Drug approval processes vary worldwide and substantially influence the availability and cost of life-saving medications, such as oncology drugs. Drugs will cost less in countries that locally manufacture medicines than in countries that depend on imported products. Countries that rely on imports typically have a long bureaucratic process to get a drug approved for use. This may explain why cheaper generic products originating from India end up for sale in African countries at exorbitant prices. Governments should be advised to improve accessibility of new and efficient oncology drugs and prevent undesirable breaks in the supply chain by promoting locally manufactured basic oncology products.
|In Ghana, drug registration takes a minimum of 6 months if there are no queries; if there is a query, drug registration may take up 10 months in the absence of any additional deferrals. The complex drug approval process leads to drug unavailability, shortages, and increased costs, and it encourages unauthorized importation of substandard drugs.|
|It takes approximately 100 working days for a drug to be approved in Nigeria, and registration is valid for 5 years. The major bottleneck in the drug approval process in Nigeria is the long paper trail, which slows down the process, and frequent strike action by government employees, which creates loopholes for the influx of unregulated drugs.|
|In Kenya, it takes approximately 90 working days for fast-tracked drug registration, which includes locally manufactured and priority medicines only. The evaluation of new drug applications takes approximately 12 months.|
Drug Approval Process in Ghana
In Ghana, the Food and Drug Authority regulates drug approval and drug safety issues. In order for a drug to be approved for use in Ghana, it must be listed in the North American or European Compendium or be on the World Health Organization (WHO) prequalified drug list. If the drug is not listed, it will require special considerations. A new drug may take 3 years to be included in a compendium. Applications for drugs to be used in clinical trials and orphan drugs should include complete master or operational files from the innovator company, ethical approval for use in country of origin, and results of preclinical or any preceding trials.
The same rules apply to biologic compounds. Complete drug dossier, including registration in the country of origin, as well as analytical evidence of biosimilarity to an original product, is required for biosimilar product registration. Emergency waiver protocols apply to orphan drugs in small quantities. This information is then reviewed by the clinical trials review board for approval.
Approval process timeline following application submission
Week 4: Applicants receive a formal acknowledgement letter.
Weeks 10-16: Technical assessment is completed following inspection of factory facilities, standard operating procedures, master file or dossier, and results of laboratory analysis, which includes accelerated decomposition testing to confirm the stated shelf life. This is the rate-limiting step because the applicant is required to bear the full cost of logistics involved in inspection of the facility (Table 1), and companies may be unwilling to release the dossier or the Good Manufacturing Practice certificate to third parties.
|Extra cost for each additional strength||
|Clinical trial registration||$5,000-$17,000 (depending on the phase of the study)|
Weeks 16-20: Application is submitted to Food and Drug Authority Product Registration Meeting.
Weeks 20-22: Decision on application (i.e., approval, deferral, or rejection of application) is communicated to the applicant by e-alert. If the drug is approved, a certificate of registration is issued. If the drug is rejected, an appeal may be made within 60 days. If the drug is deferred, the Food and Drug Authority will submit a query to the applicant. Responses to the query should be submitted no later than 12 months from the date of the first deferral, 6 months for the date of the second deferral, and 3 months for the date of the third deferral.
Deferrals significantly delay the drug approval process. Assuming query responses are sent to the Food and Drug Authority promptly, consider the following timeline for each deferral:
Week 4 post–query submission (week 26 from initial submission): A formal acknowledgment of query submission is sent to the applicant.
Week 12 post–query submission (week 34 from initial submission): A technical assessment and decision based on the recommendations of the previous product is sent to Product Registration Meeting.
Week 16 post–query submission (week 38 from the initial submission): An e-alert with the decision is sent, and a decision on the application is submitted to applicant (i.e., approval, deferral, or rejection of application) 2 weeks after the Product Registration Meeting.
It is important to note that different strengths of the same medication are registered separately, which discourages the availability of exact-dose adjustments, leading to under- or overdosing. Drug registration is valid for 3 years.
Locally manufactured drugs have the same application process, but they have shorter turnaround times because the logistics involved in the inspection process are cheaper.
In summary, drug registration takes a minimum of 6 months if there are no queries. If there is a query, drug registration may take up 10 months in the absence of any additional deferrals. Biological products may take 6 weeks for WHO-prequalified products to up to 1 year for unqualified biologics to complete the process. The same cycle is repeated for variations and different strengths and formulations of the same drug. It takes an average of 3 months for clinical trials to be registered. This complex process leads to drug unavailability, shortages, and increased costs, and it encourages unauthorized importation of substandard drugs.
Drug Approval Process in Nigeria
The National Agency for Food and Drug Administration and Control is the Nigerian government agency under the Federal Ministry of Health that is responsible for drug regulation. It has guidelines for product registration, which most pharmaceutical agencies adhere to.
For oncology products, the registration process can be classified into two groups, chemical molecules and biotech products, both of which have separate registration processes.
5-fluorouracil, for example, is classified as a small molecule. For registration of these products, the pharmaceutical company must provide documentation, such as the Good Manufacturing Practice certification for the manufacturing plant, certificate of pharmaceutical product, product dossier, and power of attorney from the foreign company confirming representation by a local company. Samples of the product must be submitted with evidence to show the product is marketed in the country of origin.
The submitted documents are legalized by the Nigerian embassy in the country of manufacture in order to confirm the existence of the pharmaceutical company in country of origin.
For biotech products (e.g., targeted therapies) the dossier is required from an originator company, with evidence that the product is registered by a stringent regulatory authority. To register a biosimilar, there must be evidence of both clinical and nonclinical data showing similarity to the original product. The major bottleneck in this process is the long paper trail, which slows down the process. Furthermore, frequent strike action by government employees creates loopholes for the influx of unregulated drugs.
It takes approximately 100 working days for a drug to be approved in Nigeria, and registration is valid for 5 years. Table 2 shows the cost of drug registration in Nigeria.
|Clinical trial registration||$500-$3,750 (depending on whether the clinical trial is from the originator or industry is sponsored)|
|Imported prescription-only drug||$1,500|
|Locally manufactured drug||$400|
Drug Approval Process in Kenya
The drug regulatory agency in Kenya is the Pharmacy and Poisons Board, which was established under the Pharmacy and Poisons Act, Chapter 244 of the Laws of Kenya.
It takes approximately 90 working days for fast-tracked drug registration. Fast-tracked applications include locally-manufactured and priority medicines only. The evaluation of new drug applications takes approximately 12 months. If additional information is required, a formal request will be completed within 6 months. The drug approval process follows the following steps:
- Receipt of applications
- Market agency authorization
- Manufacturers and manufacturing sites inspection for current Good Manufacturing Practices
- National Quality Control Laboratory analysis
- Committee on Drug Registration Recommendation
- Practice Committee review
- Full board approval
It is important to note that the above process is for new pharmaceutical products, including biotechnology-derived products. Special permits are given for narcotics and psychotropic substances for their control. Table 3 shows the cost of drug application in Kenya.
|Imported into Kenya||$1,000|
|Fully manufactured in Kenya||$500|
|Renewal of application (imports)||$500|
|Renewal of application (local)||$300|
The drug application is considered withdrawn if queries are not adequately responded to within 6 months of the request. If a drug is declined, the applicant may appeal that decision within 2 months from the date of notification. Drug registration is valid for 5 years unless otherwise suspended or revoked.
About the Authors: Dr. Vanderpuye is a clinical oncologist with the National Center for Radiotherapy and Nuclear Medicine, Korlebu Teaching Hospital, in Accra, Ghana. An ASCO member since 2003, Dr. Vanderpuye is a member of the International Affairs Committee and MCMC Working Group. Dr. Othieno-Abinya is a medical oncologist, professor of medicine, and head of Hematology and Oncology in the Department of Clinical Medicine and Therapeutics, with University of Nairobi, in Kenya. An ASCO member since 1998, Dr. Othieno-Abinya is a former member of the International Affairs Committee. Dr. Abiodun Olaniyi has been an ASCO member since 2010 and is a clinical oncologist in the Department of Radiology with Lagos State University College of Medicine, in Nigeria.