Getting your small volume parenterals manufacturing process up and running is no joke. As with any other pharmaceutical manufacturing process, the sanitary standards here are extremely high. But the risk involved in parenterals is even greater since they directly enter the bloodstream, tissues or organs, making it even more important to ensure the process is aseptic all through.
What are Parenterals?
First things first: what are parenterals? Parenterals are any pharmaceutical preparations that are meant to be delivered into the body through the skin or other external boundary tissue. By delivering active ingredients directly into the bloodstream or body tissue, the alimentary canal is bypassed entirely.
Parenterals are sterile and pyrogen-free preparations, in either liquid or solid form, which may be delivered via subcutaneous, intramuscular or intravenous injection. They may also be injected directly into more specialised tissue like the spinal cord, or be delivered by other means through external body tissue, for instance, ophthalmic preparations that can be dropped directly into the eyes.
Parenterals are divided into two main categories: small volume parenterals (SVPs) and large volume parenterals (LVPs).
What are Small Volume Parenterals (SVPs)?
Small volume parenterals refers to pharmaceutical preparations which are packaged in containers of 100 ml or less. This usually includes preparations packaged in vials, ampoules, pre-filled syringes and even squeezable containers meant for injection or topical application, with doses generally ranging from 1 ml to 30 ml, packaged either as single or multiple doses.
Large volume parenterals, on the other hand, are packaged in containers greater than 100 ml in volume. Generally, they are meant for intravenous use and are available in volumes ranging from 100 ml to 1000 ml, mostly as a single dose.
Features, Types & Applications of Small Volume Parenterals
As mentioned above, small volume parenterals differ in features from large volume parenterals in volume, number of doses, and delivery method.
According to their purpose, different types of small volume parenterals are packaged differently. You may find small volume parenterals in ampoules, vials, pre-filled syringes, cartridges, bottles or any other container that matches the volume and sterility requirements of SVPs. Other SVPs like eye drops which are applied topically may also be available in squeezable plastic containers.
Further, small volume parenterals are produced in two forms – either liquid or dry powder preparations, depending on the stability of the pharmaceutical product in liquid form. Finally, types of small volume parenterals also differ by dose – you get either single dose or multiple dose parenterals.
Aspects Involved in Small Volume Parenterals Formulation: Staff, Sections, Equipment and Machinery
Pharmaceutical manufacturing is easily one of the most complex and stringently-monitored processes in the world. And with good reason, considering the direct implications of pharmaceutical drugs on the health and lives of the people who use them.
With parenterals and otherwise, it is becoming more and more important to produce products which are acceptable for world markets. With transnational supply chains and the global movement of pharmaceutical drugs, requirements are becoming more unified, the most largely prescribed being the United States, European, and Japanese Pharmacopoeias. Today, small volume parenterals processing requirements are based on current Good Manufacturing Practices (cGMP) guidelines, with strict controls ensuring that products meet the prescribed standards for sterility, particulate matter, microbial presence, pyrogens and other potential contaminants. Even the water used in the manufacture of different types of small volume parenterals is subject to strict standards and tests, with water for injection, purified water, and pure steam being generated under strictly controlled conditions.
All the different elements of small volume parenterals manufacturing include water for injection, solutes, active ingredients, antimicrobial agents, antioxidants and many more which are brought together under controlled conditions.
The workforce requirements of small volume parenterals manufacturing range from technical workers like manufacturing and analytical chemists, quality assurance professionals and production managers, to non-technical staff including machine operators and other individuals involved in supporting activities.
Even the sections of the plant, for both dry and liquid injection manufacturing, need to be separated as per the purpose they serve in the process. A high quality SVP manufacturer who is adamant on quality and insistent on preventing cross-contamination will have different sections for warehousing, sterile raw materials, washing, sterilisation, general production, mixing, filling, sealing, packaging and labelling.
These processes should occur either aseptically or the final product must be terminally sterilised, depending on the heat stability and other features of the final product. Either way, the equipment and vessels used for small volume parenteral manufacturing include storage equipment for vials, ampoules and closures, washing and drying equipment, process vessels for mixing and holding, filtration equipment, sterilisation machines, and bacteriological filters amongst many others.
Essential Aspects of the Manufacturing Process
No matter which specific types of small volume parenterals are being produced, there are some general steps and principles you should keep in mind to ensure the sterility of your process and the integrity of your final product.
For both dry injections and liquid parenteral preparations, dispensed raw materials, APIs and packaging materials should be held in aseptic areas. Vials, stoppers, caps and any other parts of the container which will come in contact with the pharmaceutical product must be washed, dried and sterilised using the appropriate methods. This may be sterilisation by moist heat, dry heat, radiation or any other industry-accepted technique. After the product is prepared by mixing the API(s) and other raw materials in a sterile manner and filled in the appropriate containers, the filling vials must be capped, sealed, labelled and packaged.
Ideally, there are some general principles which should guide the manufacturing process throughout the small volume parenterals’ production journey. To ensure only high quality and safe products leave your manufacturing facility, different types of small volume parenterals should only be released after complete filling and testing, with results of tests measuring sterility, pyrogens and bacterial endotoxins maintained in a systematic manner. Separately, even validation details and simulation trail records should be maintained. Importantly, data concerning environmental monitoring like temperature, humidity and microbial presence should also be kept available for future reference.
Quality Control
Ultimately, even after maintaining a highly sterile environment throughout the manufacturing process, there are a set of controls that must be implemented to make sure that the final product you deliver to your consumers reaches the highest safety and quality standards.
There are a number of tests that are implemented to make sure your small volume parenterals are free of contaminants and securely packaged. While the leaker’s test ensures that ampoules are properly sealed, the sterility test, clarity test and pyrogen test ensure that small volume parenterals containers are free of pyrogens and particulate contaminants.
At TSA, our range of large and small volume parenteral processing vessels meets the highest quality standards in the industry. Our manufacturing, compounding, holding and storage vessels can be customised to your product specifications in terms of not just insulation, level sensing and load cells, but can also match up to your maintenance regime with CIP and SIP integrations. If you haven’t checked them out yet, what are you waiting for?
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