For transporting, storing, and handling drugs and other parenteral products that are unstable in solution, lyophilized vials remain the go-to solution for 80% of the industry.
Today, approximately 16% of top pharmaceutical drugs–and 35% of biological drugs–are available in lyophilized vials, with Markets and Markets predicting that more than half of all injectable drugs will require lyophilization by 2020.
Lyophilized vials provide a stable and reliable solution for compounds that cannot be stored or transported in liquid or frozen form. What does this mean for the future of parenteral manufacturing? In spite of risks and challenges associated with the lyophilization process, the industry is poised to expand considerably, and makers of lyophilized vials who can find new ways to streamline the process and reduce risks of contamination will be on the front lines of growing consumer demand.
What is the process of manufacturing lyophilized vials?
Lyophilization is a form of freeze-drying that removes water from a product such as protein, collagen, or peptides by reducing the air pressure around the frozen product through the use of a vacuum chamber or lyophilizer, allowing water to sublimate naturally while leaving the freeze-dried product intact. The resulting lyophilized product, often stored in vials, has a longer shelf life, improved stability, and is easier to transport than liquid or frozen product.
Because lyophilized vials are easier to store, handle, and transport than liquid products, there is less risk of contamination, not to mention the increased ease (and commensurately reduced cost) associated with aseptic handling. Because lyophilized vials are capped while still inside the lyophilizer, the risk of contamination within the CMO is reduced by eliminating the need for handling or moving the lyophilized product during processing. Liquids have an unpleasant habit of spilling and attracting contamninants, while the dry powders which result from the lyophilization process are easier to handle under the aseptic conditions so often required in pharmacological manufacturing, processing, and application.
While some manufacturers create lyophilized vials using a two-stage process which begins in a freezer before being transferred to a vacuum chamber, most lyophilization occurs within a dedicated freeze-drying machine or lyophilizer. This reduces the risk of contamination, as trays don’t have to be moved from the freezer to the vacuum chamber in the midst of the process.
Products are typically reduced in temperature to around -40°C, then the pressure in the chamber is reduced until the water sublimates directly from a frozen solid to a gaseous state. This allows water to be removed from the product without applying excessive heat, which can affect the chemical makeup of many pharmaceutical compounds. The result is a freeze-dried powder that can easily be stored in vials–often for two to five years–and reconstituted in labs or hospitals when it is needed.
What challenges come with manufacturing lyophilized vials for parenteral products?
According to the FDA, the lyophilization process, when performed correctly, increases the stability of parenteral products, decreases the risk of contamination, and allows products to be handled, stored, and transported more easily and safely. Of course, the lyophilization process is not without its own unique risks and challenges.
Lyophilization requires a significant capital investment up front. The lyophilizers alone can cost upwards of $3 million. That is in addition to equipment such as reusable or disposable trays and stoppers for the lyophilized vials. Plus, handling and processing time is also increased. The lyophilization process can take anywhere from 12 to 72 hours per batch, depending on the product being lyophilized.
Clean-up is also an important consideration in the manufacture of lyophilized vials. The lyophilization process itself can be messy, but it’s also vitally important that dryers be thoroughly cleaned between batches to avoid next-batch contamination. In fact, cleaning validation is reviewed by the FDA. Investing in closed or single-use trays can help make the cleanup process easier and reduce handling times for lyophilized products.
Lyophilized vials also have to be reconstituted before use. This not only requires that hospitals or labs have a sterile diluent on hand, it also adds a step of handling–and, with it, of potential contamination–to the flow from the manufacturer to the recipient of the product contained in lyophilized vials.
With so many unique challenges, why should parenteral manufacturing stick with lyophilized vials?
In spite of these risks and challenges, lyophilized vials represent a growing slice of the pharmaceutical and parenteral manufacturing industry. Today, lyophilized vials hold everything from collagen and protein to oligonucleotides, chemical APIs, enzymes, mAbs, and numerous other bulk ingredients that are unstable in liquid or frozen form, whether due to aggregation, degradation, chemical reactions, biological growth, or other factors. Oligonucleotides and peptides, for example, degrade when in liquid form, and can be stored for much longer periods of time in lyophilized vials.
As the formulations for new drugs and other parenteral products become more complex, stability becomes increasingly important, and lyophilization allows products to be stored and transported that might otherwise be too unstable for use. New advances in bulk lyophilization such as buffer-free solutions and continuous processing are also underway, as manufacturers and R&D departments continue to explore the potential applications of lyophilization technology to parenteral manufacturing of all types. The FDA has identified growing demand for lyophilized vials among anti-infectives, in-vitro diagnostics, and products derived from biotechnology, to name just a few.
The last few years have seen significant market growth in the freeze-drying technology used in the lyophilization process, as manufacturers search for cheaper, more efficient, and less bulky solutions for lyophilizing drugs and other compounds in an aseptic environment. With 80% of the market still using lyophilized vials for numerous applications that are unstable in solution–or to transport and store parenteral products for a longer period of time–there are countless opportunities available for parenteral manufacturers who aren’t deterred by the unique risks and challenges associated with the complex world of lyophilization.