Product Development

There are some very important concepts to know when embarking on product development:  

1. To bring a product into the clinic it is advisable to not sacrifice quality for cost savings.  The FDA has rigid standards for how products are tested and manufactured; inadequate quality may end up costing more to repeat testing and/or manufacturing activities to meet the FDA standards.  To avoid this search FDA guidance documents and speak with a regulatory professional who can guide you in the optimal direction.

2. Early consultation with the FDA can often save you time and money.  The FDA offers programs that allow Sponsors to consult with the FDA on product development strategy, required nonclinical testing, manufacturing, and clinical trial design.  The OCR Regulatory team can assist with requesting and preparing for the following FDA meetings: 

   • IND: Pre-IND and INTERACT Meetings; see Formal Meetings Between the FDA and Sponsors  

   • IDE: FDA Q-submission process. The following FDA guidance can be used for Pre-IDE Meeting requests: Requests for Feedback and Meeting for Medical Device Submission: The Q-Submission Program 

3. Protect your Intellectual Property!  When speaking and/or engaging in fee-for-service activities with vendors, suppliers, testing facilities, or manufacturers make sure you request a Confidentiality Agreement and that an institutional legal representative negotiates appropriate agreements.  If using an outside manufacturer, please review Investigational Product Management for more information.    

4. Conducting manufacturing activities and nonclinical studies at Penn is feasible but requires registration with The Office of Clinical Research in accordance with SOP 100 and may require a Management Plan through the Research Integrity Office.  

A manufacturer is any group that is making, preparing, propagating, compounding, processing, packaging, repackaging, testing or labeling an investigational product (drug or device (including software)). These activities may be performed by one single entity or multiple.  Regardless of who is manufacturing the investigational products, the manufacturer is required to comply with good manufacturing practices (GMP).   

Quality in the product at the earliest phases of development is strongly recommended this means well-controlled processes, good documentation, and scalable operations for technology transfer at a later date.  Some considerations include the use of USP materials and developing a quality system with SOPs or written procedures.  The OCR has Manufacturing SOPs on Training, Corrective and Preventive Action, and Good Documentation Practices as well as other templates that manufacturers can use when developing their quality system.  Penn Medicine also has a document management system developed to support quality processes. EHRS may be able to assist with environmental controls such as temperature controls and some safety aspects of quality. When transitioning from animal studies to humans, the FDA will require that your product meet specific standards.  Designing quality into your product early will allow for a smoother transition from the bench to the clinic.  

For recommendations on manufacturing please reach out to OCR regulatory at any time via email PSOM-IND-IDE@pobox.upenn.edu

The goals of the nonclinical safety evaluations generally include a characterization of toxic effects with respect to target organs, dose dependence, relationship to exposure, and, when appropriate, potential reversibility. 

The information elucidated from the nonclinical studies is used to estimate an initial safe starting dose and dose range for the human trials and to identify parameters for clinical monitoring for potential adverse effects. The nonclinical safety studies should be adequate to characterize potential adverse effects that might occur under the conditions of the clinical trial to be supported. 

The types of nonclinical studies are typically: 

• Pharmacodynamics (what the drug does to the body) (PD),  

• Pharmacokinetics (what the body does to the drug) (PK),  

• Absorption, Distribution, Metabolism, and Excretion (ADME), and  

• Toxicology testing 

Medical devices that do not have a drug attached will not undergo these tests and may go directly to good laboratory practices (GLP) testing for the safety of the device and its components. Some medical devices will also undergo biocompatibility testing which helps to show whether a component of the device or all components are sustainable in a living model. 

Before performing Nonclinical Safety Studies (e.g., toxicology), review the OCR work instructions on IND Nonclinical Safety Studies.  

When performing nonclinical studies, it is strongly recommended that the product being tested is as close to the final clinical product as possible.  Any differences between the clinical and nonclinical products must be explained.  If the differences are too significant, the Health Authority may require that the nonclinical testing be repeated. 

For additional details on the requirements for nonclinical testing, refer to the ICH safety guidelines. For assistance in interpreting these requirements, please contact OCR Regulatory. 

If an IND is the regulatory pathway to bring your drug to the clinic you should be aware of the FDA Comprehensive Table of Contents Heading and Hierarchy to understand the FDA-required sections of an IND and review in detail the FDA Guidance for Industry M4Q: The CTD – Quality which provides additional information about what should be contained in the IND for manufacturing.  

To determine if an IDE is the correct regulatory pathway to bring your device to clinical you should review the FDA website How to Determine if Your Product is a Medical Device.  If medical device regulations apply please review the FDA IDE Application and contact OCR Regulatory at PSOM-IND-IDE@pobox.upenn.edu for assistance with Significant Risk or Non significant Risk evaluations of similar products. 

For recommendations on manufacturing please reach out to OCR regulatory at any time via email PSOM-IND-IDE@pobox.upenn.edu