Trends in FDA approval of biological devices by therapeutic area and major companies

An examination of 510(k) biological medical device applications cleared (650+) and premarket approvals (35+) by the US Food and Drug Administration between 2000 and July, 2018.

Medical device products and technologies are used in the diagnosis, prevention and treatment of diseases. The global medical device market is projected to reach $478 billion by 2020, growing at an approximate 4.4% CAGR over the next five years.

The Food and Drug Administration (FDA) regulates all medical devices marketed in the United States. The Center for Biologics Evaluation and Research (CBER) of the FDA regulates the medical devices involved in the collection, processing, testing, manufacture and administration of licensed products for sale and distribution.

CBER regulates medical devices related to licensed blood and cellular products by applying appropriate medical device laws and regulations. CBER reviews the marketing and investigational device submissions (premarket notification, premarket approval, and investigational device exemption) for medical devices associated with the blood collection and processing procedures as well as those associated with cellular therapies.

It is estimated that, bringing a device to market takes an average of 3 to 7 years.

Furthermore, CBER has developed specific expertise in blood, blood products and cellular therapies and the integral association of certain medical devices with biological products.

The product classes mainly include hematology, clinical chemistry, immunology, microbiology, human cell- and tissue-based products, and xenotransplantation. The agency implemented a number of new policies and programmatic changes over the past five years to improve its performance and to adapt its oversight to the global marketplace and to new technologies.

Recently, the regulatory agency implemented a number of new policies and programmatic changes over the past five years. The changes mainly brought improvement in its performance and allowed it to adapt to the global marketplace and to new technologies.

In order to find out about the number of medical devices cleared or approved by FDA in the last couple of decades, we used curated medical device databases (US-FDA and openFDA) available in the public domain for our analysis.

This research study reviews the biological device application approvals under 510(k) premarket notification, premarket approval, and humanitarian device exemptions (HDEs) categorized by product classes (medical specialty/therapeutic area), applicants (companies), and approval dates.

510(k) Premarket Notification

A 510(k) is a premarket submission made to FDA to demonstrate that the Class I and II devices to be marketed are at least as safe and effective and substantially equivalent, to a legally marketed device that is not subject to premarket approval.

Class I devices are considered low-risk, and many are exempt from the regulatory process.

Class II devices are considered medium-risk and require special controls for “labeling, guidance, tracking, design, performance standards, and post-market monitoring,” and most require 510(k) to demonstrate substantial equivalence to a legally marketed U.S. device.

The 669 device clearances we analyzed went through the FDA’s Premarket Notification (PMN) program, more commonly known as the 510(k). This process applies to nearly all Class II devices, and less than 10% of Class I devices. All devices (including traditional, special and abbreviated) were sorted based on the date they were cleared by FDA, not the date they were submitted.

On an average, the rate of 510(k) notifications was 35 biological devices per year, and the same clearance rate is expected to continue over the next 3 years period. Overall, the number of 510(k) submissions cleared in the U.S. fell slightly in 2013 (Figure 1). This represents the fewest number of devices cleared by the FDA since 2012, when roughly 35 devices were cleared each year.

Hematology area (blood and plasma products) contributed 84.3% of the total biological device notifications, followed by clinical chemistry (5.1%) and microbiology (4.9%), respectively (Table 1).

The global blood processing devices market growing at the rate of 9.6% CAGR and estimated to reach US$ 37 Billion by 2023, due to technological advancement and increase in surgical procedures.

According to World Health Organization (WHO), 91% of the blood collected in high-income countries, 72% of that in middle-income countries and 31% of that in low-income countries is processed for safe and effective blood component processing. The national health authorities ensure maximum safety and availability of blood components; and promotion of appropriate blood component therapy.

CBER regulates the collection of blood and blood components used for transfusion or for the manufacture of pharmaceuticals derived from blood and blood components. CBER works closely with other parts of the Public Health Service (PHS) to identify and respond to potential threats to blood safety, to develop safety and technical standards, to monitor blood supplies and to help industry promote an adequate supply of blood and blood products.

Out of the 170 companies reviewed for device clearances, about 12 manufacturers received at least 10 number of 510(k) clearances for their hematology products during this period. BioMerieux, Inc. has received all device clearances in the microbiology area. Top 6 companies, namely Haemonetics Corporation, Terumo Corporation, Immucor Inc., Fenwal, Inc., Mediware Systems, Inc., and Bio-Rad Laboratories received maximum number of PMNs during this period (Figure 2).

Premarket Approval

Premarket approval (PMA) is the FDA process of scientific and regulatory review to evaluate the safety and effectiveness of Class III medical devices. The PMA process is widely viewed as a rigorous evaluation of device safety and effectiveness.

Class III devices usually sustain or support life, are implanted, or present a significant risk of illness or injury. Most class III devices require PMA, which examines a variety of factors in weighing the probable health benefits from intended use of a device versus the probable risks.

A total of 38 premarket approvals for biological devices were granted to 10 companies during this period (Table 2). The major therapeutic applications such as immunology, microbiology and hematology contributed approximately 52.9%, 23.5%, and 11.7%, respectively (internal analysis, data not shown).

The global immunoprotein diagnostics market is estimated to reach US$ 17.9 Billion by 2023, expanding at a CAGR of 4.2% over the forecast period, driven by its advantages such as high accuracy and micro-level detection levels in chronic disorders.

It is clearly evident that, in order to capture major market share, major companies are manufacturing biological medical devices that perform immunohistochemistry and/or antibody assays. Recently, FDA claimed that the regulatory reforms had sped up the average time to decision for PMAs, the lowest since 2000.

Our analysis indicated that, major manufacturers such as Bio-Rad Laboratories Inc., OraSure Technologies, Inc., Chembio Diagnostic Systems, Inc., MedMira Laboratories, Inc., and Roche Diagnostics received more than 10% PMAs (Figure 3) during this period.

Humanitarian Device Exemption

Humanitarian device exemption is a marketing application for an humanitarian use device (HUD), a medical device intended to benefit patients in the treatment or diagnosis of a disease or condition that affects or is manifested in not more than 8,000 individuals in the United States per year.

It is interesting to note that, only two HDEs comprising a human cell- and tissue-based product and xenotransplantation by Miltenyi Biotec Inc., and Vericel Corporation have been approved during the period analyzed, respectively. Although the rate of HDE approval is considerably low due to the concerns regarding the potential infection of recipients and the possible subsequent transmission, the new FDA guidelines and requirements are intended to improve protection of the public health while minimizing regulatory burden.

Viren Konde is a Consulting Analyst at iHealthcareAnalyst, Inc, Inc. with over 12+ years of industry experience. His expertise includes industry analysis, healthcare market research, and technology management spanning biotechnology, pharmaceuticals and medical devices.