A biological drug (or biologic) is one that is produced from a living organism or contains components of a living organism. They have become indispensable tools in modern medicine, for treatment of life-threatening conditions. With an aging population and a growing demand for treating chronic conditions, biologic use is on the rise. However, they are associated with high cost and limited patient access
Biosimilars are biologic medicines that are highly similar to an approved biologic product currently on the market. They are becoming an important sector in the pharmaceutical and healthcare industry. The launch of new biosimilar products could help save consumers $250 billion over the next decade.
The Middle East and North Africa (MENA) region represents about 2% of the pharmaceutical industry. The biosimilar market for the region is projected to grow from $0.71 billion in 2021 to $2.17 billion by 2026. This growth is a result of the rise in GDP and healthcare expenses, and the subsequent demand for cost-effective therapeutic solutions. Biosimilars play a significant role in minimizing public healthcare expenditure on medicines, thus increasing the accessibility of these medicines to more patients.
The use of biosimilars
Countries within the MENA region experience an increasing demand for chronic disease management. The MENA region has the highest prevalence of diabetes in the world, and cancer being a common cause of death. For this, and other conditions, biosimilar treatments exist.
The use of biosimilars is gradually increasing in MENA countries, though more awareness among health-care professionals and patients is still required. Differences remain with respect to issues regarding the regulatory approval and interchangeability of biosimilars. Organizations have taken initiatives, such as the MENA Stakeholder Meeting on Regulatory Approval, Clinical Settings, and Interchangeability and Pharmacovigilance, to address these issues by:
- establishing agreement of biosimilar monitoring, regulation, and use by various healthcare professionals;
- communicating the concept of biosimilars to patients, health-care professionals and other interested parties.
The regulation pathway for the authorization of biosimilars is different to that used for conventional drugs. Biosimilar approval pathways in major regulatory regions are scientifically aligned. However, there exist some regulatory variations due to regional differences in healthcare priorities, policies and resources.
There is no consensus on the pathways adopted by the regulatory agencies in the MENA region for the approval of biosimilars. Inconsistencies in regulatory pathways could contribute to diminished confidence regarding biosimilar efficacy, reliability and quality, and lead to a delay in biosimilar development.
It is crucial to implement robust and unified regulatory approval procedures so that these medicines can safely reach the market quicker. They should be mindful of the importance in obtaining an internationally agreed system of regulatory approval, and ensuring a global understanding of, and agreement on, interchangeability.
Saudi Arabia is one of the major Middle Eastern players in the pharmaceutical industry. It is a country that is inclined towards innovation and expensive branded products, and accounts for the largest market share within the MENA region. It is also a member of the Gulf Cooperation Council (GCC) that follows its own centralized procedures, in which different authorities are involved. The Gulf Health Council (GHC) acquires pharmaceutical products with proven efficacy, quality and safety. The Gulf Central Committee for Drug Registration (GCC-DR) oversees a range of procedures- from manufacturing site registration to post-marketing surveillance.
The Saudi Food and Drug Authority (SFDA) reviews and approves the biologic product, and its price, before it enters the market. The SFDA regulatory framework follows the United States (U.S.) FDA and the European Medicines Agency (EMA) guidelines with specificities that accommodate for the local and regional (GCC) requirements.
The regulation of biosimilars in Saudi Arabia follows a department-centric evaluation procedure for biosimilar approval. Each new therapy is separately approved by each department. Professor Aws Alshamsan, Drug Sector at SFDA for Biologics and Vaccines consultant, expressed that this system is incoherent and a lengthy process taking approximately 290 days compared to a product-centric approach, which enables departments to simultaneously work together for therapy approval therefore takes significantly less time. Binocrit, Grastofil Omnitrope, Remsima, and Zarzio are the only 5 biosimilars that have been approved in Saudi Arabia, compared to the 50 that have been approved in the European Union (EU).
Specific quality requirements for biosimilars include the following:
- The reference product can be the originator, or one that has been approved by the SFDA or a strict regulatory authority
- Composition, physical properties, and primary and higher order structures characterize the biosimilar
- The proposed biosimilar must have a primary amino-acid sequences that is exactly the same of the reference drug
- Post-translational changes in the structure of the biosimilar must be characterized. Variations between the reference product and the biosimilar must be justified and demonstrated to no affect immunogenicity or potency
United Arab Emirates (UAE)
Another member of the GCC the UAE’s requirements for biosimilar registration were introduced by Dr. Rasha Sayed Salama, Public Health Advisor for Public Health Policy and Licensing Sector at the Ministry of Health and Prevention UAE. These include data on consistency in the manufacturing process, demonstration of immunogenicity, heterogeneity assessment, safety and efficacy studies, therapeutic equivalence, and a pharmacovigilance plan where the community can directly express their concerns to the Ministry of Health.
Biosimilars that are produced in the UAE for international markets follow international guidelines set by the EMA and World Health Organization (WHO). However, for local markets they follow UAE standards and guidance set by the GCC. Changes in the specifications or characteristics of a biosimilar product is considered a totally new product and is required to follow biosimilar procedures.
Currently, the Egyptian Drug Authority (EDA) “Guideline for registration of Biosimilar products in Egypt” is in place, as of March 2020. The applicant is required to exhibit and compare the biosimilarity of their product to the innovator/reference product by completing and comparing pre-clinical and clinical studies, and quality exercises. The EDA adopts the EMA guidelines and also refers to the U.S. FDA’s safety and quality considerations, the WHO guidelines on the evaluation of similar biotherapeutic products, and, to relevant ICH guidelines.
The EDA has licensed 4 imported biosimilars, and 10 candidate products that obtained preliminary approval. Furthermore, 25 local products received preliminary approval where some already had market authorization under review.
The Jordanian FDA’s guidelines are based on the EMA, where the EMA model has been implemented for quality assessment and comparability. It also authorizes the approval of manufacturing sites as a prerequisite to product approval and filing. Till date, 6 products have been approved according to Jordan’s biosimilar guidelines. Jordan’s approach in biosimilar regulation can be considered vigilant and strict. Nonetheless, biosimilars that are manufactured and marketed in reference countries, including but not limited to UK, USA, Germany, France, Netherlands, Sweden, Australia, Austria and Japan, are usually given more privilege.
More differences in Interchangeability
A lack of agreement exists between countries of MENA regarding issues of regulatory approval, particularly in regards to interchangeability and switching. In Saudi Arabia, biosimilars are not automatically interchangeable. Ten biosimilars have been approved out of which only two are regarded as interchangeable. It is evident that, in Saudi Arabia, biosimilarity alone is not sufficient enough for substitution or switching. However, biosimilars approved by EMA are considered interchangeable. Additionally, a clinical trial that involves switching must be run in order to approve switching- this must happen before the biosimilar is approved.
Medicines in Tunisia are obtained by pharmacy centralized purchase (PCP). The Biosimilar Specialized Committee makes decisions on a case-by-case basis in regards to interchangeability. The committee comprises representatives of pharmaceutical inspection, national control laboratory, regulatory authorities and various clinicians of all expertise who utilize biosimilars. In Egypt, however, the Ministry of Health will make interchangeability decisions, where the patient will not be given a choice.
The extent of price difference… how much cheaper?
Undoubtedly, biosimilars reduce healthcare costs while securing a global supply of high quality and safe medicines. But what is the extent of price differences between the innovator and biosimilar? In Tunisia, there was a substantial decrease in price between Herceptin and its biosimilar, Hertraz. In Saudi Arabia, the biosimilar product, Zarxio, was 1/5th of the price of its innovator, Neupogen. However, there was no difference between Remicade and Remsima. Egypt’s pricing policy for biosimilars is based on the ‘second brand innovator’ concept where this exists a 30% variation in pricing for Hervive and Retuksera.
The countries in the MENA region have adopted guidelines based on the EMA, FDA and WHO guidelines. This should allow greater penetration into the market for international biosimilar developers. Local regulatory bodies may still be cautious with respect to the assessment of biosimilars. However, it can be concluded that approval from a “reference” country is significant as biosimilars are preferred when they are already approved by a strict, more established regulatory agency allowing better prospects while investing in the MENA nations.