A generic drug is a strict copy of an original or a brand name drug product for which a patent has entered in the public domain. Once the patent or patents have been expired, other pharmaceutical firms are allowed to manufacture and to market the same drug under an International Common Denomination (ICD) name or a different brand name. In some instances and by political choices and for public health policy, special arrangements may be obtained on drugs that are still protected by valid patents to accommodate public health interest to be produced by generic manufacturers. For example, several AIDS and hepatitis drugs have been authorized to be manufactured by generic drug firms for patients in developing countries. A generic drug must meet the same standards of efficacy, quality and safety than an original drug to be approved by health authorities. It is regulated by the same regulatory agency in most countries. In French Sub-Saharan Africa, the Direction de la Pharmacie et du Médicament, DPM within the Health Ministry, is the regulatory body for both innovative and generic drugs. However, a generic drug may slightly differ from the brand drug with regard to its presentation (format), its physical appearance, its marking usually the branding sign, its packaging, its labelling, its composition in terms of the nature of excipients (colouring and/or flavouring agents, preservatives, etc.). It also may bear a different expiry date. Since the branded drug has generally been on the market for several years when the marketing application is filed by a generics manufacturer, considerable information on the safety and efficacy of the brand name product is already available. This means that clinical studies for a generic drug are limited to Bioequivalence studies. A bioequivalence study is a clinical study where a generic drug and a branded drug are compared in two healthy human volunteer groups. The first group receives the generic drug and the second group the branded drug. The volunteers and the physicians, in charge of the study don’t know which group is receiving the generic drug nor the group receiving the branded drug. This is why these studies are called double-blinded. To be acceptable, the concentration of the drug in the serum at each point in time of the generic drug must be comparable to the branded drug. The results of these bioequivalence studies are part of the approval process of generic drugs by regulatory authorities, such as US FDA, Health Canada, European Medicine Agency (EMA) or DPM in French Sub-Saharan Africa. However, in certain developing countries, only in vitro, i.e. laboratory tests, are required to accept a generic drug. It is generally accepted that in vitro tests may not be sufficient to demonstrate bioequivalence. During the development and the production, a generic drug must adhere to the same level and rigorous standards of quality, safety, and efficacy as a branded drug. In addition, as for a branded drug, all production facilities used to make the generic drug must meet current Good Manufacturing Practices, cGMP. These facilities are regularly inspected by regulatory authorities such the US FDA, Health Canada, to ensure and to enforce the highest quality standards. Regarding the development of a generic drug, the manufacturer of a generic drug does not have access to the non-clinical data of a branded drug. In general, branded drug data is never revealed to third parties, including a generic manufacturer. Therefore, generic drug manufacturer must proceed with a formal research and development program to discover their own formulation, i.e., their own recipe of manufacturing the product. However, they may refer to published clinical data concerning the safety and efficacy of the reference product. Generic drugs are offered at significantly discounted prices than branded drugs because initial basic and clinical research programs do not need to be repeated in full for generic drugs. These cost savings are reflected on price paid by insurers and/or by patients. The demand for pharmaceutical products is increasing globally. This is driven mainly by a steadily increasing life expectancy, economic growth and technological progress worldwide as well as an aging population in developed countries. Consequently, healthcare costs are continuing to rise year after year. Public officials and health professionals worldwide are realizing the importance of promoting generics and are acting accordingly. The French Sub-Saharan Africa is following the same trend although lagging a bit behind. Certain developed countries like Canada have not only a long history and experience of successfully using both innovative and generic drugs but also have developed from years a secure pharmaceutical industry supply chain. We think that there are lessons that can be learned from these countries by developing countries such as Sub-Saharan Africa countries. We urge patients to use official distribution channels of drugs in Africa, for example by buying drugs at the pharmacy or official drug stores with valid permits. The attempt to use less costly drugs can lead to the use of fake drugs with a high risk to even harm more patients. Patients should rely on their healthcare professionals such as physicians, nurses, pharmacists, etc., to have access to safe drugs whenever possible. Cheaper generic drugs may be an indication that such drugs may not meet international quality standards. Patients should be cautious when buying such drugs. This article was prepared and edited by Dr. Jean-Pierre Metabanzoulou, Ph.D., MBA. He holds a Ph.D. in Chemistry from the University Louis Pasteur of Strasbourg in France, and a Master of Applied Chemistry from the same University. He also obtained a Master in Business Administration at Queen’s School of Business in Kingston, in Canada. He did his postdoctoral studies at the Institute of Inorganic Chemistry and Analytical, ICMA, of the University of Lausanne in Switzerland. After a short academic career, Dr. Metabanzoulou works for over 20 years now in the pharmaceutical industry in the private sector both for the innovative pharmaceutical industry and generic in Canada, in Switzerland, in France as well as in Africa.
A new drug, also called innovative or original drug is studied on average between 10 and 15 years from the preparation of active substances, generally called “active pharmaceutical ingredients.” The drug discovery begins with the identification of a mechanism or a series of biological mechanisms that lead to illness or disability. To modulate this deficiency in whole or in part, scientists synthesize chemical molecules or biological substances to be tested to confirm their activity on the identified mechanism. From an active pharmaceutical ingredient synthesis, a patent is filed in various national and international organizations around the world, especially in developed countries, to protect the invention of a new drug. In most countries, the duration of the period of exclusivity of these patents is 20 years. For synthetic drugs, tens of thousands of molecules are created and tested in the laboratory. Finally only the few most promising compounds will be retained. A single molecule become the commercial drug. On average, one molecule out of 10,000 molecules tested, becomes a drug. Each active pharmaceutical ingredient is first tested in the laboratory. Then it is tested on animals. Finally, the metabolism, the exposure dose, the safety and efficacy of the new drug is assessed and tested on humans. The tests on animals determine the safety profile and benefits versus the risks of future drug before giving it to human beings. Once the profile of the benefits versus the risks of a new drug is considered favorable by the pharmaceutical company that developed the drug and by regulatory agencies worldwide, the drug can be studied in humans following well-defined clinical phases. Three clinical phases are needed to test the drug in humans. During the clinical phase I, the drug is studied in a battery of clinical studies on groups of 20-100 people, usually on healthy volunteers to determine its absorption, distribution, metabolism and excretion. This allows to know the effect of drug in the body and body effect on the drug. Some drugs known to be toxic by nature, such as anticancer drugs, are not studied in healthy volunteers and can be tested directly on patients. The clinical phase II is to ensure that the drug has the desired effect in sick humans. At this stage of development, scientists determine the optimal dose of the drug and its possible adverse events on a population of fewer than 500 patients on average. Phase II clinical trials are divided into 2 phases IIa and IIb. Phase IIa considers the effectiveness of the molecule on a limited number of 100 to 200 similar patients to avoid that too much diversity makes too much variability to measure the effectiveness of the new drug. Phase IIb determine the therapeutic dose of the molecule on a larger scale of at least 100 to more than 300 patients. The true test to determine if the drug will be approved by regulatory agencies are studies Phase III or “pivotal studies” which are the comparative effectiveness studies themselves. Clinical Phase III comparing the new treatment with either a placebo or a standard treatment. Comparison to a standard treatment, when it exists, is increasingly preferred by regulatory agencies. In Clinical Phase III studies as well as in Clinical Phase II studies, patients and physicians usually ignore whether the patient receives the experimental drug, a dose it receives, or if it receives a placebo or a standard treatment. These clinical studies are called double-blinded studies. Patient cohorts are large, often several thousands, even tens of thousands of patients. Unlike Phase II, Phase III studies are in cohorts of patients who are more similar to patients in the general population. However, strict criteria applies for the inclusion of participants or not in the studies. The costs associated with this phase are very high. Given the financial interests and risks, pharmaceutical companies, regulatory agencies and ethics committees must pay greater attention to avoid ethical drifts that have been sometimes observed in certain programs. These Clinical Phase III studies will determine the usage of the new product, which is also called the indication of a drug product listed on the label of the product. Clinical Phase IV or post-marketing studies are the long-term monitoring of a new treatment after the new drug is authorized and marketed. This is a true test under “real life” of the drug. Clinical Phase IV studies can be used to detect rare adverse events or late complications related to the use of a product. Clinical Phase IV is also used to validate the prescriber patterns and patient’s compliance in the use of the product. Therefore, the development of a new drug not only requires the collaboration of a multidisciplinary team but also a lengthy regulatory approval process by Regulatory Agencies around the world as well as approval of independent research and ethical committees for clinical studies. During each clinical or non-clinical phase, the future drug must meet strict criteria. It is estimated on average between 6 and 7 years the time required to develop a new drug in clinical trials. When a new drug is finally on the market, it remains on average 10 years of a patent life for the pharmaceutical firm that has developed, to market it exclusively. Throughout the development of the drug, formulation, or simply, the recipe of the new drug is refined as to reach a final recipe at the time of a new drug submission, which is reviewed and approved by regulatory agencies. The product to be marketed is the same as the one that was used in Clinical Phase III. All parameters that influence the quality of the drug must be studied. These include the source and quality of the active pharmaceutical ingredient, its stability, the source and the quality of the excipients, primary packaging containers, the effect of temperature and humidity on the drug, including temperatures extreme temperature and humidity that may prevail during transit and during transportation, the effect of light on the drug, etc. The final result is a scientific and technical dossier prepared by the pharmaceutical company developing the new drug. This dossier is submitted to regulatory authorities around the world for registration. It takes between 1 and 2 years for regulators to make the final decision to either approve or to deny the approval of the new drug. A formal process of interaction by face to face meetings and written communications between regulatory agencies and the pharmaceutical company is required before regulatory agencies such as Health Canada make a final decision. After this process, the drug is either approved or denied. In some cases, regulatory agencies may require additional clinical studies before approving the drug. Once approved, the drug should be not only used but also manufactured, stored and distributed within the parameters, for which the drug was approved. Any changes that may affect these parameters must be approved by regulatory agencies before being implemented. This article was prepared and edited by Dr. Jean-Pierre Metabanzoulou, Ph.D., MBA. He holds a Ph.D. in Chemistry from the University Louis Pasteur of Strasbourg in France, and a Master of Applied Chemistry from the same University. He also obtained a Master in Business Administration at Queen’s School of Business in Kingston, in Canada. He did his postdoctoral studies at the Institute of Inorganic Chemistry and Analytical, ICMA, of the University of Lausanne in Switzerland. After a short academic career, Dr. Metabanzoulou works for over 20 years now in the pharmaceutical industry in the private sector both for the innovative pharmaceutical industry and generic in Canada, in Switzerland, in France as well as in Africa.
Could you rely on a complex drug supply chain? What stages your favorite drug once produced, usually go through before landing in your medicine cabinet or at least to where you keep your medication safe at home? The drug supply chain is one of the most complex supply chains either. Strict quality criteria must be met at each stage of this supply chain. A drug supply chain is often long and may involve not only several plants belonging or not to the same firm but also these plants can be located in several countries and several continents. It is not uncommon to have an active ingredient manufactured in China or India, then a drug manufacturing step begins in Canada, a second step in the United States or Europe, and finally the primary packaging in blisters or bottles and secondary packaging happens in Africa or Latin America. The choice of production sites is dictated by economic, technological imperatives, regulation and distribution channels. The production of a drug begins with the manufacture of the active pharmaceutical ingredient or active pharmaceutical ingredients usually in China or India. The facilities producing these ingredients must meet the Good Manufacturing Practice Standards, GMP. These plants must be approved by the relevant regulatory authorities in the country of manufacture and in other countries as well by well recognized regulatory agencies such as Health Canada, the US Food and Drug Administration (FDA), the French Agency for Food Safety food (AFSSA), etc. Furthermore, these plants are the subject of regular regulatory inspections from these regulatory agencies. In sub-Saharan Francophone Africa, the regulatory body of drugs is the Direction de la Pharmacie et du Médicament, DPM, from the Ministry of Health. Moreover, these manufacturing active ingredients, must meet a strict set of standards issued by pharmaceutical companies and by regulatory agencies worldwide. These standards are issued by independent national and international pharmacopoeia. This is the case for the United State Pharmacopeia (USP), the European Pharmacopeia (EP), the British Pharmacopoeia (BP), the Japanese Pharmacopeia (JP) to name only the most used and the most common. Each batch of active ingredient must be manufactured according to approved recipes by the regulatory authorities according to quality standards and must meet all quality specifications before being used in pharmaceutical production. The final manufacturing and testing records of each batch, are reviewed and approved by quality assurance professional at the active ingredient manufacturer site as well as at the final dosage form manufacturer site. To facilitate its handling during the drug manufacturing at the facility as well as at the pharmacy or at home by patients, inert substances, called, excipients are added to the active pharmaceutical ingredient at different stages of the manufacturing procedure according to approved standard operating procedures. A drug may contain more than 5 excipients, each playing a specific role. For example, an excipient can be used to facilitate dissolution of the drug, its flow in equipment’s during manufacturing, to avoid sticking to the surface of processing equipment, to mask bitterness, to add color, and so on. The list of these excipients is provided on the leaflet or on the secondary packaging box of the drug. These excipients must meet quality standards, often issued by the same pharmacopeia bodies such as the USP, the EP, the BP and the JP. A particular attention is paid to these excipients to ensure the absence of microbiological pathogens, including bacteria, viruses, prions, substances responsible for bovine spongiform encephalopathy (BSE). A certification system was developed by the European Union and is about to be adopted by all countries around the world to ensure the quality, safety, and security of APIs and excipients throughout the supply chain. Finally, the final drug dosage form is obtained by blending the active pharmaceutical ingredients (API) with various excipients to a compressed tablets, or a capsule, a vial for injection, etc., according to an approved recipe by the regulatory authorities. The final packaging in blisters, in bottles or vials for injection, is done by other facilities specialized in primary and secondary packaging. All these plants must meet Good Manufacturing Practices standards. They must be approved by the regulatory authorities from the country where the plant is located and by other regulatory authorities in other countries such as Health Canada, the US FDA, AFSSA, etc. These plants are also inspected by the same regulatory agencies at regular intervals to ensure compliance with regulations. Stiff fines and even jail time sentences can result from non-compliance with Good Manufacturing Practices to senior managers of pharmaceutical companies. Throughout the drug supply chain, including during production, transportation and storage, drugs must be stored at controlled environmental conditions, i.e., specific temperature and humidity conditions. The drug expiration date is a function of temperature and humidity. Failure to comply with these environmental conditions can alter and in some extremes cases drugs may become even toxic. It is therefore imperative that patients must adhere to the storage conditions of a drug listed on its label at home. Once the production of a drug is completed, it is stored in warehouses at controlled temperature and humidity. These warehouses must meet the Good Distribution Practice standards enacted by the World Health Organization (WHO) and other regulatory agencies around the world. These warehouses are inspected and also approved by the same regulatory agencies. It is increasingly common for pharmaceutical companies to subcontract logistic operations to firms specialized in logistics management, inventory management, transportation and storage of drugs. Firms like Bolloré Africa Logistics, UPS, DHL, etc., are more and more involved in managing these operations. The conditions of temperature and humidity must be maintained during transportation and during transit of the active pharmaceutical ingredients, excipients and drug final dosages. Firms specialized in transportation take over to ensure the integrity of the environmental conditions during transportation. However, pharmaceutical companies are responsible for ensuring that the logistic and transport companies, adhere to the Good Distribution Practice standards of Pharmaceutical products. A key element in the dug production and in the drug supply chain is traceability. All raw materials, including the active ingredients, excipients, primary packaging containers such as blisters, bottles, caps, etc., as well as secondary packaging such as cardboard boxes, must have a traceability system to ensure quality, security and safety of medicines. This system also allows efficient recall of drug products on the market of a lot of defected drugs or when quality problems are detected at a particular plant. These aspects of security and safety is now paramount to protect the integrity of this highly sensitive drug supply chain. It is the same at the private wholesalers and other organizations specialized in wholesaling and/or drug distribution. Their warehouses must also meet the same Good Distribution Practice standards than pharmaceutical companies, for both storage and transportation. The same requirements apply to your pharmacy which must maintain the temperature and humidity for the storage of drugs. In general, the pharmacist takes no chances and adopts air conditioning in his pharmacy. As the last link in the drug supply chain, the patient must not neglect this aspect of maintaining the storage of the drug at home at the right temperature and humidity level. It is therefore imperative to adhere to the storage conditions of drugs as listed on the drug label. Failure to comply with these environmental conditions may negate the beneficial effect of a drug and even in some extreme cases, drugs may become toxic. This article was prepared and edited by Dr. Jean-Pierre Metabanzoulou, Ph.D., MBA. He holds a Ph.D. in Chemistry from the University Louis Pasteur of Strasbourg in France, and a Master of Applied Chemistry from the same University. He also obtained a Master in Business Administration at Queen’s School of Business in Kingston, in Canada. He did his postdoctoral studies at the Institute of Inorganic Chemistry and Analytical, ICMA, of the University of Lausanne in Switzerland. After a short academic career, Dr. Metabanzoulou worked for over 20 years now in the pharmaceutical industry in the private sector both for the innovative pharmaceutical industry and generic in Canada, in Switzerland, in France as well as in Africa.
Dear visitor, It is with great pleasure and emotion that I would like to introduce to you our website. Our ambition is not only to present the activities of our company but also to try to popularize the science of medicine. Although drugs are an integral part of our daily life and commerce, drugs are special and specialized goods. It is imperative to follow the advice of health care professionals, e.g., your pharmacist, your doctor, a nurse, etc. for optimal use of them. We are hopeful over time to give you reliable source of unbiased information for better managing your well-being and your health. We agree that drugs are only one element among others as important as they could be, that help maintain a robust health or at least an acceptable state of health. Our approach is somewhat unique insofar as our company is both an avid fan of innovation and intellectual property as well as a fierce defender of the right to replicate an innovation once the period of patent protection has passed. This means as a prerequisite appropriate and predictable regulatory regime that ensures adherence to international quality standards so that the generic product is bioequivalent to the innovator. We firmly believe in the incentive provided by patents to discover breakthrough therapies. Without this stimulus, truth advances would not have happened so quickly. Having been part of a multidisciplinary team involved in the development and registration of new vaccines and new drugs in Canada that have revolutionized the treatment of certain diseases, I recognize that this requires significant financial resources. It is quite normal to protect these investments by patents over a reasonable period of time. However, practices which unduly extend the lifetime of these patents do not meet our approval because they deprive a large number of patients, essentially living in developing countries, with affordable medicines. Another important aspect of our advocacy is to ask our fellow industry peers whether or not licensing negotiation would be mutually beneficial for both the innovator and the generic pharma industry as well as to promote such mechanisms between industry partners. This could facilitate access to new drugs that are becoming more and more difficult provided by patents. They have to pay out of pockets these drugs. Therefore, we are open to working with innovative pharmaceutical companies in this regard and in accordance with international laws protecting intellectual property. As an organization, we have set ourselves the mission to help Sub-Saharan Africans to enjoy a rich and healthy life. This is reflected daily by providing affordable medicines which meet international quality standards to these deprived population, living in majority without health insurance. They pay out of pocket for the medicines they need. To pursue this mission, our business model unfolds in four points which are:
We believe that collaboration and cooperation with partners from both sides of the industry, i.e., the innovative and the generic pharmaceutical industry will allow to develop fair and sustainable business models to meet the challenges of providing access to affordable medicines in this region of the world. Finally, I invite you to surf on our website to find out information that we think useful to feed your own reflection on medicine. We are proposing 3 short articles that address succinctly important aspects of research and drug development.
Enjoy! Jean-Pierre Metabanzoulou President
We are proud to announce that ELPIS AFRICA CARE has received its Drug Establishment Licence (DEL) from Health Canada as a wholesaler and exporter of pharmaceutical products. We are eager to start our operations…
As we continue to move forward in the implementation of our business strategy, we are proud to announce that our company has successfully passed Health Canada Good Manufacturing Practices (GMP) inspection. Health Canada and has granted us a Drug Establishment Licence (DEL) to distribute pharmaceuticals products that we receive in the coming days. This marks an important milestone for our company. I would like congratulate the entire team that has worked hard to achieve wonderful results!
Elpis Africa Care Inc. has signed its first ever Pharmaceutical Supply Agreement with a major Pharmaceutical Company with operations in North America and in Europe. Please stay tuned to learn more!
Welcome to the new home of Elpis Africa Care. Please also visit these Websites : http://www.who.int/malaria/en/ http://www.usp.org/global-