In general, what are some current challenges facing pharmaceutical companies developing new products that require lyophilization?
A common challenge that we see our clients face when developing new products is the lack of drug substance (DS) available for development activities. Many of our clients have very costly drug substances so our development team will work with them to minimize the amount of DS required. One way that this is accomplished is to determine an appropriate surrogate for cycle development and then execute a confirmation run using DS to verify the cycle effectiveness. Alternatively, small quantities of DS vials can be interspersed among placebo vials in order to lyophilize the drug product with a commercially representative scale. Another challenge we work with our clients on is to ensure that their cycle is scalable for benchtop to cGMP manufacturing. Our development team is forward thinking during the lyophilization cycle development to ensure that the cycle is robust and easily transferable to, not just LSNE’s commercial lyophilizers, but also to any other lyophilizer on the market. Lastly, we have seen a number of products which are insoluble or poorly soluble in water and require the use of organic cosolvents or solubilizing excipients. Our formulation and development scientists have worked with both organic and solubilizing excipients and can meet the challenges that they present for lyophilization. Organic solvents can be difficult to lyophilize in high concentrations but our team has experience working with these types of formulations and developing the appropriate lyophilization cycles.
When a pharmaceutical company is looking to partner with a lyophilization services provider, are there specific questions they should ask a potential company to ensure their product receives the best developmental assistance possible?
When evaluating potential lyophilization CMOs it is important to understand their past experience with lyophilization and how it fits into their corporate focus. There are CMOs that offer lyo cycle development as an offshoot but these services can be different than they would be at a CMO whose bread and butter is lyophilization. It is important to ask questions such as “How many lyophilizers are dedicated to development services?” “How long have you been offering this service?” “How many cycles have you developed?” and “What product classes have you handled?” It is also important to understand what the analytical capabilities are at this CMO and how they can support your development project. For example, does the development lab have stability chambers and do they perform real-time in-process and finished product testing? Lastly there are advantages to working with a CMO that also produces cGMP material. This would allow the development team to collaborate with the commercial operations team to development a robust and transferable process. It would also be important to confirm the number of cycles that have been transferred from development to commercial manufacturing so you can benefit from the CMO’s past experiences.
In conjunction with lyophilization services, LSNE offers other drug development and manufacturing services. Can you tell us about these services and how they work with and complement your lyophilization expertise?
LSNE stands for Lyophilization Services of New England. We often say that “lyophilization is in our name” and it really is at the core of everything we do. LSNE has a number of services which all incorporate our expertise in lyophilization. With 23 lyophilizers located at our three manufacturing sites, we offer non-aseptic manufacturing for medical devices, bulk lyophilization in trays for bulk drug intermediates, aseptic formulation, and aseptic filling for clinical and commercial products. We also offer services to support these manufacturing activities, including ICH stability, photostability, analytical method development, regulatory writing/support, labeling and packaging.
Looking forward, are there any new technologies or services that LSNE is evaluating to better serve the drug development and manufacturing needs of its current and future clients?
As the biologics market continues to mature and new products enter the clinic, LSNE’s techniques for minimizing line-loss continue to gain efficiency. LSNE has seen a significant increase in the number of companies developing RNAi or siRNA products and the cost of the oligonucleotide drug substance is very high as well. With our years of working with monoclonal antibodies we are extremely well positioned to work with oligonucleotides in an efficient and cost effective manner.
As more companies are developing therapeutics with Orphan Drug Designation, we work with our clients to expeditiously move their product into and through clinical development. LSNE’s batch sizes are perfect for drugs that will be receiving or have received Orphan Drug Designation. Our Quality Team stays abreast of the latest regulatory changes to stay compliant and streamline support activities. Such efficiencies include in-house regulatory writing support and having a Type V DMF on file with the FDA.
To support the growth in the outsourcing industry, LSNE is continuing to expand our facilities as well as our employees. LSNE’s staff has grown significantly over the last couple of years and we are continuing to add key employees such as industry Subject Matter Experts in many fields. We are continually adding staff with industry experience to increase competitive advantage over other CMOs.