Proceedings: DIA Europe 2018

Building Efficiencies in Drug Development and Regulatory Approval
Collaborate Globally, Regulate Locally

Sandra Blumenrath
DIA Science Writer


globalized, harmonized approach to drug development and regulatory approval is typically considered the most efficient strategy to deliver the best outcome for all. However, there may be instances when multinational regulatory objectives may not serve global research needs and a local approach promises to yield better results. Below are some examples of initiatives discussed at DIA Europe 2018 that benefit from either global or local approaches.

Key Takeaways

  • PMDA’s ‘Horizon Scanning’: Japan’s Pharmaceuticals and Medical Devices Agency (PMDA) proactively researches possible future innovative technologies across the globe and their impact on regulation to ensure timely updates of their regulatory framework.
  • Advances in pediatrics: For low- to middle-income countries, unmet medical needs in pediatrics, including epidemiological research, will not be sufficiently addressed by the solutions and regulations of higher-income countries. Local and societal efforts will be critical in making progress in this area.
  • Regulatory reliance and work sharing: Current work-sharing efforts among mid-sized regulatory agencies with limited resources and staff have helped these agencies meet their regulatory responsibilities.
  • Harmonizing GMPs: The Pharmaceutical Inspection Co-operation Scheme (PIC/S) promotes mutual reliance agreements (MrAs) in alignment with the International Coalition of Medicines Regulatory Authorities (ICMRA) guidance on information sharing to harmonize Good Manufacturing Practices (GMPs).
  • Product life cycle management: ICH and WHO guidances on post-approval changes are complementary and ought to be leveraged to advance the harmonization of regulatory frameworks for product life cycle management.

Why this is important: Although the approach taken in each of the cases above may be different, the common thread linking all of these examples is communication. In any globalization setting, dialogue will lead to collaboration, which in turn will lead to the trust necessary to advance regulatory science globally.

PMDA’s ‘Horizon Scanning’

To keep up with innovation and the increasing complexity of scientific issues, regulatory requirements have to be updated more frequently. PMDA has recognized that, while technology is moving along quickly, regulation is often lagging far behind. Therefore, PMDA’s latest project proactively scans the global research landscape to identify future innovative technologies, evaluate their impact on regulation, and if necessary update the regulatory framework accordingly. Maintaining innovation in regulatory science will be key to keep up with the quickly growing regulatory demands.

Advances in Pediatrics

By implementing a system of obligations and rewards, pediatric legislation has led to a significant increase in pediatric studies. While the studies conducted are multinational, the regulatory objectives achieved in some regions may not serve the research needs across all regions. Although pediatrics has made significant progress through regulatory frameworks in the US and EU, solutions and regulations in place in these high-income regions are unable to address the specific medical and regulatory needs of low- to middle-income regions. While lessons can be learned from the global setting, each country will have to be considered independently. Society, too, will have to play a crucial role in effectively addressing the unmet healthcare needs of children in these regions.

Regulatory Reliance and Work Sharing

Regulatory agencies around the globe increasingly rely on other regulators’ work products, embarking on work-sharing concepts to leverage resources and increase efficiency. For work-sharing collaborations to succeed, however, regulators have to build trust and confidence in each other.

The ACSS (Australia, Canada, Singapore, Switzerland) Consortium, for example, is an international cooperation between medium-sized regulatory authorities that include the Therapeutic Goods Administration of Australia (TGA), Health Canada (HC), Singapore’s Health Sciences Authority (HSA), and the Swiss Agency for Therapeutic Products (Swissmedic). The outcomes and conclusions of its first Generic Medicines Work Sharing Trial were published in DIA Global Forum earlier this year. Another group, the International Generic Drug Regulators Programme (IGDRP), launched an Information Sharing pilot with Health Canada, TGA, Swissmedic, and the Taiwan Food and Drug Administration (TFDA) to explore information and work sharing models for pre-market review of generic drugs.

The results of both projects are encouraging: Sharing the workload clearly increased the effectiveness and efficiency of domestic regulatory systems while capitalizing on each country’s area of strength. The participating agencies also became more confident as they learned from each other. But aggressive timelines did require good communication and coordination among the agencies.

Harmonizing Good Manufacturing Practices (GMPs)

GMP standards and associated inspections are important components of a strong regulatory system. Although challenging, several international efforts are trying to converge these standards and align inspection processes. But GMP standardization and inspection reliance require a strong regulatory system. The PIC/S, for example, promotes mutual reliance agreements (MrAs) in alignment with ICMRA guidelines on information sharing, although the knowledge and experience of regulators (or the ‘Regulatory Maturity’) should be assessed before entering an MrA. Furthermore, the WHO’s Regulatory System Strengthening program helps national regulatory authorities fulfill their regulatory functions throughout the medical product lifecycle, including GMP inspections. With the WHO Global Benchmarking Tool, the program identifies areas of improvement and helps promote regulatory convergence and harmonization.

Product Life Cycle Management

The lack of a harmonized global regulatory framework for post-approval changes (PACs) may cause delayed and unequal access, contributing to the already widespread issue of global and country-specific drug shortages. Because PACs are necessary throughout the entire product life cycle, there are ongoing initiatives towards a sustainable global environment for pharmaceutical product life cycle management.

The International Federation of Pharmaceutical Manufacturers and Associations (IFPMA), for example, has created a ‘Life Cycle Management Team’ to encourage the implementation of the same PAC processes globally through the adoption international, complementary standards. WHO’s new PAC guidance for biotherapeutics and the ICH Q12 guidance on the management of PACs are examples of complementary standards that offer an opportunity for further global harmonization.

PAC in life cycle management is a global challenge that requires an equally global solution. The implementation of harmonized frameworks will require resources, regulator maturity, and political will.

This article summarizes key takeaways from sessions in “Topic H: Drug Development and Regulatory Approval – Reference Points around the Globe or Globalisation?”