Module 9: Introduction To Pharmaceutical R&D

Module 9: Introduction To Pharmaceutical R&D

Overview of Pharmaceutical R&D

• Cost of Drug Development: Over $1 billion is spent per new drug.

• Process Evolution: The process of bringing new medicines to market has evolved significantly, becoming more complicated and time-consuming.

• R&D Process Overview: The R&D process is intense, challenging, expensive, and essential for health advances.

  • Major requirements include:

  • Strong intellectual property protection

  • Efficient regulatory systems

  • Supportive market-based healthcare delivery systems

• Timeframe:

  • It typically takes 10–15 years to develop a new drug:

  • 3–6 years in pre-discovery and pre-clinical trials

  • 6–7 years in clinical trials

  • FDA approval can take an additional 0.5–2 years.

Financial Aspects of R&D

• Historical Cost Increase:

  • 1970s: $140 million

  • 1980s: $320 million

  • Late 1990s: $800 million

  • Early 2000s: $1.2 billion

  • Present estimates: $1.5 billion to $1.8 billion.

• Cost Breakdown: Increases accounted for:

  • Project failures

  • Out-of-pocket clinical costs

  • Discovery and pre-clinical costs

  • Clinical success and phase attrition rates

  • Cost of capital.

• Commercial Success Rate: Out of every 5,000–10,000 compounds entering R&D, only 1 is approved by the FDA. Only 2 out of 10 marketed drugs generate revenue that matches or exceeds R&D costs.

• Regulatory Environment: The last 20 years have seen co-evolution with a rigorous regulatory process, increasing demands for data on drug performance and addressing unique patient needs.

Increasing Complexity of Phase III Trials

• Reasons for complexity:

  • More sophisticated scientific tools

  • Increased regulatory processes

  • Demand for more comprehensive data by medical professionals.

• Cost and Resource Allocation:

  • 90% of new drug development costs are associated with Phase III trials.

  • Clinical staff increased by 67% from 1999 to 2005.

  • Average length of clinical trials increased by 70%.

  • Procedures per trial increased by 57%, and the number of case report form pages per protocol saw a 227% rise between 2000 and 2011.

• Advancements in Research: Pharmaceutical researchers are making progress, especially in cancer therapies that minimize damage to healthy tissue, personalized medicine, and orphan drugs. Diagnostic tools (e.g., PET scans, fMRI) now help researchers understand biological systems at the molecular level.

Historical Context of Drug Regulations

• Lack of Early Standards (Pre-19th Century): Prior to the 19th century, drug regulation was minimal, leading to ineffective and sometimes hazardous remedies.

• Formation of Standards:

  • Early pharmacy standards were established via formularies.

  • U.S. Pharmacopoeia (USP) was published in 1820, becoming the first comprehensive drug standard.

  • Over time, the American Pharmaceutical Association (APhA) established the National Formulary (NF), which merged with USP in 1975 to form USP-NF, verifying drug purity and ingredients.

FDA's Role in Drug Regulation

• Establishment: The FDA began regulating drugs more rigorously by the early 1900s, laying the groundwork via acts such as:

  • Biologics Control Act (1902)

  • Pure Food and Drug Act (1906)

  • Sherley Amendment (1912)

  • Food, Drug, and Cosmetic Act (1938)

• Mission of FDA: Ensure the availability of safe, effective drugs, keeping unsafe or ineffective drugs off the market and improving public health.

• Approval Process:

  1. Preclinical Investigation: Laboratory and animal testing to predict drug effects on humans.

  2. Clinical Investigation: Testing in humans across three phases.

  3. NDA Review: Review of New Drug Applications by the FDA (average time = 17-24 months).

  4. Post-Marketing Surveillance: Monitoring for adverse effects in larger populations after FDA approval.

• Boxed Warnings & Drug Recall: FDA issues warnings for drugs with serious risks and can mandate withdrawals from the market.

Changes and Improvements in Drug Approval Process

• Streamlining Efforts: 1992 saw the introduction of user fees to expedite drug reviews, resulting in a significant increase in drug approvals.

• Regulatory Innovation: The FDA Modernization Act allowed for the expansion of drug reviews and expedited processes for critical therapies.

• Role of Organizational Oversight: Other organizations (e.g., OIG, FTC, DEA) contribute to drug regulation by investigating infractions and preventing misleading marketing claims.

Impact of Pharmaceutical R&D on U.S. Innovation

• Investment Trends: Increased investment from pharmaceutical companies in drug development.

  • The industry spent $1.3 billion in 1997, escalating to $48.5 billion in 2012.

• Public vs. Private Funding:

  • Pharmaceutical firms invest significantly more in R&D than public entities like NIH.

  • NIH vs. Private Funding: In 2012, PhRMA member companies spent $48.5 billion, whereas NIH spent $30.9 billion.

• Benefits of Government Partnerships: The Bayh-Dole Act and related legislation fostered partnerships that accelerate technology commercialization, significantly enhancing U.S. pharmaceutical advancements.

Evolving Opportunities in Drug Development

• Modern Techniques: Advances in genomics, biotechnology, and molecular biology are redefining drug development processes.

• Market Needs: Anticipated growth in drug targets thanks to human genome mapping could lead to significant pharmaceutical breakthroughs in the future.