FDA Investigator Travels Globe to Help Ensure Safety of America’s Medicines
By: Erin Peabody
When we pick up a prescription at our local drugstore, we’re often asked by the pharmacist if we have any questions. In return we might ask: Does the drug have any known drug interactions? What about side effects?
Less often do we inquire about how our drugs were produced, and where. And if they were made using the most rigorous safety and quality standards. We generally assume the latter is true.
Fortunately for Americans, FDA consumer safety officers like Rajiv Srivastava have devoted their careers to scrutinizing the safety of pharmaceutical drugs bound for the U.S. market—and travelling halfway around the world to do so.
FDA’s frontline staff, including its investigators, flew over 25 million miles last year to conduct global operations aimed at protecting the nation’s supply of drugs, medical products, and foods.
A Special Cadre of Drug Investigators
Srivastava and his fellow consumer safety officers, also known as investigators—who work within the FDA’s field-based Office of Regulatory Affairs, or ORA—regularly inspect the facilities that make the drugs relied on by millions of Americans to treat conditions like diabetes, high blood pressure, and cardiovascular disease.
The job requires detailed knowledge of the drug manufacturing process and its many steps, from production of the active pharmaceutical ingredients, or API (the main components of a drug responsible for its intended health effects), to the pressing and the coating of tablets and capsules.
It also entails frequent travel—across long distances.
ORA’s frontline staff, including its investigators, flew over 25 million miles last year to conduct operations aimed at protecting the nation’s supply of drugs, medical products, and foods. Many of these trips were international, where the bulk of pharmaceuticals used and needed by U.S. consumers are made.
While the United States remains a leader in drug innovation, with help from federal and other investments meant to spur discovery within our own borders, most of our drugs’ APIs—more than 50 percent—are manufactured abroad. India and China lead in this production, comprising one-third of the roughly 4,800 establishments making drugs for the U.S. market. The United States, Europe, plus a smattering of other global locations round out the rest.
Awareness of this increasing drug globalization is what led Srivastava to pivot from domestic drug inspection assignments to foreign ones at the agency, including serving on a three-year detail in New Delhi, India, where the FDA has a permanent field office and sits in close proximity to several large pharmaceutical companies.
The investigator also travels throughout China and Europe to conduct drug inspections and meet with firm staff. That kind of direct oversight, he says, is invaluable.
“We’re the FDA’s eyes and ears in these facilities. We know what safety processes and controls to look for, and what questions to ask.”
After his detail in India ended, the investigator, who, lives with his wife in Albany, New York, applied to join the FDA’s elite dedicated foreign drug cadre—a group of ORA investigators who specialize in foreign pharmaceutical inspections and have committed themselves to regular international travel, on tours typically lasting three weeks at a time.
It wasn’t the first time Srivastava had shifted his career, to find a more meaningful niche in the far-flung pharmaceutical industry. Before coming to the FDA in 2016, he’d worked for almost 20 years for various drug makers, as a medicinal chemist, process chemist, and manufacturing chemist.
“That’s when I knew I wanted to be closer to the end-user,” said Srivastava, “for my years of experience to have a greater impact on patients and consumers.”
Keeping Statins Safe
The investigator has done that.
Every day, about 47 million Americans take cholesterol medication, often in the form of a statin. You or someone in your household may be one of them. Statins help clear excess cholesterol from the blood and reduce the amount of cholesterol the liver makes. For Americans with heart disease, especially atherosclerosis, statins, if tolerated, are usually considered a must.
Srivastava has conducted several inspections of facilities that make statin drugs. During these evaluations, which can run for an intensive five to seven days, he examines manufacturing processes and procedures to ensure a firm is adhering to the fine print of its FDA drug application and in accordance with current Good Manufacturing Practice (cGMP) requirements.
You can access drug application details, too, at the agency’s Drugs@FDA database. Simply plug in the name of a drug that you or a family member takes and learn about its history, the names of companies that make it, and other details.
A central part of the drug manufacturing process is, of course, equipment. That’s why ORA drug investigators dedicate a fair amount of their inspection to scrutinizing these specialized instruments—especially any tucked-away, inner components.
“That’s where unwanted substances, like dirt and other impurities can hide,” explains Srivastava. These are also points of contact, which, if unclean, could potentially contaminate all drug products passing through them.
A few years ago, the investigator was at a statin manufacturer inspecting a piece of equipment that helps control how quickly, or slowly, a statin drug tablet releases its active ingredients within a patient. The instrument physically shakes, sifts, and screens tiny particles of the drug, to achieve a precise and uniform size.
Srivastava was peering inside the equipment’s discharge tube when he paused. He waved over a nearby drug company employee and directed him to swipe a sample of the interior of the tube. Srivastava worried that a harmful impurity, known as nitrosamine, might be present.
Nitrosamines are potent carcinogens that can cause cancer. They form during certain chemical processes, including drug manufacturing, if adequate controls aren’t in place.
The swab that exited the tube was covered in a black-brown residue. It tested positive for nitrosamines.
Srivastava’s nitrosamine findings kicked off a series of communications and regulatory actions designed to protect consumers back in the United States. These actions can include recalls, in which unsafe products are removed from U.S. commerce, including drugstore shelves—as well as import alerts, in which ORA staff at borders and ports, and their Customs and Border Protection partners, block harmful products from entering the country in the first place.
FDA’s teams of staff, in the field and at headquarters, deployed the steps needed to stop unsafe statin drugs from reaching Americans. It was a broad agency response, all precipitated by the watchful eyes of an ORA investigator.
A Gold Standard, Worldwide
The job of an investigator is challenging Srivastava admits. But FDA’s globally recognized standards—a culmination of decades’ worth of consumer protection laws, regulations, policies, and science, going back to the agency’s 1906 origins—set a clear expectation around the world.
“If I conduct an inspection of a drug maker and find that all is in compliance,” says Srivastava, “the staff are usually relieved. They know they’ve achieved the highest standard there is.”
On the other hand, regulatory audits can lead to changes at a facility, including a shutdown of operations, if immediate safety issues are uncovered by FDA staff.
That was the case last year, when Srivastava’s investigations into an overseas eye drops manufacturer revealed that unsterile conditions had caused microbial contamination of eye drops products, tragically causing blindness and death in some users.
His detective efforts, though, along with ORA scientists’ findings that products made at the facility were highly contaminated with bacteria, helped avert further harm.
A Public Promise
ORA’s top administrator, Michael C. Rogers, has a special appreciation for this kind of work. The Associate Commissioner for Regulatory Affairs, who oversees all ORA staff working at ports, borders, farms, and food and medical product facilities, here and around the world, began his FDA career over three decades ago—as an investigator himself.
Rogers says he’s still inspired by a case that he supported years ago, when his team of investigators tracked down the evidence needed to stop a pair of fraudulent doctors from selling fake cancer cures to vulnerable U.S. patients and their families.
“The chance to make a difference and protect innocent consumers is a huge motivator in this line of work,” he says.
Even, he acknowledges, when the job requires time spent away from family and loved ones—for weeks at a time.
“That’s what makes the job more than a career,” says Rogers. “It’s a mission. And I couldn’t be prouder of what our teams do every day in an effort to keep the public safe.”