Introduction

Once an invention has been patented, the next step to commercialization is to either license the invention or find a partner to commercialize the invention. The inventor can create a startup company or an established commercial entity can negotiate with INVO for a proprietary license to commercialize the invention. INVO also provides assistance to prepare startups to market their assets. Alternately, INVO and the inventor can decide to form a partnership with a pharmaceutical company to develop and commercialize the invention.

This section of The Guide provides links to the appropriate INVO web sites for discussions of licensing, partnering and marketing assistance. The section also provides contacts for potential NU proprietary and other funding opportunities. Further, it contains a list of scientific steps that could lead to the creation of an IND. Each scientific step contains a description of the activity and the fee-for-service NU Core Facilities that can provide assistance in completing the scientific step.

How to create a startup company
How to license my invention
Potential Funding

 

 

How to manufacture my lead compound

Research objective: It is critically important to utilize the same drug substance and drug product in the IND enabling animal pharmacology and toxicology studies that will be administered to human subjects in the Phase I trial.  Therefore, the lead compound must be manufactured under Chemistry/Manufacturing/Control (CMC) regulations.  The CMC information must establish that any clinical trial materials will be manufactured and supplied under an established set of quality standards.  These exacting procedures and documentation of quality assurance should be carried out at a certified facility.  Therefore, it is highly recommended that a Contract Manufacturing Organization (CMO) be identified and used for manufacturing of the lead compound that will be taken into IND enabling pre-clinical trials.  In searching for a CMO, one should insure that manufacturing will be done under CMC regulations, the organization has appropriate experience in manufacturing the dosage form selected, and it has a positive experience in working with FDA and has passed all recent FDA inspections.  Further, insure that the regulatory group at the CMO can provide the CMC section to your IND.

Project Team:

Funding: See “How to create a funding plan”

Development and Regulatory Plans

Research objective: The Development Plan and the Regulatory Plan are linked in that FDA Regulations will determine the components of the Development Plan.  FDA will generally require the same pre-clinical information from sponsors developing drugs in the same therapeutic category, mechanism of action, chemical classification, route of delivery etc.   Therefore, when developing a new drug, the innovator should look for drugs with similar characteristics that have been approved by FDA and attempt to determine what the requirements were for approval , i.e., what studies were included in the approved INDs.  This may require reviewing development documents from a number of compounds that have the same characteristics as your compound.  See “IND Regulatory Development Plan Flow Chart” for recommendations for specific classes of drugs.  

Project Team

Funding: See “How to create a funding plan”

 

IND Development/Regulatory Plan

A.  IND Application Contents 

B.  General Overview of the development of an IND

FDA likes repetition so one needs to find approved, similar drugs and what they have done to gain approval- try to recreate their IND(s).  Identify your indication and look for appropriate FDA Guidance Documents.

Guidance documents represent the Agency’s current thinking on a particular subject. They do not create or confer any rights for or on any person and do not operate to bind FDA or the public. An alternative approach may be used if such approach satisfies the requirements of the applicable statute, regulations, or both. For information on a specific guidance document, search Guidance Documents 

FDA also publishes reviewers comments sections of approved NDAs and these provide valuable information about what other sponsors were required to submit for approval.  These are referred to Summary Basis of Approval.  

C.  General Flow Charts for the development of an IND

  1. If FDA has approved a drug in your indication in the same chemical class (small molecule, antibody etc) and route of administration
  • List all the studies reported In the Package Insert of the latest approved drug
  • Obtain the Summary Basis of Approval (SBA) for the latest approved drug                                                                                                                         Example: Search for SBA for Sutent

https://www.accessdata.fda.gov/scripts/cder/daf/

  • click on Sutent from the alphabetical list;
  • Go to NDA 021938
  • Go to Approval Dates and History, Letters, Labels, Reviews for NDA 021938
  • Under Original Approvals or Tentative Approvals go to Reviews

Additionally

  • Search for the Phase I-III protocols for approved drugs in clinicaltrials.gov
  • Search PubMed for all pre-clinical trials
  • Identify drugs under development for the indication and search PubMed for all pre-clinical trials and clintrials.gov for clinical trials

Match all pre-clinical and Phase I trials that you find with the appropriate categories in the  IND Expanded Contents.pdf

                 2.  FDA has approved a drug in your indication but not the same chemical class (small molecule, antibody etc) and/or route of administration

  • List all the studies reported In the Package Insert of the latest approved drug
  • Obtain the Summary Basis of Approval (SBA) for the latest approved drug
  • Identify additional drugs with your chemical class and/or route of administration and compare to above to identify additional required studies

https://www.accessdata.fda.gov/scripts/cder/daf/

Example: See Sutent example above

              3.  FDA has not approved a drug in your indication

               Look for approved drugs 

  • in similar indication
  • in similar chemical class
  • with similar MOA
  • with similar route of administration
  • Select model drugs from above
    • Review Package Inserts
    • Review Summary Basis for Approvals (SBA’s)

https://www.accessdata.fda.gov/scripts/cder/daf/

  • Look for Phase I trials on clinicaltrials.com
  • Search PubMed for pre-clinical trials of selected drugs
  • Identify other drugs under development for the same indication and review pre-clinical and Phase I clinical trials

 

 

How to create an FDA Target Product Profile

Research Objective: The objective is to identify unmet medical needs for your chosen indication and how your innovation will satisfy those need(s).  Unmet medical needs generally fall into the following categories: a drug for a new indication; increased efficacy and/or safety and/or convenience; improvement on patient reported outcomes; or more convenient and/or safer and/or effective route of administration

The requested wording column of the Product Profile contains claims the sponsor intends to make about the drug and is heavily dependent on the Commercial Target Product Profile. Once the claims have been listed, the scientific studies that support these claims are listed. These studies are identical to those described in the Development/Regulatory Plan. The Target Product Profile is submitted to the FDA in advance of each formal meeting. The FDA will provide comments regarding the adequacy of the planned studies and the data to support each claim. The FDA is not bound by the comments regarding an FDA Target Product Profile, but it does recommend development of such a document by the sponsor to focus future meeting discussions and document prior discussions.

The FDA Guidance Document for a TPP:  Download Here.

Project Team:  
Entrepreneur-in-Residence
INVO
NUCATS

Funding: See “How to create a funding plan”

TPP Example

  Scientific Trials Projected outcome Package Insert Wording
Therapeutic Area      
Indications and Usage      
Special Population(s)      
Dosage Form and Strengths      
Dosage and Administration      
Clinical Pharmacology      
Proposed Clinical Program      
Expected  Efficacy      
     General population      
     Special populations      
Nonclinical toxicology Program      
Contraindications      
Drug Interactions      
Adverse Reactions      
Storage and Handling      
Warnings and Precautions      
Overdose      
Potential for abuse      

 

How to request a Pre-IND Meeting

Research objective: A Pre-IND meeting is offered and encouraged by FDA.   Initial FDA reactions and comments are critical at this time, prior to spending time and money on the most expensive portions of the clinical development plan.  During these meetings, the FDA Target Product Profile, GLP preclinical animal studies (pharmacology and toxicology), CMC issues, and the design of the Phase I protocol can be discussed. https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM590547.pdf

Note:  If your Sponsor is Northwestern University or you have not designated a Sponsor, you will need to gain approval from the Office of Research (Ann Adams at a-adams@northwestern.edu) to contact FDA about a meeting. 

Project team: 

 

Funding: See “How to create a funding plan”

How to manufacture my lead compound

Research objective: It is critically important to utilize the same drug substance and drug product in the IND enabling animal pharmacology and toxicology studies and the Phase I trial in humans.  Therefore, the lead compound must be manufactured under Chemistry/Manufacturing/Control (CMC) regulations.  The CMC information must establish that any clinical trial materials will be manufactured and supplied under an established set of quality standards.  These exacting procedures and documentation of quality assurance should be carried out at a certified facility.  Therefore, it is highly recommended that a Contract Manufacturing Organization (CMO) be identified and used for manufacturing of the lead compound that will be taken into IND enabling pre-clinical trials.  In searching for a CMO, one should insure that manufacturing will be done under CMC regulations, that the organization has appropriate experience in manufacturing the dosage form selected; and that it has a successful track record of working with the FDA and has passed all recent FDA inspections.  Further, insure that the regulatory group at the CMO can provide the CMC section to your IND.

Project Team:

 

Funding: See “How do I create a funding plan”

Pre-clinical Pharmacology and Toxicology

Pre-Clinical Development

Good Laboratory Practice (GLP) is a quality system concerned with the organizational process and the conditions under which non-clinical health and environmental safety studies are planned, performed, monitored, recorded, archived and reported.    

FDA Guidance 

All animal pharmacology studies required to be included in the IND must be conduct in laboratories that are GLP certified.  Northwestern University does not maintain any GLP certified laboratories so investigators must go to the University of Illinois at Chicago pre-clinical pharmacology and toxicology GLP laboratories through the Chicago Biomedical Consortium or CROs.

Animal efficacy models can be determined by a review of the literature and by a review of drugs already approved for the indication by accessing their Summary Basis for Approval 

FDA Guidance Documents

The components of the pre-clinical pharmacology development are:

Primary Pharmacodynamics

  • Research objective: Describe the in vivo and in vitro pharmacological effects and the mechanism(s) of action of the drug related to the desired therapeutic target.  Selection of appropriate animal models, that represent the human disease condition, is critical.  Review the Summary Basis for Approval of licensed drugs and review the most recent pre-clinical literature to determine the most appropriate animal models.
  • Project team:
    • UIC Pre-clinical GLP Toxicology Lab (CBC)  University of Illinois at Chicago pre-clinical pharmacology and toxicology GLP laboratories through the Chicago Biomedical Consortium
    • CROs.
  • Funding – see “How to create a funding plan”

Secondary Pharmacodynamics

  • Research objective: Describe the in vivo and in vitro pharmacological effects and the mechanism(s) of action of the drug not related to the desired therapeutic target.  These studies are expected to provide data to calculate a projected safety margin, implications for clinical safety monitoring and mitigation strategies. 
  • Project team:
    • UIC Pre-clinical GLP Toxicology Lab (CBC) University of Illinois at Chicago pre-clinical pharmacology and toxicology GLP laboratories through the Chicago Biomedical Consortium
    • CROs
  • Funding – see “How do I create a funding plan”

Pharmacokinetics

  • Research objective: Describe the absorption, distribution, metabolism and excretion of the drug using appropriate in vivo and in vitro models
  • Project team:
    • UIC Pre-clinical GLP Toxicology Lab (CBC)
    • University of Illinois at Chicago pre-clinical pharmacology and toxicology GLP laboratories through the Chicago Biomedical Consortium
    • CROs
  • Funding – see “How do I create a funding plan”

Safety pharmacology

  • Research objective: Describe the off target pharmacological effects of the drug on the following systems:  neurological, cardiovascular, pulmonary, renal, gastrointestinal, other systems as appropriate and abuse liability.  These studies are expected to provide data to calculate a projected safety margin, implications for clinical safety monitoring and mitigation strategies. 
  • Project team:
    • UIC Pre-clinical GLP Toxicology Lab (CBC)
    • University of Illinois at Chicago pre-clinical pharmacology and toxicology GLP laboratories through the Chicago Biomedical Consortium  
    • CROs
  • Funding – see “How do I create a funding plan”
How to complete IND enabling toxicology studies

Pre-Clinical Toxicology

All pre-clinical toxicology studies to be included in the IND must be performed in GLP-compliant laboratories.

FDA Guidance documents:

 

Research objective: Describe the toxicological effects of the drug.  Depending on the nature of the drug and the phase of the investigation, the description is expected to include:  the results of acute, subacute, and chronic toxicity tests; the results of tests of the drug’s effects on reproduction and the developing fetus; any special toxicity test related to the drug’s particular mode of administration or conditions of use (e.g., inhalation, dermal, or ocular toxicology); and any in vitro studies intended to evaluate drug toxicity.  Genetic toxicology, carcinogenicity, reproductive and developmental toxicology and additional special toxicology studies may be required.  The pre-clinical toxicology studies must be conducted in a GLP laboratory.  This plan is generally discussed with FDA during the pre-IND meeting.

Project team:

Funding– See “How to create a funding plan”

How to complete the CMC section of the IND

Research objective: It is critically important to utilize the same drug substance and drug product in the IND-enabling animal pharmacology and toxicology studies and the Phase I trial in humans. Therefore, the final compound to be used in human trials and preclinical pharmacology and toxicology studies must be manufactured under Chemistry/Manufacturing/Control (CMC) regulations. The CMC information must establish that any clinical trial materials will be manufactured and supplied under an established set of quality standards. These exacting procedures and documentation of quality assurance should be performed by a certified facility. Therefore, it is highly recommended that a Contract Manufacturing Organization (CMO) be used for manufacturing the lead compound and the compound used in human trials. In searching for a CMO, one should insure that: manufacturing will be done under CMC regulations, that the organization has appropriate experience in manufacturing the dosage form selected, and it has a successful track record in working with the FDA and has passed all recent FDA inspections. Further, insure that the regulatory group at the CMO can provide the CMC section for your IND.

Project Team:

Funding: See “How to create a funding plan”

How to design the Phase I Trial

Research objective: Phase I studies are designed mainly to investigate the safety/tolerability (if possible, identify the Maximum Tolerated Dose), pharmacokinetics and pharmacodynamics of an investigational drug in humans. These studies are generally conducted in healthy human subjects but can be conducted in patients if the drug presents unreasonable risks for non-patients, i.e., cancer drugs. For more information, see the FDA’s Phase 1 Studies and Early Drug Development presentation.

It is also important to review previous Phase I protocol designs from drugs that have been approved in your indication.  You can do this by searching for the Summary Basis of Approval documents for approved drugs or search ClinicalTrials.gov for Phase I protocols.

Project team: The Feinberg School of Medicine has numerous areas of support for the design, conduct, evaluation and reporting of Phase I clinical trials. The Entrepreneur-in-Residence, INVO, Feinberg Department of Medicine and NUCATS also provide support in organizing the appropriate project team.

Funding: See “How to create a funding plan”

How to complete the Investigator’s Brochure

Research objective: The Investigator’s Brochure (IB) is a document meant to inform clinical investigators about the drug and provide a basis for its safe usage.  It should include:

  • Brief description of the drug substance and the formulation, including the structural formula, if known
  • Summary of the pharmacological and toxicological effects of the drug in animals and, to the extent known, in humans
  • Summary of the pharmacokinetics and biological disposition of the drug in animals and, if known, in humans
  • Summary of information relating to safety and effectiveness in humans obtained from prior clinical studies
  • Description of possible risks and side effects to be anticipated on the basis of prior experience with the drug under investigation or with related drugs, and description of precautions or special monitoring to be done during the investigational use of the drug.  Adverse Events (AEs) described in the IB help determine whether an AE that occurs during a clinical trial is “expected” and, if so, how it will be reported to FDA. 

Guidance for Industry: E6 Good Clinical Practice: Consolidated Guidance 

Project team:                                                                                  

  • Entrepreneur-in-Residence                                                   
  • INVO   
  • NUCATS                                              
  • Regulatory Consultants, medical writers.  

 

Funding: See “How to create a funding plan”

How to compile the IND