This article is the fourth in a series intended to share insight and provide guidance for the pharmaceutical industry through a proven set of best practices and case studies within the strategic consulting, business intelligence, data warehousing and data management disciplines. The series focuses on Drug Discovery and Development as the pressure for bringing newer, safer and more appropriate drugs into the market. This must be done in a cost-efficient, effective and timely manner.  

Drug Discovery and Development
Drug Discovery and Development is a business process supported by several line functions, including Research, Pre-Clinical Safety, Clinical Pharmacology, Clinical Research and Development, Regulatory Affairs, Clinical Safety & Epidemiology and Marketing. These departments must continually work together with the highest precision to capture information and share results from countless sequential and parallel tasks. As demanding and sophisticated as this seems, their greatest challenge lies in the application architecture where they process the operation. Drug Discovery and Development architectures consist of numerous applications, storing data in different physical formats and diverse DBMS/storage technologies. While they deliver rich functionality on the front end, they are marred on the back end with resulting silos of data. These silos are neither integrated, nor easy to access. This “data rich, but information poor” paradigm is overcome through the determination of highly-motivated team members, who exhaust every option for extracting data, consolidating information and formalizing results for review and distribution. But it is achieved at a significant cost to the operational environment! This is where the value of data warehousing—with an accompanying self-service analytic and reporting environment—is gaining traction. Such an approach not only empowers teams with insight and the information they need to manage their areas of responsibility, but also serves as the conduit for increasing operational efficiencies, reducing costs and accelerating decision-making processes. 

Drug Safety
The need for drug safety is a critical concern in the corporate boardroom. As a result, significant capital is being invested in operational areas supporting pre and post market surveillance, since the early recognition of risks associated with the use of drugs in humans is very important. However, the area providing the greatest opportunity to mitigate this risk and maximize the return on investment is within Pre-Clinical Safety.  Pre-Clinical Safety is responsible for all non-clinical safety evaluation. This area is also comprised of four core sub-functions: Toxicology, Pathology, Drug Metabolism and Pharmacokinetics and Quality Assurance. The ability of these core sub-functional teams to understand the mechanism of drug toxicity and metabolic effects in experimental animals, coupled with the knowledge of human biochemistry and physiology, establishes a solid foundation for predicting whether a drug is likely to be safe and effective. But the reliability of their predication is dependent on experience, interpretation skills, judgment, and the capability to use all underlying study data to its fullest extent. This article focuses on this last, critical point. Through the sub-functions of Toxicology and Pathology, I will outline the business value for investing in Pre-Clinical Safety Data Warehousing.   

Toxicology and Pathology 
Toxicology and Pathology plays an integral role within the Drug Discovery and Development process. This area is responsible for delivering a scientifically sound safety assessment through a series of sophisticated studies on animals. These studies encompass the interaction of all the disciplines of toxicology and pathology, including genetic toxicology, general toxicology, reproductive toxicology, pathology, experimental toxicology and interactions with animal laboratory services. Toxicology and Pathology  uncover and identify target organs that are adversely affected by the drug; narrow the formulation approach (e.g., capsules, powder, ointment, creams, etc.) for routes of administration; confirm dose response and dose exposure relationships; provide preliminary information on possible mutagenic effects; determine levels of irritation and sensitization; verify how fertility and general reproductive performance are affected; substantiate the manifestation of tumor development and/or carcinogenicity; and validate post-natal development affects within newborns. 

There is, however, a major obstacle for toxicology and pathology. Their study data is often stored in different geographic sites, in different operational systems, and in different physical and logical formats. As a result, the review of and correlation of data between toxicology and pathology studies are a manual process and extremely labor-intensive. This is due to the number of varied and voluminous paper printouts. Furthermore, with study data being neither standardized nor consolidated, crucial modeling, simulation and data mining processes are hindered.

Pre-Clinical Safety Data Warehouse
The Pre-Clinical Safety Data Warehouse, along with an accompanying self-service analytic and reporting environment, enables pathologists, study directors, lab managers, data managers, toxicology scientists and management to assess study data in an efficient, effective and consistent manner. This also allows for the retrieval of findings and information on a particular drug or class of drugs within a study, across different studies and across geographic sites—anytime and anywhere!

There are numerous benefits for this investment:

• Breaks down existing barriers among functional areas, operational systems and geographic sites.
• Allows the Pre-Clinical Safety constituency to focus energy on the meaning of the data, rather than tracking down, collating and preparing it.  
• Improves the speed and quality of decision-making, because data is stored at the right level of detail. There is less reliance on memory as well. 
• Optimizes the value of Pre-Clinical Safety data for other line functions, and strengthens ongoing research programs and clinical projects.   
• Fortifies the overall safety profile of the drug with precise starting dose regiments and safety margins for clinical trials. 
• Reduces the attrition rate with effective lead selection and optimization due to the detection and resolution of toxicity, absorption, distribution, metabolization and excretion (ADME) issues earlier in the drug discovery and development cycle.  
• Accelerates bi-directional data exchange with Pre-Clinical Safety contract facilities.
• Facilitates modeling, simulation and data mining processes with historical data and disparate data types. 
• Prevents unnecessary testing as the history of toxicological changes and metabolic effects in similar drugs narrows future studies to only solving specific issues that might occur.   
• Reduces the number of experimental animals required for testing due to the ability to efficiently model, predict and assess toxicological changes and metabolic effects.
• Increases the intellectual capital and knowledge of the Pre-Clinical Safety constituency. This occurs as the ability to analyze the overall impact of similar studies and the involved drug is perfected. 
• Enhances Health Authority relationships with the ability to respond to requests and inquiries in a more timely manner, which can lead to faster approval of IND and NDA applications 
• Speeds up drug discovery and development throughput with faster and improved study success rates.

In terms of quantitative benefits, there are numerous examples from recent case studies:  

• Core members of the Pre-Clinical Safety constituency can spend as much as 40 percent of their time analyzing, preparing and reporting study data. An efficiency gain of up to 50 percent can be expected within this process. Depending on the number of personnel involved, the savings can be significant. In a recent case study with a core constituency of 25, estimated savings were $500,000.    
• Members of the Pre-Clinical Safety constituency typically spend as much as 20 percent of their time tracking down and collating study data. An efficiency gain up to 70 percent can be expected within this process. Depending on the number of personnel involved, the savings can be significant. In a recent case study with a constituency of 200, estimated savings were $2.5 million. 
• Core members of the Pre-Clinical Safety constituency can spend as much as 50 percent of their time “quality assuring” pre-clinical studies. An efficiency gain of up to 50 percent can be expected within this process. Depending on the number of personnel involved, the savings can be noteworthy. In a recent case study with a core constituency of ten, estimated savings were $200,000.  
• With the ability to respond to Health Authority requests and inquiries more quickly, the NDA review/approval process can be accelerated by one to five days—leading to earlier or additional sales revenue. In a recent case study, the estimated sales revenue was $1,000,000 per day for a total of $3,000,000.  
• Better predictive judgments through the capability of utilizing all underlying study data to its fullest extent can kill at least one drug per year earlier in the drug discovery and development cycle. Such judgments can prevent one from entering the clinical program as well. Note that 9,999 out of 10,000 drugs fail to make it to the marketplace. Within that failure rate, 10 to 20 percent are attributed to issues with toxicology, whereas up to 40 percent of those failures are attributed to issues with absorption, distribution, metabolism and excretion (ADME). In a recent case study, the savings were estimated to be in the millions.   
• If the history of toxicological changes and metabolic effects in similar drugs are known and accessible, then repeat or unnecessary testing can be prevented. In a recent case study, the annual savings was conservatively estimated at $5,000,000.    

Without question, the greatest opportunity to maximize the return on investment in Drug Safety and mitigate the risk associated with the use of drugs in humans is within Pre-Clinical Safety. Arming this line function with the right tools and technologies to predict and evaluate drug effects on animals—prior to their use on humans—is the answer for bringing newer, safer and more effective drugs to the market. 

The next article in the series focuses on reducing costs, accelerating decision-making processes and achieving operational efficiencies. These can be accomplished in planning, conducting, financing and managing global clinical trials.  

Recent articles by Tim Furey

• Quality Assurance Framework Lowers Total Cost of Ownership
• Spending Trends Demonstrate Value of Business Intelligence and Data Warehousing
• Pharmaceutical Drug Discovery and Development: Serious Adverse Events
• Pharmaceutical Industry: Business Intelligence for Drug Discovery and Development