CHIR Best Brains Exchange 22 January 2016

Quality of drugs manufactured in emerging economies: Are cost containment strategies heightening the likelihood of substandard drugs in Canada?

CIHR BEST BRAINS EXCHANGEFRIDAY, JANUARY 22, 2016. CIHR’S OFFICES 160 ELGIN STREET, 9TH FLOOR OTTAWA, ON

Ajaz S. Hussain, Ph.D. @ CIHR Best Brains Exchange, Ottawa, ON, January 22, 2016

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Key Questions

What regulatory, policy, and/ or governance changes are needed to address new and increased risks?

How can Canada prevent and reduce health risks that emerge when the pharmaceutical industry adopts globalized production strategies?


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Speakers & Assigned Topics

• Scene Setting Presentation – Challenge of substandard drugs for public health

Mark Paxton, Chief Executive Officer, Rx-360

• Tension between the affordability and the access to drugs that emerges due to cost containment strategies

Suzanne McGurn, Assistant Deputy Minister and Executive Officer, Ontario Public Drug Programs Ontario Ministry of Health and Long-Term Care

• What is driving globalized production strategies in the pharmaceutical industry?

Ajaz S. Hussain, Executive Director, The National Institute for Pharmaceutical Technology and

Education

• Potential risk factors that emerge, or are increased, when drug production is performed in emerging economies

Andy Stergachis, Director, Global Medicines Program, School of Public Health, University of

Washington


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What is driving globalized production strategies in the pharmaceutical industry? AJAZ S. HUSSAIN, EXECUTIVE DIRECTOR, THE NATIONAL INSTITUTE FOR PHARMACEUTICAL TECHNOLOGY AND EDUCATION

[email protected]


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Manufacturing in Emerging Economies for Canada, USA, …:‘Better than Placebo’

“Rest bring data”

Application: NDA,.., ANDA

“Scale-up & Process Validation”

CGMP Compliance, “Certification”


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Globalization Drivers?Manufacturing in Emerging Economies for Canada, USA,..:


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COGS

Direct MaterialsBeginning Inventory 0

Purchases 9,000

Direct Materials Available 9,000

Ending Direct Materials Inventory (4,000)

Direct Materials Used 5,000

Direct Labor 2,000

Factory Overhead 1,100

Total Manufacturing Cost 8,100

Add: Beginning Work-in-Process Inventory 5,000

Total Manufacturing Cost to Account For 13,100

Less: Ending Work-in-Process Inventory 4,500

Cost of Goods Manufactured 8,600

At a lower costs for development & manufacturing

Capability to satisfy

regulatory requirements in Canada, US,,..

Globalization of costs & not accounting for differences in quality understanding

Served as a ‘stress test’ for the regulatory systems in Canada, USA,…

Exposed prevailing intra- and inter-agency heterogeneity and capacity constraints

Eroded public’s confidence in quality; palpable increase in nocebo effects

Reminded us that complexity and uncertainty remains underappreciated

Design, Controls, Specifications

CGMP Compliance

QMS & assurance of data integrity

Review & Inspection


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“…..When the drug safety system fails, people get sick. Some die. It is hard to detect harm. Some of these people are already very vulnerable…and proving the cause of harm from impurities,

adulteration, and counterfeits can be elusive. FDA

inspectors look for a culture of quality at manufacturing

facilities. Certainly the companies are obligated to ensure

a culture of quality and maintain vigilance as well. This

reflects a systems approach to safety. This system

approach wasn't at play here….”


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http://www.spokesman.com/stories/2008/apr/23/house-panel-criticizes-fda-on-foreign-inspections/

Congressman Shimkus

http://www.spokesman.com/stories/2008/apr/23/house-panel-criticizes-fda-on-foreign-inspections/

Breaches in assurance of data integrity is a Global Issue!

•Probe Finds Kaketsuken’s GMP Violations “Extremely Malicious”, MHLW to Impose Penalty(3 Dec. 2015)

Mr. Shiozaki, Head of MHLW

regrets they could not find GMP

violation (Dec 8, 2015)

PMDA says Routine GMP

Inspection to be done without

prior notice ….8 Dec 2015

Einstein’s challenge….

we will never solve the problems

tomorrow with the same order of

consciousness we are using to

create the problems of today!


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http://pj.jiho.jp/servlet/pjh/regulatory/outline/1226583374392.html

http://pj.jiho.jp/servlet/pjh/regulatory/outline/1226583374392.html

Use of foreign-sourced materials creates vulnerabilities in the U.S. drug supply. …FDA has been working for over a decade to stimulate modernization

QbD … an opportunity to reduce manufacturing

costs while ensuring that consumers receive high-

quality drug products…. with the proper strategies,

revitalize pharmaceutical manufacturing in the

United States.


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http://www.pharmaceuticalonline.com/doc/cder-s-janet-woodcock-nobody-can-really-tell-me-if-fda-inspections-are-effective-0001 andhttp://www.fda.gov/NewsEvents/Testimony/ucm378343.htm

http://www.pharmaceuticalonline.com/doc/cder-s-janet-woodcock-nobody-can-really-tell-me-if-fda-inspections-are-effective-0001

http://www.fda.gov/NewsEvents/Testimony/ucm378343.htm

FDA/CDER/OPQ = “Integrated”

How did we get here?

Pre-OPS to OPS to OPQ

Assuring Same Quality Standards

to Safeguard Clinical

Performance

Enhancing Science-and Risk-based

Regulatory Approaches

Transforming Qualitative-

Quantitative and Expertise-based

Product Quality Informatics

Quality MetricsQuestion-based

Review

New Inspection Protocol

Integration of Review, Inspection, Surveillance, Policy,

and Research

Team-based Integrated Quality Assessment (IQA)

Program Alignment across FDA

EncouragingDevelopment of

Emerging Technology

Quality Information BLAs/NDAs/ANDAhow does it link to

patients?


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CDER Office of Pharmaceutical Quality

Immediate policy considerations: Appreciate complexity and uncertainty

• Regulatory review – ask the right questions

• An harmonized, integrated (review-inspection),

life-cycle approach to analytical & process

‘validation’

• Product risk-assessment criteria when deviations

from CGMPs occur

• Quality metrics – supply chain reliability;

distinguish between malicious and misguided

behaviors

• Focus on quality system & systems thinking –

recognize the difference between complicated vs

complex

Risk-assessment & classification

Quality Metrics

Culture of Quality


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Invest in Pharmaceutical Technology Research & EducationThe Nation Needs a

Comprehensive Pharmaceutical

Engineering Education and

Research System. Ajaz S.

Hussain. Pharmaceutical

Technology. September 2005


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Summary

Capability to satisfy regulatory requirements in Canada, US,…, at a lower development & manufacturing costs.

Key drivers: EBITDA

Exposed prevailing intra- and inter-agency heterogeneity and capacity constraints

Globalization of costs

Complexity and uncertainty in the assurance of ‘pharmaceutical quality’ remains underappreciated

Non-compliance: Global Issue

Product risk-assessment criteria & Quality metrics – for supply chain reliability; distinguish between malicious and misguided behaviors

Immediate policy

considerations

Catch-up with the paradigm long-shifted: “compounding” to “manufacturing”; “compendia” to “statistical confidence”

Invest in Research & Education

Manufacturing in

Emerging Economies

for Canada, USA,..


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CHIR Best Brains Exchange 22 January 2016

Government & Nonprofit

Transcript of CHIR Best Brains Exchange 22 January 2016