About 30 percent of all parenteral drugs approved by the FDA in the past few years involved freeze-dried substances. Experts are predicting a possible rise to even 50 percent in the future. It's definitely a challenge for R&D as well as commercial filling. Therefore, many pharmaceutical and biotech companies rely on outsourcing partners. But how do you find the right partner for the challenge?
Lyophilization of substances is a convenient solution to increase chemical and physical stability, but a challenge for development and manufacturing. Efficient lyophilization processes have to be implemented and life cycles to be considered.
Also important is simple and safe handling of the application device. Healthcare professionals and patients are calling for user-friendly systems. The slightest variation in reconstitution speed can be a critical aspect for the patient. Outsourcing partners have to meet sophisticated standards concerning experience, process reliability and technology know-how.
In the beginning
Right from the start manufacturers have many questions on their minds: In what phase of product life is the support needed? What will commercial manufacturing necessitate? Will support be required during all life cycles, and can the partner provide a comprehensive solution?
Contract development and manufacturing organizations (CDMOs) can offer support and experienced-based solutions during clinical development phases and market supply. Risk of knowledge loss is minimized when they partner with a drug company already in an early phase. Commercial process know-how can be applied early on to offer possibilities of starting life-cycle management. Beyond those competencies, the CDMO must provide the needed capacity and efficient production processes.
Experience and commitment
The increasing complexity of substances contributes to the challenge. Pharmaceutical and biotech companies should look for a service provider with a recognized reputation. Experienced specialists, who have already worked successfully with freeze-dried products, can provide hands-on solutions to optimize lyophilization cycles and processes.
Knowledge of the requirements for clinical and commercial manufacturing is also important. Moreover project management skills to streamline processes from conception through final delivery are required as well.
However, what makes a partner stand out is the ability to combine manufacturing and lyophilization process know-how and adapt to the customer product’s needs. The success of the project depends on the flexibility and commitment of the partners.
Understanding the process
In spite of its long history, freeze-drying is not a standardized process. In drug manufacturing, complex molecules often determine special lyophilization processes. For instance, a lyophilized substance can contain sucrose for the isotonic formulation, disodium hydrogen phosphate as a lyoprotector, sodium hydrogen phosphate as a buffer system and polysorbate as a tenside. In addition, water for injection or a customized diluent is used for the purpose of reconstitution.
The formulation’s composure determines the duration of the freeze-drying cycle and the critical values that must not be exceeded. In our example, sucrose has a glass transition temperature of minus-34 degrees C. If you add a phosphate buffer, the critical temperature drops considerably; the freeze-drying cycle must be adjusted accordingly.
For an optimal process in commercial manufacturing, several test runs have to be performed in the laboratory followed by fine-tuning in the commercial machine. Depending on the active substance, this step will require approximately two to eight months. A definition of the optimal lyophilization cycle should happen as early as possible — at best with a partner understanding the nature of lyophilized products.
Intelligent technologies for the product's future
A market launch often demands easy packaging. Vials are the most common system to market lyophilized substances but require trained staff for handling the application properly. Healthcare professionals would like to see more manageable systems.
However, new delivery technologies are not only relevant in the matter of user-handling. Competitive products require new solutions during their life cycle to remain successful on the market. The future of a product has to be in one's sights right from the start. And so has the choice of a reliable partner. What can a partner’s support look like during life-cycle management? Can the partner provide other approaches to simplify vial handling, i.e. prefilled syringes with water for injection? Does the partner have experience with solutions like dual-chamber systems, which allow for instant reconstitution?
Taking all these aspects into consideration will help finding the right outsourcing partner: a CDMO with a wide expertise in the field of freeze-dried processes and innovative packaging solutions will support you in solving your lyophilization challenge.
