Around the Globe

Joint Assessment of Marketing Authorization Applications:
Cooperation Among ASEAN Drug Regulatory Authorities
Rosilawati Ahmad
National Pharmaceutical Regulatory Agency, Malaysia
Tharnkamol Chanprapaph
Food and Drug Administration, Thailand
Samvel Azatyan
World Health Organization
Valerio Reggi
World Health Organization
Prapassorn Thanaphollert
World Health Organization

he first steps toward harmonization of ASEAN pharmaceutical regulations started in 1992 through the establishment of the ASEAN Consultative Committee for Standards and Quality (ACCSQ). In 1999, the ACCSQ established a Pharmaceutical Product Working Group (PPWG).

The objective of the PPWG is to develop harmonization of pharmaceutical regulations across ASEAN member countries to complement and facilitate the ASEAN Free Trade Area (AFTA), particularly the elimination of technical barriers to trade posed by these regulations, without compromising on drug quality, safety, and efficacy.

Harmonization and cooperation ensure that no regulatory work is conducted in isolation, without taking into account that a similar product or manufacturing site has been or is being assessed in several other countries by authorities with different capacity, resources, and skills. In addition, harmonization and cooperation leads to improving access to essential medicines and building regulatory capacity and trust. Most regulatory authorities face limitations which prevent them from performing all regulatory functions at the highest possible level of competence, efficiency, and effectiveness.

The best approach is effective collaboration among National Regulatory Authorities (NRAs), which can take place in two main ways: formal agreements (e.g., mutual recognition agreements), which require establishing an appropriate legal framework (and therefore may take a very long time to achieve); and reliance, i.e., work done by a trusted authority (e.g., an assessment or inspection report) is shared with a receiving authority, who uses the reports to make its own decisions without duplicating the work.

For more than 20 years, the PPWG has developed a number of important initiatives and tools to support harmonization and regional cooperation (see accompanying box). The effective implementation of these tools and initiatives is crucial to achieve the overall goal, established by the ASEAN Economic Ministers, of removing technical barriers to trade and gradually broaden pharmaceutical export markets.

PPWG Initiatives and Tools to Support Harmonization and Regional Cooperation
ASEAN Common Technical Dossier (ACTD)
ASEAN Common Technical Requirements (ACTR)
ASEAN Sectoral Mutual Recognition Arrangement for GMP Inspection of Manufacturers of Medicinal Products (GMP MRA)
ASEAN Post-Marketing Alert System (PMAS)
ASEAN Mutual Recognition Arrangement for Bioequivalence Study Reports of Generic Medicinal Products (BE MRA)
ASEAN Guidelines on stability study, bioequivalence and bioavailability studies, manufacturing process validation, validation of analytical procedures, and variations
ASEAN Joint Assessments Coordinating Group (JACG) to pilot the implementation of joint assessment of marketing authorization applications.
Close cooperation and collaboration among ASEAN NRAs on the basis of similar procedures, common standards, and joint assessments are necessary operational steps that will gradually lead to work sharing; elimination of duplicated effort; timely access to high-quality, safe, efficacious pharmaceutical products; recognition of each other’s regulatory decisions; and better regulatory outcomes for all ASEAN citizens.

Establishment of Joint Assessment Coordinating Group (JACG)

In 2015, the PPWG started a WHO-supported project aimed at strengthening the implementation of ASEAN harmonized regulatory requirements (SIAHR). The project analyzed gaps and country-specific requirements and reported its findings to the PPWG. After thorough discussion, the PPWG decided that further action is required to address the issues. In particular, it was recognized that issues related to different implementation or interpretation of harmonized requirements are the result of several factors that can be addressed through further cooperation among NRAs, such as joint assessment of applications for marketing authorization, hands-on training, and other similar activities where staff of different NRAs can work together. PPWG also recognized that these measures require important funding and specific input from other parties such as industry and ad hoc expertise from well-resourced NRAs.

On this basis, the PPWG decided to work toward the establishment of a Joint Assessment Coordinating Group (JACG) to focus on activities related to intensified collaboration among ASEAN NRAs, such as joint assessment of applications for marketing authorization and similar activities where staff of different NRAs can work together, respecting national decision-making processes.

The PPWG has assigned several responsibilities and functions to the JACG. In particular, the JACG shall develop and update, as required, procedural documents to enable implementation of joint assessments in line with ASEAN Common Technical Requirements (ACTR) and the ASEAN Common Technical Dossier (ACTD); assist NRAs to identify products eligible for the joint assessment procedure; facilitate communication and collaboration among Member States participating in joint assessments; and establish a Panel of Experts (PoE) for particular joint assessment projects.

The JACG operates under the overall guidance of the PPWG, has at least one representative from each ASEAN NRA as well as representatives from the ASEAN Secretariat, and is managed by a Chair and a Vice-Chair who shall not be from the same ASEAN Member State. Resource persons from organizations such as WHO and/or ASEAN Dialogue Partners can be invited by the JACG Chair to provide technical advice.

Progress Made by JACG

The JACG has developed procedural documents to facilitate and manage joint assessments. A joint assessment is defined as a formal procedure in which the same marketing authorization application is simultaneously submitted to all participating NRAs. Assessment work is then conducted together by all participating NRAs, and a joint assessment report is prepared. At the end of the process, the final decision on the application is taken by each individual NRA through their normal decision-making process based on the joint report and, where applicable, nationally relevant considerations.

The JACG has stated that the primary purpose of joint assessments (JAs) is to strengthen NRAs’ technical capacity and to foster mutual trust and reliance among ASEAN Member States through a platform for communication and cooperation which ensures each NRA that pharmaceutical products meet requirements of quality, safety, and efficacy and that regulatory work is conducted in a timely and efficient manner. An additional important purpose of JAs is to facilitate review of priority medicines throughout ASEAN while respecting existing national decision-making processes.

Participation in joint assessments is open to all ASEAN NRAs on a voluntary basis. A list of priority pharmaceutical products will be periodically published (and reviewed) for industry to gauge products of interest for joint assessment. Participation is specific to each product being assessed. Therefore, each NRA will be able to participate for certain products and decline to participate for others, at its discretion. Joint assessments will be implemented when a minimum of three NRAs decide to participate.

For each joint assessment, participating NRAs will appoint one as Lead NRA to coordinate and facilitate the assessment work, liaise with the applicant, and (where possible) facilitate support from a well-resourced NRA.

JACG has completed two joint assessments concerning two antimalarial medicines. The most recent assessment, concerning tafenoquine, including all steps from availability of the full dossier, list of questions sent to the applicant, discussion of applicant response, to release of final joint assessment report, took less than five months. Participating NRAs benefited from the technical support of Australia’s TGA through the provision of internal and unedited assessment reports, and the participation of TGA experts in virtual meetings during the assessment process.

JACG is now working on the establishment of an operational mechanism consisting of appropriate administrative tools and an IT platform, called Joint Assessments Information Management System, which will provide the following functionalities:

  1. Applicants upload application dossiers choosing either ASEAN or ICH format.
  2. Participating NRAs work online to review the dossier and input observations/questions for the applicants.
  3. Lead NRA consolidates observations from all participating NRAs, generates a single List of Questions, and sends it to the applicants.
  4. Applicants respond online.
  5. Lead NRA assists participating NRAs to finalize and share joint assessment report.

It is envisioned that this IT platform, when fully operational, can be gradually developed to become a stable ASEAN-wide platform that will continue to support and accompany the joint assessment process and may also support other collaborative processes such as:

  1. Enabling authorities to exchange information, avoid duplication of work, foster cross-reliance, and filter out substandard products;
  2. Permitting immediate dissemination of alerts on safety concerns, quality defects, and falsified products;
  3. Streamlining availability and exchange of manufacturer-related information, facilitating timely action in situations involving defective products;
  4. Acting as a platform for referencing and benefiting from evaluations and decisions made by better-resourced authorities within and beyond the regional level; and
  5. Enabling businesses and citizens to access selected information on medicines approved across a number of countries.

By working together, regulatory authorities can more reliably ensure that safe, effective, high-quality medicines are authorized in a timely manner and that patients, healthcare professionals, and businesses are provided with adequate and consistent information about these medicines.