Center for Biologics Evaluation and Research

Based on Wikipedia: Center for Biologics Evaluation and Research

A Horse Named Jim and the Birth of American Vaccine Safety

In 1901, a retired milk-wagon horse named Jim became an unlikely catalyst for one of the most important pieces of American health legislation. Jim had been put to work producing diphtheria antitoxin—a lifesaving serum extracted from horses that had been exposed to the diphtheria bacteria. The process was straightforward: inject a horse with diphtheria toxin, wait for its immune system to produce antibodies, then harvest its blood to treat infected children.

Jim was a champion producer. Over his career, he provided serum for thousands of doses of antitoxin.

But then Jim contracted tetanus. And the contaminated serum, drawn before anyone realized the horse was sick, killed thirteen children in St. Louis.

The tragedy wasn't isolated. That same year, contaminated smallpox vaccines caused tetanus deaths in Camden, New Jersey. The American public was horrified. Within months, Congress passed the Biologics Control Act of 1902, creating federal oversight of vaccines and blood products for the first time. The agency responsible for this oversight would eventually become what we now call the Center for Biologics Evaluation and Research, or CBER.

What Exactly Is a Biologic?

To understand CBER, you first need to understand what makes a biologic different from an ordinary drug. The distinction matters more than you might think.

A traditional pharmaceutical drug is typically a small molecule—a chemical compound that can be precisely defined, manufactured through chemical synthesis, and reproduced identically batch after batch. Aspirin is aspirin. The molecule is simple enough that you can draw its structure on a napkin.

Biologics are different. They're derived from living systems—cells, tissues, blood, or microorganisms. They're large, complex molecules that can't be synthesized chemically. Instead, they must be grown or harvested from biological sources. This makes them inherently more variable and, historically, more dangerous.

Consider the difference between making table salt and making wine. Salt is a chemical compound: two atoms bonded together, always the same. Wine is biological: the product of living yeast acting on grape sugars, influenced by temperature, timing, and countless other variables. You can write an exact recipe for salt. Wine requires craft, judgment, and quality control.

Biologics are the wine of the pharmaceutical world.

What CBER Actually Regulates

Today, CBER oversees an astonishing range of products, all unified by their biological origin or their connection to living systems.

Blood products form a major part of their portfolio. This includes blood for transfusion, plasma derivatives like immunoglobulins, and even the reagents used for blood typing. If you've ever donated blood or received a transfusion, CBER's regulations were at work behind the scenes.

Vaccines represent perhaps their most publicly visible responsibility. Every vaccine administered in the United States—from childhood immunizations to annual flu shots to the COVID-19 vaccines that dominated headlines in 2020 and 2021—falls under CBER's jurisdiction.

But their reach extends further. Gene therapies, which modify a patient's DNA to treat disease. Cell therapies, where living cells are administered as treatment. Tissue products used in surgeries and transplants. Allergenic extracts used in allergy shots. Even certain probiotics, officially called "live biotherapeutics," which contain living microorganisms intended to treat disease.

Then there's a category you might not expect: certain medical devices. Specifically, CBER regulates HIV test kits, blood donor screening tests, blood bank collection equipment, and the computer software that blood banks use to manage their operations. The logic is that these devices are so intimately connected to blood safety that they belong under the same regulatory umbrella.

And there's xenotransplantation—the transplantation of organs, tissues, or cells from one species to another. If scientists ever successfully transplant a pig heart into a human, CBER will have been the agency reviewing that approval.

What CBER Doesn't Regulate

Here's where it gets confusing. Not all biologics go through CBER.

Monoclonal antibodies—those drugs with names ending in "-mab" like adalimumab or rituximab—are biologics by any reasonable definition. They're large protein molecules produced by living cells. But they're regulated by CBER's sibling agency, the Center for Drug Evaluation and Research, commonly called CDER.

This division happened in 2002, when the Food and Drug Administration transferred responsibility for most therapeutic proteins from CBER to CDER. The reasoning was partly practical: these protein drugs behave more like traditional pharmaceuticals in how they're prescribed and used, even if their manufacturing is biological.

The result is a regulatory landscape that can seem arbitrary. Two products made through similar biotechnology processes might be regulated by entirely different centers within the FDA, with different cultures, different review timelines, and different regulatory expectations.

The Legal Foundation

CBER's authority rests on two main pillars of law.

Section 351 of the Public Health Service Act requires that biological products traveling in interstate commerce be licensed by the federal government. This is different from how drugs are regulated. Drugs need approval; biologics need a license. The distinction is more than semantic—it reflects the historical understanding that biologics required ongoing oversight of manufacturing facilities, not just approval of a product formula.

Under this authority, CBER can deny a license application, or suspend or revoke an existing license if a manufacturer falls out of compliance. Interestingly, blood products that stay within state boundaries aren't subject to this federal licensing requirement, though they're still regulated under other FDA authorities.

Section 361 of the same act grants broad authority to control the interstate spread of communicable disease. This power originally belonged to the Surgeon General but has been delegated to the FDA. It's the legal basis for regulations on human cells, tissues, and cellular products—things like skin grafts, bone grafts, and corneas for transplant.

The regulations themselves fill hundreds of pages in Title 21 of the Code of Federal Regulations. Most CBER-specific rules live in sections 600 through 680. Human cells and tissues get their own section at 1271. And because many CBER-regulated products are also legally considered drugs, they're subject to all the standard drug regulations too.

The Guidance Documents

Beyond formal regulations, CBER publishes guidance documents. These occupy an interesting legal gray zone.

Officially, guidance documents aren't requirements. They're recommendations. Industry is free to follow them or not.

In practice, they function almost like regulations. Licensed manufacturers are expected to either follow the guidance or demonstrate that they've adopted an equivalent process. And some guidance documents are written specifically to clarify existing regulations—meaning that ignoring them might mean violating the underlying rule they're explaining.

This creates a system where the letter of the law and the practical reality diverge. A company technically has regulatory flexibility, but exercising that flexibility requires convincing CBER that your alternative approach is at least as good as their recommended one. Most companies simply follow the guidance.

A Bureaucratic Journey

CBER's institutional history is a story of organizational ping-pong.

The agency that grew out of the 1902 Biologics Control Act originally lived within what would become the National Institutes of Health. This made a certain sense: biologics regulation in that era was as much about science as enforcement. The agency's mission explicitly included fostering the development of new vaccines, not just policing existing ones.

In 1972, the bureau transferred to the FDA, where it was renamed the Bureau of Biologics. The move reflected a growing emphasis on regulatory oversight rather than research collaboration.

Then came the biotechnology revolution of the 1980s.

Suddenly, the neat distinctions between drugs, biologics, and devices started breaking down. Was a therapeutic protein produced by genetically engineered bacteria a drug or a biologic? Was a diagnostic test that used biological reagents a device or a biologic? The categories that had made sense in 1902 were becoming unworkable.

In 1982, under Commissioner Arthur Hayes, the FDA merged its Bureau of Biologics with its Bureau of Drugs to form a combined Center for Drugs and Biologics. The reasoning was organizational efficiency—why maintain separate bureaucracies for products that were increasingly similar?

The merger lasted five years.

Why the Split?

By 1987, it was clear the marriage wasn't working.

The two groups had fundamentally different cultures. The biologics people had traditionally taken a collaborative, public-health-oriented approach to working with industry. They saw their job as helping good products reach patients. The drugs people operated more adversarially, viewing their role as protecting patients from industry's natural tendency to cut corners.

These weren't just philosophical differences—they showed up in approval timelines. In the 1980s, CBER was actually faster at approving products than their drug-regulating counterparts. For an era that saw bitter criticism of FDA slowness, this was notable.

The breaking point came with a dispute over Genentech's Activase, a tissue plasminogen activator used to dissolve blood clots in heart attack patients. Officials from the former Bureau of Drugs and officials from the former Bureau of Biologics couldn't agree on whether or how to approve it. The internal fight became a symbol of deeper dysfunction.

Meanwhile, the AIDS epidemic was forcing urgent questions about blood safety. HIV had spread significantly through blood transfusions and blood products like clotting factors used by hemophiliacs. The agency needed clear lines of authority.

Commissioner Frank Young separated CBER and the Center for Drug Evaluation and Research into their present forms in 1987. CBER was designated the primary agency for HIV and AIDS-related products, given its existing authority over blood and blood products.

The User Fee Transformation

The next major change came not from a reorganization but from a funding shift.

In 1997, Congress reauthorized user fees—charges paid by pharmaceutical companies when they submit products for FDA review. The idea was that industry should help fund the regulatory process rather than relying entirely on taxpayers.

The effects were profound. Research that CBER had previously conducted at government expense began to be charged to manufacturers. Over time, CBER's research function diminished dramatically. The agency that had once been charged with fostering vaccine development became more purely regulatory.

Whether this was good or bad depends on your perspective. Proponents argued it made the approval process faster and more responsive to industry needs. Critics worried it created inappropriate industry influence over the agency. Both might be right.

Advisory Committees: Where Science Meets Policy

CBER doesn't make decisions in isolation. For major questions, it convenes advisory committees—panels of outside experts who review evidence and vote on recommendations.

The most famous of these is the Vaccines and Related Biological Products Advisory Committee, known by the awkward acronym VRBPAC (pronounced "ver-back"). This committee meets annually to advise on the composition of next year's flu vaccine—a decision that affects the health of millions. During the COVID-19 pandemic, VRBPAC meetings became must-watch events for public health officials and journalists as the committee deliberated on vaccine authorizations and boosters.

Other committees cover blood products, allergenic products, and cellular and gene therapies. There's even a committee specifically for patient engagement, reflecting modern emphasis on including patient perspectives in regulatory decisions.

These committees are purely advisory. CBER isn't bound by their votes. But in practice, the agency rarely goes against committee recommendations. The committees provide scientific legitimacy and political cover for difficult decisions.

The Vaccine Adverse Event Reporting System

How do you know if a vaccine is causing problems after it's approved and millions of people have received it?

The answer is the Vaccine Adverse Event Reporting System, or VAERS. Anyone—patients, parents, healthcare providers, manufacturers—can report suspected adverse reactions to vaccines. CBER and its partners then analyze these reports to look for safety signals.

The system has important limitations. Reports to VAERS don't prove causation. If someone gets a vaccine on Monday and develops a headache on Tuesday, they might report it to VAERS, but that doesn't mean the vaccine caused the headache. Humans are constantly having health events, and some of those events will happen to occur after vaccination purely by chance.

What VAERS excels at is detecting unexpected patterns. If thousands of reports mention a particular symptom that wasn't seen in clinical trials, that's a signal worth investigating—even if any individual report might be coincidental.

As of 2003, the system ran on data integration software from a company called Informatica. The technology has presumably been updated since then, though the basic function remains the same: aggregating reports, identifying patterns, and triggering deeper investigation when warranted.

The Numbers Game

How long does it take to get a biologic approved?

In 2001, CBER reviewed sixteen Biologics License Applications with a median review time of 13.8 months and a median approval time of 20.3 months. The difference between review time and approval time reflects the back-and-forth that typically occurs: the agency reviews, requests additional information, the company responds, the agency reviews again.

These numbers have likely changed significantly since 2001. User fee agreements have imposed performance targets on the FDA, generally pushing toward faster reviews. But biologics remain complex products that demand careful evaluation. There's an inherent tension between the desire for speed and the need for thoroughness.

The Current Landscape

Today, CBER stands at the intersection of some of medicine's most exciting and controversial frontiers.

Gene therapy, once a theoretical possibility, is now a clinical reality. Products that modify a patient's DNA to treat previously incurable genetic diseases are receiving CBER approval. Cell therapies, including CAR-T treatments that reprogram a patient's own immune cells to fight cancer, represent another frontier.

These technologies raise novel regulatory questions. How do you ensure quality control for a product that's manufactured individually for each patient? How do you assess long-term safety for a treatment that permanently alters someone's genome? CBER is developing frameworks to answer these questions in real time.

Meanwhile, the basics continue. Blood banks still need oversight. Flu vaccines still need annual reformulation. The agency that started because of a contaminated horse named Jim still guards the nation's supply of biological medicines.

Looking Forward

CBER's current director, as of May 2025, is Vinay Prasad, a physician and epidemiologist known for his outspoken views on evidence-based medicine and his criticism of certain regulatory decisions during the COVID-19 pandemic. His appointment signals potential shifts in how the agency approaches its mission.

Previous directors included Peter Marks, who led CBER through the pandemic years from January 2016 to April 2025, and Karen Midthun, who served from around 2010 to January 2016.

What remains constant is the fundamental challenge: how to ensure that biological products are safe, pure, potent, and effective, without creating barriers that keep beneficial treatments from reaching patients who need them. It's a balance that's been difficult since 1902.

The stakes have only grown higher. The biologics of the early twentieth century were relatively simple—vaccines made from killed or weakened pathogens, sera extracted from immunized animals. Today's biologics include products that seemed like science fiction a generation ago: living cells programmed to hunt cancer, genetic instructions that teach your body to fight disease, tissues grown in laboratories.

Jim the horse couldn't have imagined any of it. But the regulatory framework his death inspired continues to evolve, trying to keep pace with biological medicine's accelerating advance.