Table 2.

Overview of pathways involving repeated, increased interaction between the regulator and the sponsor

Country	Procedure name	Available since	Eligibility	Scope	Characteristics and Data requirements	When and how to apply/timelines	References
Australia	Not applicable
Brazil	ANVISA advice on innovative approaches/new science	2017	Medicines to treat rare diseases	Initial MAA, post-authorisation (new therapeutic indication, generic drug to avoid shortages in the market, vaccines), prior consent in clinical research of drugs	Provides advice on innovative approaches or new science prior to submission		[29]
Canada	Not applicable
China	Breakthrough designation (BTD)	2020	Innovative or modified new medicine for prevention and treatment of: • Serious debilitating disease; • Disease associated with irreversible morbidity or high mortality No other treatment or prophylaxis or clinical superiority over standard of care in China Not open for products approved outside China Note: Drug will be removed from program in case of safety issues or lack of superiority	Initial MAA or new indication	The scheme foresees additional interactions/meetings during drug development at key stages with prioritized resource allocation. BTD gives high possibility of priority review (see Table 3) and rolling submission Prioritizes on-site inspections and QC testing	Application to be made for each eligible indication separately. To be requested during clinical trials (before start phase 3). Application procedure 45 + 5 days. Within 6 months after inclusion in the program, applicant can submit application for first communication in accordance with category I meeting	[48]
European Uniona)	Priority Medicines (PRIME)	2016	Medicines that may offer a major therapeutic advantage over existing treatments, or benefit patients without treatment options	Initial MAA	Close interaction at key development milestones providing support to optimize generation of robust data Early appointment of rapporteur Potential for accelerated assessment (Table 3) and conditional marketing authorization	To be requested during exploratory clinical development based on availability of preliminary clinical evidence in patients substantiating that the product may offer major therapeutic advantage over existing treatments or benefit patients without treatment options. Designation in 40 days	[49]
Japan	Pioneering drug designation (formerly known as Sakigake)	2015	• Innovative medicine (e.g., first in class); • Serious target disease (life-threatening, high impact on daily life; • Outstanding efficacy/safety; • Early development in Japan and at least simultaneous MAA with other countries	Initial MAA	Offers priority consultation (one month consultation compared to 2 months in regular process), prior assessment, built-in rolling review, priority review (see Table 3) Request for designation to be substantiated with clinical data Of note, in case of developments requiring companion diagnostics these will have to be reviewed (by PMDA) in parallel with the medicine	Granted twice a year (April and October) Granted in approx. 60 days	[50, 51]
Republic of Korea	Not applicable
Singapore	Not applicable, regular pre-submission consultation
Switzerland	Not applicable, regular pre-submission consultation, scientific advice and clarification meetings
Taiwan	Breakthrough Therapy	2019	All criteria must be met • New medicines and indications in the areas of unmet medical need; • Serious or rare target disease; • At least one clinical trial in Taiwan, especially clinical trials in the early phase	Initial MAA and new indications	Characterized by early interactions with the Health Authority, including intensive guidance during drug development (every 3 months), possibility to apply for Module-based rolling review and eligibility for priority review (Table 3) Application based on early clinical evidence for substantial improvement over existing therapies	To be applied for before the end of phase 2 study final report. Designation in 1–2 months	[43]
United States of America	Breakthrough Therapy Designation	2012	Serious condition and possibility to demonstrate substantial improvement over available therapies	Initial NDA/BLA and new indications for approved products	Access to FDA’s intensive guidance on efficient drug development from Phase 1 onward FDA commitment to involve senior managers Access to rolling review (see Table 3) Potential for priority review (see Table 3) Application based on preliminary clinical evidence indicative of potential substantial improvement on clinically significant endpoint over available therapies	Request should be made with IND or after; ideally, no later than the end-of-phase 2 meeting FDA aims to respond within 60 calendar days Designation can be lost if data no longer support eligibility	[47]
United Kingdom	ILAP (Innovative Licensing and Access Pathway)	2021	• Life-threatening or seriously debilitating condition or significant patient or public health need; • Innovative medicine or medicine for rare disease/special populations or development aligning with UK public health priorities; • Medicine has potential to offer benefits to patients	Initial MAA (multiple indications) and clinically significant new indication for already approved medicine	Early stage discussions involving also National Institute for Health and Care Excellence and Scottish Medicines Consortium	First step is Innovation Password application. Within 4–6 weeks after receipt of application form, meet with MHRA to discuss how eligibility criteria are fulfilled. Designation granted in 8–10 weeks (4 weeks after meeting) Multiple entry points depending on stage of development as early as availability of non-clinical data	[52]
United States of America	Regenerative Medicine Advance Therapy (RMAT) Program	2016	Regenerative therapies (cell therapy, therapeutic tissue engineering products, human cell and tissue products or combinations of these) intended to treat, modify, reverse or cure a serious or life-threatening disease or condition	Initial MAA	Offers all breakthrough therapy designation features (see above) including early interactions to discuss surrogate or intermediate endpoints	To be requested preferably at the time of IND but no later than end of phase 2 meeting	[53]

^aUntil 2018 EMA ran a pilot scheme under the name Adaptive Pathway for approval in stages (e.g., starting with a restricted patient population, then expanding to wider patient populations as more data are generated). For this pathway existing tools such as conditional marketing authorization and scientific advice were used [54]