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Effective Communication for GRM

• Practices in PMDA-

November 15, 2016

Eriko Yamazaki Office of New Drug I Pharmaceuticals and Medical Devices Agency (PMDA), Japan

1

Disclaimer

2

The views expressed in this presentation are those of the presenter and do not necessarily reflected the official views of the PMDA.

Outline

• Introduction
• Communication between applicant and regulatory

agency

• Pre-submission
• Post-submission
• Post-approval
• Q&A/Discussion

3

Concept of Good Registration Management (GRM)

4

Synergic effects by parallel promotion of GRevP and GSubP

Applicants Review Authorities Applicants

Good Submission Practice

(GSubP)

Good Review Practice

(GRevP) Good Registration Management

GRevP and GSubP: Table of Contents

GSubP Guideline for Applicants 1. Introduction 2. Glossary 3. Principles of a good review 4. Managing the review 5. Communications 6. Review personnel 7. Conducting the review Bibliography GRevP: Guidelines for national and regional regulatory authorities

APEC-LSIF-RHSC endorsed GSubP Guideline in April 2016

1. Introduction 2. Principles of good submission 3. Management of submission 4. Communications 5. Competency and training 6. Glossary 7. Reference

4.1 With review authorities 4.2 Within applicant’s organization 5.1 Intra-agency 5.2 Interagency 5.3 With applicants 5.4 With external experts 5.5 With the public

Communication in GRevP

Regulatory agency Reviewer s Product A

academia

Health Care Professional s Patients and Family

Transparency

Product B

Regulatory agency

Efficient development Efficient review

External Experts

Collaboration Additional perspective

Communication between regulator and applicants

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To accomplish good submission and shorten review time…

PMS and PhV

Review

Review time is limited…Good submission is needed for regulatory authority to shorten NDA review time  No additional study and massive analysis  Less inquiry/response and additional analysis

Non- clinical

Phase 1 Phase 2 Phase 3

J-NDA prep

Communication between regulator and applicants

8

Review To accomplish good submission and shorten review time, communication between applicants and regulatory authority is needed from development stage

Non- clinical

Phase 1 Phase 2 Phase 3

J-NDA prep

Review time is limited…Good submission is needed for regulatory authority to shorten NDA review time  No additional study and massive analysis  Less inquiry/response and additional analysis

★ ★ ★ ★

Scientific Advices during development phase

Review

PMS and PhV

Communication between regulator and applicants

9

Review Review

Shorten review time ・・・ ・・・ Prompt reply to the queries Managing the review process Good communications Regulator s applicant s

To accomplish effective registration, good communication between the regulators and applicants is needed after submission

PMS and PhV

Number of approvals and review periods in Japan

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Months # of approvals

New Drugs ～FY2013: 50th percentile FY2014～: 60th percentile 107 112 130 134 138 117 116 11.9 9.2 6.5 6.1 7.2 8.8 8.7 19.2 14.7 11.5 10.3 11.3 11.9 11.3 20 40 60 80 100 120 140

FY2009 FY2010 FY2011 FY2012 FY2013 FY2014 FY2015

5 10 15 20

Number of approved applicants Priority Review Products Standard Review Products

（12 12） （9）

Principle of new drug evaluation in Japan

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• New drug evaluation processes based on the

Pharmaceutical and Medical Device Act should be undertaken by confirming that the new drug applied for does not fall under the “conditions for refusal of approval” defined in the Act.

Condition for refusal of approval

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• The applicant does not have the marketing

business license (for the category of the product applied).

• The manufacturing sites are not licensed or

accredited for manufacturing of pharmaceutical products (for the category of the product applied).

(According to Pharmaceutical and Medical Device Act Article 14 Paragraph 2)

Condition for refusal of approval

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• Manufacturing site of the drug applied does

not comply with the standard for manufacturing control and quality control defined in Ministerial Ordinances.

(According to Pharmaceutical and Medical Device Act Article 14 Paragraph 2)

Condition for refusal of approval

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• When the drug applied for approval falls under the

followings, as a result of review of its quality, efficacy and safety: – The indication of the drug applied has not been demonstrated. – The drug applied is found to have harmful effect that

• utweighs its intended effect, thus considered not of

value as a drug. – The drug applied corresponds to a case specified in a Ministerial Ordinance as inappropriate, other than the above.

(According to Pharmaceutical and Medical Device Act Article 14 Paragraph 2)

Benefit/risk balance

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• Approvals are not granted when

– The indication of the drug applied has not been

• demonstrated. (lack of efficacy)

– The drug applied is found to have harmful effect that

• utweighs its intended effect, thus considered not of

value as a drug (too much risk)

The approval does not mean the drug has no risk.

Roles of PMDA and MHLW

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• Scientific review
• Discussion with the

applicant and external experts

• Inspection
• Approval
• Enforcement of

administrative measures

• Management of the

Committees

PMDA MHLW

ICH Guidelines

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Category Topic Quality Q1:Stability, Q2:Analytical Procedures, Q3: Impurities, Q4: Pharmacopoeial Texts, Q6:Specifications, Q8-Q11: QbD, etc. Safety S1: Carcinogenicity, S2; Genotoxicity, S3: Toxicokinetics, S4: Chronic Toxicity, S5: Toxicity to Reproduction, etc. Efficacy E1: Clinical Safety for Drugs used in Long-term Treatment, E2: Pharmacovigilance, E3: Clinical Study Reports, E4: Dose Response Studies, E5: Ethnic Factors, E9: Statistics Principles etc. Multidisciplinary M1: MedDRA, M3: Nonclinical Safety Studies for Conduct of Clinical Studies, M4: CTD, M7: Genotoxic Impurities, M8: eCTD, etc.

Good Review Practice

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Japanese: http://www.pmda.go.jp/files/000164631.pdf English: https://www.pmda.go.jp/files/000153830.pdf Points to Be Considered by the Review Staff Involved in the Evaluation Process of New Drug (FINAL)*

Objective and Scope

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The objective of this document is to promote an understanding among the review staff involved in the evaluation of new drugs, of the basic principles and major points that need to be considered in being involved in the drug evaluation process at PMDA.

• This document summarizes basic points to be considered during

the actual evaluation process after submitting new drug application.

• This document mainly describes points related to clinical studies,

because it has been major issues of discussion for approval in the past.

Scope

Review Points

1. Has the reliability of the conducted studies and submitted documents been ensured? 2. Is the efficacy in the study population considered to be more effective than placebo according to the results of properly designed clinical studies? 3. Do the obtained results have clinical significance? 4. Are there any unacceptable risks as compared to the benefits? 5. Can the drug be supplied continuously with stable efficacy and safety from a quality assurance standpoint?

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Check Sheet in Good Review Practice

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Check sheet is based on the accumulating review information/experience of various disease area (cross-sectional discussion)

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Scientific Consultations & Drug Development Stage

Pre P-I Clinical End of P-II Pre NDA NDA Non-Clinical Review Pre P-II Post-Market Pre-post marketing End of Re- evaluation period Phase I Phase II Phase III Phase IV

Prior-Assessment Consultation

IND

Modified from Figure by Ichimaru K et al, Clin Pharmacol Therapeut, 88: 454-457, 2010

Pharmaceutical Affairs Consultation on R&D strategy

<Clinical trial consultations>

Consultation Category

23 NOTE: The list shown here is only on

• drugs. Another list available for

medical devices

So many categories to support a drug development - a sponsor can consult basically on ANYTHING, ANYTIME!

PMDA consultation process (example)

PMDA consultation PMDA Pre- Inquiries Response Pre-Inquiry

Submit FAX

Monday -5 wks Sponsor submit consultation questions and materials PMDA’s Opinion Sponsor’s response to PMDA’s opinion View

• 4 weeks

Sept 9 Oct

• 2 weeks

Oct 11

• 1 week

Oct 17 0 day Oct 24 Sponsor Submit Request for Consultation

2 mo. in advance of the request month, on the 1st working day

Date arranged

Approx 1 week from request submission 24

Aug 1 Aug 8

Draft minutes Minutes finalized

By Dec 7 Within 30 working days

Pre-meeting

• Seek advise on the following

 Consultation items (questions)  Background information to be included  What kind of data should be presented

• Evaluation of data will not be done until

the consultation meeting

• No charge, no minutes, applied at any

timing

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Based on available data of non-clinical studies, studies and experiences in other countries, information of similar drugs..

• The validity of applying the drug to a person for the

first time

• Clinical study design of Phase I, etc.

For example… Q：Are non-clinical data sufficient to begin a phase I trial ? Q：Are the initial dose and subsequent dose escalation schemes of the Phase I trial acceptable? Q： Are the parameters for clinical monitoring acceptable ?

Pre-phase I Study Consultation

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Based on the results of Phase I trials, studies and experiences in other countries, information of similar drugs…

• Clinical study design of phase II etc.

For example… Q：Are the selection of doses in dose-finding study in patients rationale ? Q：Are the design and monitoring of dose-finding study acceptable ?

Pre-phase IIb Study Consultation

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Based on available data of clinical trials…

• Clinical study design of phase III etc.

For example… Q：Are the recommended dose based on dose-response assessment appropriate ? Q：Are selection of control products and endpoints in the confirmatory clinical trials acceptable ? Q：Is data analysis protocol such as the method of sample size calculation suitable ? Q：Does the design of long-duration trial meet the related GLs ? Q：Is the sample size of Japanese subjects in the multi regional trial sufficient ?

End of phase II Study Consultation

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Based on available data of clinical trials…

• The way for compiling the application document
• Sufficiency of the application data package

For example… Q： Are the non-clinical and clinical data sufficient for the application ? Q： Are the proposed dosage & administration and indication appropriate ? Q：Is the data package including foreign clinical data acceptable ?

Pre-application Consultation

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Example- Clinical data package and study design

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• Clinical data package and study design

Studies required in general have been conducted Considering the study objectives, the protocol is appropriate

Points to be considered by the review staff

Example- Clinical data package and study design

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 Phase I: PK study (foreign and Japanese subjects)  Phase II: Dose titration design study  Phase III: Efficacy and safety confirmatory study Long-term safety study (MRCT incl. JP, one dose based on PII) Proposed clinical data package

Implementation status of each consultation

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Fiscal year

FY2010 FY2011 FY2012 FY2013 FY2014 FY2015

Total * 356 440 365 329 373 363 Pre-phase I study 64 67 44 30 42 45 Pre-phase IIa study 13 15 10 2 7 6 Pre-phase IIb study 44 45 32 37 34 36 End of phase II study 96 163 142 131 154 127 Pre-application 27 49 29 30 38 34 Additional 42 53 49 41 34 37 The protocols of clinical trials for reevaluation and re-examination 2 2 2 6 4

At completion of clinical trials

for reevaluation and re-examination 1 Application procedure consultation 22 6 6 2 7 8 Quality 24 17 20 21 17 36 Safety 12 13 18 16 18 23 On bioequivalence testing, etc. 8 6 11 12 18 11 On GLP/GCP compliance On document maintenance of Cell-and-tissue-based products 3 1 Pharmacogenomics (PGx)/ Biomarker 1 1 2 Total number of each IND scientific consultation about the new medical products (case)

*：including a withdrawal

Reference Guidelines

• Disease-area specific guidelines

 Clinical Evaluation of Hypnotics (2011)  Clinical Evaluation of Heart Failure Drugs (2011)  Clinical Evaluation of Oral Hypoglycemic Agents (2010)  Clinical Evaluation of Antirheumatic Drugs (2006)  Clinical Evaluation of Anticancer Drugs (2005)  Clinical Evaluation of Antiosteoporotic Drugs (1999)

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Reference Guidelines

• ICH E5, E8, E9, etc.
• Guidelines on MRCT

 Basic Principles on Global Clinical Trials (2007)  Basic Principles on Global Clinical Trials (Reference Cases) (2012)  Basic Principles for Conducting Phase I Trials in the Japanese Population Prior to Global Clinical Trials(2014)

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Utilization of consultation for GSubP

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 Benefit for applicants  Seek confirmation / advise from PMDA on key product development questions  Allow to inform PMDA on the development status  Benefit for PMDA  Chance to learn about product development status => allow PMDA review team to be prepared for submission  Chance to inform applicant on any items needed for submission that applicant is not aware of => leading to less post-submission inquiry, shorter review period !

WIN-WIN

• Agreed clinical data package
• Better submission package

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Pre P-I Clinical End of P-II Pre NDA NDA Non-Clinical Review Pre P-II Post-Market Pre-post marketing End of Re- evaluation period Phase I Phase II Phase III Phase IV

Prior-Assessment Consultation

IND

Modified from Figure by Ichimaru K et al, Clin Pharmacol Therapeut, 88: 454-457, 2010

Pharmaceutical Affairs Consultation on R&D strategy

<Clinical trial consultations>

Scientific Consultations & Drug Development Stage

Purpose and contents

• f the prior assessment consultation

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By implementation of this consultation before formal NDA О Shorten NDA review time

• Identify major discussion points and tasks for NDA

submission

• Help applicant to prepare a good CTD with the inclusion
• f PMDA’s view points

 Quality, Toxicology （non-clinical）, Pharmacology (non- clinical), Pharmacokinetics (non-clinical), Phase I study, Phase II study, Phase II/III study

• Data evaluation before a formal NDA submission
• PMDA provides a prior-assessment report for the submitted

data/study

Purpose Consultation contents

Flowchart of Prior assessment consultation

15 day* 30 day* 120 day*

（6 months） rough standard

Accept tentative application Inform acceptability pre-meeting（Informally） Accept application Inquiry Review response Evaluation report Review the documents Evaluation report writing PMDA’s Action Consulter’s Action

*working day

Submit application Submit document Submit the response to inquiry Confirm the evaluation report

40 day* 35 day*

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Tentative application

Fiscal year

FY2010 FY2011 FY2012 FY2013 FY2014 FY2015 Total * 23 24 41 15 44 8 Quality 4 6 8 3 11 1 Toxicity 6 4 9 2 7 2 Pharmacology 5 4 9 3 6 2 Pharmacokinetics 4 5 7 2 8 2 Phase I study 3 3 5 2 5 Phase II study 1 1 1 1 Phase II /III study

• 1

2 3 6 1 Number of prior assessment consultations on new medical products

*：including a withdrawal

Implementation status of prior assessment consultation

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Utilization of prior-assessment consultation for GSubP

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 Benefit for applicants  Clarify issues to be resolved in advance of submission  Focused discussion/less inquiries after submission  Benefit for PMDA  Opportunity to inform applicant on items to be resolved before submission  May allocate review effort more on important issues after submission

WIN-WIN!

• Assessment ahead of formal review
• Less inquiry issued post-submission
• Effective review after submission

PMDA-ATC Pharmaceuticals Review Seminar 2016 in Bangkok, Thailand

Process of new drug approval

Applicant Pharmaceuticals and Medical Devices Agency (PMDA) External experts

Pharmaceutical Affairs and Food Sanitation Council

Ministry of Health, Labour and Welfare (MHLW)

Review team Review report (1) Review report (2) Interview review meeting (major issues) GMP inspection results

Report on compliance GCP, GLP

Expert meeting I Interview (including initial meeting) Inquiry/Response Approval Expert meeting II (major issues)

Committee

• n Drug

Review conclusion

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Improvement of predictability of approval of new drugs

• Points to Consider for Reducing Total Review

Time for New Drug Applications

 PtC on preparing application dossiers, submission of additional data during review, etc.

• On Confirmation of Progress of New Drug Review

 Information shared between review team and applicants and review team in each stage of review

• On the Standard Review Timeline for New Drug

Applications (2012)

• Handling of Application and Total Review Time for

Improvement of Predictability of Approval (2015)

 Recommendation of pre-meeting on review schedule etc.

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Pre-meeting on review schedule

• Purpose

 Confirmation of review schedule and

• ther items between applicants and

PMDA prior to submission of an application

• Timing

 One to three months before submission of application

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Pre-meeting on review schedule

• Confirmation of review schedule

 Planned timing of application submission  Number of copies of dossier that need to be submitted  Rough schedule of each review events according to standard timeline  Timing of submission of long-term study data (final report) and long-term stability data  Timing of submission of other additional data

• Confirmation of inspection schedule

 GMP inspection: rough schedule of inspection application, timing of process validation, etc.  Conformity audit/GCP inspection: rough schedule of inspection, status of inspection overseas, etc.

• Others

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Review timeline for new drugs (standard review)

PMDA Applicant MHLW GLP/GCP inspection GMP inspection Initial Meeting Inquiry on important items Committee

• n Drug

Submission Approval

Review periods

[25%tile– median – 75%tile]

2.3 – 2.4 – 2.8 0.5 – 0.6 – 0.7 5.1 – 5.7 – 6.8 1.2 – 1.5 – 2.0 0.7 – 0.9 – 1.6

12 months

Expert Discussion Review report finalized

Review report #1 prepared

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Pre-Inquiry

Review timeline for new drugs (priority review)

PMDA Applicant MHLW GLP/GCP inspection GMP inspection Initial Meeting Inquiry on important items Committee

• n Drug

Submission Approval

Review periods

[25%tile– median – 75%tile]

1.6 – 1.9 – 2.0 0.2 – 0.3 – 0.7 4.2 – 4.4 – 5.6 1.1 – 1.3 – 1.5 0.8 – 0.8 – 1.1

9 months

Expert Discussion Review report finalized

Review report #1 prepared

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Pre-Inquiry

47

http://www.cirsci.org/june-2016/

Median Approval Time for New Active Substance

Common Technical Document (CTD)

48

(ICH M4 guideline)

Points to Consider in Preparing Applications for New Drug, etc.

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Administrative notice dated January 28, 2002 issued by Evaluation and Licensing Division, Pharmaceutical and Food Safety Bureau, MHLW

Sorry…Japanese only

Applicants can get a better understanding about point to consider in preparation of J-NDA for each review part (Quality, Pharmacology, ADME, Toxicology, Clinical)

Format for Preparing the CTD for Submission of NDA to Reduce Total Review Time

50

Administrative notice dated January 17, 2011 issued by Evaluation and Licensing Division, Pharmaceutical and Food Safety Bureau, MHLW

Sorry…Japanese only

Provides standard format on certain contents of CTD to avoid major revision after submission

• Quality (Process parameters)
• Clinical Safety (AE summary and analysis)

Review Team in Office of New Drug

51

Quality Pharma macolo

• logy

gy ADME Toxico colog logy Clinica cal Bio-stat atisti istic Pharmaceutical Veterinary Medical Bio-statistic

Office Director Review Director Review team leader Deputy team leader

Applicant Review team Inquiry Reply

The role of deputy team leader

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• Contact point of the review team for applicants

 Inform schedule of each review event (Interview, Inquiry/Response, Committee on Drug, etc.) to the applicant

• “Manager” of the review schedule of each product for

the review team  Aware of the review progress of each product and keep track of each review event according to SOP

• In case the applicants want to clarify and understand

the background of the query, they can ask for clarification through deputy team leader.

• Meeting with the review team is organized when

necessary.

Filing

• Check if the dossier is complete

 If not, the applicant will be asked to submit the missing part as soon as possible  In case of major deficiency, time to correct the dossier may be eliminated from the total review time

• Confirmation of review schedule

 Any update from schedule informed at the pre-meeting will be shared (based on latest review situation)  If submission is made without pre-meeting, time to reach agreement on review schedule may be eliminated from the total review time

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Initial meeting

• Timing

 2.0 - 2.5 months after submission

• Prior inquiries

 Sent in advance of the meeting  Response is required prior to the meeting (views exchanged in writing in advance)

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Initial meeting

• Face-to-face discussion

 PMDA review team discuss major issues with applicant which should be resolved prior to approval and other important discussion point  Applicant presents their thought and discuss how to approach the issue with the review team

55

Initial meeting

• Cases when initial meeting is held

 Submitted clinical package does not support efficacy and safety of the drug

• Requires additional study(ies)
• Cannot be approved unless resolved

In some cases applicant is informed that approval is difficult

 Other

• Share major issues to be resolved

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Initial meeting

• Other items to be informed to the

applicant

 Acceptability of brand name  Need for major change in specifications

• r strength of drug product (which will

require additional data)

57

Identify issues, exchange views and and share review status in the early stage

Inquiries and Responses

58

Applicant A Applicant B Need to send out additional query Cause the delay of review schedule query query clarification response response deputy team leader deputy team leader

Inquiries and Responses

• Inquiries

 Clear writing  Including examples of analysis tables may be useful  Post-query meeting may be held to convey the intention accurately

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Inquiries and Responses

• Responses

 Clarify the intent before responding as necessary (through contact point or by meeting)  Accurate response and concise representation of data  Controversial points which may lead to additional inquiry may be responded early

60

Review report (1)

• e.g. Sitagliption Phosphate Hydrate -

Summary of study results, applicant’s responses and PMDA’s evaluation. Applicant is asked to check the content (study results and applicant’s responses part) Reports excluding confidential information are available on PMDA website.

Contents of Review Report(1)

• I. Product Submitted for Registration
• II. Summary of the Submitted Data and the Outline of Review

by PMDA

• 1. Origin or history of discovery and usage conditions in

foreign countries etc. (p.4)

• 2. Data relating to quality (p.5)
• 3. Non-clinical data (p.9)

(i) Summary of pharmacology studies (ii) Summary of pharmacokinetic studies (iii) Summary of toxicology studies

• 4. Clinical data (p.36)
• III. Results of Compliance Assessment Concerning the Data

Submitted in the New Drug Application and Conclusion by PMDA (p.105)

• IV. Overall Evaluation (p.105)

Expert Consultation and post-Consultation Inquiry

• Review team consults experts on main

discussion points

• After expert consultation, review team

reaches conclusion

 Indication  Dosage and administration  Precautions on Package Insert  Risk Management Plan

• Identified risk, important potential risk and

important missing information

• Post-market surveillance
• Risk minimization activity (Information leaflet etc.)

63

Expert Consultation and post-Consultation Inquiry

• Post-consultation inquiries

 Applicant is asked to respond in a limited timeline  Prompt response and early negotiation  Meeting is recommended to clarify the background and reach mutual agreement

64

Communication involving stakeholders

65

Applicant A query response advise consultation External Experts

• Considering the external experts’ advise, PMDA

will reach conclusion with applicant on risk mitigation measures

Communication involving stakeholders

66

Applicant A query response response query

• Sometimes product approved overseas may be

an issue in regional regulation

• Compatibility with the regulatory framework may

have to be confirmed with MHLW

Review report (2)

• e.g. Sitagliption Phosphate Hydrate -

The contents are summary expert consultation and PMDA’s evaluation ◆Applicant is provided of draft/finalized report  Reports without confidential information are available on PMDA website.

Contents of Review Report(2)

• I. Product Submitted for Registration (p.106)
• II. Content of the Review (p.106)
• 1. Use in patients with renal insufficiency
• 2. Caution about combination therapy with other anti-

hyperglycemic agents

• 3. Post-marketing surveillance
• III. Overall Evaluation (p.111)

Preparation for MHLW Committee on Drug

• Revision of CTD

 CTD M1, M2 will be officially revised for MHLW Committee on Drug  PMDA reviews the draft if results of review are appropriately reflected

69

Follow-up meeting

• May be held upon request of either

applicant/regulator and agreement of both parties for efficient and improved future review

• Exchange of views
• PMDA’s view on NDA process
• Favorable aspects of applicant’s responses
• Suggestions for future application
• Applicant’s view on NDA process
• Lessons learned through NDA submission

70

Release of information regarding approval review of new drugs

Information released on PMDA’s website

• “Review Reports” that describe the details and results of

reviews

• “Summaries of Product Application” that summarize

submitted data by applicants

 Several review reports are translated into English.  The summaries of product application are available only in Japanese.

71

Medical Product Information page of PMDA website (Japanese)

• Information Related to Drugs

http://www.info.pmda.go.jp/info/syounin_index.html

• Information regarding the application review of new drugs (listed deliberation

products basis) http://www.pmda.go.jp/operations/shonin/info/new.html Medical Product Information page of PMDA website (English)

• Information Related to Drugs

http://www.pmda.go.jp/english/service/index.html

• Information regarding the application review of new drugs (listed deliberation

products basis) http://www.pmda.go.jp/english/service/list_s.html

Communications in post-submission stage

Factors to cause the delay of review schedule… 1. The applicant’s evaluation about the sufficiency of J-NDA package is different from that of regulatory authority  Need additional study 2. Having the information of safety risk in overseas after J- NDA  Need additional safety measures based on the management in overseas 3. Issues found on GMP inspection  Need additional time to address the issue 4. Having communication issues within applicants, or between regulatory authority and applicant  Need longer time to prepare response  Need additional query to response for potential issue from regulatory authority

72

Communications in post-submission stage

To avoid the delay of review schedule… 1. Effective use of consultation in each developmental stage  Prior-assessment consultation, pre J-NDA submission consultation 2. Comprehend the situation change in overseas during new drug review 3. Understand the requirement and schedule for GMP inspection 4. Having close communication within applicants, or between regulatory authority and applicant  Clarification of the background of query if necessary  Ask for a meeting with review team to discuss how to deal with

73

Communication with Industry

74

To update on regulatory environment …

• Seminar for regulatory affairs professionals
• Co-hosted by MHLW, PMDA and FPMAJ*

*Federation of Pharmaceutical Manufacturers’ Associations of Japan

• Attendee: Mainly RA experts from industry
• Annual update on related laws and regulations on

review, safety measures and inspections as well as points to consider in preparing application  Opportunity to communicate to industry on cases that needs attention  Optimization of submission package

Communication with Industry

75

To Aim for the achievement of more effective review…

• Review WG
• Attendee: PMDA (cross-sectional) and

representatives from industry

• Discuss current issue during review and work out

a solution based on the accumulating review information/experience  Promotion of streamlining of drug review process  Optimization of submission package

Re-examination

Drug Approval

4-10 years (8 years for new drug)

Post-approval Safety Measures

76

ADR and Infection Reporting

PMS EPPV

EPPV：Early Post Marketing Vigilance PMS：Post-Marketing Surveillance

Post-approval Communication

77

Collection of safety information Safety measures Hearing Report Request of PI revision

• Analysis
• Discussion with experts

ADR ADR Medical Institutions Public MAH Medical Institutions

Post-approval Communication

• Consultation framework on safety

measures

 Revision of PI/ Information for patients  Other safety measures

78

Communication between regulator and applicant is important throughout product life cycle

Consultation Advise Office of Safety Office of New Drug

Wrap-up

• Early communication is important in each

stage of product lifecycle

 Development stage  During review  Post-approval

• Good communication improves quality

and efficiency of review

79

WIN-WIN

• Less addition of documents in post-

submission

• Reduction of unnecessary operation

before NDA and during review

80

For the expedite approval of good medicine Good Submission Applicants Good Review Reviewers

Thank you for your attention

Questions/Discussion

• (to regulators) How is the environment
• f regulatory communication in your

country?

• (for applicants) What is an user-friendly

communication system? Has it been sufficiently implemented?

81