Industry research shows that an estimated 94% of drugs that pass animal and non-animal preclinical tests will fail in human tests,¹ and only 11.8% of products that enter clinical development receive regulatory approval. With an estimated cost of development to bring a drug product to market of $2.6 billion and an investment of up to 15 years² the failure rates are devastating.

Considering the increasing pressures on the industry to reduce clinical time and cost, it is clear the industry must find ways to improve these dismal success rates and speed the course of development. A 10% improvement in cycle time and success rates can reduce the total capitalized cost to bring a new drug to market by $634 million.²

Although the pharmaceutical and biotechnology industry has traditionally been slow to embrace new processes and technologies, effective methods to improve productivity, build pipelines faster, streamline infrastructure, lower costs and shorten time to market are extremely valuable — an industry imperative in today’s marketplace. To achieve the needed efficiency, the traditional linear path to early drug development will no longer suffice.

To meet today’s demands, including more rigorous regulatory expectations, drug sponsors are relying more heavily on integrated development services from outsourcing contractors, such as BioDuro, that have the specialized expertise, technologies and innovations to improve efficiency. BioDuro, a U.S.-owned research and development contractor with laboratories in San Diego, Beijing and Shanghai, is a full-service preclinical research and clinical development service provider that offers discovery and development solutions from lead generation through to dosage form development and manufacturing. This article explains how companies such as BioDuro, a pioneer of integrated drug discovery and development services, saves considerable time and costs by utilizing innovative methodologies.

Overcoming Inefficiencies In Clinical Development

The FDA has issued guidance documents describing specific ways for drug developers to advance the earliest phases of clinical research to evaluate scientific advances discovered in their laboratories much more efficiently.³ Yet the drug development process remains highly inefficient, fraught with delays and rising costs. Late-stage failure for novel compounds is high. Attrition rates are as high as 40%, due to drug metabolism and pharmacokinetic (DMPK) issues alone.

Often, various steps in the development process are provided by different service contractors in a sequential manner. This traditional pathway of drug development is no longer adequate.

To speed the development pathway, drug development service providers, such as BioDuro, are integrating discovery and development services by conducting interdisciplinary studies in areas such as formulation development and DMPK.

BioDuro, a hybrid contract research and development & manufacturing organization (CRO-CDMO), takes a multidisciplinary approach, integrating project management throughout full development services in a seamless transition between processes, utilizing the same team of experts in all contributing areas. Its combined team of experts provide solutions in discovery chemistry, biology, DMPK, pharmacology, formulation development and cGMP drug product manufacturing.

Incorporating Early Dmpk Studies and Translational Medicine

BioDuro integrates various key disciplines required to achieve the program goals of development, including drug discovery, early-stage characterization, preformulation and formulation testing, in vitro testing, drug design and DMPK studies. Uniting the key disciplines involves integrating chemistry, physical sciences, computer-aided drug discovery (CADD), biology, ADMET/PK and disease models.

Since the preclinical studies, formulation development, in vitro and animal tests are conducted in tandem by the same outsource partner along parallel paths, drug sponsors save considerable time — and consequently costs — by utilizing a single team of experts throughout development.

Another benefit of this integrated approach is that the early completion of characterization and other studies provides valuable information earlier, to guide formulation development and the final dosage form. As a result, companies can realize at an earlier stage whether the formulation will work or carries too much risk, which can save millions of dollars.

Early Optimization of a Drug Candidate

The rejection of a potential drug candidate may occur because of molecular issues, such as poor solubility or absorption, dissolution issues or the need for specialized drug delivery. A more effective approach to identify the best drug candidate is for the same development team to test and optimize the molecule first, which causes no meaningful time delay. Utilizing the same provider and an integrated approach can reduce the risk of eliminating a potentially strong candidate, which might result in bypassing a possibly valuable treatment for patients.

After a target is identified and a molecule is selected for further processing, BioDuro chemists first optimize the properties of the molecule, improving its characteristics for further testing in in vitro and in vivo assays. Utilizing advanced and proprietary technologies, the company provides services to enhance the bioavailability of poorly soluble compounds, and has the equipment, scientific tools and expertise to overcome issues quickly.

At a very early stage, BioDuro chemists utilize solubility enhancement or other technologies to provide error-free assessment of candidate pharmacological properties. Toxic and potentially interfering use of organic solvents or surfactants is replaced by approaches that not only can provide good exposure in preclinical efficacy and toxicological examination, but also suggest approaches for eventual larger scale formulation pathways. Its formulators typically utilize intermediates in milligram quantities, to enhance its characteristics for testing in in vitro and in vivo DMPK studies and for initial formulation.

BioDuro has the ability to provide solutions related to increased solubility and bioavailability from preclinical drug discovery through final dosage form development and GMP manufacture.

Solubilization has the following possible applications in Drug Discovery:

1. To provide higher aqueous solubility in target screens, where low solubility may give false negatives, and using organic solvent or surfactants can sometimes affect the target enzymes or receptors.
2. To give higher exposure in toxicological screens without using organic solvents or surfactants, to better establish accurate NOAELs (no observable adverse effect levels), uncomplicated by solvents or surfactants.
3. To provide better exposure in preclinical animal models (as with toxicology), without use of solvents or surfactants.
4. To provide insight into the “drug-ability” of the compound (the capability of the compound to be formulated and the formulation manufactured), one consideration for selecting a primary candidate from a panel of leads.
5. To provide early indications of approaches and excipients that can be used in late-formulation development efforts (approach screening).

Conclusion

Using translational medicine to bridge the gap between research and applied science enables faster, more focused research and development and can reduce risks before making big investments in later development stages. Since the molecule selected as a candidate may have multiple therapeutic uses, formulators must determine the use that can be most effectively and efficiently developed for clinical trials.

References

1. Cohen, C. M., “A path to improved pharmaceutical productivity.” Nature Reviews Drug Discovery, 751-753. Sept 2003.
2. “Innovation in Drug Development Process Remains a Key Challenge.” Tufts Center for the Study of Drug Development. Oct 20, 2015. http://csdd.tufts.edu/news/complete_story/rd_pr_october_2015.
3. FDA Guidance for Industry, CGMP for Phase 1 Investigational Drugs, Jul 2008, and FDA Exploratory IND Studies and INDs—Approaches to Complying with CGMP During Phase I, Jul 2006. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM070273.pdf, and http://www.biosciencetechnology.com/articles/2006/01/fda-simplifies-earliest-clinical-studies-1-17-06.