Survey Respondents

Of the 164 affiliates who were sent the survey, 108 survey responses were received [Australia (n = 19); Canada (n = 20); Singapore (n = 24); Switzerland (n = 22); UK (n = 23)], resulting in a response rate of 66% (108/164). Figure 1 shows affiliates’ participation in Access (n = 108). Two key types of respondents were identified: a majority of affiliates who had not yet taken part in Access (62%, n = 67), and a minority of affiliates who had taken part in Access (38%, n = 41). Australia had the highest number of affiliates that had participated in Access (n = 12). The UK, the latest country to join the Access Consortium, had the lowest number (n = 2) (Fig. 1).

Fig. 1

Affiliates’ participation in Access (n = 108)

Reasons for not Participating in Access and Changes Suggested by Affiliates

Affiliates who had not yet taken part in Access (n = 67, 62%) selected the following reasons for their lack of participation (each affiliate could select more than one option): risk of divergent decisions between participating RAs (39%, n = 26); process too complicated to manage (37%, n = 25); differences in requirements and review practices between countries (36%, n = 24); resources and cost (30%, n = 20); and slower approval times compared to national review (22%, n = 15). Around half of the respondents (48%, n = 32) added “other” reasons for not participating (not listed as response options), including: not having identified a suitable medicinal product for the Access pathway, lack of clear written process guidelines, lack of experience with the process, and absence of the European Medicines Agency (EMA) and US FDA in the initiative. Additionally, two UK affiliates mentioned preference for the “reliance” route—presumably referring to the European Commission Decision Reliance Procedure (ECDRP) introduced after Brexit, which allows the MHRA to rely on a European Commission decision to grant a marketing authorization for a therapeutic product [7].

According to affiliates who had not yet taken part in Access (n = 67, 62%), the following changes would be required to encourage participation in Access (several options could be selected): shorter review timelines versus national review (78%, n = 52); better alignment of process for priority applications in all countries (75%, n = 50); improved guidance on Access pathway and procedures (73%, n = 49); joint scientific advice meetings (43%, n = 29); and acceptance of conditional/provisional applications (36%, n = 24). Other suggested changes (not listed as response options) included: removal of country-specific requirements, provision of training and examples for affiliates, financial incentives such as reduced fees, having a common electronic platform for information sharing, and convergence of approval timelines among RAs so that they are more similar.

Affiliates’ Experiences with Access

Affiliates who had taken part in Access (n = 41, 38%) were asked to share insights on their experience with the different phases of this pathway.

The Expression of Interest (EoI) Phase

Overall, most affiliates reported a positive experience with the Expression of Interest (EoI) phase. In particular, 10% (n = 4) of affiliates rated their experience with this phase as “excellent,” 66% (n = 27) as “good,” 19% (n = 8) as “average,” and 5% (n = 2) as “bad.” Comments on this phase varied; some affiliates appreciated open dialogue with RAs, swift responses from RAs and the simplicity of the EoI form; while others mentioned feedback from RAs taking longer than expected. Most affiliates (71%, n = 29) reported receiving timely feedback from their RA after submitting the EoI form or requesting feedback or advice. The majority of affiliates requested a logistics meeting prior to filing each submission (61%, n = 25), with some affiliates commenting that such meetings were useful for the first submission/s, but no longer necessary for subsequent submissions as queries could be addressed via email. Most affiliates (76%, n = 31) thought that the evaluation plan, milestones, and review responsibilities among the participating RAs had been made clear to them prior to filing their submission.

The Work-Sharing Phase

Affiliates’ experience with the work-sharing phase was also mostly positive; 5% (n = 2) of affiliates rated this phase as “excellent,” 73% (n = 30) as “good,” 20% (n = 8) as “average,” and 2% (n = 1) as “bad,” Some affiliates highlighted positive progress in comparison with previous experiences with this phase, progress to a single LoQ, clear timelines, and improvement in guidelines and communication with affiliates. However, some other affiliates reported challenges related to this phase, such as receipt of rolling questions from Health Canada which slowed applications and made timelines unpredictable, non-consolidated questions, and separate country-specific questions.

According to most affiliates (66%, n = 27), the process and milestone dates were adhered to during this phase, while a minority (34%, n = 14) thought this was not the case, with reasons for deviation from milestones including rolling questions and unexpected rounds of questions.

The National Decision-Making Phase

The experience with the national decision-making phase was rated as “excellent” by 5% (n = 2), “good” by 54% (n = 22), “average” by 29% (n = 12), and “bad” by 12% (n = 5) of affiliates. Several affiliates stressed their appreciation for the flexibility, responsiveness, and organization of RAs. One affiliate, referring to a specific submission, questioned if the advisory committee meeting was strictly necessary and noted this contributed to a delayed national approval compared to approvals of other RAs.

The Impact of Participating in Access

Among the affiliates who participated in Access (n = 41, 38%), 80% (n = 33) thought that approval via Access had had “no impact” on pricing and reimbursement timelines in their country and 5% (n = 2) thought that there was “negative" impact. The remaining 15% (n = 6) reported a “positive impact,” with some affiliates noting that the HTA (Health Technology Assessment) processes were able to start earlier due to the earlier regulatory approval via Access.

Affiliates who had participated in Access (n = 41, 38%) were asked to outline what impact a review via the Access pathway had had on resource requirements, from the perspectives of both their local affiliates and their global organizations. Figure 2 outlines the resources required from (a) local affiliates and (b) global organizations compared to national procedures (Fig. 2).

Fig. 2

Resources required to participate in Access from a local affiliates and b global organizations compared to national procedures (n = 41)

Most affiliates believed that the same resources were needed from their local organization (51%, n = 21) and their global organization (44%, n = 18) when participating in an Access review. Fourteen affiliates (34%) thought that an Access review required “less resources” from their global organization compared to a national procedure, while only 5 affiliates (12%) thought the same was true for their local organization. One affiliate noted that by participating in Access, more resources were required due to additional alignment and communication with other affiliates, while their global organization benefitted more from the reduced number of questions which had been consolidated.

Perceived Benefits of Access and the Influence of the Participation of Other Countries

According to affiliates who had participated in Access (n = 41, 38%) the pathway offered the following benefits (several options could be selected): gaining experience with an evolving work-sharing pathway (76%, n = 31); near simultaneous approval in multiple countries (73%, n = 30); shorter review compared to national timeline (61%, n = 25); and reduced number of RA questions overall (61%, n = 25). Some respondents (34%, n = 14) added "other" benefits (not listed as response options), including: ensuring their country remains a tier one country for global submissions, reduced workload for regulatory affairs teams, and receiving RAs questions simultaneously. Affiliates who had participated in Access (n = 41, 38%) also rated the importance of three proposed factors when deciding to use the Access pathway: decrease in average time to market; reduced effort and duplication for industry and regulators; and reduced submission lag time versus the US or European Union (EU). Figure 3 outlines the number of affiliates who rated these factors as “very important” (five ratings were possible, ranging from "very important" to "not at all important"), with “decrease in time to market” considered “very important” by the largest proportion of affiliates (85%, n = 35) (Fig. 3).

Fig. 3

“Very important” factors when deciding to use Access (n = 41)

When all affiliates (n = 108) were asked if participation of any specific country/countries would encourage them to participate in Access, 47% (n = 51) of affiliates responded “No” and 53% (n = 57) mentioned one or more countries. Among those affiliates who indicated one or more countries (n = 57), the majority indicated the UK (91%, n = 52), followed by Australia (81%, n = 46), Canada (74%, n = 42), Switzerland (49%, n = 28), and Singapore (35%, n = 20). Reasons for mentioning the UK included the MHRA being perceived as being a “lead authority,” the possibility for smaller RAs to learn from them, and its attractive advertised review timeline of 150 days. When asked if participation of any specific country would discourage affiliates from participating in Access, the vast majority (n = 94, 87%) responded “No.” Among the very few respondents who did mention one or more countries (n = 14), some (n = 10) indicated Switzerland, followed by Singapore (n = 4), the UK (n = 3), Canada (n = 3) and Australia (n = 1).

Proposed Changes and Recommendations to improve Access

All affiliates (n = 108) shared their views on possible changes to Access. Most affiliates (65%, n = 70) agreed that there would be a benefit in developing a framework more similar to Project Orbis to allow for sharing of reviews without formal work-sharing. Some of these affiliates commented that Project Orbis allows the RAs to leverage regulatory assessments and to reduce questions to sponsors, potentially contributing to shorter approval timelines (also because the US FDA leads the initiative) and that this framework is helpful for those RAs with resource constraints. Among the affiliates who did not see a benefit in developing a framework more similar to Project Orbis (35%, n = 38) some commented that Orbis’ timelines are more unpredictable compared to Access’ timelines and highlighted their preference for the work-sharing typical of Access (as opposed to simple sharing of reviews of Orbis) which leads to reduced workload for RAs and encourages regulatory decisions in the same timeframe.

Affiliates who had participated in Access (n = 41, 38%) were asked to rank eight proposed process improvement options for the Access pathway, giving scores from 1 to 8 (from the most to the least important). Figure 4 shows the affiliates’ ranking of these options (Fig. 4). ‘Shorter review timeframes vs national procedure’ was ranked by 78% (n = 32) of affiliates among their top 3 options, followed by ‘single consolidated list of questions’ (66%, n = 27), and ‘better alignment of processes for priority applications’ (37%, n = 15). Notably, ‘shorter review timeframes vs national procedure’ was also rated as the single most important improvement by most affiliates (58%, n = 24) (not shown on Fig. 4).

Fig. 4

Affiliates’ ranking of Access process improvement options (n = 41)

According to 94% (n = 102) of all affiliates, an Access industry/RA Forum should be established to ensure processes remain fit for purpose in the face of rapidly evolving new technologies. According to affiliates, potential benefits of such a Forum included: allowing the RAs and the industry to engage, sharing of best practices and challenges, increasing transparency, allowing the industry to help to drive actions to improve the initiative, and maintaining the pathway’s agility with treatment advances (such as cell and gene therapy).

Finally, when all affiliates (n = 108) were asked if they saw advantages in broadening the scope of Access to full life-cycle management, 63% (n = 68) of affiliates agreed. Some affiliates noted that broadening the scope would avoid companies having to submit the same package in multiple countries for the same variation, and that this may increase efficiency and decrease duplication of work. It was also suggested that this could be reserved for complex variations only and that variation requirements should be aligned as much as possible among countries. Reasons for not seeing advantages in broadening the scope of Access to full life-cycle management (37%, n = 40) included the potential risk of complicating processes and variation categories among countries being too different.

Table 1 provides a summary of the key recommendations from affiliates to improve Access. Recommendations were categorized into six areas (Table 1). 

Table 1 Summary of recommendations from affiliates to further improve Access