Interpretation of Pharmacovigilance Guidances & Regulations Solutions

In 2019, 4.2 million babies were born in the European Union. In the same year, the number of live births in the United States was around 3.75 million. While the mothers may have needed to take medicines during their pregnancies (drug utilization studies estimate that between 44% and 99% of pregnant women will take medication during pregnancy), only very few are approved for use during pregnancy and breastfeeding.

Understanding the global landscape of existing and evolving regulations & guidance on monitoring the safety of medicines taken during pregnancy and breastfeeding is a challenge for researchers, be it in industry or academia. Addressing this challenge is precisely what the Interpretation of PV Guidances & Regulations (Pregnancy and Breastfeeding Topic) working team is currently doing. Using a phased approach, the team has started to analyze the current regulatory ecosystem (and relevant initiatives) in focused territories, covering drug safety regulations and guidances addressing pregnancy and breastfeeding from early clinical development to post-marketing settings. Based on the insights obtained, in the second phase, the team will propose solutions to help pharmaceutical companies better understand and comply with ambiguous or inconsistent regulatory requirements or guidance. These solutions will also help companies meet Health Authorities’ expectations by more effectively and efficiently operationalizing the development of applicable processes and tools to monitor medication exposures and safety events in pregnant and breastfeeding women. Ultimately, this initiative aims to help women, their partners, and health care professionals make informed decisions when medical treatment is required.

Status: In Progress

Guidance: A list of guidances and regulations will be provided with released solutions.

Agency: Multiple

Guidance Date: Multiple

Deliverables:

Asset Type	Title	Description
	​
	Initiatives & Regulatory Landscape Assessment Output	The Landscape Assessment summarizes the current regulatory ecosystem (and relevant initiatives) in selected territories, covering drug safety regulations and guidances addressing pregnancy and breastfeeding from early clinical development to post-marketing settings.
	Regulatory Landscape Comparison by Regulation Topic	Comparison of in-scope guidances and regulations in the selected territories, against ICH and CIOMS pregnancy and breastfeeding provisions.

Guidance: See list of guidances considered in “A Framework on the Presentation of Safety Risks Throughout the Product Lifecycle” below.

Agency: Multiple

Date: Multiple

Approach:

1. The topic team reviewed definitions of risks in key guidances (GVP and ICH).
2. The topic team then provided clarity through a Framework that describes how to present risks in key safety documents throughout the product lifecycle in a manner that complies with the relevant guidances.

Value:

This topic’s objective was to support the presentation of risk information in accordance with Health Authority expectations, through developing a Framework that maps out regulatory requirements and operational considerations for presenting risks at the various product lifecycle stages.

Deliverables:

Asset Type	Title	Description
	A Framework on the Presentation of Safety Risks Throughout the Product Lifecycle	A Framework including a comparison of regulatory requirements for presentation of risks across the guidelines and phases of the product lifecycle, along with operational considerations on how to present risks in key regulatory/safety documents.
	Presentation of Risks Overview Video	An introduction and high level overview of what can be found in “A Framework on the Presentation of Safety Risks Throughout the Product Lifecycle.”

Implementation Experience:

As solutions are used throughout the R&D ecosystem, TransCelerate receives feedback related to solution implementation experiences. Below is a featured example for this topic:

“Sponsor uses ‘Presentation of Safety Risks’ Framework for training and improving how to categorize safety risks” 

Anyone can submit an experience through the Engage with Us page and in select cases, we share the experiences on Our Impact page in a blinded way.

This topic’s objective was to support patient safety commitments by identifying various approaches to meet Health Authority expectations for safety issue notifications in an effective and efficient manner.

Guidance: See a list of guidances considered in the Safety Issue Notification Guide below

Agency: Australian Therapeutic Goods Administration, Health Canada, Ministry of Health New Zealand, Risk Management and Drug Information Department (Israel), Saudi Food and Drug Administration, SwissMedic, and Turkish Ministry of Health

Guidance Date: See a list of dates for the guidance considered in the Safety Issue Notification Guide below

Deliverables:

Asset Type	Title	Description
	Safety Issue Notification Guide	A guide to aide understanding of safety issue notification guidances for in-scope countries.
	Webinar: Safety Issue Notification Guide	A webinar presentation where TransCelerate team members provide an overview of the Safety Issue Notification Guide.

This topic is intended to enhance patient safety by facilitating adherence to unclear regulatory guidance calling for applicants to take a more holistic view of combination products.

Guidance: Postmarketing Safety for Combination Products Draft Guidance for Industry & FDA Staff

Agency: FDA

Guidance Date: March 2018

Deliverables:

Asset Type	Title	Description
	FDA Post Marketing Safety Reporting for Drug-Device Combinations Implementation Guide	An Implementation Guide to aide pharmaceutical manufacturers’ understanding of ambiguous areas of the PMSR for Combination Products Draft Guidance for Industry and FDA Staff (March 2018).
	FDA Post Marketing Safety Reporting for Drug-Device Combinations Implementation Guide: Webinar	A webinar presentation where TransCelerate team members provide an overview of the FDA Post Marketing Safety Reporting for Drug-Device Combinations Implementation Guide.

This topic’s objective was to interpret ambiguous portions of Reference Safety Information Guidance Q&A, engage with regulators and share findings on implementation challenges and approaches.

Guidance: CTFG Q&A Document – Reference Safety Information (Nov. 2017)

Agency: EMA

Q&A Date: November 2017

Deliverables:

Asset Type	Title	Description
	Call for Reharmonization: Clinical Trials: Global Pharmacovigilance Regulations	To meet these goals, we at TransCelerate implore representatives for regulatory authorities to work with industry sponsors, in the spirit of ICH, to identify potential ways to re-harmonize global pharmacovigilance processes and requirements.
	Publication on the Evolving Remit of the Reference Safety Information: Observations on Implementation of the 2017 Clinical Trials Facilitation Group (CTFG) Question & Answer Document	This manuscript highlights industry challenges in operationalizing the requirements of the 2017 Clinical Trial Facilitation Group (CTFG) Question & Answer document. Surveys reveal actions taken in the creation, submission and implementation of the Reference Safety Information (RSI) to meet the requirements of the CTFG and EU national competent authorities whilst staying compliant with global regulatory requirements.

This topic’s objective was to interpret ambiguous portions of the draft guidance, engage with regulators, and share findings on implementation challenges and approaches.

Guidance: Draft Guidance for Industry: Safety Assessment for IND Safety Reporting (Dec. 2015)

Agency: FDA

Guidance Date: December 2015

Deliverables:

Asset Type	Title	Description
	Publication on TransCelerate Experience with FDA’s 2015 Safety Assessment Guidance	In this publication, TransCelerate member companies summarize their experience in operationalizing FDA’s clinical trial monitoring and reporting requirements with a key focus on FDA’s Draft 2015 Safety Assessment Guidance.