013

1 (C) Frederick H. Branding 2013

Re Reas asons f for FDA FDA Admi dmini nistrative Inspe pections ns

• Routine
• For Cause
• Warning Letter or Enforcement Action
• Complaints - Consumers, Industry, and

Current or Former Employees

• Recall Effectiveness Check
• Pre-Approval Inspection
• Special Enforcement Initiative

2 (C) Frederick H. Branding 2013

Pre Pre-App pproval I Inspe pections

FDA FDA appro approval of

• f N

NDAs s or

• r ANDAs

Only if the methods used in, and the facilities and controls used for, the manufacture, processing, packing, and testing of the drug are found adequate to ensure and preserve its identity, strength, quality and purity.

21 U.S.C. §§ 355(d)(3) and 355(j)(4)(A)

3 (C) Frederick H. Branding 2013

Pre Pre-App pproval I Inspe pections (cont.)

FDA’s s On S n Site O e Obj bject ective: e:

• Readiness for Commercial

Manufacturing (Compliance with cGMPs, equipment, etc.)

• Conformance to Application
• Data Integrity

4 (C) Frederick H. Branding 2013

Fo Focus us o

• f Pre-App

pproval I Inspe pection (cont.)

Areas C eas Cov

• vered I

ed Inc nclude: ude:

• Data Audits to Assess cGMP Compliance
• Batch Record Review
• Manufacture of Drug Substances
• Excipients
• Raw Materials (cGMP Controls)

5 (C) Frederick H. Branding 2013

Fo Focus us o

• f Pre-App

pproval I Inspe pection cont nt.

Areas C eas Cov

• vered:

ed:

• Raw Materials (Tests, Methods, and

Specifications)

• Composition and Formulation of Finished

Dosage Form

• Container/Closure System(s)
• Analytical Methods Validation
• Product (cGMP) Controls

6 (C) Frederick H. Branding 2013

Fo Focus us o

• f Pre-App

pproval I Inspe pection (cont.)

Areas C eas Cov

• vered:

ed:

• Product Tests, Methods, and

Specifications

• Product Stability
• Comparison of the Relevant Preapproval,

Validation and Proposed Commercial Production Batches (scale-up)

7 (C) Frederick H. Branding 2013

Fo Focus us o

• f Pre-App

pproval I Inspe pection (cont.)

Areas C eas Cov

• vered:

ed:

• Product Tests, Methods, and

Specifications

• Product Stability
• Comparison of the Relevant Preapproval,

Validation and Proposed Commercial Production Batches (scale-up)

8 (C) Frederick H. Branding 2013

Fo Focus us o

• f Pre-App

pproval I Inspe pection cont nt.

Areas C eas Cov

• vered:

ed:

• Facilities, Personnel, Equipment

Qualifications

• Equipment Specification(s)
• Packaging and Labeling (cGMP Controls)
• Process Validation
• Reprocessing
• Ancillary Facilities

9 (C) Frederick H. Branding 2013

Statutory A Aut uthor

• rity t

to Con Condu duct Estab ablishme ment I Ins nspection

• ns
• Section 704 [21 USC § 374]
• Reasonableness of the Inspection
• Frequency of Inspections
• Consent Unnecessary
• Inspection Warrants
• Warrant Unnecessary
• Miranda Warnings Unnecessary

10 (C) Frederick H. Branding 2013

Proced edure f e for Co Cond nducting I Inspections

• Investigation Operations Manual (IOM) Ch. 5
• Guidance documents
• Present Credentials and Notice of Inspection

(Form FDA 482); 21 USC § 374

• Entry may be refused if the investigator fails

to show credentials or does not issue a 482

11 (C) Frederick H. Branding 2013

Scope

• pe o
• f Inspec

pecti tion

• n
• FDA i

is Not

• t Expr

press ssly A y Aut uthor horized t zed to

• Obt

btai ain, n, But ut May May A Attem empt pt t to

• Obt

btai ain: n:

– Affidavits from individuals – Interviews of employees

• FDCA does not expressly authorize

investigators to interview a company’s employees –Non-managerial employees –Managerial employees: firm “admissions”. Notice to firm and opportunity to be

• present. – U.S. v. Bhutani (Criminal)

12 (C) Frederick H. Branding 2013

Scope

• pe o
• f Inspec

pecti tion

• n
• FDA i

is Not

• t Expr

press ssly A y Aut uthor horized t zed to

• Obt

btai ain, Bu But t May May Attempt pt t to

• Obt

btai ain:

– In-plant photographs

• Not specifically authorized

–Dow Chemical Co. –Acri Wholesale Grocery Co. – NB: Draft Guidance for Industry: Circumstances that Constitute Delaying, Denying, Limiting or Refusing a Drug

• Inspection. (July 12, 2013).

13 (C) Frederick H. Branding 2013

Scope

• pe o
• f Inspec

pecti tion

• n
• FDA’s A

s Aut uthor hority t to

• Ent

nter er and and to

• Ins

nspect pect Establ ablishm hment ents

– Prescription drugs or nonprescription drugs – Medical device records – Biologics establishments – Animal drugs and animal feeds – Food and cosmetic establishments – Radiation emitting electronic products – Internal quality audit reports (CPG Sec. 130.300) – Reasonable time, limits, and manner

14 (C) Frederick H. Branding 2013

Scope

• pe o
• f Inspec

pecti tion

• n
• Li

Limi mitation

• ns

s to

• the

he Scope

• pe of
• f Ins

nspe pect ction

• n

– Retail pharmacies (regular course, retail) – Licensed practitioners – Research, teaching, or chemical analysis – Exempted by regulation

21 USC § 374(a)(2)(A)-(D)

15 (C) Frederick H. Branding 2013

Scope

• pe o
• f Inspec

pecti tion

• n
• Inspection is authorized to the extent necessary

to ensure compliance with the Act and regulations.

• FDA may review any Records required to be

kept under the Act and regulations to determine compliance – No authority to review financial, sales, pricing, personnel, and research data – No express authority to review location of files – No clear authority to obtain background documents

16 (C) Frederick H. Branding 2013

Refus using a ng an Inspec pecti tion

• n

FDA Op Opti tions:

• Administrative Inspection Warrant
• Prohibited Acts; Refusal to permit:

– (e) Access to or copying of Required Records – (f) Entry or Inspection [21 U.S.C. § 331(f); 333(a);

CPG 130.100]

• Adulterated Drug: Delays, Denies, Limits,

Refuses Inspection. [21 USC § 351(j)]

• Guidance: “…Delaying, Denying, Limiting or

Refusing a Drug Inspection” (July 12, 2013)

17 (C) Frederick H. Branding 2013

“…Del Delaying, De Deny nying ng, Limi miting or

• r

Re Refus using a a Dr Drug Inspection” n”

FDA S Saf afet ety and y and Innov nnovat ation A

• n Act (

(“FDASIA”)

Amended ended § 704(a)(4): FDA may request required records prior to or in lieu of an inspection, within reasonable time, limits, and manner. [21 USC §374(a)(4)] Added dded § 501(j): deems a drug adulterated where inspection is delayed, denied, limited, or refused. [21 USC § 351(j)] Required FDA to issue Guidance – July 12, 2013.

18 (C) Frederick H. Branding 2013

Guidanc idance: D Delay laying, ng, D Deny nying ing, L Limit iting ing

• r R

Refus using ing a a Drug ug Inspe pection ion

• Del

elay of ay of Ins nspect pection

• ns

– Scheduling Pre-Announced Inspections – During an Inspection – Producing Records

19 (C) Frederick H. Branding 2013

Guidanc idance: D Delay laying, ng, D Deny nying ing, L Limit iting ing

• r R

Refus using ing a a Drug ug Inspe pection ion

• Deni

enial al of

• f Ins

nspect pection

• n

– Rejects attempt to schedule inspection – Does not allow inspection to begin – No inspection due to absence of certain staff – False statement re: non-manufacture of drugs

20 (C) Frederick H. Branding 2013

Guidanc idance: D Delay laying, ng, D Deny nying ing, L Limit iting ing

• r R

Refus using ing a a Drug ug Inspe pection ion

• Limit

iting ing o

• f I

Inspe pection ion

– Access to Facilities and/or Manuf. Processes

• Limited time to view operations
• Restricts entry to certain areas

– Limiting Photography

• Rodent/insect infestation
• Construction, Maintenance – equip., facility
• Contamination – raw materials, finished

product

• Labels, Labeling

21 (C) Frederick H. Branding 2013

Guidanc idance: D Delay laying, ng, D Deny nying ing, L Limit iting ing

• r R

Refus using ing a a Drug ug Inspe pection ion

• Li

Limi miting of ng of Ins nspe pect ction ( n (cont

• nt.)

– Access to or Copying of Required Records

• Refuses review of shipping records
• Partial record production
• Records unreasonably redacted

– Limiting/Preventing Collection of Samples

• Environmental, raw mtrls., finished products, etc.

22 (C) Frederick H. Branding 2013

Guidanc idance: D Delay laying, ng, D Deny nying ing, L Limit iting ing

• r R

Refus using ing a a Drug ug Inspe pection ion

• Ref

efusal usal t to

• Per

ermi mit E Ent ntry or y or Ins nspect pection

• n

– Action or Inaction:

• Bars Investigator from entering facility/areas
• Fails to unlock areas or take other action
• Fails to answer calls from FDA

23 (C) Frederick H. Branding 2013

Inspe pection F ion Frequ quenc ency

• Bienni

ennial al I Ins nspect pection

• ns f

s for

• r Dev

evices es

– Beginning with date of Registration

• Risk

sk-Based S ased Schedul hedule f e for

• r Drug

ugs

– Established by FDA considering Factors such as:

• Compliance History
• Record, history, nature of Recalls
• Inherent Risk of a Drug
• Inspectional Frequency and History
• Inspected by “recognized” Foreign Government
• “Other Criteria” deemed necessary & appropriate

(C) Frederick H. Branding 2013 24

Prepar paring ng f for F FDA I Inspec pecti tions

• ns
• Foresight. Assume FDA will come.
• Be Prepared. Audits
• Know/anticipate what the inspectors will do.
• Be vigilant. Monitor people, procedures,

progress.

• Have an “Establishment Inspection Plan”.

25 (C) Frederick H. Branding 2013

SOP for

• r FDA

FDA Inspe pections

• Elem

emen ents of

• f an

an Ins nspe pection

• n S

SOP – Access to documents not expressly required – Handling Confidential Documents – Sampling – Employee Interviews – Signing/not signing Affidavits – Permitting/not permitting Photographs – Corrections made during inspection – Response to a 483 (Inspectional Observations) – Internal communications about Inspection – Responses to inquiries generated by a 483

26 (C) Frederick H. Branding 2013

SO SOP for P for F FDA Ins DA Inspections

Reso esour urces es:

– FDA’s Investigations Operations Manual www.fda.gov/ora/inspect_ref/ – CBER Office of Compliance & Product Quality – CDER Office of Compliance – CDRH Office of Compliance – Office of Regulatory Affairs

• Published 483s, Warning Letters, legal actions

27 (C) Frederick H. Branding 2013

FDA P Prepar pares es f for I Inspec pecti tions

• ns
• Investigators review:

– Firm’s history – 483s, WLs & responses; EIRs, if any – Compliance Policy Guides, inspection programs – Firm’s Registration and Listing Information – Information provided by the Center, if any – Public Financial Records

• e.g., Annual Report, SEC filings, news, firm’s

website

• Investigators prepare needed equipment and any

sample collection materials, preprinted seals, etc.

28 (C) Frederick H. Branding 2013

During a ng an Inspec pecti tion

• n

Bef efor

• re I

e Issui ssuing ng a a 483: 483: “...investigators should make every reasonable effort to discuss cuss all observations with management... as they are obser

• bserved, or on a

dai daily basis to minimize sur surpr prises, er error

• rs, and

misun unde derst standi ndings gs when an FDA 483 is issued.”

IOM 5.2.3

29 (C) Frederick H. Branding 2013

During a ng an Inspec pecti tion

• n

Quest uestion

• ns, cl

clar arificat ation, n, et etc. c.

“Industry may use this opportunity to ask questions about observations, request clarification, and inform the [FDA] inspection team what corrections have been or will be made during the inspection process.”

IOM 5.2.3

30 (C) Frederick H. Branding 2013

Asking Q ng Questi tions

• ns
• Strings attached:

– If we do x, will the firm “pass” the inspection?

• Uninformed:

– “How should we do it?” – May I release product even though only technically OOS?

• The “one too many” question.
• Do not ask a question unless you’re willing to

accept the answer.

31 (C) Frederick H. Branding 2013

• 1. That will put us out of business!
• 2. Impossible!
• 3. Everyone else is doing this!
• 4. No one else has to do this!
• 5. Other inspectors never wrote us up for this!
• 6. You don’t understand how we do business.
• 7. No one died!
• 8. I won’t get my bonus if you write that 483.
• 9. I know the Commissioner.
• 10. Only one person died!

Wha What No Not t to Say

32 (C) Frederick H. Branding 2013

Ins nspectional O Obser ervations Fo Form FDA m FDA 4 483 83

FDA’s A s Aut uthor hority t to

• Issue a

sue a 483 483 “The observations of objectionable conditions and practices listed on the front of this form are reported:

• Pursuant to Section 704(b) . . .
• To assist firms inspected in complying

with the Act and regulations enforced by the FDA.”

Form FDA 483

33 (C) Frederick H. Branding 2013

Ins nspectional O Obser ervations Fo Form FDA m FDA 4 483 83

What hat i is a a 483? 483?

• “This document lists observations made by

the FDA representative during the inspection of your facility. They are inspectional observations; and do not represent a final Agency determination regarding your compliance.”

Form FDA 483; IOM 5.2.3.1.4

34 (C) Frederick H. Branding 2013

Fo Form FD FDA-483 O 483 Obser ervati tions

• ns

Pur urpose: pose:

• Notify top
• p management

management, in writing, of significant objectionable conditions, relating to products and/or processes, or

• ther violations of the FD&C Act and

related Acts which were observed during the inspection.

• These observations represent the

Investigator's judgment.

35 (C) Frederick H. Branding 2013

Fo Form FD FDA-483 O 483 Obser ervati tions

• ns

Timi ming: “Upon com compl pletion

• n of
• f any

any such i such inspe nspection

• n… the
• fficer or employee making the inspection shall

give to the owner… a report in writing setting forth any conditions or practices observed by him [her] which, in his [her] judgm udgmen ent, indicate that any [article]… in such establishment (1) consists…of any filthy, putrid or decomposed substance, or (2) …prepared, packed or held under conditions whereby it ma may have become contaminated with filth, or whereby it ma may have been rendered injurious to health.”

21 U 21 U.S.C § 374. 374.

36 (C) Frederick H. Branding 2013

Fo Form FD FDA-483 O 483 Obser ervati tions

• ns

Gener eneral Pri rinc ncipl ples:

• 1. Observations … should be significant and

correlate to regulated products or processes being inspected.

• 2. Observations of questionable significance

should not be listed on the FDA-483, but will be discussed with the firm’s management so that they understand how uncorrected problems could become a violation. This discussion will be detailed in the EIR

IOM 5.2.3

37 (C) Frederick H. Branding 2013

Fo Form FD FDA 48 483 O Observations

Char haract cter erist stics t s to

• be

be us usef eful ul and and cred edibl ble: e:

• Clear and Specific
• Significant (Length ≠ Significant)
• Not repetitious
• Ranked in order of Significance
• Legible
• Note uncorrected/recurring observation(s)

IOM 5.2.3

38 (C) Frederick H. Branding 2013

Conc ncludi ding ng an Inspec pecti tion

• n

Te Team A am Appr proa

• ach

– FDA Discussion with Management - Critical – Presentation of Form FDA 483 – Opportunity for questions, clarifications – Discussion of a Response

39 (C) Frederick H. Branding 2013

Post st-Ins Inspec pecti tion F

• n FDA A

Acti tiviti ties es

• Investigator(s) prepare Establishment

Inspection Report (EIR); recommend inspection classification.

• District Office supervisory review.
• Inspection classification: NAI, VAI, OAI
• OAI – DO Compliance Branch review;

potential further action.

40 (C) Frederick H. Branding 2013

Estab ablishme ment I Ins nspection

• n Rep

Repor

• rt

(“E (“EIR”) Inc nclude udes, s, among ot among other her i item ems: s:

• Investigator’s Narrative Report – in English.
• Individual Responsibility/Persons Interviewed.
• Supporting Evidence and Relevance.
• Discussion with Management.
• Inspectional Observations.
• Samples collected.
• Exhibits (BRs, SOPs, Schematics, etc.).

41 (C) Frederick H. Branding 2013

Evidenc ence D e Devel elopm

• pment

ent

42 (C) Frederick H. Branding 2013

Docum umentati ntation n is is the Evidence

. . . of

• f Viol
• lat

ation

• ns

s and and Prohi

• hibi

bited ed Acts and s and may may inc nclude: ude: –Establishment Inspections - 483s; EIRs –Untitled and Warning Letters –Correspondences to/from FDA –Inadequate responses to inspections

43 (C) Frederick H. Branding 2013

Fol Follow

• wing

ng an an Ins nspec pection

• n

Res espondi ponding ng to

• Ins

nspec pectional

• nal

Obs bser ervat ation

• ns – 483s

483s

44 (C) Frederick H. Branding 2013

To To Res espon

• nd or

r not to Res espond?

• No statutory or regulatory requirement to

respond to a Form FDA 483.

• Potential Negative Implications/Inferences

for not responding. (Don’t know/Don’t care?).

• Time frame to respond: 15 business days.

– 74 FR 40211, August 11, 2009

45 (C) Frederick H. Branding 2013

Ti Time Fr me Frames ames for

• r 48

483 Re 3 Responses and nd Wa Warning Le Letters

• FDA P

Policy N cy Notice ce (FR Notice Aug. 11, 2009)

– Purpose: Timely issuance of Warning Letters and prompt voluntary compliance. – Delayed and multiple 483 Responses lead to: – Delays in issuing Warning Letters while responses were reviewed.

• FDA Po

A Policy/ cy/Prog rogram ram – 15 Business Days to respond to 483 Observations. – “Detailed” review by FDA before WL decision. – If WL issued, it will acknowledge receipt of response and adequacy of corrective actions.

(C) Frederick H. Branding 2013 46

Ti Time Fr me Frames ames for

• r 48

483 Re 3 Responses and nd Wa Warning Le Letters

• FDA P

Pol

• licy/

cy/Progr

• gram

am

– Response after 15 business days:

• No routine comment on adequacy of CAs
• Evaluate 483 response with WL response
• FDA T

Time me Frame ames on s on War arni ning Let ng Letter ers

– 15 days after inspection: DO referral to Center – 15 days after HQ receipt: Notify DO of decision – 30 days after HQ declining: Memo. to DO – ?? days approval: FDA review and concurrence

(C) Frederick H. Branding 2013 47

Assessing 4 483 Observations

• Read

ead the Observations carefully - repeatedly.

• Under

nderst stand and FDA’s concerns.

• Ident

dentify each issue that requires a response.

• Inv

nvol

• lve

ve subject matter experts and firm’s escort; possibly outside advisors/consultants.

• Determine Scope
• pe of each observation.
• Evaluate from a Syst

ystem emic perspective.

48 (C) Frederick H. Branding 2013

Assessing 4 483 Observations

• Consider:

– System-wide implications – Global implications – Impact on product quality – Root cause analysis – Potential regulatory implications

• WL, Recall, FAR, MDR, AER, etc.

49 (C) Frederick H. Branding 2013

Assessing 4 483 Observations

• Consider:

– Developing immediate, mid, and long term Corrective and Preventive Action Plan(s). – Should the firm retain outside assistance? – Designating persons responsible for specific tasks and overall supervision and monitoring of response and implementation

• f corrective actions.

50 (C) Frederick H. Branding 2013

Responding t to 483s

Object ctive ves o s of Satisf sfact actory R y Respo ponse nses: s:

• Firm’s Understanding of Act and regulations.
• Firm is in compliance or taking appropriate

corrective action(s) to achieve compliance.

• Demonstrates firm knows what to do.
• May prevent increased regulatory scrutiny,

including increased frequency of inspections; further regulatory actions, e.g. WL.

51 (C) Frederick H. Branding 2013

Pre reparing a g a 48 483 Response

• Factual
• Complete
• Demonstrates understanding of issues and

regulatory requirements

• Supported by documentation
• Easy to read
• Reasonable and realistic time lines – prioritize

corrective actions

• Item-by-item responses

52 (C) Frederick H. Branding 2013

Pre reparing a g a 48 483 Response

• Include corrective actions done/planned:

– Specific actions – Complete descriptions – Realistic objectives and completion dates – Address product impact and support for

• decision. “What about product on the market?”
• Keep on schedule with commitments.
• Keep District Office informed.

53 (C) Frederick H. Branding 2013

War Warning L Let etter/48 483 Ina nadequate Re e Respon

• nses

“…[Y]our responses continue to be specific spot fix t fixes and have failed to achieve the necessary syst ystem emic appr c approac

• ach to

comprehensively address the violations.” “We acknowledge the receipt of your firm’s responses to our Investigators’ FDA – 483 dated…[4 responses over 8 months]. We do not not consider your responses to be adequat adequate because of the following…”

54 (C) Frederick H. Branding 2013

Warni ning L ng Letter er/48 483 Inadequ adequat ate R e Respons ponses

“…[T]he cGMP deficiencies need mo more re t time mely and com compr prehen hensive corrections than the actions you have proposed or taken.” “We note in your response that you have established a [redacted] plan to complete such validation for all products by the forth quarter of

• 2008. Please indicate if you int

nten end t d to

• shi

ship any pr product

• duct that has been manuf

anufac actured w d without

• ut a

val valida dated ed sterilization process. If so, then please identify the product and provide your justi tifi ficati tion for releasing such product.”

(Warning Letter dated December 2006)

55 (C) Frederick H. Branding 2013

War Warning L Let etter/48 483 Ina nadequate Re e Respon

• nses

“…[T]he failure to ext extend end the investigation to

• t
• ther

her bat batches ches of the sam same dr e drug ug product and

• t
• ther

her dr drug pr ug produc

• ducts that may have been

associated with the specific failure or discrepancy as required by 21 CFR 211.192.” “In your response to the Form FDA 483 you do not acknowledge any deficiencies in the investigation of these…failures, and you provide no no addi additiona

• nal i

inf nfor

• rmat

ation t n to

• suppor

support the conclusion… based on inaccurate and/or insufficient data, that the cont contam amina nation

• n

lead[ing] to the pr product

• duct f

fai ailur ures es was isol

• lated

ed to the two lots.”

56 (C) Frederick H. Branding 2013

“…[I]n light of the significant problems you

encountered with the control of the…facility…as well as the significant CGMP deviations documented during the current inspection, our

• ur

conf nfide dence in your investigat ative c conclus usion

• n for the

sterility failures noted above is further er w weakened ed.” “…[Y]ou do not address why you failed d to take appropriate action at the time of this incident to assess the scope of the problem and implem ement nt approp

• priat

ate c corrective action

• n to prevent r

recurren ence

• f this potential contamination

Warni ning ng Lette ter/4 /483 Inadequ adequat ate R e Respons ponses

57 (C) Frederick H. Branding 2013

War Warning L Let etter/48 483 Ina nadequate Re e Respon

• nses

“Due to the sever everity of the violations and the inadequat nadequate FDA-483 response esponses, we are reques equesting ng that you and/or your representatives come i

• me int

nto the _______ Distr tric ict Offic fice for a meet meeting ng and present your cor

• rrect

ctive ac ve action

• n pl

plan an to the agency. We We have tentatively schedu heduled ed a time of . .

• n [date] . . .”

58 (C) Frederick H. Branding 2013

Corpor porate W ate Warni ning L ng Letter ers

“We realize [redacted] has multiple locati ations

• ns. This letter is an offici

cial notification that FDA expects al all of your locati ations ns to be in compliance. We recommend al all of your locati ations ns be ev eval alua uated and that correct ctive ve a action be taken corporat

• rate-wi

wide if deficiencies are found.”

(Emphasis in original)

59 (C) Frederick H. Branding 2013

Corpor porate W ate Warni ning L ng Letter ers

“We request a pr prompt

• mpt meet

meeting ng with your

• firm. For this meeting, you should come

prepared to discuss your current corporate strategy to bring all of your facilities into

• compliance. You should also come

pr prepar epared ed to discuss the recent rec ecal alls at your facilities and your ongoing cor

• rpo

porat ate e ef effor

• rts to pr

prev event ent the rec ecurren ence ce of these violations.”

60 (C) Frederick H. Branding 2013

Corpor porate W ate Warni ning L ng Letter ers

“The purpose of this letter is to appri

pprise top

• p ma

mana nageme gement nt of your ina nade dequ quat ate cor

• rpor

porat ate-wide co correct ctive ve act ction pl plan an as evidenced by the co continuing seri erious

• us

defici cienci cies identified at each of these [redacted] facilities and to remind you of your responsibility to ensure that al all faci cilities continuously comply with the Act and all pertinent regulations.”

(Emphasis in original)

61 (C) Frederick H. Branding 2013

Common

• n R

Respons ponse M e Mistak takes es

• 1. Failing to Respond or Being Nonresponsive
• 2. Rushing
• 3. Being Defensive
• 4. Being Argumentative
• 5. Demonstrating a Lack of Understanding,

e.g., Ignoring the Root Cause

• 6. Making Unreasonable or Unrealistic

Commitments

• 7. Making Blanket Admissions
• 8. Failing to Provide Documentation, Specifics
• 9. Failing to Include “Preventive” Actions
• 10. Failing to Meet Commitments

62 (C) Frederick H. Branding 2013

Disagreeing/ Negotiating with FDA

• Science and Data to Support Position
• Public Health Risk
• Medical Necessity
• Risk Assessment

And possibly identify… – Arbitrary and Capricious Agency Conduct

• Change in Policy versus Enforcement

Discretion

63 (C) Frederick H. Branding 2013

FDA R Response se C Checkli klist st

DO

• Respond
• Demonstrate Understanding of the Issues
• Take Ownership
• Discuss Root Cause Analysis
• Discuss CAPAs in Detail
• Make Appropriate, Realistic Commitments
• Establish Milestones
• Disagree with Science, Facts, and Reason

64 (C) Frederick H. Branding 2013

FDA R Response se C Checkli klist st

DO NOT DO NOT

• Provi
• vide I

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65 (C) Frederick H. Branding 2013

Eighth Annual FDA Inspections Summit Bethesda, MD September 23-25, 2013

Thank hank Y You!

• u!

Frederick H. Branding, RPh, JD OFW LAW fbranding@ofwlaw.com 847-687-8415 202-286-0067

66 (C) Frederick H. Branding 2013