The Economics of a Sound Regulatory Strategy

The initial steps for medtech product development can be exciting and typically include designing initial concepts, branding logos, and tackling market assessments. Regulatory requirements, however, can quickly dampen the excitement. And while it might be tempting to put off these requirements, a regulatory assessment should be performed fairly early in a project. This assessment will provide direction related to device classification, submission pathway, testing strategies, and quality system mandates. Subsequently, a project plan can be developed to account for the resources, milestones, and activities that must be completed before commercialization.

The regulatory assessment and project plan can provide clarity about cost and timing, as well as interactions between activities (i.e., parallel versus codependent actions). The sections review various topics a company should consider in preparing a project plan and market release schedule. This column addresses the FDA classifications and requirements involved in medtech product development; other regions outside the United States may have additional mandates.

Startup companies must have an end goal in mind before embarking on their product development journey. These firms should decide if they want to operate independently as a medical device manufacturer, partner with a larger company, or sell their intellectual property. This decision will impact everything from quality system requirements to the necessary amount of testing and validation. The key question is “who will be the legal manufacturer of the medical device and what company name will be on the labeling?”

The answer to that question will dictate whether a quality management system (QMS) should be implemented. Obviously, legal manufacturers without a QMS must implement one. But companies that provide product design and either partner with a legal manufacturer or sell their product rights do not need to implement a full quality system. Still, consideration should be given to implementing portions of the QMS related to design control, document control, supplier control, and risk management. Such documentation will likely make the product more appealing during the due diligence process.

Clinical study requirements can be tricky to decipher. If the medical device under development is new and does not have a Class I exempt pathway or Class II pathway with a 510(k), clinical data will most likely be required. This will significantly increase time to market and product cost. An initial determination must be made about approving the study through the FDA’s Investigational Device Exemption (IDE) pathway or Investigational Review Board (IRB) channel (a non-significant risk trial). Regardless of the decision pathway, clinical studies can vary significantly depending on follow-up timing, requirements for radiographic images, blood testing, etc. All clinical studies used to support regulatory submissions must also be conducted under Good Clinical Practices to ensure proper site initiation, data monitoring, and final reporting. While short studies might be conducted for less than $1 million, it is difficult to match that cap for multi-year trials due to long-term follow-up requirements (implants, biologics, etc.), and the particular FDA regulatory pathway.

Devices with user interfaces (patient monitors, infusion pumps, etc.) and/or those used at home without direct access to health facilities or medical practitioners are subject to recent standards such as IEC 62366 and FDA guidance documents related to usability (human factors) testing. These studies will not be as extensive as a clinical trial conducted for an IDE approval, but their overall design will be different than a clinical study. Thus, additional time and cost will be required. Additional consideration should be given to post-market studies, especially those pertaining to marketing claims and reimbursement.

Besides clarifying a product’s clinical trial requirements, a regulatory assessment can help identify mechanical testing requirements based on existing FDA predicates (similar devices), product codes, and guidance documents. This testing must be performed on production-equivalent devices to ensure it is representative of what will eventually be distributed. Mechanical testing is typically outsourced and ranges from a few thousand dollars to $20,000-$30,000 per test. Animal studies (for safety or effectiveness purposes) hikes both costs and timelines. Animal studies typically take at least six months and can sometimes last one or two years depending on the follow-up time frame. These studies can cost anywhere from thousands to hundreds of thousands of dollars.

Biocompatibility has always been important for FDA submissions, but the agency’s 2016 guidance document and subsequent updates to the ISO 10993:2018 standard have resulted in additional testing and biocompatibility risk assessments by independent microbiologists/toxicologists. These assessments are typically a few thousand dollars, but can easily approach $100,000 depending on the kind of testing required.

Additional considerations for testing include electrical assays that should comply with IEC 60601 and relevant subparts. This kind of testing is extremely expensive, costing upwards of $60,000 or more, and must be conducted by a qualified test group.

Validation is a key component of any regulatory submission. Companies submitting an application to the FDA or finalizing a design control file must complete applicable cleaning, sterilization, reliability, packaging, shipping, and shelf life validation. Decisions about sterilization methods (steam, gamma, EO) and the packaging configuration (individually packaged, non-sterile trays, kits) can significantly impact the timing and cost associated with these development activities and validations. These validations cost at least a few thousand dollars but can reach $50,000 or more.

Any devices that have software or firmware components and/or transmit data must include software validations and also be assessed for cybersecurity. The time and cost associated with these validations are extremely variable and should be mapped out per project.

Manufacturing is typically considered a post-market cost, but all products must be assessed for manufacturability and generate prototypes before commercial production begins. Once the overall manufacturing process steps are determined, validations must be conducted to ensure equipment, cleaning, set up, and inspections are in place prior to product distribution. Manufacturing times and costs are extremely variable and should be mapped out per project. Companies now must also consider the unique device identification and labeling requirements, validations, and accounts required to control barcodes/traceability.

After collecting data, validating designs, performing other necessary validations, and initiating manufacturing, companies can circle back to the regulatory process. Only after all the information is available for a medical device can organizations submit their 510(k), De Novo, or Premarket Approval applications for FDA review. The company can prepare the submission itself or pay a consultant to prepare the submission. If a consultant is used, the cost varies significantly depending on the type of submission required, but the price tag is typically thousands of dollars. FY20 time frames and user fees associated with these submissions for standard and small business designation (SBD) are as follows:

• 510(k): $11,594 ($2,800 for SBD)
  • Target FDA review time is 90 days but actual review time is typically four to five months
• De Novo: $102,299 ($25,575 for SBD)
  • Target FDA review time is 150 days but actual review time varies. Companies should expect to wait at least eight months
• PMA: $340,995 ($85,249 for SBD)
  • Note: Small businesses with approved SBD and gross receipts or sales of $30 million or less are eligible to have the fee waived on their first PMA
  • Target FDA review time is 180 days, but actual review time is typically 12-18 months. The review time can vary greatly depending on whether a panel is required and the timing to schedule an on-site audit

Once a medical device’s classification is determined (Class I, Class II, or Class III) and the company is within 30 days of commercial distribution, an establishment registration user fee must be paid to FDA. This fee must be paid annually going forward, regardless of product sales. The FDA’s FY20 user fee is $5,236; there is no reduction in the establishment registration fee for small businesses.

Conclusion
Medtech firms should be careful in weighing the regulatory costs associated with getting devices to market. They should take into account considerations outlined in this column and prepare a project plan and schedule that makes allowances for all variables. These considerations pertain only to the U.S. market and FDA. Many of the testing mandates and validations will be applicable in other geographies, but every country has its own regulatory requirements, user fees and time frames to be considered. 

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Christine Scifert is co-founder of MRC-X LLC (previously Memphis Regulatory Consulting LLC), which offers medical device regulatory, quality and clinical services. She has been consulting for 10 years and has assisted both small and large medical device companies with strategy, regulatory submissions, quality systems, training, due diligence, and other activities. Prior to consulting, Scifert spent nine years at Medtronic Spinal and Biologics directing the regulatory department. Prior to Medtronic, she performed evaluations of injury mechanisms associated with automobile collisions, slip and falls, and sport/recreation accidents. Scifert earned a bachelor of science degree in physics from Hamline University and a master of science degree in biomedical engineering from the University of Iowa. She also completed a Master’s course in engineering management from Christian Brothers University.

Before joining MRC-X in 2014, Dawn Norman spent 15 years in the medical device industry working with venture capital-backed startups and larger companies. She focused on regulatory strategy and submissions, along with clinical study design and study execution, for products such as magnetic navigation devices for neurosurgical, neurovascular, and cardiac indications; high intensity ultrasound for cardiac ablation; recombinant proteins for bone fusion; orthopedic trauma; and imaging technologies. Norman earned a bachelor of arts degree in biological sciences and chemistry, and a master of science degree in biomedical sciences from Southern Illinois University at Edwardsville.