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.
Could you rely on a complex drug supply chain?
By Jean-Pierre Metabanzoulou|2020-05-23T09:41:15-05:00May 12th, 2015|Health & Wellness|0 Comments