Review Models

McAuslane and colleagues previously characterised three types of scientific regulatory review. Type 1 or verification review requires the previous approval of a medicine by two or more reference agencies, with the agency verifying that the locally marketed medicine conforms with the approved product. The type 2 or abridged review requires the previous approval of a medicine by at least one reference agency and the review centres on aspects of the medicine that must be assessed in the local environment. This type of review is often limited to an assessment of the country-specific requirements for product quality and the clinical data associated with the local benefit risk assessment of the product. Type 3 or full reviews consist of a complete review of a medicine’s quality, safety (pre-clinical), and efficacy (clinical) data, with type 3A also requiring previous approval by a reference agency, which is not a requirement for type 3B [11]. The GCC-DR conducts type 3A reviews for all major applications (NASs and major line extensions). A priority review track is in place for vaccines and anti-carcinogenic therapies. However, if a product has been approved by two Gulf States or by the United States Food and Drug Administration (US FDA), European Medicines Agency (EMA) or the WHO prequalification (as reference agencies) then the GCC-DR will conduct an abridged review. If a product is registered in all member states, then the GHC will conduct a verification review, which is normally achieved within 21 days.

Data Requirements

A Certificate of Pharmaceutical Product (CPP) is required before final authorisation and no other documentation is accepted as evidence of registration. However, consideration should be given to no longer requiring a formal CPP but substituting alternative ways of verifying registration in the reference countries such as letters of authorisation or Internet reference. A full ICH electronic common technical document (eCTD) is required, including full non-clinical and clinical data (Modules 3, 4, 5).

Key Points in the GCC-DR Review Process 1.

Validation of marketing authorisation applications consists of a verification of legal, good manufacturing processes, patent and intellectual property status, confirmation of an acceptable format and content of the application and payment of fees.

2.

Queueing for the scientific assessment can take 60–180 calendar days, although priority products may be taken out of the queue to be the subject of an expedited review.

3.

All member states receive dossier files and have the option to review, but two member states are specifically named by the Expert Committee to review the files for quality, safety and efficacy in parallel and provide their recommendations to the GCC-DR.

4.

Questions to the sponsor are batched and there is a target time of 180 calendar days for the sponsor to respond to queries.

5.

The Expert Committee provides a peer review of the dossier and issues its recommendation, which the GHC is mandated to follow. However, authorisation does not depend on pricing agreements.

6.

There are no target times for validation, scientific assessment, or Expert Committee evaluation, but there is an overall review target time of 365 days for a full review and 120 days for priority review and this includes both agency and manufacturer’s response time (Fig. 1).

Fig. 1

Gulf Centralised Committee for Drug Registration procedure process map and milestones, simplified to show when an application goes to approval in one cycle

Number of Product Approvals

Over the period 2015–2020 (Fig. 2), the fewest NASs (4) were approved in 2016 (4) and the most (13) in 2019; while the fewest generics (45) were approved in 2019 and the most (189) in 2020. The substantial increase in the number of medicines approved in 2020 was due to several factors, including the introduction of a significant digital transformation for all stakeholders, which included a shared file storage system in which applicants’ dossiers were easily accessible by all member states, resulting in a faster review process for new and pending applications.

Fig. 2

Total number of medicines approved by the Gulf Centralised Committee for Drug Registration 2015–2020. NAS new active substance

Review Times

Review times also significantly decreased with the implementation of a reliance strategy by the end of 2019. The average approval time for generics and NASs decreased from 838 calendar days in 2015 to 321 calendar days in 2019 and 411 calendar days in 2020 (Fig. 3). In addition, when products were registered in two Gulf States, an abridged review was conducted in an average review time of 61 calendar days and when products were registered in all member states, a verification review was conducted in an average of 21 calendar days. However, the product cannot be the subject of a GCC joint procurement unless it has a centralised certificate. Reasons for the reduction in review times included an increase in the number of committee meetings. In 2019, the number of drug registration committee meetings was increased to once a month by teleconferencing in addition to a face-to-face regulatory meeting every quarter, for a total of 16 meetings per year. Prior to that, there were only 5 committee meetings in 2017 and 10 meetings in 2018.

Fig. 3

Average approval time for all new active substances and generics approved by the Gulf Centralised Committee for Drug Registration by approval route 2015–2020

Moreover, the following pharmaceutical legislation and regulatory procedures were implemented as part of the principle of reliance:

Products registered in the six GCC member states are directly approved (this indicates that the registration department of the GCC will be responsible for issuing the registration certificate). Products registered in two or more GCC member states are registered and the registration certificate is issued after 60 days, unless observations or comments from GCC member states are received on the reports issued. The review process involves a comparative assessment between the peripherally submitted dossiers and the centrally submitted ones, alongside a validation of submitted certificates.

If a product is registered in two or more GCC states, then this means that the GHC can issue a product certificate whilst the manufacturer is still undergoing the process centrally.

The inspection visit to the manufacturer is bypassed if a visit has been made by one of the member states to the manufacturer within the past 2 years and no issues have been raised.

GCC member states rely on approvals issued by the GHC for variation requests of pharmaceuticals products, where the company has the right to start implementing the approved variation in the GCC countries, and the company must provide member states with product files according to the life cycle of the registration of the product if they differ from that presented centrally (eCTD sequence).

Electronic communication with applicants and member states has also expedited the review process for new and pending application requests, also resulting in reduced approval times. Altogether, these factors led to the reduction in approval times seen in 2019 and 2020.

Prior to the implementation of reliance, approval times had been reduced when member states began to depend on their own scientific reports for the national procedure, but this practice was replaced by reliance at the end of 2019.

Good Review Practices

The importance of establishing good review practices (GRevPs) is recognised by the GHC and these have been implemented in the GCC-DR review; they include standard operating procedures (SOPs) for the guidance of scientific assessors, the use of a standardised assessment templates, shared/joint reviews within the Gulf Region, and a formal training programme for assessors as well as an electronic tracking system for monitoring the progress of applications. However, some GRevPs, such as an internal quality policy, SOPs for the guidance of advisory committees and internal or external peer review, remain to be implemented.

To bring about continuous improvement in the assessment process, GCC-DR assesses the feedback of reviewers and other stakeholders and takes necessary action, monitors the progress of applications through an electronic internal tracking system and carries out training through both internal and external courses, on-the-job learning and participation in external workshops. Training is tested through examinations and is required for professional advancement. In addition, the assessment report (AR) is shared with other regulatory authorities if requested and the sponsor also get a copy of the full AR. However, currently the ARs are not released to the public.

Decision-Making Frameworks

The GHC has a systematic structured approach to decision making, with clearly assigned roles and responsibilities. They assign values and relative importance to decision criteria, evaluate both internal and external influences/biases, re-evaluate decisions as new information becomes available and effectively communicate to the pharmaceutical company the basis of the decision.