03_Quality Related Topics

7/29/2019 03_Quality Related Topics

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All Rights Reserved 2008 Health Sciences Authority | 2

Quality-Related Topics

Ms Yusyanti Mat TAHIRSenior Regulatory Specialist

Pharmaceuticals & Biologics BranchTherapeutics Products Division

Health Products Regulation GroupHealth Sciences Authority


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Overview of guideline revision

Quality Documents (additional information)

- Drug Substance Drug Master File, CEP

- Drug Product Control of Excipients

Singapore Quality Overall Summary (SQOS)

Minor Variation Applications (MIV)

Summary

Scope


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Overview


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Overview

Revised guideline layout

Quality related changes only (6.4.4, Appendix 13,14and 15)

Provide additional information in certain sections

Improve clarity and better aid applicants in the

submission process Major amendments

- require further explanation

- new requirements

Minor amendments- self-explanatory

- editorial


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Quality Documents

(Section 6.4.4, page: 45)


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Quality Documents

Module 3 (ICH CTD) or Part 2 (ACTD)

Drug Substance- Drug Master File (DMF)

- Certificates of Suitability (CEP)

Drug Product

- Control of Excipients (3.2.P.4)

Pg 45


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S2.2: Description of manufacturing process

S2.3: Control of materials

S2.4: Control of critical steps and intermediates

S2.5: Process validation and /or evaluation

S2.6: Manufacturing process development

Content of the DMF

Open / Applicants Part Closed / Restricted Part

S1-S7

Drug Substance : DMF

S2: MANUFACTURE


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Submissions by:

Drug Substance : DMF

Applicant:Open Part

DMF Holder:Open + Closed Parts

Letter of Access+

Complete S section

Pg 45


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Drug Substance : CEP

Issued EDQM.

Conforms to Ph. Eur.

Additional physico-chemical characteristics


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Drug Substance : CEP

Submission:

CEPS1

S2 S3 S5

S6

+

S4.4 S7** If re-test period not in CEP

Pg 46


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Drug Product : Control of Excipients

- Trade names, international codes or officialacronyms Acceptable

- Qualitative and quantitative contentscapsule shell/coating/printing ink X PRISM

- Ingredients derived from human plasma:Appendix 10 + supporting documents

- Ingredients derived from animal sources:Appendix 11 + supporting documents


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Singapore Quality

Overall Summary(SQOS)

(Appendix 8 and 9)


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SQOS Drug SubstanceS1 (Chemicals)

DMF

Letter of accessDMF No.

Date of submission

Yes No


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SQOS S1 (Chemicals)

Grade claimed

EP

Non-EP

S1, S2.1, S4.4, S7*

S1, S2.1, S4.1-S4.5, S7*

*retest period not in CEP


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SQOS S2.1 (Chemicals)

For information only.

NO further documents are required.


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SQOS S3.2 (Chemicals)

Eg:Degradation product of drug substance

Synthetic impurity arising from raw material X


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SQOS Drug ProductP3.1 (Chemicals)

Sites intended for Singapore ONLY.

Eg: MLT, Stability testing

PRISM

Eg: ABC Manufacturing, 123, Never ending

Road, Nowhere

Eg: As above

Eg: As above

Eg: ABC Manufacturing, 123,Never ending Road, Nowhere


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SQOS P3.5 (Chemicals)

3 consecutive production-scale batches

Concurrent validation Consult HSA


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SQOS P8 (Chemicals & Biologics)


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SQOS - Others

S1, S1.1-1.3, S2.2, S4.1,S4.4-4.5, S5, S6, P1,P3.1, P3.3, P3.5, P5.1,P5.4, P5.6, P6 and A3.

S1.1-1.3, S2.2, S4.4-4.5,S5, P3.3, P5.4-5.6, P6and A3.

Biologics (Appendix 9)Chemical (Appendix 8)

Applicants Signature


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Minor VariationApplications (MIV)

(Appendix 14, 15)


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Minor Variation Applications (MIV)

Appendix 14 (Chemical MIV) & 15 (Biologics

MIV): Guideline and Checklists Appendix 13 (MIV Filling and SubmissionInquiry Form)

Changes include:

Additional notes specific to MIV

Documentary requirement

Streamline appendices for consistency

PRISM Interface MIV changes

Timelines


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Appendix 13


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MIV : Documentary Requirement

Hardcopies E-copy

Module 1/ Part 1

Labels

ALL


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MIV : Documentary Requirement


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MIV : PRISM Interface

Change in PRISM Interface

Change of DP specs

-


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Assay: 90-

110%

Assay:

95-105%

Tightening

of specs toalign withEP

Approved

in US,Australia

P5 Control

of DP

MIV : PRISM Interface


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MIV : Appendix 14 (Chemical) Change in the layout

Conditions MIV-1 Removed

MIV-2 Retained

Sections combined

Re-categorised

Editorial changes

Additional explanatory notes

Change in submission requirements Change of PI/PIL : approval from at least one competent

agency


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New MIV-1 categories

Change in DS manufacturing process

Change of DS/DP specifications (for changes notcovered by MIV-2 C13 and C31)

Change or inclusion of scoring/breaking line oftablets

Change of batch size of DP (for other batch scalechanges not covered in MIV-2 C24)

MIV : Appendix 14 (Chemical)

App 14Pg5-9


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MIV : Appendix 14 (Chemical)

Re-categorise, combine sections, editorialchanges:

MIV-1:

Change in DP site (editorial)

Change in DP manufacturing process (re-

categorise) Change in CCS (editorial)

Change of shelf life and/or storage condition(combine sections)

Change of shelf life after reconstitution or firstopening (combine sections)

- MIV-2: editorial changes only

App 14Pg5-9

App 14Pg10-25


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No major changes to Appendix 15, except:

Seasonal variation of influenza strains of vaccine =change ofonly influenza strains

MIV : Appendix 15 (Biologics)


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Timelines

Submission

Screening

Acceptance

Evaluation

Regulatory decision

Within 6 months,Excluding stop-clock

Within 25

Working Days


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Summary


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Summary DMF and CEP

Singapore QOS changes Appendices 8 and 9

Amendments made for Chemicals and Biologics

SQOS

MIV changes - Appendices 14 and 15

Change to PRISM Interface

Documentary requirement: e-copy

Change in submission requirements

New MIV-1 (Chemicals) categories

Change in MIV-1 Biologics

Administrative Changes


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Thank You