The drug approval process is a complicated and often time-consuming regulatory procedure, regardless of one’s geographical location. Regulatory agency drug approval plays an important role in confirming the safety and efficacy of new drugs and ensuring patients have access to the best treatments in a timely manner. The following article outlines the drug approval process in Lebanon, Egypt, Algeria, and select Gulf Arab countries.
In Lebanon, the pharmaceutical company importing the drug must be registered with the Ministry of Public Health.1 The drug must have been proven safe and effective through clinical trials and preferably approved by the U.S. Food and Drug Administration (FDA) and/or European Medicines Agency (EMA) for the specific indication requested. Drug application must include chemical structure, pharmacologic and chemical properties, and Anatomical Therapeutic Chemical classification relating to the active ingredients of the drug according to the organs or systems upon which they act, as well as their therapeutic value.
The application should include information about manufacturing factory, drug Plant Profile (a form that includes information about the principal active ingredients of the drug), all dosage forms of products that can be manufactured from the drug, available reference laboratories for the drug,2 origin of material, a Good Manufacturing Practice certificate, and a Technical File. The Technical File should contain the properties of the product including methods of preparation, stability data, storage conditions, bioequivalence, quality (a measure of compliance with the quality standards, set by the marketing authorization, that make it appropriate for its intended use),3 and the suggested price.
The application is studied by a review committee within the Ministry of Public Health, which issues its report in approximately 2 months. That report is forwarded first to the Drug Import Department and then to a Drug Registration Technical Committee, which includes the director of the Ministry of Public Health, chairs of the Pharmacy and Import Committees, and representatives of the both the Lebanese Order of Physicians and the Lebanese Order of Pharmacists. The Drug Registration Technical Committee issues final recommendations within an additional 2-3 months and sends those recommendations to a Pricing Committee.
In addition to the bureaucratic delays that may occur during any of the above steps, drug approval may be delayed an additional 2-3 months if the country of origin is not listed among defined “Reference Countries,” such as the United States, France, Germany, and the United Kingdom. In such cases, the drug will first be sent to a Lebanese Reference Laboratory for evaluation. From there, the Pricing Committee reports to the Drug Import Department, which issues a Marketing Authorization signed by the Minister of Public Health. The entire process takes approximately 8-12 months.
The pertuzumab example
After importation and registration at the Ministry of Public Health, public and private insurance companies have their own drug approval process, which takes an additional 3 months. For example, pertuzumab was approved by the FDA for treatment of metastatic breast cancer on June 8, 2012. In Lebanon, process initiation had to wait until the drug was approved in its country of origin, in this case Switzerland, which occurred on March 5, 2013. Two vials of the drug were imported to Lebanon for process initiation on November 20, 2013. The Ministry of Health Technical Committee accepted the files on January 16, 2014. Study and price approval required for obtaining a legalized Certificate of Pharmaceutical Product that included all product manufacturing information from the manufacturing country of origin and official documents stating drug prices in the country of origin, seven European countries, and seven countries neighboring Lebanon. Final approval by the Ministry of Health was obtained on July 3, 2014. Applications were then submitted to public and private insurers. Pertuzumab was presented to the pharmacy committee at the American University of Beirut Medical Center and was approved and placed on formulary on January 26, 2015. This process illustrates how administrative and bureaucratic practices can delay drug approval for 1-2 years and prevent patients from gaining access to drugs in a timely fashion.
Patients’ access to cancer drugs varies among different regions of the world because of timing of regulatory approval and the differences in national procurement procedures.
Drug approval takes 8-12 months in Lebanon; up to 5 years in Egypt; 3 or more months in Algeria; 18 months in Saudi Arabia; 3-6 months in Bahrain; and 6-12 months in Oman.
Low- and middle-income countries need to adopt resource-adapted guidelines and perform local research for better utilization of their resources and new drugs.
Pending formal approval, a temporary, special, and fast importation can be obtained as soon as drugs are approved by the FDA or EMA, making drugs immediately available to some patients in Lebanon. This can be obtained by the academic institutions in Lebanon authorized to import drugs directly for its own patients, for research purposes, or upon request by physicians for specific patients. Patients who can afford it would then pay out of pocket the international price for the drug as fixed by the pharmaceutical company in the country of origin.
In Egypt, the drug approval application is viewed by multiple committees, and the approval process can take up to 5 years. The application consists of the drug’s legalized Pharmaceutical Product Certificate, clinical data, and international registration status and price. In addition, 20 drug samples must undergo analysis. Bioavailability testing can be waived by the Egyptian Ministry of Health if the product is FDA or EMA approved.
In Algeria, drug registration requires submission of a Pharmaceutical Products Registration application to the Algerian Ministry of Health, which must include all drug information, such as mode of administration, pharmacological properties, efficiency, and evaluation of risks.4 Two drug samples, including the final drug sample and the raw material used, are sent to the Pharmaceutical Products Control National Laboratory along with the drug’s dosage information. Revision of the Drug Record file generally takes 3 months or more, after which the Ministry of Health grants a 1-year provisional registration. The 5-year registration is granted only after the laboratory drug evaluation comes out positive.
In Saudi Arabia, drug approval takes place through a Drug Sector in the Saudi Food and Drug Authority.5 Applicants submit a Marketing Authorization application to the Drug Sector, which ensures accuracy of all information submitted, compliance with requirements and guidelines, and an assessment of drug quality and efficacy. Recommendation for approval or rejection is forwarded to the director of the Product Licensing Department within 4 months. Samples are tested by a laboratory and inspection unit at the Ministry of Health within another 4 months. Finally, all reports are forwarded to a Registration Committee that issues approval usually within an additional month. From start to finish, the entire drug approval process can take 18 months.6
In Bahrain, the average time for approval of new drugs is 3-6 months. However, in order to authorize local marketing of a drug, it has to have been marketed in another country for a minimum of 2 years to ensure sufficient pharmacological efficacy and safety.6 Also, prior to importing a drug, it should be first licensed in Saudi Arabia and in one other Gulf Cooperation Council country.
In Oman, registration of a pharmaceutical product generally requires 6-12 months. However, if a drug is not imported within 1 year of approval, it may be deregistered, which implies that the process must be repeated for reregistration.6 Also, renewal of registration on a 5-year basis is required. Similar to Bahrain, in order to authorize local marketing of a drug, it has to have been marketed in another country for a minimum of 2 years to ensure pharmacological efficacy and safety.
Varied Drug Access Worldwide
Patients’ access to cancer drugs varies among different regions of the world because of timing of regulatory approval and the differences in national procurement procedures. Patients in some regions may need to wait years more than their counterparts elsewhere for the new drug to get approved.
As referenced earlier, a study conducted by Kasteng et al. compared the time between the introduction and drug approval of new cancer drug therapies in nine Middle Eastern countries to that of the United States, United Kingdom, France, and a group of 13 European countries that constitute the majority of the European pharmaceutical market.6 The time between introduction and drug approval ranged from 0.3-2.0 years. In Middle Eastern countries, median time ranged between 0.3 years in Bahrain and 1.75-2.0 years in Saudi Arabia and Qatar, respectively. In Europe, the average total time was 0.9 years. In the United States, the median total approval time was 0.5 years for priority new molecular entities and 1 year for standard New Drug Applications and biologics. It is important to note that those regulations apply only to brand-name drugs, and the process for generics is a totally different and variable issue. Availability and quality control of generic drugs remain important international issues.
In order to overcome delays in patient access to new medicines, authorities need internal resources within the ministries of health to harmonize regulatory requirements. Better collaboration between physicians and health authorities, who watch for indiscriminate use and abuse of new drugs that are generally highly priced by pharmaceutical companies, is needed. Low- and middle-income countries also need to adopt resource-adapted guidelines and perform local research for better utilization of their resources and new drugs.7
About the Authors: Dr. El Saghir is a medical oncologist at the American University of Beirut, in Lebanon. An ASCO member since 1984, Dr. El Saghir is the immediate past chair of the ASCO International Affairs Committee, a member of the Global Oncology Leadership Task Force, and the co-chair of the Resource-Stratified Guideline Advisory Group. Dr. Kreidieh is a research fellow at the American University of Beirut Medical Center, in Lebanon.