Understanding the Comparable Overseas Regulator (COR) report-based process

In January 2018, the Australian Therapeutic Goods Administration (TGA) implemented a transformative regulatory measure to streamline the approval of prescription medicines – the Comparable Overseas Regulator (COR) report-based process.

This initiative marked a significant departure from the previous Category 2 applications, aiming to bolster international collaboration and alleviate regulatory burdens by leveraging assessment reports from recognized Health Authorities (HAs) and replacing the need for prior approvals and independent evaluation reports from two acceptable countries.

The COR report-based application process is not limited to specific types of prescription medicines. Instead, it encompasses a broad spectrum, including new chemical entities, fixed-dose combinations, generics, biological medicines, and biosimilars.

The eligibility criteria for this process involve a stringent assessment of the overseas HA's capabilities and regulatory framework before their granting of Marketing Authorisation (MA).

The chosen COR must not be an Agency that granted the MA based on an approach similar to the COR report-based process.

Moreover, the COR report-based process is applicable for variations to prescription medicines already approved by the TGA. This includes extensions of indications, introduction of new dosage forms, safety-related changes affecting product information, and changes necessitating the evaluation of clinical data.

As per the TGA's guideline on "Comparable overseas regulators (CORs) for prescription medicines", an application must meet specific criteria to be considered suitable for the COR report-based process.

Notably, the application should not have encountered delays, deferrals, rejections, refusals, or withdrawals in any country at any time.

The establishment of acceptable CORs is based on a two-stage set of criteria.

Stage 1 involves four criteria designed to confirm the presence of sufficient regulatory similarities between the overseas HA and the TGA.

These criteria ensure that the overseas HA conducts comprehensive quality, safety, and efficacy assessments; maintains good manufacturing practice (GMP) inspection programs; performs pre- and post-market assessments; has established a formal cooperation framework with TGA; adheres to identical international guidelines and standards; and possesses the capacity to conduct business and generate assessment reports in English.

Stage 2 introduces five criteria tailored to each specific application. These criteria determine if the assessment reports from the proposed COR can be used, and are as follows:

• The manufacturing process must be the same as the one approved by the COR. The COR application to the TGA may encompass additional manufacturing sites.
• The proposed indication should be equivalent, substantiated by similarities in population demographics and disease profiles.
• Assessment reports provided by the COR must be unredacted and prepared following the same guidelines and standards applied by the TGA. Importantly, these reports should not be subject to any specific restrictions that impede their use or disclosure, allowing them to contribute to the preparation of Australian Public Assessment Reports.
• The COR report-based application submitted to the TGA must mirror the one approved by the COR. It should not represent a subset or a modified version, ensuring consistency in the regulatory approach.

Submission process

Applicants must submit COR report-based applications in the electronic Common Technical Document (eCTD) format, employing an Australian-specific Module 1.

A comprehensive COR application checklist determines the choice between COR-A and COR-B approaches. All essential COR-related documents, as specified by the TGA, must be included in Module 1.

It is crucial to note that these reports need to be in English or translated by the COR.

Bioequivalence studies for generic applications

For generic submissions, applicants must demonstrate that the reference product used in bioequivalence studies is identical to the Australian reference product.

The TGA guideline on biopharmaceutic studies defines four scenarios with different levels of evidence required.

Biosimilar applications

Biosimilar applications, on the other hand, necessitate evidence establishing the identicality between the overseas reference product and the Australian reference product, with TGA guidelines providing detailed scenarios and strategies.

COR approaches (COR-A and COR-B)

Upon submission, the TGA determines whether to employ the COR-A or COR-B approach based on the extent of data requiring review (which is linked to the depth of the assessment required by the TGA).

TGA encourages applicants to request a pre-submission meeting and discuss their application before submission to ensure that all Australian requirements for the COR report-based application are met.

Based on the Stage 1 criteria, TGA has established that Health Canada, SwissMedic, MHRA, EMA, the Japanese PMDA, the Singapore HSA, and the US FDA are acceptable CORs.

The TGA has provided a complete list of documents that need to be provided from each specific COR for the application to be considered a complete assessment.

At a minimum, all quality, safety, and efficacy assessment reports, questions received from the COR and the answers submitted, summaries of any meetings held with the COR (i.e., pre-submission meetings, scientific advice meetings), approval letter, and post-marketing reviews (i.e. PSURs) are required. A comprehensive list of documents specified for each COR is provided in the TGA guidelines.

COR-A entails a condensed 120-working-day review with TGA examining COR assessment reports, the Australian label, Product Information (PI), and where required, the Risk Management Plan (RMP).

This shorter process is contingent on specific requirements, including:

• identical manufacturing processes,
• a COR approval not exceeding one year, and
• no additional evaluation of Australian-specific data other than the label, PI, and RMP (where required).

COR-B extends the review to 175 working days, involving the assessment of additional data.

The type and extent of additional data to be evaluated will also determine whether the application is best to be assessed through the COR-B or the Category 1 application (full application supported by clinical, nonclinical, and/or bioequivalence data).

For applications made through the COR-B approach, there is no limit on the time that has passed since the approval of the medicinal product by the COR.

Critical considerations

• All COR report-based applications follow the standard registration process and its distinctive milestones, with no formal Milestone 1 as described in the prescription medicines registration process.

• Applications utilizing Drug Master Files (DMF) must include COR assessment reports related to the restricted part of the DMF. These are provided to TGA from the DMF Holder(s) along with the submission of the DMF(s).

• Literature-based applications or those involving medicinal products which include a medical device component may not be suitable for the COR report-based process. In these instances, applicants should seek advice from TGA by requesting a pre-submission meeting.

Results and impact

Since its inception, the COR report-based process has proven effective in expediting the approval of new Marketing Authorization Applications (MAAs) and various regulatory activities.

Table 1 (below), summarizes the information from July 2018 to June 2023, as published by TGA.

With the exception of two submissions, all applications were completed within 120 working days for COR-A and 175 working days for COR-B. One application was withdrawn, and no applications were rejected.

Conclusion

The COR report-based process represents a change in thinking in regulatory approval methodologies, allowing the use of expertise from other HAs and showcasing success in accelerating the availability of medicinal products to patients.

With the global adoption of similar procedures, such as the International Recognition Procedure by the MHRA, this approach reflects a concerted effort to balance accelerated approval timelines with international standards and guidelines, ensuring the continued quality, safety, and efficacy of approved medicines.

References:

1. Criteria for COR report-based process: TGA Link
2. Administrative information and prescribing information for Australia: TGA Link
3. Mandatory requirements for an effective application: TGA Link
4. COR-A and COR-B application checklist: TGA Link
5. Guidance on Biopharmaceutic studies: TGA Link
6. Biosimilar medicines regulation: TGA Link
7. Prescription medicines registration process: TGA Link
8. TGA annual performance statistics report July 2017 to June 2018: TGA Link
9. TGA annual performance statistics report July 2018 to June 2019: TGA Link
10. TGA annual performance statistics report July 2019 to June 2020: TGA Link
11. TGA performance statistics report July 2020 to June 2021: TGA Link
12. TGA Performance Report: July 2021 - June 2022: TGA Link
13. TGA Performance Report: July 2022 - June 2023: TGA Link

Table 1: Applications submitted to TGA using the COR approach from July 2018 to June 2023

¹NCE: New Chemical Entity, NBE: New Biological Entity

²Product Information