Implementation Outside of the U.S. and E.U. -...

Implementation Outside of the

U.S. and E.U.

I-Chen Sun, Ph.D.

2016 PQRI/USP Workshop

Disclaimer

The opinions expressed in this document are

those of the author and do not necessarily

represent the views at Center for Drug Evaluation

and Food and Drug Administration, Taiwan.

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Outline

• Q3D guideline position

• Implementation outside of the U.S. and E.U.

– Australia (Therapeutic Goods Administration;

TGA)

– Canada (Health Canada)

– Japan (Ministry of Health, Labour and Welfare;

MHLW)

– Switzerland (Swissmedic)

– Taiwan (Food Drug Administration; FDA)

• Conclusions

3

ICH

Members


Q3D Guideline Position

• Implementation date of new applications is not

identified (subject to each agency’s decision).

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Implementation of

existing products > 36 months

Publication of

the guideline

Dec. 2014

Implementation of

new applications

• Application of Q3D to existing products is not

expected prior to 36 months after publication of the

guideline by ICH.


Australia TGA

• Q3D applies to registration applications for

prescription medicines

• The date for coming into effect aligns with

implementation in the EU

– New products containing new drug substance/s:

from June 2016

– New products containing existing drug

substance/s: from December 2017

• No official statement for current marketed product

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https://www.tga.gov.au/quality-guidelines

https://en.wikipedia.org/wiki/File:Flag_of_Australia.svg


Document for new application/supplement Implementation date

Submission of a new abbreviated new drug

submission (ANDS) or drug identification

number (DIN) application for a drug product

should include the content requirements as

per Q3D

Submissions received

after December 31,

2016

Submission of a new Supplemental (A)NDS

or Post-DIN Change for a major change to

an existing Drug Product as a result of the

risk assessment per Q3D

Submissions received

after December 31,

2016

Health Canada

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A DIN is assigned to all authorized prescription and over-the-counter drugs

except for Schedule C drugs (i.e., radiopharmaceuticals, kits, and generators).

http://www.hc-sc.gc.ca/dhp-s/prodpharma/applic-demande/guide-

ld/ich/qual/ q3d-rec-eng.php

http://www.hc-sc.gc.ca/dhp-s/prodpharma/applic-demande/guide-ld/ich/qual/










Health Canada

• OTC should comply with Q3D; natural health products excluded

• The risk assessment should be documented and available for

inspection.

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Document for marketed drugs Implementation date

Completion of the risk assessment for

elemental impurities

January 1, 2018

Implementation of any manufacturing

changes to control the levels of


January 1, 2018

Updated drug product specifications with

a statement confirming compliance with

ICH Q3D

January 1, 2018


• The locations where the elemental impurities-related

information can be placed for new submissions?

– Summarized in Module 2.3.P.5: Control of Drug Product

of the Quality Overall Summary

– Module 3.2.P.5.6 Justification of Specifications

– Risk assessment for the container closure system may

be cross-referenced to a master file

– Toxicology data to support limits above the Permitted

Daily Exposure or for routes of administration not

covered by ICH Q3D should be placed in Module

4.2.3.7.6 Other Toxicity Studies: Impurities

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Health Canada


• The locations where the elemental impurities-related

information can be placed for currently marketed products?

– Quality Overall Summary Module 2.3.P.5: Control of

Drug Product: a summary of the Module 3 locations

where the elemental impurities-related information can

be found

– Module 3.2.P.5.6 Justification of Specifications includes

the overall risk assessment summary for elemental

impurities

– Appropriate data to support any changes made to

comply with Q3D or Canadian changes guidance

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Health Canada


• If the risk assessment indicates that previously

manufactured and unexpired batches have levels of

elemental impurities that could pose a potential risk to health

– The appropriate Directorates in Health Canada should be

notified. • Health Product Compliance Directorate (formerly Inspectorate)

• Biologics and Genetic Therapies Directorate (BGTD) for lot

releases of biologics

– If necessary, appropriate corrective action should be taken • conducting recalls of any affected lots in accordance with

recall procedures

• developing an action plan to avoid a product shortage

situation

• filing a drug submission with appropriate manufacturing

changes to effectively address the potential safety concerns.

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Health Canada


• For new drugs

– Implementation date: from April 1, 2017

• For marketed products

– Application of Q3D to existing products approved

before April 1, 2017 will not be expected to 36

months (January 1, 2018) after publication of the ICH

guideline.

– The sponsor should study the feasibility of Q3D.

– MHLW will evaluate applicability of Q3D to existing

products.

Japan MHLW

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医薬品の元素不純物ガイドラインについて -薬食審査発０９３０第４号(平成２７年９月３０日)


Swissmedic

• For new drugs

– Both new drug substances and existing drug

substances apply

– Implementation date: July 1, 2016


– Implementation date: Jan. 1, 2018

– Complied with Ph. Eur. Supplement 9.3

– During the transition period the companies should

perform a risk assessment covering all potential

sources of elemental impurities

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Swissmedic Journal 07/2015


Taiwan Food and Drug

Administration (TFDA)

One of the core task: to

ensure the quality and

safety of medicinal product

• Pre-marketing approval

• Post-marketing risk

management

• Policy establishment

Taiwan FDA

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Center for Drug

Evaluation (CDE)

• Consultation Services

• International cooperation

• Technical Review

– New drug applications

– Abbreviated new drug

applications

– Medical device

Assisting the TFDA in

performing the tasks


Taiwan FDA

• For new drugs

– Both new drug substances and existing drug

substances apply

– Implementation date: July 1, 2016


– Implementation date is not published

– Guiding principle would be

• Perform risk-based assessment according to Q3D

Guideline

• Reduce regulatory reviewing burden without

oversight

14


Marketed products are subject to submit applications

including those for

• post-approval changes

• extension of validity of product license (every 5

years after product approval)

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Taiwan FDA


Drug Substance

16

Elemental

Impurities in

Drug Product

Utilities*

Excipients

Container Closure

System

Manufacturing

Equipment

Potentially Higher Risks Leading to Elemental

Impurities for Post-approval Changes

• Change synthetic process

& metal catalysts

• Delete/widen

specification limits of


• New

manufacturers

2016 PQRI/USP Workshop 17

Elemental

Impurities in

Drug Product

Utilities*

Drug

Substance

Container Closure

System

Manufacturing

Equipment



• Change source of mined excipient

• Change synthetic process

• Change composition

• Delete/widen specification limits of


Excipients


Container Closure

System 18

Elemental

Impurities in

Drug Product

Utilities*

Drug

Substance

Manufacturing

Equipment



Excipients

• Change primary package

material for injection, eye, and

inhalation

• Change primary package material,

storage temperature/duration or

terminal sterilization for liquid or

semisolid preparation

2016 PQRI/USP Workshop 19

Elemental

Impurities in

Drug Product

Utilities*

Drug

Substance

Container Closure

System Manufacturing

Equipment



Excipients

• Warning

letter with

utility

issues

• GMP

violations


Conclusions

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• New drugs (new drug substances and existing drug

substances)

– The health authorities in ICH countries (Canada

Japan and Switzerland) and non-ICH countries

(Australia and Taiwan) announced the Q3D

implementation schedule.

• Currently marketed products

– Canada and Switzerland announced the Q3D

implementation schedule

– Risk assessment is a must

– Australia, Japan and Taiwan are still on planning


Acknowledgement

• PQRI/USP invitation and financial support

• Dr. Lucio Porporini (Swissmedic)

• Drs. Churn-Shiouh Gau, Ywan-Feng Lee, Dr.

Kai-Ling Chang (Center for Drug Evaluation,

Taiwan)

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Thank You Very Much for Your Attention!

22

Chiang Kai-shek Memorial Hall Taipei 101 Yehliu Geopark Sun Moon Lake

Penghu Night Markets Temples Pingxi Flying

Lanterns

North-East coast

of Taiwan

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