Catalent: Leveraging Formulation Experience to Bring Products to Market
It’s a well-documented fact that the financial cost and time spent to discover, develop, shepherd through clinical trials, and manufacture/package anew pharmaceutical are astronomical.
Many large pharmaceutical companies, which at one time could doeverything in-house, simply do not have the resources to do it intoday’s economic climate. For small pharmaceutical companies and“virtual” pharmaceutical companies the need for help is even greater.
This is why so many companies are looking for the help and experienceonly an accomplished pharmaceutical contract development and manufacturing firm can provide. Catalent, a drug development, delivery and supply partner for drugs,biologics and consumer health products with offices and facilities around the world, is a partner that can be looked to by sponsor companies to ensure products get the research, development and manufacturing technologies, and the attention they deserve.
A Focus on Drug Development
While all phases of pharmaceutical research, development and manufacturing are important, perhaps the one that gives sponsors themost anxiety is the early drug development process. This is particularly true if you have a promising drug candidate that exhibits poor solubility/bioavailability.
To enhance its capabilities and assist companies in developing small molecule and peptide drug candidates, Catalent recently acquired Pharmatek Laboratories, Inc., in San Diego, California, which offers a range of early-phase development solutions, including Catalent Pharmatek SD® Spray Drying technologies.
Spray drying has been proven to improve the bioavailability of poorly soluble compounds. A spray dry dispersion (SDD) is an amorphous molecular dispersion of a drug in a polymer matrix created by dissolving drug and polymer in an organic solvent and then spray drying the solution. SDD technology offers proven performance, stability and manufacturability.
This technology is being put to good use by Catalent, and as Elizabeth Hickman, Catalent’s Strategic Marketing Director for Oral Drug Delivery explains, it has positioned the San Diego facility at the forefront of the company’s early development service offering, “This site is our center for excellence in early phase development for both oral and injectable drug products. We have extensive experience in the development of enabling formulations, including spray dried dispersion.”
Hickman continues, “We take an agnostic approach to formulation development, relying on accurate characterization of a molecule and eighteen plus years of experience to make confident data-driven development decisions. A molecule’s physiochemical characteristics, as well as dosing requirements, should be carefully assessed while multiple formulation types are considered, such as API-in-a-capsule, simple blends, particle size reduction, amorphous dispersions and melt granulations, to determine the best path forward. Our goal is to match the best formulation technology for clinical success with our customer’s business and program goals, time-lines and budget. Often,in the very early phase when a molecule is nominated for clinical development, a company’s goals are driven by timelines. We work with those companies to develop a clinical strategy that accelerates timelines, such as API-in-capsule or powder in a bottle for first-inhuman clinical studies. The key is to ensure the chosen strategy is backed by data, especially for poorly soluble molecules.”
An important part of pharmaceutical development is the tech transfer – the handing off of the project from one stage of development to the next, and sometimes from in-house to an outsourced provider or vice versa.
Catalent, with its extensive offerings of R&D, clinical and manufacturing capabilities takes tech transfer very seriously and puts forth a lot effort to make it as easy as possible.
“We focus on ensuring that when projects graduate out of one Catalent facility to another, perhaps due to scale, the formulations are robust and systems are streamlined and seamless for the customer,” says Hickman. “Since the acquisition of Pharmatek, Catalent has put a lot of attention and effort into harmonizing our capabilities with other sites to further optimize efficient transfer.”
Returning to the San Diego facility’s offerings, Hickman explains that they are very focused on their preclinical capabilities. The facility is very adept at taking a promising molecule from the bench, assessing its developability, and then moving it into efficacy testing.
Making the “Go/No-Go” Decision
Advanced technologies such as High-Throughput Screening (HTS) have gone a long way to help pharmaceutical developers find promising candidates, and weed out poor ones quickly and economically. But even with these new tools, the decision must be made to either continue development or end it. That’s when the expertise and experience of the Catalent network can help and offer guidance.
“We do a lot of go/no-go stuff here,” says Hickman. “During late phase discovery, we help customers quickly solubilize their molecules for preliminary efficacy confirmation. This is the point where customers are really just trying to determine if they have a hit. They can then next step and nominate that molecule for preclinical development,” explains Hickman. “Once the customer gets the PK data, we can help them interpret results and model human PK/PD.”
“Once a customer nominates a molecule for development, we provide formulation and analytical services to support preclinical testing,” says Hickman. “We do all of the preformulation studies to develop a solid, comprehensive understanding of the molecule’s physiochemical characteristics. We also work with our site in Research Triangle Park, North Carolina, which has expertise in solid state, to assess the compound’s polymorphs, and to determine solubility and stability improvements with salt screening and polymorph screening.”
Hickman continues, “Then, for GLP studies, we provide formulation development for toxicology studies. These can be very challenging, especially those with poor solubility. Poorly soluble molecules require formulation enhancing techniques to obtain the required concentrations needed for the dosing study. Toxicological studies are a critical component of development, and the development of effective formulations aids candidate selection and optimization that will ensure safety in subsequent human trials. Again, once the customer gets the PK data, we can refine the PK/PD model and help them to better predict PK and PD in humans.”
“PK and PD modeling can help them assess DMPK challenges in humans. It can predict questions such as: What would it look like in a human? What additional formulation technology is needed to achieve our targeted profile? What dosage strengths should they consider, or problems they are going to have with their molecule.”
Moving Beyond – “Low-Hanging Fruit”
As the industry looks toward finding more viable molecules to move forward there is a sense that many of the “easier” molecules have already been discovered – leaving those that have potential but exhibit poor solubility or bioavailability behind. And to go along with this there is always the question of formulation, especially if it’s a poorly soluble molecule.
“That’s when our bioavailability enhancement capabilities come in,” says Hickman. “We can conduct parallel screening programs, which is the core component of OptiForm Solution Suite.” (see sidebar 1).
She continues, “OptiForm started off as just a bioavailability screening tool, but we have expanded it to be the full continuum for early phase development. With it, we can take a molecule from the bench to the clinic.”
And yet, while Catalent offers OptiForm as a potent solution to solving bioavailability and solubility problems they are aware that sometimes the molecule being developed might need other technologies – it all depends on the data.
“Because we take a very agnostic approach to formulation development and let the molecule guide us to the best path, as well as what the customer is trying to do from a strategic standpoint,” says Hickman. “We test it, and we allow the data to define what the compound needs. We are not married to any one formulation technology here, we’re going to look at the data and then we’re going to apply the right technology to that compound.
With the screening programs that we do in the very early phase, we are going to look at various types of formulations and the technologies to produce them. We try to keep it as simple as possible for the customer, especially in the early phases, because the more complex it gets, the more expensive it gets for the customer as well.”
A Closer Look at Spray Drying
As mentioned earlier, Catalent’s San Diego facility is home to the company’s Pharmatek SD spray drying technology.
Spray drying is another tool Catalent can offer customers with difficult to develop molecules in order to help them move forward. In particular, spray drying offers the following benefits:
- Enhanced bioavailability of poorly soluble compounds
- Consistent particle size distribution
- Long-term stability
- Robust, scalable process
- Higher drug loading
- Enables taste masking or controlled release dosage forms
“Our spray drying is really focused on bioavailability enhancement,” says Hickman. “There are a lot of things you can do with spray drying, such as taste masking and particle design for inhalation, but our core expertise is for the bioavailability enhancements of poorly soluble molecules.”
Catalent’s spray drying technology is a key part of its holistic approach to drug development. The company is adept at combining its expertise in formulation and process development with capabilities in spray drying to get over the most difficult product development challenges.
As data is the key to a successful product formulation program, the Pharmatek SD spray drying team is skilled at analyzing and interpreting data to fully characterize an API and help usher it through feasibility, development, and commercialization to provide a robust data package in support of regulatory filings.
Summing it All Up
It’s apparent that Catalent’s San Diego early phase development facility is a key cog in the company’s global offerings for product development and scale-up. Looking forward, as molecule solubility become increasingly difficult and bioavailability becomes even more important, Catalent is well-positioned to help companies bring much needed pharmaceuticals to market.
“What we are most interested in doing is driving molecules to the clinic and helping our customers get the data that they need, “says Hickman. “Data is so important for advancing their molecule and making decisions about what customers want to do. By leveraging our OptiForm Solution Suite with our spray drying capabilities, we feel we can provide valuable formulation and development assistance to any customer with any molecule.”