Biopharmaceuticals are large, complex, fragile molecules requiring specialized handling during fill-and-finish. In addition to needing an aseptic environment, biologics are sticky and pressure sensitive. To accommodate these special needs, CMOs routinely use coated or nonreactive components and gentle pumps to preserve the biological activity of the final drug product. Increasingly, new products in the pipeline require further special handling.
For example, antibodies conjugated to cytotoxic small molecules need sophisticated containment to protect personnel or live bacterial vaccines that must be kept alive and prevented from escaping. These new products provide an opportunity for CMOs to develop different specialized expertise rather than increasing capacity for biologics with routine manufacturing needs.
Biotechnology companies also use CMOs for innovative stabilization formulation. Lyophilization is the most frequently used stabilization technology, but it is a finicky procedure and challenging to scale up. Many biotechnology companies can accommodate their liquid-fill drug products with internal resources but will outsource any lyophilized products. Biotechnology companies are seeking formulation processes other than lyophilization in order to reduce the cost and problems associated with lyophilization. In addition, certain biopharmaceuticals are not stabilized by lyophilization; therefore, they need a different stabilization method.
An example of a CMO investing to meet these needs is Boehringer Ingelheim Pharma. According to Friedrich Haefele, head of fill-and-finish biopharma, “We offer the whole range from drug product development to final packaging. We have expertise in pre-formulation/formulation, packaging and process development as well as clinical supply capabilities for Phases I–III and we are very flexible regarding packaging formats and a wide range of batch sizes.”
Haefele also notes that Boehringer Ingelheim has addressed these specialized needs by “implementing innovative drug delivery technologies according to the trends on the current global market for vials (liquid and freeze-dried) in isolator technology and pre-filled syringes in a restricted access barrier system. We are currently constructing a new line in isolator technology for liquid and double chamber cartridges. We expect installation at the end of 2011, and operation in 2013. We have high flexibility to manufacture a wide range of batch sizes and primary packaging formats.”