SRI International, Biosciences Division
SRI International, Biosciences Division

Headquarters
Menlo Park, California

Location(s)
SRI has more than 20 sites around the world, including Menlo Park, CA; Princeton, NJ (Sarnoff Subsidiary); Arlington, VA; Harrisonburg, VA; and Tokyo, Japan.

Years in Drug Formulation
Over 30 Years

Spokesperson
Helen Parish, Senior Director, Pharmaceutical Sciences

Web site 

Company's role in drug discovery and developmnet
SRI International is a leading, independent, nonprofit research institute. Our Biosciences Division is fully integrated “from idea to IND”. We conduct basic research on disease mechanisms like an academic institution, perform drug discovery like a biotechnology company, and offer preclinical development services like a contract research organization (CRO). Our unique business model combines government-funded research and biomedical discovery with commercial partnerships to develop preclinical product candidates at reduced risk and increased value. In addition to our own research and discovery programs, SRI’s CRO capabilities include comprehensive preclinical development, pharmaceutical sciences, and support through regulatory filing to begin clinical testing.

Company's experience and expertise in drug formulation
SRI’s drug formulation experience and expertise ranges from preparation of dose formulations for in vitro and in vivo safety studies to finished drug product dosage forms for clinical trials. We have more than 30 years of direct experience solving challenging formulation and drug delivery problems. We have specialized expertise working with drugs with poor solubility, low bioavailability, short half-life, and gastric intolerability. SRI routinely performs preformulation development studies such as physicochemical characterization, excipient compatibility studies, high throughput solubility screening, and in vitro drug permeation studies. Dosage forms include capsules, tablets, liquids, emulsions, suspensions, and semisolids. Specialized alternative drug delivery systems have been developed such as bioadhesive nasal films, bioerodible implants, enteric coated capsules and tablets, vaginal gels, and multiparticulate systems. Our R&D, GLP, and cGMP facilities and equipment are designed to support early phase development in which only small batch sizes of material may be available.

Relationship with pharma companies
SRI’s approach to drug formulation is customized according to the needs of the program. We routinely integrate physicochemical property information, in vitro characterization, and pharmacokinetic data. The objective is to develop a product with the correct amount of drug in the right form, and to maintain its chemical and biological integrity for delivery at or over the proper time at the proper rate in the desired location.

SRI can undertake the entire effort independently or supplement a client’s existing capabilities. SRI has its own drug pipeline available for licensing but most commonly works on a contractual basis, either directly for a corporate or governmental agency or in a teaming arrangement as a subcontractor on a Small Business Innovative Research (SBIR) or Small Business Technology Transfer (STTR) program. We also serve as the prime contractor on collaborative efforts for specialized tasks on behalf of a sponsor.

Factors critical for drug formulation
Safety and efficacy are the two most critical factors in drug development. The formulator must design a product to maintain a drug’s chemical and biological integrity for delivery at or over the proper time at the proper rate in the desired location. We start with an understanding of the bulk drug’s physical and chemical properties. The compound is screened to determine its permeability characteristics and susceptibility to metabolizing enzymes. Once the pharmaceutical profile of the drug has been determined, the appropriate route of administration can be identified and designed. Excipients are selected to overcome potential problems in manufacturing and stability and to address factors impacting delivery issues such as solubility and absorption. Bench studies are performed on pilot batches to establish excipient compatibility and dosage form specifications. The final formulation design is optimized to take into account the pharmacokinetic properties of absorption, distribution, metabolism, and excretion.

Scientific/business/regulatory trends impacting drug formulation
There are two scientific trends that impact drug formulation today. Modern drug discovery activities are leading to more drug candidates that are highly insoluble or potent. Insoluble drugs generally have poor bioavailability and the formulation must incorporate solubility or permeation enhancers to allow an oral drug to enter systemic circulation. It is also difficult to formulate injectables in high enough dose concentrations to determine maximum tolerated doses in preclinical safety studies. Rational drug design has led to drugs with highly selective activity. These potent drugs must be administered in low dose amounts and maintaining content uniformity is challenging.

Emerging global markets have special needs and problems including a significantly higher risk of counterfeit pharmaceuticals, lack of cold chain controls, substandard health provider infrastructures, and suspension of patent rights. Yet, burgeoning social consciousness demands that treatments be made available to all, not just developed nations with idealized logistic and monetary advantages. Regulatory expectations must not be compromised for those least able to pay. In fact, the controls set in place to ensure safe and effective drugs are even more critical in hostile environmental conditions and where minimal professional health care supervision and controls are available.

Success story
SRI has been working on formulation and delivery approaches to permit the treatment of disease with currently approved drugs in a more economical and practical manner. A specific example is the development of an oral formulation of the antibiotic vancomycin. Once considered the “drug of last resort,” vancomycin is now commonly used in hospital settings for the treatment of systemic infections caused by antibiotic-resistant Gram-positive bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis (MRSE). These resistant bacteria are frequently the cause of hospital-acquired infections and are increasingly found in infections occurring in the community, posing a serious health problem to the general public.

“Improving the oral absorption of vancomycin has the potential to improve the quality of patient care and to reduce overall healthcare costs,” says Gita Shankar, Ph.D., Director of Formulations R&D at SRI. “An oral form of vancomycin will allow patients to leave the hospital earlier and to continue their treatment at home, where they will not need to maintain an intravenous line.”

Early proof-of-concept work at SRI to develop an orally bioavailable vancomycin formulation was funded by a contract from the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health. Under a recent licensing and research agreement with AuricX Pharmaceuticals, SRI will complete its formulation studies and fully optimize the oral bioavailability of vancomycin.

How will roles of CROs and contract manufacturers change over the next few years?
Reduced interest from investors in early stage R&D and widespread Big Pharma staff cuts will lead to emptier pipelines. CROs and contract manufacturers need to provide innovation, not just capacity. SRI has an integrated business model that provides CRO services coupled with its own pipeline development and licensing efforts.