If there’s one thing we can never stress enough, it is the significance of sterility in pharmaceutical manufacturing. The products prepared by pharma manufacturers are intended to improve the health and lives of people. Be they vaccines, biological drugs, small molecules, injectables or other parenterals, their consequences on human health are significant – if highly safe and effective, pharma products can keep people free of disease and more capable of living their lives to the fullest; but if, on the other hand, pharma products aren’t safe, they can have disastrous effects on human health.
That’s where sterilizer equipment comes in – it’s the equipment that lies at the very foundation of sterile pharmaceutical manufacturing. Without sterilizer equipment, there is no way you can achieve the extremely high levels of hygiene demanded by the pharma industry. Without sterilizer equipment, you cannot guarantee the absence of pyrogens or other contaminants; basically, you cannot guarantee the safety of your products unless you rely on autoclaves, sterilization in place systems, dry heat sterilizers, and other sterilizer equipment.
What is sterile pharmaceutical manufacturing?
As we’ve just established, as a pharmaceutical producer, you need to produce drug products with the highest levels of purity and safety for your customers. This means that you have to eliminate physical and chemical, visible and invisible contamination. And sterile production of drugs, vaccines and other products if what will help you.
Sterile pharmaceutical manufacturing refers to all the processes employed to ensure that the pharma preparations that you make and sell are free of particulate matter, microbial contamination, and other impurities which could affect the safety or efficacy of the product. These processes and best practices are functional through the life cycle of the drug; they involve the product and its raw materials’ interactions with the air, storage containers, manufacturing vessels, distribution networks (or process piping), personnel, and packaging. So you can imagine that this is a complex operation which requires sophisticated systems and equipment.
Types of sterile production: Aseptic manufacturing v Terminal sterilization
Not all sterile production of drugs is the same. When you hear the words “sterile pharmaceutical manufacturing”, what do you imagine? This phrase is often used interchangeably with the term aseptic manufacturing, however, the two aren’t the same process. They have a great number of differences in terms of complexity, application, cost, and process.
Technically, sterile production or sterile manufacturing is what is referred to as “terminal sterilization”. Naturally, there are hygiene measures adopted at every stage of sterile production, but this process is more concerned with the final product of the pharma manufacturing process. Employed when the final pharma preparation is fairly stable – including IV solutions like saline and dextrose, diluent solutions, and small molecule drugs – terminal sterilization via heat or radiation is undertaken to sterilize the final pharma preparation, packaging and all. Though absolutely crucial for some therapeutic products, this process is relatively simple, convenient and economical.
On the other hand is aseptic manufacturing. More complex than terminal sterilization, this method of sterile production involves maintaining sterility at every stage of the production process – storage, formulation, filling, and packaging. The entire process is carefully controlled and monitored to avoid contamination from microbes or other unwanted substances. Each element that makes up the process – each raw material, each piece of process machinery, the packaging – is made perfectly sterile independently, before they are all brought together. Specialised facilities called cleanrooms and well-trained personnel are crucial to the success of an aseptic manufacturing operation. This process is used in the production of pharmaceuticals whose composition or quality would be altered by heat or radiation. This includes vaccines, biological drugs, many oncology therapies, and parenterals, especially those meant for nasal, otic, or ocular administration.
Good manufacturing practices for sterile production of drugs
Contaminants can sneak into your products from a variety of sources. From the air, your equipment, personnel, and more. One of the most significant ways this happens is through cross-contamination, with bacteria, viruses or other pathogens travelling from other parts of your facility or from outside your facility altogether into a cleanroom or other sterile production space. It would certainly be extremely difficult for you alone to detect and protect against all these possible routes of contaminant entry, which is why we have GMP, or good manufacturing practices, for sterile pharmaceutical manufacturing operations worldwide.
These GMP cover requirements for cleanrooms, personnel training, and equipment quality. Sterile production must take place in cleanrooms which are constantly monitored for air quality, particulate matter, temperature, humidity, pressure, and microbial presence. Depending on the product they are intended for, cleanrooms have different classifications. Cleanrooms also have specifications when it comes to surface design and material of construction, air filtration systems, a positive pressure differential, and routine environmental monitoring.
When it comes to equipment, specialised machinery which complies with ISO 5/Class A conditions is recommended. Meanwhile, storage containers should be rendered sterile before use, written procedures should guide validation and revalidation procedures, closure systems should prevent microorganism penetration, and only high-purity water should be used for their wash and rinse cycles. And finally, personnel. Here, the risks are highest because they enter and exit the facility repeatedly; their skin, hair, garments and shoes all carry the risk of bringing contaminants into sterile spaces. So GMP concerning personnel include appropriate protective garments as well as movement within sterile spaces. They also highly stress training for the sterile production workforce as any kind of manual errors or lapses of judgment can have disastrous effects.
Selecting sterilizer equipment
Though sterilization can be carried out using heat, chemicals, radiation, and filtration, heat sterilization is the most commonly used method in sterile production. There are a number of methods that pieces of sterilizer equipment use to achieve heat sterilization. They need to maintain a minimum temperature-time relationship throughout to achieve good results. Depending on the product in question, its volume, and the chosen temperature, exposure times can vary in the sterilizer. Overall, understanding some fundamentals of sterilizer equipment can help you arrive at informed purchase decisions:
Standards. Good sterilizer equipment complies with stringent manufacturing standards like internationally-accepted cGMP or the guidelines issued by the US FDA, the UK’s MHRA, or the EU’s EN285 standards. ISO 9001 and GAMP also guide the manufacturing of sterilizer equipment.
Types of sterilizer equipment. Even restricting ourselves to just heat sterilizers, there are quite a few types of sterilizer equipment we want to tell you about.
First, autoclaves. What you might think of as the pharma industry’s pressure cookers, autoclaves have many applications in sterile pharmaceutical manufacturing. They are used in sterile facilities in hospitals, pathology labs, academic institutions and their facilities, and pharmaceutical laboratories. Their main use is to sterilize surgical instruments, glassware, tubes, waste, and infectious material cultures. Most critically, they are used in the terminal sterilization of ampoules, vials and other glass containers which have heat stable pharma preparations in them. Autoclaves may come with customisations to include features like control systems, vacuum pumps, feed pumps, and fast heating and cooling cycles.
Dry heat sterilizers, meanwhile, are stainless steel sterilizer equipment pieces which use air as a medium of sterilization. Operating at temperatures as high as 300°C, they require pharma raw materials or products to be exposed to the sterilization process for up to two hours to get the job done effectively. Dry heat sterilizer equipment is used to achieve sterility of vials, ampoules, containers made of glass, stainless steel and aluminium, and certain powdered products like sulphonamides.
Superheated water spray sterilizers are used for terminal sterilization rather than aseptic manufacturing. Such machines comprise carriages and trays, with low bio-burden purified water in a closed loop. They use centrifugal pumps, heat exchangers, and perforated distribution plates to achieve sterility. Their main use is in the sterilization of filled HDPE and LDPE bottles, PVC pouches, and large volume parenterals in plastic bags or glass bottles.
There are also ventilator sterilizers which use a mixture of air and steam to terminally sterilize LVPs in plastic pouches, heat stable solutions either open or semi-closed containers, contact lenses in blisters packs, and pre-filled syringes. After such sterilization, the product emerges from the system completely dry.
Sterilizer equipment features. Naturally, different types of sterilizer equipment has different product features and benefits. But there are some general principles you can keep in mind as you research the market. Temperature and pressure monitoring systems inside the sterilizing chamber are incredibly useful; you would do well to pick sterilizer equipment with this feature. You should also seek out sterilizer equipment with automated systems, in-built steam generators, user-friendly design, and compact construction. You should also always prioritise machines constructed with stainless steel SS316L. Efficient control systems are also indispensable.
From our other blog posts, you already know that sterilization in place is a critical component of modern pharmaceutical manufacturing. In aseptic manufacturing, especially, you absolutely cannot do without including SIP systems in your collection of sterilizer equipment. Overall, different sterilizer equipment all serves different purposes. They all may not be relevant to the particular pharma operation you are involved in. Nonetheless, mastering sterilization and all its components will hold you in good stead as you navigate the choppy waters of sterile production in the pharma industry.