This model 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 authorised by one or more recognised reference agencies, elsewhere. The main responsibility of the authority in the importing country is to ‘verify’ that the product intended for local sale has been duly registered as declared in the application and that the product characteristics (formulation, composition) and the prescribing information (use, dosage, precautions) for local marketing conform to that agreed in the reference authorisation(s).

This model also conserves resources by not reassessing scientific supporting data that has been reviewed and accepted elsewhere but includes an ‘abridged’ independent review of the product in terms of its use under local conditions. This might include a review of the pharmaceutical quality (CMC) data in relation to climatic conditions and distribution infrastructure and a benefit-risk assessment in relation to use in the local ethnic population, medical practice/culture and patterns of disease and nutrition.

In this model the authority has suitable resources, including access to appropriate internal and external experts, to carry out a ‘full’ review and evaluation of the supporting scientific data (quality, preclinical, clinical) for a major application. A type III assessment could be carried out on a new application that has not been approved elsewhere, but in practice legal requirements may dictate that the product must be authorised by a reference authority before the local authorisation can be finalised.

The models of the review process carried out in the GCC states significantly vary according to the respondent’s perceptions and views of their own review practices. The level of data assessment in each authority depends on the type of product and/or its regulatory status with other authorities. The three types of assessment models were explored and the extent of the scientific reviews was examined for each GCC authority.

Five GCC authorities stated that they perform an abridged assessment (Bahrain, Kuwait, Oman, Qatar and UAE). This is a critical practice to ensure the appropriateness of the product under local conditions. Bahrain carries out a verification review for biological and biotech products because they have to be registered in other reference authorities to be accepted for review in Bahrain and an abridged review for other major applications. The UAE conducts an abridged review for biological and biotech products because they are only registered if they are approved by advanced regulatory authorities and conducts a full review for other major applications. Saudi Arabia is the only country that performs a full review for all types of applications (Table 2.2).

Furthermore, the extent of the scientific assessment was evaluated in the six GCC authorities, and the results revealed that six GCC authorities perform detailed assessment on the pharmaceutical quality (CMC) data. The six authorities have assessors with the required skills and experience to evaluate the CMC data. Oman and Kuwait perform detailed assessment on products which are not registered in countries with reference authorities, whilst they review the pharmaceutical quality data for products which are registered in recognised agencies when there is a query to be examined. Detailed nonclinical and clinical assessments are performed by Saudi Arabia and UAE. In UAE, these detailed assessments are performed on products which are not approved by recognised authorities, whilst those which show evidence of authorisation in reference regulatory authorities are only examined when there is a query.

Bahrain, Kuwait, Oman and Qatar perform the nonclinical and clinical assessment when there is a critical issue to be evaluated. This may be due to the lack of expertise to carry out nonclinical and clinical assessment in these four authorities.

Three common phases are thoroughly examined and described for each GCC regulatory review process, namely, the submission phase, the evaluation phase and the authorisation phase. These data reflect the situation at the time the study was carried out (2010) and subsequent changes in the regulatory environment will need to be monitored.

Bahrain has a unique medicines policy that clearly states the aims, the current situation and the objectives of the Bahraini medicines control system. It is called the ‘Bahrain Medicines Policy – BMP’. The goal of the policy is to serve as a guide for action and commitment to provide good-quality, safe and effective medicines which are rationally used and provided at reasonable costs for the people in Bahrain and for coping with new developments in the field of pharmaceuticals (Bahrain Ministry of Health 2008). The regulatory review process in Bahrain is illustrated in Fig. 2.1 comprising the critical steps that form substantial parts of the review process.

Initially, the sponsor submits the product registration dossier with the complete documents for the official acceptance of the dossier to be made. The authority does not specify information about the logistics involved at the receiving stage.

However, the dossier is validated before it is accepted for review, and the aspects such as legal status of applicant/local agent, GMP status of manufacturer, patent/IP status of active ingredients, acceptable format of the application, organised format of the registration dossier including the three sections of scientific data (quality, safety and efficacy) and CPP authenticated by the respective embassy or consulate general are checked accordingly.

The target validation time within the authority is 2 weeks after which it is officially accepted for review once all the missing data has been provided and the date of acceptance is recorded. The Bahraini authority refuses an incomplete application and generates an official letter indicating the missing data and a time period of 2–4 weeks for the application to be completed. The dossier, then, joins the queue for a period of 2–8 weeks before entering the scientific assessment stage. The authority recognises the medical urgency of the priority review process, and therefore emergency, life-saving and important medicines are always taken out of the queue for the accelerated review process.

When the product enters the scientific assessment stage, the dossier is split into three sections, which are assessed in parallel by the appointed reviewer who completes a product assessment template and collects all the resulting questions as they arise during the review into one batch for the sponsor including the laboratory requirements. After sending the queries, the sponsor is given a time limit of 6 weeks to respond, and all inquiries regarding the product labelling information are negotiated with the sponsor during the evaluation phase. The sponsor holds meetings with the authority’s staff to discuss any questions that arise during the assessment. Finally, the product is sent to the quality control laboratory to carry out sample analysis to determine the eligibility of the product for approval.

The procedures of the scientific committee for the assessment stage are integrated into the authority’s own internal/external scientific review process. The committee’s experts (internal and external) carry out the review process, and the authority is mandated to follow the committee’s recommendations. The time for the committee review is 30–90 days, after which the decision is made to grant the marketing authorisation.

The pricing process is the final step and price negotiations occur at the end of the scientific assessment. The sponsor is informed of a positive scientific opinion within 90 days of issuing the authorisation. At this point the pricing negotiations and scientific assessment procedures are complete, and the product is ready for approval. The company is now required to pay the fees to receive the registration certificate, and the product is ready to be marketed in Bahrain.

The key milestones in the approval process and target approval time in Bahrain are illustrated in Fig. 2.1. The authority has not set a target time for the scientific assessment stage, and therefore it was not possible to calculate the final product approval time.

The regulatory review process in Kuwait focuses on the quality review for pharmaceutical products to be authorised for marketing in Kuwait (Fig. 2.2).

The most important goal of the Kuwaiti review process is to ensure that (a) the product is registered and marketed in countries with recognised and competent regulatory authorities for at least 12 months; (b) that the product meets the desired, internationally recognised, quality standards to ensure that the product was manufactured for its intended use; (c) that the product is stable for the entire proposed shelf life and for 6 months under the stressed conditions of 40 °C/75 % relative humidity; and (d) that the product price must be reasonable and affordable for local patients.

The review process starts with the local agent (or the sponsor) submitting the registration dossier along with a covering letter to the Director of Kuwait Drug and Food Control (KDFC) officially requesting the registration of the pharmaceutical product. The authority, then, transfers the registration dossier to the registration department, and the Drug Registration and Release Superintendent (DRRS) acknowledges the receipt and appoints a reviewer to undertake the assessment of the dossier. The product is placed in a queue for review by the department’s administrative staff member who is responsible for keeping a record of the dossiers to be transferred to the appointed reviewing staff member.

After entering the scientific review stage, the reviewer evaluates the chemical and manufacturing control (CMC) data focusing on the following data:

Even though the authority does not evaluate safety and efficacy data, it considers documentation of such data as an important part of a successful approval process. Therefore, sponsors must ensure that safety and efficacy data are submitted to the authority along with all other registration documents. These are addressed when further investigations are necessary and then the following procedure occurs. The authority indicates that New Active Substances (NAS) companies must submit clinical studies as a major requirement for a successful approval of their NAS. Clinical studies are sent to the relevant specialised hospital or health institutions for evaluation by clinical experts, and a report is sent back to the regulatory authority stating the clinical effectiveness of the product on selected patient volunteers and whether there is a significant clinical need for such a medicine in Kuwait. The authority appends this report to the scientific assessment report. In the case of an EAS, the sponsor must submit bioequivalence studies to provide evidence of bioequivalence between the locally marketed NAS and its EAS counterpart under registration.

Kuwait requires suitable facilities, expertise, resources and proper settings to be able to conduct the desired standard safety and efficacy assessments. Therefore, the main focus of the authority is on the pharmaceutical quality data that provide the assurance that the drug was formulated for its intended use. Furthermore, administrative documents such as the certificate of pharmaceutical product (CPP), the list of countries where the product is registered and marketed with the registration dates, the good manufacturing practice (GMP) certificate and a manufacturing licence authenticated by the health authority in the country of origin are the official documents that are requested from the sponsor to overcome the shortage in resources and expert capacities to evaluate the safety and efficacy studies. For completion of the review process, NASs do not enter the quality control analysis stage as long as the sponsor has provided complete pharmaceutical quality documents to ensure that this product is of the desired quality. Once this is achieved, the NAS is ready for approval. EASs, however, are sent to the QC laboratory for sample analysis. The results must comply with analytical results and ranges provided by the manufacturer’s certificate of analysis of the finished product. Moreover, the results must not be outside the ranges and limits provided by the NAS company’s patent counterpart. Furthermore, to overcome the lack of post-marketing surveillance (PMS) capacity, the authorities request the necessary pharmacovigilance reports as part of the safety studies submitted along with the registration dossier.

After reviewing the dossier, questions are collected as they arise during the scientific assessment and sample analysis. These are sent to the sponsor after the Drug Registration and Release Superintendent (DRRS) has given their advice by signing the question/query form. The authority places no limit on the sponsors’ processing time and the scientific assessment clock stops at this point until a reply is received from the sponsor. This step affects the overall approval time when delays in the sponsor’s reply are encountered. However, the authority does not exclude it from the review process but considers its impact on the final approval time.

When the full assessment has been successfully completed, the final approval decision is made by the DRRS which is officially endorsed by the director of the authority. At this stage, the pricing negotiations have been completed and an agreement has been reached. Once the review and pricing procedures are completed, the product is finally approved and the sponsor is then required to pay the fees to receive the registration certificate. The agreed product price is listed in the next supplement to be presented for approval by the Health Minister. Once the Minister approves the price, it is officially published in the locally distributed business magazine called ‘Kuwait Today’, after which the product is ready to be marketed.

The key milestones in the approval process and the associated timelines in Kuwait are illustrated in Fig. 2.2. The target approval time in Kuwait is 120–180 days for both NASs and EASs. However, this timeline is not fully enforced due to many interfering factors that hinder its implementation such as the clock stop during the sponsor’s response time with no specific time limit for the sponsor to process the authority’s questions and queries. Nevertheless, if the sponsor does not respond to the authority’s question within a maximum period of 2 years and is still willing to complete the registration process in Kuwait, the original dossier is returned to the sponsor and a new application must be made.

A thorough evaluation of the regulatory process in Oman was undertaken and the milestones identified. The regulatory review process in Oman comprises ten stages, which are considered critical and have an impact on the approval time of medicines (Fig. 2.3).

An evaluation of the regulatory review process in Qatar was undertaken and the milestones were identified. The regulatory review process in Qatar is illustrated in Fig. 2.4 and consists of 13 critical steps that have an impact on the overall time of patient access to the medicines.