Ensuring safe medicines access for all: Good manufacturing practices for pharmaceuticals
Time and again, concerning reports of eyedrops with bacterial contamination, ineffective medications, mislabelled tablets, or the like surface globally. Not all such products are counterfeit or falsified; some are made with the intention of providing consumers with a quality health product, but there may have been lapses along the way. Across these different challenges, quality assurance has become an important concern for the pharma industry.
That’s why we have good manufacturing practices for pharmaceuticals. The implementation of GMP rules in pharmaceutical industry companies can help manufacturers avoid the costly risk of producing substandard drugs.
What are substandard drugs?
Médecins Sans Frontières (MSF) explains that a substandard drug is a medicine which does not match quality standards. It may be contaminated with substances that have no business being in medicine; it may contain too much or too little of the active ingredient; its packaging may be of poor or inappropriate quality; or it may fail to meet quality standards in terms of raw material, aseptic processing, personnel requirements, storage, transportation, or any other criteria affecting drug safety, quality, and effectiveness.
Both originator drugs and generic drugs could be of substandard quality. This is because, unlike intentionally falsified drugs, substandard medicines are often legitimately produced, with mistakes either occurring unknowingly or when manufacturers compromise in certain respects to save costs.
The problem of substandard drugs is a global one, exacerbated by long and complex pharmaceutical value chains. Pretty much every continent grapples with drug quality issues. However, low- and middle-income countries (LMICs) and areas plagued by conflict, civil unrest, and weak or absent health systems carry the heaviest of burdens. The World Health Organisation (WHO) notes that about one in 10 medical products in LMICs is substandard or falsified.
The consequences of this problem are dire, emphasising the critical need to enforce good manufacturing practices in the pharmaceutical industry. For starters, the health effects of substandard drugs are questionable. Based on the specific nature of quality issues, the drugs may pass the digestive system without being absorbed. If there is an insufficient amount of the active substance, patients may be underdosed and not enjoy the therapeutic effects promised to them. If there is too much of the active ingredient, there may be side effects and other complications.
Second, the use of such drugs contributes to drug-resistant infections and antimicrobial resistance. Third, all kinds of substandard drugs are a waste of money – for patients, for governments and other healthcare payers, and even for the manufacturer of the drug, who will likely have to shell out large sums of money to rectify errors. Finally, and most importantly, substandard drugs can, over time, erode public confidence in the health sector. Essentially, implementing GMP means investing in good-quality pharmaceuticals.
What are good manufacturing practices in the pharmaceutical industry?
As defined by the WHO, GMP or cGMP (current good manufacturing practices) is a system to ensure that products are consistently produced and controlled according to quality standards. Good manufacturing practices for sterile pharmaceutical products are designed to minimise the risks involved in pharma production, which cannot be eliminated by testing the final product.
GMP rules in the pharmaceutical industry cover every aspect of production. They encompass raw materials, personnel training and hygiene, premises, equipment, logistics, and more. They are expressed as detailed, written procedures for each process involved in making drugs, vaccines, and other medical products. Systems are also established to document evidence that appropriate procedures are consistently followed every step of the way, every single time the product is made.
What good do such global pharmaceutical regulations achieve?
Quality cannot be tested or introduced at the final stage of aseptic pharma production. This is because quality testing is a destructive process, i.e. by the very nature of testing, contaminants may be introduced into the product, so the particular tablet, capsule, etc., which is tested cannot then be used by patients. So good quality must be built into the manufacturing process. Good manufacturing practices for pharmaceuticals prevent errors which cannot later be eliminated by terminal sterilisation. Without these GMPs, it is impossible to be certain that every unit of medicine being sold for use is of the same quality as those that are tested in the lab.
Another important advantage of implementing GMP is that it boosts pharma export opportunities. Most countries only accept pharma imports when the products have been manufactured according to global pharmaceutical regulations. To ensure competitiveness and success in the international pharmaceutical market, following good manufacturing practices in pharmaceutical industry products is non-negotiable.
Global pharmaceutical regulations
While the WHO has established detailed GMP rules in pharmaceutical industry manufacturing, some countries have instituted their own requirements drawing from the WHO GMP. Multilateral groups and authorities like the European Union (EU), the Association of South-East Asian Nations (ASEAN), and the Pharmaceutical Inspection Convention have also harmonised their GMP requirements. Not all countries, however, have the resources to localise global pharmaceutical regulations to their own context. In such situations, governments may rely on trusted regulations from other countries’ authorities – like the United States Food and Drug Administration (US FDA) – to determine GMP for manufacturers in their own country.
Below is a glimpse of the good manufacturing practices for sterile pharmaceutical products as outlined by the US FDA.
US FDA standards for pharmaceutical factory systems
As aforementioned, GMP rules usually outline procedures for everything in the pharma value chain, like personnel training and hygiene, inputs, and transport. Here, we’re only taking a look at the requirements for buildings, facilities, work areas, and other aspects of establishment standards.
For instance, the US FDA’s establishment standards for biological products call for all rooms and work areas where pharma products are manufactured or stored to be “orderly, clean, and free of dirt, dust, vermin and objects not required for manufacturing”. These good manufacturing practices for pharmaceuticals also demand that precautions be taken to avoid clogging and back-siphonage of drainage systems. Ventilation system arrangement should prevent microorganisms from travelling from one manufacturing area to another. Laboratories should be designed to be free of flies, vermin, dust and smoke while filling procedures should control for any contaminant that could adversely affect the purity, potency, and safety of the product.
Meanwhile, the US FDA also has different cGMP for finished pharmaceuticals of all kinds, barring positron emission tomography drugs. Good manufacturing practices for pharmaceuticals production buildings and facilities call for suitable size, construction, and location. The building design should prevent the possibility of mixups between components, containers, in-process materials, and drug products. The flow of all these elements through the facility could be unidirectional or bidirectional, as long as it prevents contamination. There should be separate areas for each process involved in converting raw materials into finished and packaged pharma products that consumers can safely use.
Floors, walls, ceilings, and other surfaces should be easily cleanable. The good manufacturing practices for sterile pharmaceutical products also specify procedures and standards for temperature and humidity controls, air supply and filtration, environmental monitoring, cleaning and disinfection, equipment maintenance, lighting, ventilation, plumbing, sewage, sanitation, and beyond.
Prefabricated infrastructure to meet factory system-related GMP
As you can tell, implementing GMP to ensure safe medicines access is hardly a walk in the park. These challenges are exacerbated in LMICs with poor access to infrastructure, resources, and training. In these settings, meeting GMP rules in the pharmaceutical industry relating to factory systems can be made a whole lot easier by using prefabricated infrastructure.
Prefabricated factory systems and cleanrooms, like the podules™️ designed by PodTech™️, are based on a concept that is common in the West. Such prefabricated factories are approved by the US FDA, the UK Medicines and Healthcare products Regulatory Agency (MHRA), and the EU GMP. They take care of the initial set-up of air handling, fire protection, electrical and process utility distribution, and building management systems so that you don’t have to. Being pre-validated before they are shipped to pharma manufacturers in different parts of the world, they are ready to be plugged into electricity and other utility supplies to begin operations in record time, all with the robustness of a traditional factory system.
As LMICs in Africa, Asia, and South America begin to ramp up their pharma manufacturing capabilities, they must be careful not to risk quality and safety in the process. By maintaining the highest quality standards, not only can they improve health outcomes for their populations, but they can also enhance their pharma export opportunities. Modular prefabricated factory systems present the fastest way to build pharma production infrastructure while prioritising health, sustainability, safety, and profits all at once.