Pharmaceuticals in the Environment & Antimicrobial Resistance

Presented at CleanMed Europe Copenhagen D.J. Caldwell, October 2016

Topics for discussion

1. What are the concerns about PIE? 2. What are the major sources of PIE? 3. Industry’s Eco-Pharmaco-Stewardship Framework 4. How we manage PIE & AMR 5. Curated database and publicly available list of

Predicted No Effect Concentrations 6. Are there opportunities for collaboration?

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PIE has Gained Global Attention ICCM-4 Meeting, October 2015 EPPP adopted

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In 2006 SAICM was adopted. Emerging Policy Issues: • Lead in Paint • Chemicals in Products • Endocrine Disrupting Chemicals • Hazardous substances in electrical

and electronic products • Nanotechnology and manufactured

nanomaterials • Highly Hazardous Pesticides • Environmentally Persistent

Pharmaceutical Products

Stakeholder Concerns

We share the same concerns

What are the Major Sources of PIE? Patient use and excretion is accounts for over 90%

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Eco-Pharmaco-Stewardship (EPS) A life-cycle approach

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Objective: Providing knowledge and data enabling assessments of sustainability of pharmaceuticals

Priority EcoPharmacoStewardship Activities

Extended Environmental

Risk Assessment (eERA)

Effluent emission control from

manufacturing

Extension of Scientific Knowledge Base

(multi-stakeholders)

IMI “iPIE”project Industry Guidance for effluent control

• Provides a framework for ongoing environmental review post launch and

• a mechanism to follow up on identified risks

• Not compromising patient access to medicines

• Establish risk based control

• Give technical guidance • Sharing practices • Evaluate environmental

aspects of AMR

Post-Authorisation ERA model

• Developing a high quality eco-database

• Develop effects & exposure prediction models

• Addressing prioritization methodology for legacy products and R&D

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Vision : No negative human health or environmental impact of our pharmaceutical ingredients and personal care products Mission: Ensure that our pharmaceutical ingredients and personal care products, either by use or manufacturing, do not negatively impact human health or the environment. Understand the potential impact of these products and create sustainable processes to analyze and mitigate the PIE/PCPE risks . Make stakeholders aware that we control the PIE/PCPE risks.

STRATEGIC GOALS

KNOW OUR IMPACT

CONTROL OUR IMPACT

STAKEHOLDER OUTREACH

EXTERNAL SUPPLY

PRODUCT STEWARDSHIP

PRODUCT STEWARDSHIP

J&J PIE/PCPE Strategic Plan 2016-2020

PNEC data gap closed Risks identified

Guide actively implemented

PIE considered in procurrement process

Stakeholder collaboration

Accountability for our prodcuts

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• Develop new science • Review data for major pharmaceutical products

and prioritized legacy products • Monitor risks with top tier external suppliers • Partner with a wide range of stakeholders

• Trade associations • Pharmaceutical Supply Chain Initiative • Academic institutions • Others

• Work with regulatory agencies

What we are doing?

The Maturity Ladder Concept

Requirements • Basic awareness • Legal compliance

Manage Supply Chain Risk • Assess & control risk • Integrated Supply Chain

Mature Company/Partner • Benchmarking • Continuous improvement

A Curated Database of Pharmaceutical PNECs Constructed from Vestel et al. 2016 with additional data

• Data – Acute effects data generated to support regulatory requirements – Chronic effects data generated to support Environmental Risk

Assessments for new drug/medicinal authorization applications – Good Laboratory Practice (GLP) and some non-GLP studies included

• Sources – Unpublished aquatic toxicity data (various pharmaceutical companies) – Published aquatic toxicity data – Data published on some companies public web sites (e.g.,

www.astrazeneca.com/Responsibility) – Data published by a national medicinal agency (www.fass.se) – Data gaps filled with peer-reviewed literature values, when available,

after extensive data review

Chronic PNECs by Therapeutic Class (Vestel 2016)

Benefits and Uses of the Database

• Increased transparency on part of industry • Supports Eco-Pharmaco-Stewardship framework

• Publicly accessible list of PNECs • Can be used as screening values to evaluate local conditions • Capacity building for external suppliers

• Underlying data can be provided to Environment Agencies upon request and approval of data owner • Prioritization of additional ERA activities • Basis for regulatory EQS

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Risk Assessment, all units in ug/L Aus Der Beek et al. Env Tox Chem 35:823-835, 2016 Compound Name MEC PNEC Risk Ratio Diclofenac 0.032 32 0.001 Estradiol 0.003 0.002 1.5 Estriol 0.009 0.060 0.15 Estrone 0.016 0.006 2.667 Ethinylestradiol 0.043 (0.0003) 0.0001 430 (3) Ibuprofen 0.108 1 0.108 Naproxen 0.050 4.2 0.012 Carbamazepine 0.187 0.50 0.374 Paracetamol 0.161 95 0.002 Clofibric acid 0.022 0.2 0.11 Acetylsalicylic acid 0.922 28 0.033

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Antimicrobial Resistance (AMR)

• European Commission PIE Strategy may address AMR • External suppliers weakest link in Supply Chain • US State Dept investigating AMR in Southeast Asia as

part of life cycle assessment project with SETAC* • Leading pharmaceutical companies developed an AMR

Roadmap and committed to address the issue at UN General Assembly

* Society of Environmental Toxicology and Chemistry

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International Federation of Pharmaceutical Manufacturers and Associations

• Research-based pharmaceutical companies and associations across the globe

• Official recognition by the United Nations • contributes industry expertise to help the global health community

find solutions that improve global health • engaging SAICM on environmentally persistent pharm pollutants

• The industry’s AMR Roadmap is hosted on IFPMA site

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The AMR Roadmap Reduce environmental impact from production of antibiotics

i. Review our own manufacturing and supply chains to assess good practice in controlling releases of antibiotics into the environment.

ii. Establish a common framework for managing antibiotic discharge, building on existing work such as PSCI*, and start to apply it across our own manufacturing and supply chain by 2018.

iii. Work with stakeholders to develop a practical mechanism to transparently demonstrate that our supply chains meet the standards in the framework.

iv. Work with independent technical experts to establish science-driven, risk-based targets for discharge concentrations for antibiotics and good practice methods to reduce environmental impact of manufacturing discharges, by 2020.

* Pharmaceutical Supply Chain Initiative

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How Johnson & Johnson is addressing AMR Environmental Aspects

• Implement the AMR Roadmap through industry coalition • Our interim approach:

• Calculate PNEC from standard ecotoxicity tests • Follow minimum inhibitory concentration approach to determine

preliminary resistance protection concentrations • Evaluate facilities on a case by case basis • Continue to build capacity and assess external supply chain (PSCI)

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We’ll make the places we live, work and play healthier by using fewer and smarter

resources.

Places

We’ll team up with partners and employees to

create a culture of health and well-being.

Practices We’ll help people be healthier

by providing better access and care in more places

around the world.

People

Johnson & Johnson Citizenship & Sustainability 2020 Goals will help more people live healthier lives. With the ideas we generate, products we

make and good habits we create, we can do more than ever before.

Photo Credits: Julien Harneis, dsorich, J&J

References

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• Caldwell DJ. et al. 2016. A Risk Based Tool to Manage Active Pharmaceutical Ingredients in Manufacturing Effluent. Environ Toxicol Chem 35: 813–822. (DOI: 10.1002/etc.3163)

• Vestel J. et al. 2016. Use of Acute and Chronic Ecotoxicity Data in Environmental Risk Assessment of Pharmaceuticals. Environ Toxicol Chem 35: 1201-1212. (DOI: 10.1002/etc.3260)

• AMR Roadmap: http://www.ifpma.org/partners-2/declaration-by-the-pharmaceutical-biotechnology-and-diagnostics-industries-on-combating-antimicrobial-resistance-amr/

• Temple PNEC list: http://www.nsfwetcenter.org/left-sidebar-page/pnecs/

• For more information on our full set of goals and targets visit http://www.jnj.com/caring/citizenship-sustainability/2020-Goals