Mapping The Biosimilar Regulatory Landscape In The Middle East
By Guriqbal Singh, RegWeb
Biosimilars are becoming increasingly popular for treating a wide range of life-threatening diseases. When compared to other emerging regional markets, the Middle East has one of the strongest and most alluring biosimilar markets.
The biosimilar market in that region is expected to surge ahead at a compound annual growth rate of nearly 4% and reach $623.7 million by 2027, according to an IQVIA analysis. A looming exclusivity cliff and a breathtaking difference in price — up to 80% savings compared to the reference for some drugs — are driving development.
Any company entering the market must navigate a patchwork regulatory landscape. We could say the whole region is emerging, but some countries have exceptionally young and lean biosimilar regulatory frameworks while others are racing to keep pace with the industry.
Here we provide a brief overview of the regulatory frameworks in nine key Middle Eastern and North African nations playing the biosimilar game. Then we look at the challenges the fledgling industry faces and explore some possible solutions.
Let’s get started.
Algeria
Legal Basis And Regulatory Framework
The following documents set the framework for biosimilar governance in Algeria.
- Executive Decree No. 20-325 related to Pharmaceutical Products Registration Modalities dated Nov. 22, 2022
- Algerian Health Law No. 18-11 dated July 2, 2018
Biosimilar-Specific Regulation Or Guideline?
No. An Algerian draft guideline for biosimilars exists but it is not yet shared with the industry. It is highly inspired by EU biosimilar guidelines. No final version is available as of August 2023.
Registration Requirement
There is no specific application procedure. The same EU standards are adopted for the review of biosimilars. EU or U.S. approval of biosimilars is highly recommended for registration in Algeria. GMP inspection is likely to happen for biosimilars.
Dossier Requirements
Like the biological innovator products, all modules (1 through 5) are required, with comparability data for quality, non-clinical, and clinical parts.
Interchangeability
Biosimilar substitution is not a common practice because of a lack of clear guidelines on interchangeability. In practice, interchangeability and pharmacy-level substitution practices follow evidence-based decisions.
Acceptable International References
EMA
Country-specific Information
EU guidelines are always adopted as reference documents for the evaluation of biosimilar dossiers.
Bahrain
Legal Basis And Regulatory Framework
The following documents set the regulatory framework for biosimilars in Bahrain, including one specific to biosimilar medicinal products.
- Biosimilar Medicinal Products Licensing Guideline, March 2023, Version 1.0
- Medicine Licensing Guideline, July 2023, Version 4.0
Registration Requirement
There is no specific application procedure. The product must be registered in the country of origin — either the country of batch release or marketing authorization.
Dossier Requirements
Modules 1 to 5 are required with comparability data for quality, non-clinical, and clinical parts.
Interchangeability
Interchangeability is not a common practice due to a lack of experience with biosimilars in Bahrain. Physicians and patients prefer first-hand evidence rather than evidence provided by regulators.
Acceptable International References
EMA, U.S. FDA
Country -specific Information
The reference medicinal product (RMP) could be either the innovator product registered in Bahrain or the innovator product registered at the stringent regulatory authority (SRA).
Egypt
Legal Basis And Regulatory Framework
The following documents set the framework for biosimilars governance in Egypt.
- Decree No. 343 of 2021, amended by Decree No. 38 of 2022
- Registration of Biological Products dated Jan. 24, 2022
- Guideline for Content File of Biological Products for Registration and Pre-Registration dated Jan. 1, 2023
- Guideline for Registration of Biosimilar Products in Egypt dated Sept. 11, 2023
Registration Requirement
Specific registration procedures exist for imported biosimilars and locally manufactured biosimilars. GMP inspection could happen for imported products.
Dossier Requirements
Modules 1 through 5 are required, with head-to-head comparability data for quality, non-clinical, and clinical parts.
Interchangeability
Interchangeability can be done by pharmacists. In health insurance hospitals, the cheapest biosimilar is dispensed regardless of the brand on the prescription.
Acceptable International References
EMA, U.S. FDA, WHO
Country-specific Information
RMP could either be the innovator product approved in Egypt or the innovator product registered and marketed in one of the SRAs. It will be the applicant’s responsibility to demonstrate that the proposed RMP version is comparable to the registered version in Egypt, and this will be evaluated on a case-by-case basis.
Iraq
Legal Basis And Regulatory Framework
The Guideline for Drug Registration Regulations (2008) provides the regulatory framework.
Biosimilar-Specific Regulation Or Guideline?
No.
Registration Requirement
There is no specific application procedure. EU standards are used for review since there are no local guidelines. EU, U.S., Canadian, Japanese, Swiss, or Australian approval is highly recommended to register a biosimilar in Iraq.
Dossier Requirements
Requirements are like those for biological innovator products. Company and product registration files are required, with similar sections as for biological products.
Interchangeability
Biosimilar substitution is not a common practice due to a lack of guidelines on interchangeability.
Acceptable International References
EMA
Country-specific Information
EU guidelines are always adopted as reference documents for the evaluation of biosimilar dossiers.
Jordan
Legal Basis And Regulatory Framework
The following documents set the framework for biosimilars governance in Egypt, including the 2015 registration guideline specific to biosimilars.
- Drug and Pharmacy Law No. 12 of 2013
- Guideline for Registration of Biosimilars dated May 2015
Registration Requirement
The registration requirement is the same for new drug registrations.
Dossier Requirements
Modules 1 through 5 are required, with comparability data for quality, non-clinical, and clinical parts.
Interchangeability
Automatic interchangeability cannot be applied to biosimilars. Interchangeability could be done following the opinion of a qualified health professional.
Acceptable International References
EMA
Country-specific Information
RMP is an innovator biological medicinal product either already approved/registered in the reference countries of the EU, U.S., Australia, Canada, or Jordan.
Kuwait
Legal Basis And Regulatory Framework
The Ministerial Decree No. 361 of 2019 Registration of Pharmaceuticals provides the regulatory framework for biosimilars in Kuwait.
Biosimilar-Specific Regulation Or Guideline?
No. Gulf Cooperation Council (GCC) Guideline on Biosimilars dated 2016 is used.
Registration Requirement
A registration pathway for biosimilars is available. The product must satisfy the technical and product class-specific provisions set out in the Gulf Health Council (GHC) guidelines and must be registered with one of the reference authorities, such as the EMA or U.S. FDA.
Dossier Requirements
Modules 1 through 5 are required, with comparability data for quality, non-clinical, and clinical parts.
Acceptable International References
EMA, U.S. FDA
Country-specific Information
RMP could either be the innovator product approved in Kuwait or the innovator product registered in the EU or in Saudi Arabia.
Lebanon
Legal Basis And Regulatory Framework
The following documents provide the regulatory framework for biosimilars in Lebanon, including biosimilar-specific guidelines.
- Law No. 530, The Conditions of Registering, Importing, Marketing and Classifying Pharmaceuticals, dated July 16, 2003
- Decree No. 571, Application of the provisions of the Articles 3 and 5 of Law No 530 and Articles 52, 53, 54 and 60 of Law No.367, dated Oct. 23, 2008
- Guidance for Registration of Similar Biological Medicinal Products (Biosimilars), dated May 20, 2016
Other Biosimilar-specific Guidelines
In addition to the 2016 Guidance for Registration of Similar Biological Medicinal Products, Lebanon also follows the WHO Guidelines on Evaluation of Similar Biotherapeutic Products.
Registration Requirement
Registration pathways are available for locally manufactured products and imported products.
Dossier Requirements
Modules 1 through 5 are required, with comparability data for quality, non-clinical, and clinical parts.
Interchangeability
Automatic substitution at the pharmacy level is not allowed, and interchangeability should be the decision of the healthcare professional only. A non-medical switch — which often is driven by economic need instead of clinical need or a treating physician’s recommendation — is not allowed.
Acceptable International References
EMA, U.S. FDA, WHO
Country-specific Information
As per Decision 538 of 2017 and Memorandum No. 113 of 2016, because of the increase in drug registration applications, the accepted number of imported and registered biosimilars cannot exceed six drugs in Lebanon (in practice though, this is no longer implemented). However, priority for registration of biosimilars is given when there are fewer than three registered drugs in the market.
Saudi Arabia
Legal Basis And Regulatory Framework
The following documents provide the regulatory framework for biosimilars in Saudi Arabia and include biosimilar-specific guidelines.
- Guideline on Biosimilar Products Quality Considerations, Version 1.0, 22 Aug-2017
- Guideline on Drug Master File Requirements for the Registration of Biosimilars, 12 Dec-2010
- GCC Guidelines on Biosimilars, Version 1.0, Aug 2016
Registration Requirement
Registration requirements are the same as those for biological products.
Dossier Requirements
Modules 1 to 5 are required, with comparability data for quality, non-clinical, and clinical parts.
Interchangeability
The Saudi Food and Drug Authority (SFDA) recommends the following:
- Changing from an innovator drug to a biosimilar drug, which used that same innovator drug as its RMP for comparability (or vice versa), can be accepted after physician and patient discussion.
- Changing from a biosimilar drug to another biosimilar drug from a different manufacturer can be accepted after physician and patient discussion and only if they both used the same RMP for comparability purposes.
- Changing from one innovator drug to another innovator drug for the same indication, or from one biosimilar drug to another biosimilar drug that did not use the same innovator drug as an RMP for comparability, is not acceptable in ordinary situations. In extreme situations, the decision-making process requires physician and patient discussions and hospital administration involvement.
Acceptable International References
EMA, U.S. FDA
Country-specific Information
The RMP to be used for comparability purposes through the process is required to be that of the innovator, which should have been approved by EMA and preferably registered in the Kingdom of Saudi Arabia. It is of particular importance to state that the same RMP should be used for all parts of the DMF to be submitted to the SFDA.
United Arab Emirates
Legal Basis And Regulatory Framework
The Central Registration of Pharmaceutical Companies and their Products of January 2012 provides the regulatory framework.
Biosimilar-specific Guidelines
No.
The UAE Ministry of Health and Prevention is working toward issuing national guidance for the registration of biosimilars. Imported products must meet the requirements of EMA and U.S. FDA guidelines for biosimilars. Local products must meet the UAE standards and follow the GCC guidelines on biosimilars.
Registration Requirement
In the absence of specific guidance as of now, all biosimilar registrations are handled on a case-by-case basis. Biosimilars intended for registration in the UAE must pass WHO and EMA standards.
Dossier Requirements
Modules 1 through 5 are required, with comparability data for quality, non-clinical, and clinical parts.
Interchangeability
Interchangeability is only possible if the pharmacist has first obtained the consent of the prescribing physician.
Acceptable International References
EMA, WHO, and U.S. FDA
Country Specific Information
According to UAE standards, any change in a biosimilar product’s specifications or characteristics is considered a new product and will follow biosimilar procedures.
Challenges And Solutions
The Middle East and North African markets face numerous challenges to bringing biosimilars to market more broadly. Let’s talk about the most pressing of them now and explore some possible solutions.
Regulatory Framework for Biosimilars
Challenges
- Many countries in the Middle East region lack well-established regulatory frameworks specifically tailored to biosimilars.
- The absence of clear guidelines can result in inconsistencies in approval processes, quality standards, and labeling requirements.
Solutions
- Biosimilar development should be performed in accordance with EMA/U.S. FDA standards.
- Prior consultation with regulatory authorities to follow EMA, U.S. FDA, or WHO standards.
Reference Medicinal Product Availability
Challenges
- Access to the reference biologic can be limited in some Middle Eastern countries, making it challenging to conduct comparative studies necessary for biosimilar development.
- Availability and affordability of reference products may vary, affecting the demand for biosimilars.
Solution
- Reference medicinal products approved in the EU or U.S. could be used for comparability along with valid justification.
Pricing and Reimbursement
Challenges
- Most Middle Eastern markets run price-conscious health systems, with drug prices and clinical outcomes having an impact on reimbursement decisions.
- Establishing appropriate pricing and reimbursement mechanisms for biosimilars can be complex, as it involves negotiations with healthcare authorities and payers.
Solution
- Engage early with policymakers regarding pricing.
Pharmacovigilance
Challenges
- Monitoring the safety of biosimilars after market approval is crucial. However, some Middle Eastern countries may have limited pharmacovigilance infrastructure and expertise.
Solution
- Consult with regulatory authorities to confirm if any extra monitoring is needed for biosimilars.
Market Access
Challenges
- Establishing distribution channels and ensuring widespread availability of biosimilars can be a logistical challenge, especially in geographically dispersed Middle Eastern countries.
- Market access barriers, such as preferential treatment for originator products, can hinder biosimilar market penetration.
Solutions
- Establish a robust supply for cold chain shipments and warehousing.
- Adopt a pragmatic approach and educate healthcare professionals on the benefits of biosimilars.
Political and Economic Factors
Challenges
- Political instability, economic challenges, and healthcare system variations across Middle Eastern countries can affect the regulatory environment and market dynamics for biosimilars.
Solutions
- Vary on a case-by-case basis.
Conclusion
Efforts to address these challenges in the Middle Eastern market may involve collaboration among regulatory authorities, industry stakeholders, and international organizations to promote biosimilar development, streamline regulations, and ensure patient access to safe and affordable biologic therapies.
About the Author:
Guriqbal Singh is the founder and director of RegWeb, a regulatory consulting firm in Ontario, Canada. He has been working in the pharmaceutical industry since 2006 with experience in international regulatory, CMC, and regulatory intelligence. He has extensive experience in the project management of regulatory maintenance activities for global markets involving initial MAA, variations, renewals, and responses to questions. He has conducted conformance reviews on regulatory dossiers and reviews of pre- and post-approval documentation for regulatory submissions. He is a subject-matter expert for registration requirements in emerging markets with a special focus on ASEAN, APAC, GCC, and Africa. Reach him at guriqbal.singh@regweb.ca or 1-647-673-1718.