The Benefits of Lyophilization in Polymer Manufacturing
From the earliest civilizations to astronauts in space, drying out food to preserve it and retain vital nutrients has been a common practice. Today, the same fundamental strategy of lyophilization is becoming a key method used by drug and medical device manufacturers for the development of polymers used in medical devices and for drug delivery.
Lyophilization allows them to preserve valuable chemical materials by first freezing them and drying them under a vacuum at low temperatures to essentially dehydrate them. The benefit is that batches can be stored much longer than untreated samples.
Interest continues to grow, due mainly to the large and growing number of biologic drugs in development. Drugs that are delivered through the skin (through an injection or IV) deliver active pharmaceutical ingredients (APIs) directly to the bloodstream for faster response times, yet since they are highly potent, they must be extremely sterile and stable.
According to BCC Research, “16 percent of the top 100 pharmaceutical drugs are lyophilized and 35 percent of biologic drugs are lyophilized.”
The growth of lyophilization can be attributed to the fact that we are seeing more and more material being produced in an aqueous medium, even when developing small molecule drugs. In drug synthesis we often use organic solvents that are easier to remove than water. However, there are chemicals for which water is a better solvent despite the fact that it is much more difficult to separate and remove.
Lyophilizing Drug Substances
Lyophilization has become necessary in biologics, since they must be produced in an aqueous medium. If you were to place a protein, peptide, or fermented product into a chemical medium it would be killed, so growing them in an aqueous medium allows them to remain in low concentrations. The challenge, however, is that removing the water with lyophilization is time consuming but remains the most efficient method of producing an Active Pharmaceutical Ingredient (API) that can be packaged as a dry powder and later reconstituted just before being injected into patients.
There are essentially three factors that contribute to the challenges of lyophilizing a chemical:
- Generally, a tremendous amount of material is required for a small amount of output—50 gallons of solution might yield only 100 gm of powder. The process may need to be repeated until we have sufficient product for the use intended. And nothing is routine. Each API, depending on its physical characteristics and desired result, requires a different temperature, pressure and time setting.
- The lyophilization process requires placing material in reusable containers, which require rigorous cleaning before the next batch is added.
- The extensive QA oversight needed to assure that cleanliness has been maintained, and the paperwork involved in each of the steps involved—pretreatment, loading, freezing at atmospheric pressure, primary and secondary drying under vacuum, and removal of dried product from the equipment—all play a role in increasing the time it takes to produce lyophilized material.
Lyophilizing Polymers
The growing GMP polymer market is driven by the increase in chronic diseases combined with a better understanding of drug metabolism in patients. The lyophilization process lends itself to the development of numerous polymeric applications, such as implantable devices that administer medications consistently to patients, for the delivery of cancer therapy, in imaging applications, formulation of coatings and in RNA/DNA drug synthesis. It’s beneficial in polymer manufacturing since it’s a sublimation process – the liquids in the product go from a frozen state to a gaseous state without going through a liquid phase, leaving behind dry solids.
The Challenges of Lyophilization
Despite new technologies, equipment and instrumentation, such as condensers that can handle high-vapor loads, lyophilization remains time-consuming and as such, a costly process for the development of APIs and medical polymers.
As we lyophilize more and more in drug product and polymer development, there are critical factors that must be considered to ensure its success:
- Product temperature
- Shelf temperature
- Chamber pressure
- Sublimation rate
- Freezing methods and their impact on crystal structure
Given the specialized expertise required for lyophilization and the costly equipment, the cost can be prohibitive for many drug developers to set up their own GMP manufacturing suites and invest in the infrastructure. They are increasingly turning to Contract Development & Manufacturing Organizations (CDMOs) to perform the development process for them.
From its origins as a method of food preservation, the need for lyophilization continues to grow as it keeps pace with the sheer number of biologic drugs in development and extends the stability and duration of these pharmaceutical products. Despite the high cost and unique expertise that is required, its ability toprovide longer shelf life and faster delivery to patients make it an invaluable process that will only continue to evolve.
Author Biography
Ed Price is President and CEO of Seqens North America (formerly PCI Synthesis), an integrated global provider of pharmaceutical synthesis and specialty ingredients. From the company’s Newburyport, Mass. operations, Seqens N.A. provides emerging and mid-sized pharmaceutical companies access to the expertise needed to develop and manufacture complex small molecules.