Lonza Pharma & Biotech is a contract development and manufacturing organization (CDMO) and as a partner of biotech and pharma companies, enables them to bring large and small molecule medicines to patients in need. Contract Pharma recently spoke with Dan Dobry, head of drug product commercial development at Lonza Pharma & Biotech about oral solid dose market and technology trends.
 
Contract Pharma: How would you describe the current state of the oral solid dose manufacturing market?
 
Dan Dobry: The current state of oral solid dose manufacturing is both mature—in that conventional tablet formulations and capacity exist—and immature—in that new formulation capabilities need to be developed and improved for more complex problem statements like bioavailability enhancing technologies and patient centric dosage forms like pediatric controlled release products.
 
One example is tablet formulations for amorphous solid dispersions (ASD). Typically, the resultant formulation has low drug loading due to dilution of the drug concentration both by dispersion excipients and tablet excipients. Recently, Lonza has developed a new, higher active loading ASD formulation platform enabling decreased tablet size or reduced dosage units for high doses and potentially improved patient compliance.
 
Contract Pharma: What are some key trends driving the contract solid dosage business?
 
Dobry: A key trend in the solid oral dosage form business is the focus on integrated services. A majority of new chemical entities (NCEs) in the pipeline belong to small biopharma companies and are being advanced on expedited approval pathways. This creates a need for CDMOs to provide drug substance synthesis and characterization, drug product intermediates and drug product for the clinic in a seamless fashion.
 
Not only is phase-appropriate scale needed for rapid advancement, but it is also critical for the CDMO to have a line-of-sight to commercial for each stage of development to minimize technology and methods transfers. Additionally, it is critical that service providers have the technologies, assets and expertise in bioavailability enhancement technologies since more than 70% of compounds are considered low solubility and poorly bioavailable.

 
Contract Pharma: Where are the opportunities for growth in the market?
 
Dobry: Two major areas of opportunity for growth include improved decision making using a proven scientific approach to selecting the right technology and product profile, and integration of dosage form capabilities with drug substance supply. These capabilities allow for the necessary speed to clinic and to market that is required of new chemical entities being developed by small biopharma companies that control the bulk of the pipeline of molecules. 
 
Manufacturing potent and highly potent molecules, and the ability to safely and efficiently take these assets through any required particle engineering to drug product formulation and manufacture, is another growth area.
 
Contract Pharma: Conversely, what are the major challenges and/or obstacles in the market?
 
Dobry: Today’s small molecule drug products continue to be directed toward urgent unmet medical needs in a wide range of therapeutic areas and patient classes. This leads to drug product development in a highly variable environment where agility and problem solving are needed, and products are often progressed on accelerated or non-traditional regulatory pathways. Significant pain can be minimized by using technologies and partners in early development that have a clear line of site to acceleration and commercialization without switching technology or requiring technology transfer.
 
Contract Pharma: What are the most recent advances in oral solid drug delivery technology?
 
Dobry: Amorphous solid dispersion technology’s use in addressing the pervasive challenge of poor bioavailability continues to advance. The utility of spray drying technology has been expanded through processing innovations to address highly insoluble molecules using a superheated feed system that makes many previously undruggable candidates viable as amorphous solid dispersions.
 
A significant new development in oral solid drug delivery technology is a lipid multi-particulate (LMP) platform aimed at tunable release and enablement of range of patient centric dosage form. In this technology, the drug is encapsulated in a molten lipid mixture that is atomized on a spinning disk and congealed prior to collection. This technology produces 100 – 300 micron spherical particles with good mouth feel. The product can be encapsulated for adult populations but can also be used for pediatric and geriatric populations due to ease of swallowability. Because this process is semi-continuous, it allows for LMPs to be used in early clinical trials and into the commercial phase with a common process scale. In addition to tuning the lipid excipients for function, the LMPs can be coated for delayed release or taste-masking applications.
 
Contract Pharma: What’s new at Lonza on the oral solid dosage front?
 
Dobry: Recent highlights from Lonza include expansion of our SimpliFiH Solutions integrated first-in-human service offering which allows biopharma companies to have a single source for drug substance to drug product for early phase clinical trials. The expansion includes early-phase drug substance synthesis, our newly launched solid form selection services, and technology selection for poorly soluble molecules, all of which tie to our drug product services.  These services include powder-in-capsule first-in-human services through clinical tablet development. In addition, we recently announced a significant investment dedicated to early phase product development and GMP manufacturing of enhanced oral solid dosage forms to enhance agile, early-phase clinical program support where both operational flexibility and problem solving must be balanced with quality and reliability. 
 
Coupled with these expansions is our work behind the scenes to ensure that our site network operates as a single entity. All CDMOs offering integrated services across drug substance and drug product are made up of formerly independent companies with their own approach to project management, quality systems, data management, etc. Lonza is no different and we have multiple ongoing initiatives to integrate our site network into a seamless operation that can meet accelerated project timelines.  
 
We also continue to expand our integrated service offerings for antibody-drug conjugates (ADCs). ADCs are a growing class of biopharmaceutical drugs designed as an effective targeted therapy for treating cancer. These products consist of a highly selective monoclonal antibody, a HPAPI or payload for killing the tumor cell, and a linker. Lonza has invested heavily to ensure that all ADC elements are available under a single quality system at our Visp, Switzerland site. Recent investments include new 4 cubic meter multiproduction lines for HPAPI, a dedicated ADC payload facility for bench scale through to 10 cubic meter production—with containment to 1 ng / cubic meter—and an expanded bioconjugation facility for development through commercial scale capacity.
 
In addition to oral solid dosage form services, Lonza is pleased to offer particle engineering services for the oral inhaled and nasal pulmonary delivery market. Either through traditional milling services or by spray-drying, we can provide inhalation particles and dosage forms (blisters or capsules). These capabilities are being expanded given the increased utilization of inhaled delivery and specifically dry powder inhaler applications. Investments include expanded spray drying, analytical and encapsulation capabilities.