Biotech and medtech startups must understand regulatory affairs in order to succeed.
Regulatory affairs is the process that oversees how drugs, biologics, medical devices, and food are developed, tested, manufactured, and marketed in order to make sure they are safe and effective for human use. The standards for safety and efficacy are set by government policies, or regulations. Since companies must comply with these regulations in order to sell their products, the topic of regulatory affairs is highly relevant even to early stage startups in the biotech and medical device spaces.
The regulatory body that oversees all biomedical products is the Food and Drug Administration (FDA). The US Government has monitored food products in order to protect consumers since 1848, and the modern FDA evolved to take on this responsibility in 1930. The policy of requiring that a new drug be shown to be safe before it is marketed didn’t come into existence until 1938, as part of The Federal Food, Drug and Cosmetic Act of 1938. In 1972 responsibility for biologics was given to the FDA, and in 1976 new laws regulating medical devices were instituted. The FDA is the United States’ oldest consumer protection organization.
Within the larger topic of regulatory affairs there are a number of sub-topics that are relevant to startups:
Quality assurance is the practice of setting up policies and procedures to prevent issues with a finished product. These are implemented before the product is manufactured. Quality control, on the other hand, happens after the product is manufactured. Quality control is the practice of detecting deviations and defects in a product.
For an early-stage startup that is still conducting primarily research and development, a full-blown quality management system is probably not called for. However, part of quality management is documentation, and that is certainly needed in any setting that involves experimentation.
For drugs and biologics, there is an internationally recognized system for quality management systems, the ICH Q10. It describes the parts of a quality management system as the following:
For medical devices, the requirements for quality are different but also substantial:
The biggest factors in the success of quality control and quality assurance come down to documentation, implementation, reporting, audits, inspections, and learning. These factors, whether working with biologics, drugs, or devices, ensure that problems are prevented or caught early, and fixed.
The FDA requires that companies who want to test their drug candidates on people apply to do this via what is known as an investigational new drug application, or IND. An IND includes preliminary data in the form of animal toxicology and pharmacology studies, manufacturing information, and clinical protocols/investigator information. The full requirements for an IND are included in Title 21, Code of Federal Regulations, Part 312.
The animal studies supporting an IND must be conducted under good laboratory practices, or GLP. This is a set of regulations described in 21 CFR Part 58 that are designed to ensure the quality, reproducibility, and integrity of products that are in development. GLP studies are often outside the scope of an early stage research and development lab, so many biotech startups outsource these to contract research organizations.
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Because new drugs are well, new, the regulations do not spell out exactly what companies must do in order to meet the regulations. Therefore, many questions arise in the process of preparing to submit an IND, and the FDA does its best to answer those questions in the form of guidance documents.
Biologics are treated in a similar manner to drugs by the FDA, though with distinct differences. They are regulated by the Center for Biologics Evaluation and Research (CBER), whereas drugs are regulated by the Center for Drug Evaluation and Research (CDER). Biologics must also go through the IND process, but the final stage before a biological product can be put on the market is called a Biologics License Application (BLA), whereas a drug goes through a New Drug Application (NDA).
510K is the shorthand term for the pre-market notification, a requirement that medical device manufacturers must notify the FDA at least 90 days before they market a new device. This is stipulated in section 510K of the Food, Drug and Cosmetic Act. The FDA--specifically the Center for Devices and Radiological Health (CDRH)--then determines if the device is similar enough to another device they have already approved within one of the three device categories. If the device is determined to be in Class I or Class II, the 510K submission will be sufficient. However, Class III devices require another regulatory approval, the PMA.
The process for a 510K is to demonstrate to the CDRH that a device is sufficiently similar to another, already approved device. This requires submitting information from a design controls process as well as design validation.
Pre-Market Approval, or PMA, is required for devices that are implantable or that sustain life--devices in other words, which are classified as Class III. The requirements for a PMA are more in-depth than for a 510K, requiring clinical trials that demonstrate safety and efficacy for the patient.
A PMA must include both non-clinical laboratory studies with data that was collected under GLP conditions, plus clinical investigational studies. The CDRH then evaluated the application and determines whether or not to file it.
Startup founders usually do not have regulatory experience and are focused solely on perfecting their technology from the standpoint of whether or not it works. However, regulatory affairs is an essential component of moving a biologic, drug, or medical device to market, and it pays for startups to understand the potential pathways before them early on. The route of regulatory approval that a startup chooses to take can determine the types of testing they need to complete, the contract research organizations they choose to work with, and the funding they need to raise in order to succeed.
Therefore, startups can significantly improve their chances of success by taking a good look at the potential regulatory pathways they may want to take, and by setting aside part of their budget for some quality regulatory advice.
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