Objectives Roles & Responsibilities of the Sponsor

1 Objectives Roles & Funding for clinical research comes from the federal government or the private sector. In addition to providing financial resources, some funding groups also provide the Responsibilities of the investigational agent. They are referred to as the Sponsor and are responsible for the initiation and management of a Sponsor new agent under the FDA's Investigation New Drug (IND). Application (Title 21 Part 312). This module will review the role of the IND Sponsor . At the conclusion of this module, you will be able to: Sponsored by Define what is meant by a Sponsor . Center for Cancer Research List the 4 broad areas of Sponsor Responsibilities National Cancer Institute Describe the purpose of FDA Form 1571. List 5 items that are submitted with an initial IND application Who is a Sponsor ?

2 Definition of Sponsor . The Sponsor can be: An individual, company, institution or organization which takes responsibility for Individual the initiation, management, and / or Pharmaceutical company financing of a clinical trial. (ICH). Government agency A person who takes responsibility for and Academic institution initiates a clinical investigation. The Private organization Sponsor does not actually conduct the Other organization investigation unless the Sponsor is a Sponsor -investigator. (CFR)..Definition of Sponsor Drug/Biologic Development Discovering and developing safe and In general, the Sponsor is the effective drugs is more promising as our commercial manufacturer that has knowledge of disease increases Human genome sequencing developed a product in which it holds Increase understanding of disease at the molecular level Advances in genomics and proteomics the principal financial interest Advances in informatics ( computational power).

3 Holds the IND (Investigational New Researchers work to: validate the targets Drug) application and files the NDA / discover the right molecule (potential drug/biologic) to interact BLA (New Drug Application/Biological with the target chosen test new compound in the lab and clinic for safety and efficacy Licensing Application) gain approval and get the new drug into patients 1. What is a Drug? What is a Biological Articles intended for use in the diagnosis, Product? cure, mitigation, treatment, or prevention of virus, therapeutic serum, toxin, disease antitoxin, vaccine, blood, blood Articles (other than food) intended to affect component or derivative, allergenic the structure or any function of the body of product, or analogous product.

4 Man or other animals applicable to the prevention, Articles recognized in the official treatment, or cure of a disease or Pharmacopeia, National Formulary, condition of human beings.. Hom opathic Pharmacop ia of the Section 351 of the Public Health Service (PHS) Act or any supplement to any of them Food Drug and Cosmetic Act, sec. 201(g)(1). Public and Private Finding a Drug Collaborations Roles are interdependent to translate basic research into interventions Biopharmaceutical companies are primary source of R&D Basic Science Drug Discovery Pre- clinical NIH: Provides leadership and funding support to universities, medical schools, research centers and other non-profit institutions Stimulates basic research and early stage development Disclaimer.

5 Drug development refers to both drug and biologic agents Basic Science Basic Science Understand the disease to be treated Choose a molecule to target Unravel the underlying cause of the Typically a single molecule ( , gene or condition protein) which is involved in a particular Understand how the genes are altered disease Target needs to be one that can potentially How that affects the proteins interact with and be affected by a How those proteins interact with each other drug/biologic How those affected cells change the specific tissue they are in Test the target and confirm its role in the How the disease affects the entire patient disease 2. Drug Discovery Sources of Drugs Find the lead compound Plant A promising molecule that could become a Animal drug by acting on the target to alter a disease Mineral Complicated, time-consuming and costly process microbiology 5-20 years Semi-synthetic/Synthetic For every 5,000- 10,000 compounds that enter the research and development (R&D).

6 Recombinant DNA. pipeline, ONE receives approval Estimated to be $800 million to $1 billion Includes the cost of the thousands of failures Sponsors Responsibilities : Naming of Drugs 4 Broad Areas Chemical name Preclinical / non- clinical Scientific name based on the compound's chemical structure Manufacturing Almost never used to identify the drug in a clinical or marketing situation clinical Generic name Post-approval Granted by the International Union of Pure and Applied Chemistry (IUPAC) May use a CRO. Commonly used to identify a drug during its clinical lifetime Appears with the company's trade name on drug labels, (Contract Research advertisements, and other information Organization). Brand name (Trademark). Created by the company that patents the drug Identifies the drug during the years that the company has exclusive rights to make, sell, and use Preclinical Goals Preclinical Studies Find a product Purposes of PRECLINICAL studies are Pharmacological activity to: Reasonably safe Determine the optimal formulation of Conduct pre- clinical studies the product animal pharmacology, toxicology, and Select an initial safe starting dose for carcinogenicity human trials Identify potential target organs of toxicity Recommend appropriate types of clinical monitoring 3.

7 Manufacturing Responsibilities clinical Responsibilities Obtain manufacturing information: Submit & maintain Investigational Characterization of the product New Drug Application (IND) with FDA. Preliminary stability studies Conducting Phase 1, 2, 3 clinical Trials Submit New Drug Application (NDA). to FDA for drugs Submit Biological License Application (BLA) to FDA for biologics Investigational New Drug IND Sections Application (IND). FDA Form 1571 clinical protocols CMC (chemistry Sponsor submits to the FDA Table of contents manufacturing and Descriptive notification of intention to Intro statement control) data General Pharmacology &. conduct clinical studies with an toxicity data investigative plan investigational drug or biologic Previous human Investigator's experience Allows for transportation of product Brochure (IB) Additional information (non-approved drug) across state lines FDA From 1571 FDA From 1571.

8 Page 1 page 2. Submitted with the The FDA has 30-days initial IND submission to review the protocol. and each subsequent FDA will not contact submission to the IND Sponsor if all is OK to proceed, only if a hold is needed. 4. Conducting clinical Trials Investigator Selection Assess qualification of PI and Sub- Selecting qualified investigators and investigators monitors Qualified by training & experience Ability to supervise administration of product Informing Investigators Investigational Product shipped to them Assess site (physical plant capabilities). Reviewing ongoing studies Examples: Record keeping and record retention Is there adequate pharmacy space for drug storage? Ensuring the return or disposition of Are there SOPs for freezer alarms?

9 Unused investigational drug supplies Review Ongoing Informing Investigators Investigations . All investigators must be fully informed of Investigator compliance - is conducting the investigational product research findings study in compliance, with the protocol, with the Federal Regulations, and with GCP? Investigator Brochure Is there unreasonable & significant risk to Reprints / published articles the study subjects? Reports / letters to investigators Monitor clinical trial conduct IND Safety Reports Medical Monitor - individual responsible for the development and oversight of all clinical trials in a portfolio of study agents Review of Ongoing Potential Actions for Non- Investigations compliance Review and evaluate Secure compliance Safety and effectiveness data OR.

10 Provide FDA Stop product shipments to the Annual reports investigator Summary of accrual statistics, safety, toxicity Terminate the investigator's and efficacy data, as well as ongoing non- participation in the study clinical and manufacturing progress Secure return or disposal of investigational product 5. Actions for Unreasonable and Significant Risk Monitoring of clinical Trials . Monitoring function may be Stop clinical trial: permanent vs. temporary performed by: Notify the FDA, all IRBs, all investigators of The Sponsor the risk(s) Contract staff Assure the disposition of all outstanding product or resume trial with amendment Provide FDA full report on actions taken Monitoring of clinical Monitoring of clinical Trials Trials Sponsor may designate 1 or more Sponsor must have written monitoring appropriately trained and qualified procedures (SOPs) to assure the quality of individuals from various backgrounds to the study and ensure that each person monitor the trials involved carries out their duties MD's Nurses SOPs should include.