Expedited Regulatory Pathways in Established and Emerging Markets

Cristina Mota
Scientific Regulatory Policy & Intelligence, Latin America

Jarbas Barbosa
Former Director-President

Lawrence Liberti
Executive Director
Center for Innovation in Regulatory Science

Denise Bonamici
Regulatory Science & Policy, LATAM

Alberto Grignolo
Corporate Vice President


egulators in both established and maturing agencies are facing opportunities and challenges in their effort to provide faster access to effective, safe, and quality medicines to patients who need them. At a panel discussion during the 2018 DIA Global Annual Meeting, experts from the Center for Innovation in Regulatory Science (CIRS), ANVISA (Health Regulatory Agency for Brazil), Sanofi, AbbVie, and PAREXEL discussed how regulators are approaching this situation in different parts of the world, where a number of agencies appear to be responding creatively to what has been called “the need for speed.”

The panel provided a variety of perspectives ranging from the US FDA, EMA, and Japan PMDA as agencies with well-established expedited registration pathways, to agencies like China CDA, Korea MFDS, ANVISA, and others that have established or updated such pathways in the past year.

Why do we need expedited registration pathways?

  • Breakthrough science and innovative medicines address unmet medical needs.
  • Patients are demanding faster access to these medicines.
  • Although access does not depend solely on regulatory approvals, regulatory approvals are an important gateway to access.
  • Regulators should look at ways to conduct reviews in a rapid manner, without compromising the safety, efficacy, and quality of the medicine.
  • Alternative registration pathways are needed to expedite access, but must be established within a framework that is sustainable for all stakeholders.
  • Improved allocation of local resources, improved patient access, and increased equity of access are urgent global needs.

FDA led by example in the 1980s and 1990s by establishing a number of expedited pathways; regulators in Europe and Japan followed suit more recently by announcing their own pathways for accelerated development and registration.

The “facilitated regulatory pathways” at these mature agencies include frameworks for accelerated approval or progressive rollout of drugs to speed innovation to patients, more agile interactions with sponsors and with each other, and stricter public accountability for their own performance.

In the US, companies have regularly been using available expedited pathways such as Priority Review, Accelerated Approval, Breakthrough Therapy Designation, and Fast Track for many years.

This has been emulated in other agencies such as Health Canada, China CDA, and Korea MFDS with their recent establishment of pathways to accelerate the review of certain types of products or to establish conditional approval based on a more limited clinical data package.

Other regulatory advances are surfacing in other regions, as reflected in the EFPIA Position Paper and White Paper on reliance and expedited pathways in Emerging Markets. Many agencies are seeking ways to most effectively use their resources for medicines reviews; the approaches often involve assessing the outcomes of the reviews previously conducted by other agencies and then ensuring that any additional work conducted by the local agency adds value to prior work. This approach centers on the use of two related but different concepts:

  • Reliance, whereby a regulatory authority in one jurisdiction may take into account/give significant weight to work performed by another regulator or other trusted institution in reaching its own decision.
  • Recognition, the routine acceptance of the regulatory decision of another regulator or other trusted institution. Recognition premises that evidence of conformity with the regulatory requirements of country A is sufficient to meet the regulatory requirements of country B.

The regulatory pathways categorization utilized in this article follows these documents listed above.

Reliance Pathways to Facilitate Regulatory Decisions

  1. Recognition procedures: Authorities review/offer to review medicinal products intended to be marketed in countries or regions other than their own. Examples: EMA Article 58, WHO pre-qualification, Swissmedic MAGHP.
  2. Verification review procedure: Verification review is used to reduce duplication of effort by agreeing that the importing country will allow certain products to be marketed locally once they have been authorized by one or more SRAs (Stringent Regulatory Authorities). Review on the basis of CPPs, GMP certificates, and/or the assessment reports of reference authorities. Examples: Argentina (small molecules), Ecuador, Egypt, Jordan, Saudi Arabia, Singapore (any non-biological product).
  3. Abridged review procedure: Relies on assessments of data that have been already reviewed and approved by SRAs but includes an abridged independent review of a certain part of the dossier relevant to use under local conditions. This review could be of the Module 3 of the CTD, GMP inspections reports, and CPPs from reference authorities. Examples of this procedure come from Costa Rica, Mexico, Indonesia, Panama, Singapore, and Taiwan.

    “Equivalence agreements” represent a reliance regulatory pathway with abridged review. Other good examples of reliance models are emerging from Central America and the Caribbean. In Mexico, “equivalence agreements” provide the benefit of moving approval times from nine months to three to four months; the regulatory authority in Mexico (COFEPRIS) approves applications for innovative molecules by relying on SRAs, such as FDA, EMA, Swissmedic, TGA (Australia), and Health Canada. This pathway applies when the pursued therapeutic indication is the same as the one approved in the above-mentioned countries.

    Other emerging markets, such as Saudi Arabia, Egypt, Jordan, and the UAE, have recently announced accelerated pathways with review timelines ranging from 60 to 90 days.

Expedited Regulatory Pathways for Medicines Targeting Unmet Medical Need

  1. Expedited review: Regulatory authorities speed up the review of certain products to enable faster approval Examples come from Brazil, China, Egypt, Saudi Arabia, Singapore, Indonesia, South Korea, and Israel.
  2. Expedited submission (rolling submissions): Information and data-packages can be submitted and reviewed as they become available. South Korea provides an example.
  3. Expedited development: Earlier submission and approval with a data set which may be less complete than from a standard development program (e.g., surrogate endpoints, phase 2 data only). Examples come from Brazil, South Korea, and Taiwan.

Points to consider to accelerate access to medicines

Regulatory agencies should:

  • apply the principles of WHO draft guidelines on Good Regulatory Practice and Collaborative Registration Procedures when establishing expedited regulatory pathways;
  • focus submission documents on what is absolutely required for purposes of local assessment; and
  • consider allowing face-to face meetings with applicants to discuss the overall filing strategy, especially for products addressing unmet medical needs.

Recently, ANVISA published two new guidelines with the purpose of accelerating the approval of medicines in Brazil:

Resolution 204/2017 establishes “Priority Review” criteria for products that meet at least one of the eligibility criteria; for example, medicines for neglected diseases, and vaccines to be incorporated in the national immunization program. This guidance also addresses priority review processes for post-approval applications when there is a public health risk of drug shortages. Publication of a special procedure for registration of drugs intended to treat rare diseases was another effort to expedite drug approvals.

Resolution 205/2017 establishes expedited procedures for clinical trial applications, certificate of good manufacturing practices, and registration of new drugs intended for diagnosis, prevention, or treatment of rare diseases.

Service Orientation 45 is another recent (February 2018) regulatory advance from ANVISA, which establishes optimized review for registration and post-registration changes for biological products. According to the agency, this is also being considered a “Reliance Pilot Project” open for one year. Products already approved by the FDA and EMA with same indications, dosage, adverse reactions, and precautions are eligible. Applicants must submit reports containing the criteria used by both agencies to review and approve these applications.


The needs of patients and the demands of global drug development have led to the use of expedited and reliance pathways in established and emerging markets to provide faster access to medicines for patients in need. This is the key consideration as regulatory agencies facilitate review and approvals, simplify procedures, and reduce review timelines and backlogs. Progress has been remarkable and has not been limited to developed agencies; it is an increasingly global phenomenon that reaches into the developing and emerging markets.

Regulatory pathways must be tailored to the local country situation and current registration procedure. With strong collaboration among regulatory agencies, it may be possible to build upon existing frameworks and global standards, building trust and sharing resources and experiences. Regulatory reliance has emerged as an exciting and viable way to avoid duplication of review effort, ease the burden on under-resourced regulatory agencies, and still deliver new medicines to patients who need them.