he stream of complex and cutting-edge therapies sourced from the innovative industry can inundate emerging or less-resourced regulatory agencies that may not have the capacity to properly review them. Regulatory reliance ensures that life-saving therapies that were reviewed stringently by highly developed regulatory authorities can quickly and efficiently reach patients in emerging markets.

Reliance in Vietnam

The keynote speech, delivered by an official from the Vietnam Ministry of Health (MOH), framed the context of the event and highlighted the Asia-Pacific Economic Cooperation’s (APEC’s) critical role in improving healthcare access and outcomes through regulatory harmonization. She also commended the Drug Administration of Vietnam’s (DAV) efforts to evolve the regulatory landscape.

Reliance in Australia

In Australia, the Australian Public Assessment Report (AusPAR) plays an important role in transparency in reliance by ensuring that critical aspects of TGA’s regulatory review are made public, in line with the World Health Organization’s (WHO) Global Benchmarking Tool (GBT) for objectively evaluating regulatory systems. Australia employs reliance to ensure that scarce regulatory resources are appropriately allocated (and not, for example, duplicating a review previously done by a stringent authority) through its COR-A and COR-B regulatory pathways.

Relying agencies can access the AusPAR to inform their reliance reviews. Some jurisdictions may require additional information beyond what is included in the AusPAR, but this document remains a good starting point for regulators outside Australia to understand the scientific basis of TGA’s regulatory decision-making.

However, there is a time lapse between the TGA’s regulatory decision and publication of the AusPAR, and the AusPAR will not reflect any post-approval changes (PACs) approved in that interim. PACs such as minor variations will need to be subsequently assessed by the relying health authority. This and similar technical aspects of implementing reliance can be challenging but can be refined by experience and underpinned by trust between health authorities.

Reliance in the Philippines

The Philippines FDA has optimized their reliance guidelines over time, to allow for the incorporation of more reference agencies for example. They have also increased their participation in the ASEAN Joint Assessment (AJA) Pathway, a regional batch filing pathway for both New Drug Application (NDA) and PAC filings that employs reliance on a stringent agency’s assessment report to inform regulatory decision-making in an AJA filing. Regulatory review times for NDAs in the official guidelines are now at 45 and 30 working days for Abridged and Verification Review respectively.

Challenges to reliance in the Philippines include regulatory staffing shortages that continue to lengthen review times beyond those that are stated in official guidelines, and in changing the mindset of reviewers in reliance pathways to focus on conducting a partial review instead of a full review. In addition, as also seen in other markets beyond the Philippines, a lack of official communication channels or formal agreements (memoranda of understanding, etc.) between reference and relying authorities has hampered information exchange, especially when confidential information is required to respond to an inquiry or request. For example, the reference agency cannot provide the complete, unredacted assessment report to another agency without a memorandum of understanding.

Closing Thoughts

Key points from the closing panel discussion, provided in response to audience feedback about commonly misunderstood concepts about regulatory reliance, included:

• The “extent of reliance” on a reference agency’s review, which is for the relying agency to decide independently, is based on trust. The relying country retains their sovereignty; reliance is not a unilateral acceptance of the reference agency’s decision.
• Because the relying agency conducts a partial dossier review—on sections of the application that have not been reviewed by the reference agency (like local stability data and pharmacovigilance requirements)—instead of a full dossier review, reliance should lead to shorter approval timelines than standard approval pathways.
• Relying agencies should decide on what documents to review based on the “extent of reliance.” Public Assessment Reports (PARs), like the AusPARs mentioned earlier, are important sources of information focused on the scientific basis of regulatory decision-making, and relying agencies should leverage them if relevant to their review objective.
• In Europe, the EMA European public assessment report (EPAR) provides comprehensive information very close to the information in a nonpublic unredacted assessment report (UAR). Although TGA and Philippines FDA acknowledged that a nonpublic UAR can help the reliance reviewers to build capacity for the review process, they are not necessary for every reliance review. The process of obtaining the nonpublic UAR from the reference agency may be difficult and delay approval. If the intention of the reliance reviewer is to learn about conducting a full evaluation, WHO Collaborative Registration Procedure (CRP) reliance may be helpful (with WHO serving as facilitator).
• The Certificate of Pharmaceutical Product (CPP) was originally developed and promulgated by WHO to help resource-strapped health authorities assess the safety, quality, and efficacy of a product for import into their market. But as the global regulatory environment matures and more health authorities issue PARs to facilitate reliance, the review of this additional certificate is no longer useful. Several AP markets, such as the Philippines, still require CPP submission as part of legacy practices; this practice should be reexamined in the course of regulatory harmonization.

Photo:
Gunawan Kartapranata
/

CC BY‑SA 3.0