The regulatory process in Brazil, previously seen as complicated and convoluted, just got simpler and more logical. The country has been a familiar destination for sponsors for at least a dozen years. It ranks up there with China, India and Russia. But Brazil’s regulatory structure has been slow, rigid, and some would say illogical by comparison.

In June of this year, Brazil’s Health Care Surveillance Office (formally, the Agência Nacional de Vigilância Sanitária or “Anvisa”), considered the Brazilian FDA, restructured the regulatory process. Instead of having to obtain approval from various bodies sequentially, a sponsor or contract research organization (CRO) can pursue many of the steps simultaneously. The change became effective in July. Its effects are expected to really kick in early in 2009.

Faster Approvals

The regulatory shift is expected to greatly expedite the trial approvals process, which now can take between nine months and a year. Some, like Vitor Harada, president of the two-year-old Brazilian Association of CROs (known in Brazil as “Abracro” ) and director of clinical operations in Brazil for Icon Clinical Research, think the time line could drop dramatically.

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“Things are changing for the best,” Harada says, excitedly, “We may be able to get approval times down by a month and a half.” 

190 Million People

That could bring a healthy influx of new trials. And there are already plenty of trials underway in Brazil, the largest country in Latin America and the fifth most populous country in the world. According to ClinicalTrials.gov, 1,039 trials have taken place or are under way in Brazil. The numbers in Mexico (845) and Argentina (738) are significantly lower. In 2007 alone, according to Frost & Sullivan, 645 trials were being conducted in Brazil.

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Putti of Frost & Sullivan

Brazil’s main selling point: its population. The country is geographically and demographically huge, with 190 million people. Eight of every 10 residents live in or near a city. Sao Paulo alone, Brazil’s largest and wealthiest city, has a population of 20 million. Almost all the CROs in the country are headquartered there. (Only one, Kendle, is in Rio De Janeiro.) Also conveniently, the hospitals within the cities are huge, some with 1,000 beds, so often a trial just needs to have a few key hospitals signed up as sites.

Uninsured Patients

Only about 20 percent of Brazilians have health insurance. The rest use the public health system, which is sorely lacking, explains Daniela Putti, industry analyst for Frost & Sullivan who focusses on the pharmaceutical and medical device market in Latin America. “We have lots of people that expect to wait six months to a year for a basic exam, or to get an X-ray,” she says.

Brazilians, she reports, generally view clinical trial participation as a valuable opportunity to get care. “It’s seen as good for a patient to participate in a trial because the patient will then have assistance, all exams and medicines provided for them, and they have access to good doctors and nurses,” Putti says, adding that a huge swath of the population is still treatment-naive.

Enrollment, Retention

All of this makes for robust enrollment. Retention is good as well: patients want to keep care arranged through a trial. And they don’t have to travel far to get it. “Enrollment and retention are so great here, it usually makes up for the long start-up times,” says Harada.

A healthy crop of strong, experienced investigators is also present. Latin America has a long tradition of Western medicine; many of the physicians were trained in the U.S. or Europe. They tend to be eager to participate in clinical trials, and, without managed care pushing them to rush patient visits, have more time to devote to clinical trials than investigators in the U.S. The data is very clean. Most investigators in Brazil speak English. Some CROs require it.

The lion’s share of trials that take place in Brazil are global. Almost none of the sponsors that send trials there are from Brazil, and usually Brazil is just one of many countries where the trial is taking place. That makes Brazil a destination for “rescue trials,” a place to go when recruitment or other matters have gone awry elsewhere. Some CROs, like Mexico City-based Mmatiss, which has an office in Sao Paulo, say as many as 40 percent of their trials in Brazil are rescue trials.

CRO Market

Therapeutic areas that lead the market: cardiovascular, central nervous system, diabetes, analgesics and oncology.

About half the trials taking place in Brazil are manned by CROs. And the local CRO market, says Putti, is fragmented. There are just a handful of big, multinational CROs. The majors include PPD (by far the biggest presence there, with 300 employees); Quintiles (165 employees); Icon (56 employees); Kendle (45 employees); and Parexel (which doesn’t disclose staffing by country). Medium-sized CROs include PRA, i3, and InTrials, which is one of the few CROs that’s headquartered in Brazil. Beyond the large and medium-sized players, there are many small CROs, mostly working with very small pharma companies based in Brazil, says Putti.d9A2t49mkex

Massive Taxes

The costs of conducting trials in Brazil? Not as cheap as you might think. Harada says costs had been 20 to 30 percent lower than in the U.S. But that discount is starting to fade as more and more CROs establish themselves in Brazil and compete for patients. According to Dennis Hurley, Kendle’s president of global clinical development for Latin America, the savings are approximately 15 percent less than what a trial would cost in the U.S.

Brazil is the most expensive research market in Latin America. Elsewhere on the continent, Hurley says, trials save about 25 percent of the cost of doing research in more saturated markets. Blame Brazil’s tax system, which demands that employers pay huge taxes on each employee. If you want to pay an employee in Brazil a salary of $50,000, the loaded cost is closer to $90,000 when the tax burden is considered, Hurley says.

Argentina First

Clinical trials in Latin America began in Argentina, then spread to Brazil, says Putti. The market started to evolve in 1996, when the country established regulations in adherence with the International Conference on Harmonization guidelines, and then established a national bioethical committee to investigate institutional review boards. Other countries there did much the same, and trials in Latin America saw an explosion in the late 1990s that continues to this day.

The FDA is encouraging the Latin American market, pushing for the inclusion of under-represented Hispanic patients in clinical trials; they are the largest minority in the U.S., at 12 percent of the population. 

Old and Young

Brazil has a few unique upsides. One is that about a quarter of its population is 14 years old or younger, making it an attractive place for pediatric trials. It also offers an aging population with patients with chronic conditions. And the fact that it’s summer in Brazil when it’s winter in the U.S. allows companies to test drugs for seasonally induced diseases year round.

Brazil is also quite ethnically diverse. It has the largest concentration of Italians outside of Italy, and the largest number of ethnic Japanese outside of Japan. Sponsors who need to study those groups can find them in Brazil. This is especially useful in Japanese populations; Japan is the second largest consumer of pharmaceutical products, but it’s not easy to enroll patients there because of all the competition among sponsors. The adoption of the international guideline on Ethnic Factors in the Acceptability of Foreign Clinical Data allows Japan’s drug approval authorities to accept data from studies that include ethnic Japanese living outside of Japan.

Language(s) Barrier?

There are also negatives. There is a potential language barrier: all documents must be submitted in Portuguese. (But some say at least that’s just a single language, and simpler than the situation in Europe.) Also, any drug that comes into the country that isn’t already approved by the FDA must go through a lengthy importation process. Finally, investigator sites tend not to be as up on things like software and patient databases, but they are improving rapidly, says Harada.

Infrastructure is improving, as the country has prioritized upgrading its public health system. That should soon translate into more modern investigator sites, says Putti. So Brazil is nowhere near saturated, trials-wise. Hurley, from Kendle, believes the country could easily handle about three times the number of trials it has now.

Sponsors in the U.S. now outsource 40 percent of their clinical trials. That figure is expected to rise to 65 percent by 2013. Brazil, especially now with a faster regulatory process, seems poised to get a healthy portion of that.

by Suz Redfearn

Editor’s note: This artice is the first in a series. Here’s the second installment, concerning its regulatory system; the third, about its association of contract research organizations; and the final installment, examining a large and small CRO operating in the country.

 

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