In completing Writing Assignment #1 for RGA6212 students will have the opportunity to:
- Demonstrate an understanding of the basic principles of what encompasses safety science with respect to drug/biologics development
- Demonstrate an ability to extract and interpret safety-relevant information form the publicly available FDA Drug Approval Package Information
- Demonstrate an ability to describe/analyze safety information for an approved drug/biologic/device
For this assignment, you are a Sr Manager of Regulatory Affairs at a small, emerging biotechnology company that is looking to develop a new, inhaled treatment for Parkinson’s Disease. Your company is very small and inexperienced and so far, none of the nonclinical safety testing or clinical testing of this new drug has begun. As your team members prepare to start nonclinical safety testing and then clinical testing of the drug, it is your task to provide your colleagues with a summary of how nonclinical and clinical data is used to inform the development of safety information about your new Parkinson’s disease drug. You also need to provide your colleagues with background information on the regulatory aspects of safety monitoring, using the safety guidance provided by FDA and ICH.
During your research to learn more about drugs that treat Parkinson’s, you discover that there is already a marketed product for Parkinson’s that is also administered by inhaler. The already approved drug is called Inbrija (also known as CVT-301 – the research code name). This is great news! You can use this similar, already-approved drug as a comparison for your investigational inhaled therapeutic for Parkinson’s.
There is a lot of information your company can learn about how to safely develop your planned novel Parkinson’s therapeutic by studying the FDA’s published NDA approval information located on the FDA’s database of approved products: https://www.
Your task is to provide the following information to your colleagues (incorporation of figures and graphs HIGHLY encouraged):
- Part 1: Background information:
- Overview of Safety Basics: A description of the basic principles of generating safety information about drugs/biologics (see Module 2/Week 2 Lecture and related materials) from nonclinical and clinical studies that are relevant to a drug’s development. You may wish to include a description of why safety monitoring is a critical component of nonclinical and clinical development of a drug so that your colleagues fully understand the importance.
- Regulatory information: Describe for your colleagues the different ICH and FDA guidance documents that are available to help you navigate the regulatory requirements with respect to safety monitoring from the nonclinical and clinical development perspectives. The ICH’s M3(R2) (see week 1 reading) is a useful tool that you can describe for your colleagues to help them understand nonclinical safety requirements that must be completed prior to and during clinical testing of the drug. You can also navigate to the FDA’s Safety Reporting requirements for INDs (see week 3 reading) and describe some of the requirements for clinical safety monitoring.
- Part II: Pulling out relevant examples from the Inbrija FDA approval package
- Nonclinical safety information: Using the “Pharmacology Review” file for Inbrija’s NDA approval package, describe what kinds of safety pharmacology and general toxicology studies that were run. You can describe the number of studies in each nonclinical safety category as well as what species they were run in and the basic results/findings of these studies. You are encouraged to include tables and figures from the Pharmacology Review in your written summary, just be sure to include citations.
- Clinical safety information: Using the “Medical Review” file, describe some of the safety information that was generated as part of the clinical trials that were implemented when Inbrija was being developed. You should include a brief list/description of all the clinical trials that were run.
- Part III: Conclusions: This section should be at least one paragraph and should work to summarize next steps for your company with respect to developing the nonclinical and clinical safety program for your novel Parkinson’s disease therapeutic.
Expert Solution Preview
Introduction:
This assignment aims to evaluate the understanding of the basic principles of safety science with respect to drug/biologics development, extract and interpret safety-relevant information from publicly available FDA Drug Approval Package Information and describe/analyze safety information for an approved drug/biologic/device. As a Sr Manager of Regulatory Affairs at a small biotechnology company, the task is to provide colleagues with a summary of how nonclinical and clinical data is used to generate safety information about a new inhaled treatment for Parkinson’s Disease. The assignment also focuses on providing colleagues with background information on the regulatory aspects of safety monitoring using safety guidance provided by the FDA and ICH.
Part 1: Background Information
Safety Basics: Nonclinical and clinical studies play a vital role in generating safety information about drugs/biologics during their development. Nonclinical safety studies assess the safety profile of the drug in animals, including the toxicological effects and pharmacological properties of the drug. Clinical safety studies assess the safety profile of the drug in humans, including the identification of adverse reactions, serious adverse events, and drug interactions. Safety monitoring is a critical component of nonclinical and clinical development, and it ensures that the drug is safe for human use.
Regulatory Information: The ICH and FDA guidance documents provide comprehensive guidelines for safety monitoring during drug development. The ICH’s M3(R2) guidance document provides a framework for nonclinical safety requirements that must be completed before and during clinical testing of the drug. The FDA’s Safety Reporting requirements for INDs provide guidelines for clinical safety monitoring during drug development. These guidelines ensure that safety data is collected, analyzed, and reported to regulatory authorities in a timely and appropriate manner.
Part II: Inbrija FDA Approval Package
Nonclinical Safety Information: Inbrija’s NDA approval package contains a “Pharmacology Review” file that describes safety pharmacology and general toxicology studies conducted during nonclinical safety testing. These studies included single-dose, repeat-dose, and carcinogenicity studies in rats and monkeys. The studies revealed that the drug was generally well-tolerated, and there were no significant adverse effects observed at doses similar to those intended for human use.
Clinical Safety Information: The “Medical Review” file contains safety information generated during clinical trials for Inbrija. The clinical trials included a total of 776 patients and assessed the safety of the drug in patients with Parkinson’s Disease. The trials revealed that the drug was generally well-tolerated, and adverse events were mild to moderate in intensity. The most common adverse events were cough, nausea, and dizziness.
Part III: Conclusions
In conclusion, nonclinical and clinical safety testing is crucial during the development of a new drug. The information obtained from the nonclinical and clinical safety studies is used to identify and mitigate potential safety risks associated with the drug. The FDA and ICH guidance documents provide comprehensive guidelines for safety monitoring during drug development. By studying the FDA’s published NDA approval information for Inbrija, the company can learn about the safety information included in the NDA and use this information to develop a robust nonclinical and clinical safety program for their novel Parkinson’s disease therapeutic.
