The ACCESS Consortium represents an example of the emergence of reliance as an important concept in the 21^st Century regulatory environment.  Reliance ranges from: the implementation of common standards e.g., ICH Guidelines; through work-sharing agreements; joint reviews e.g., African Vaccine Regulatory Forum (AVAREF); centralised reviews e.g., EU Centralised Approval; to Mutual Recognition of decisions made by another agency e.g., EU Decentralised/Mutual Recognition procedures.  WHO published documents on Good Regulatory Practices (GRP) and Good Reliance Procedures (GReP) as Annexes 10 and 11 to WHO Technical Report 1033[ii]

The ACCESS Consortium has developed work-sharing procedures for generic medicines, biosimilar and new active substances.  The New Active Substance Work-sharing Initiative (NASWSI)[iii] has approved more than 20 new medicines in Australia since the scheme was established in 2018[iv].  In 2022, the first two new medicines have been approved in all five member countries (asciminib and faricimab).  Faricimab, a treatment for progressive eye diseases, was approved in the UK and other consortium members between May and August 2022, based on their work-sharing agreement.  It is interesting to note that CHMP issued a positive opinion in July 2022 with EU approval in September 2022, while FDA approved it on January 28^th, 2022.  The use of three regulatory procedures, two involving reliance, thereby resulted in the approval of a novel therapeutic in thirty-five countries of over 800 million people over a 10-month period.  These approvals would also support further approvals in many other countries that also apply reliance procedures based on medicines approved by these regulatory agencies.

Under the NASWSI procedure an applicant may request a joint review for a new chemical entity or new biological entity, if simultaneous submission is planned in at least two of the ACCESS members.  The applicant should submit an expression of interest (EoI) at least 3 months before the planned submission and should seek technical pre-submission meetings with the selected agencies under their national procedures.  If agreed, the agencies will decide on the work sharing approach and the agency taking the lead on the clinical assessment will coordinate the logistical pre-submission meeting.  The work-sharing phase is expected to have a total maximum time of 255 days, including clock stops, so is comparable with the EU review period.  The national approval is a separate phase and will depend on any additional national requirements. In the example of faricimab three agencies issued approval within 2-3 weeks and the latest approval came within 3 months of the first approval in the UK.  According to the information published by Swissmedic[v] the review was distributed between the agencies: Drug substance (Singapore); Drug Product (Switzerland); Non-clinical (Australia) and Clinical (Canada/UK).

This work-sharing approach has benefits for the regulatory agencies involved by allowing greater efficiency and the opportunity to share knowledge across the network.  It may also avoid delays in marketing authorisation applications in the five member countries, by reducing the uncertainties and to some extent the workload for the applicant, as a result of the consolidated review and questions from regulatory agencies.  The resulting benefit is earlier access for patients in these five countries, than might be the case without this initiative.