The facility at the University of Bloemfontein's Department of Pharmacology will analyse urine samples taken from players after each of the tournament's 64 games.
"We are the only one in South Africa doing this work and so we were asked by FIFA to do it for the World Cup," Van der Merwe told Reuters during a visit to the lab.
The World Cup's most infamous doping scandal was in 1994, when Argentina's Diego Maradona was sent home from the United States after failing a test for ephedrine doping.
Maradona, who is in South Africa this time round as Argentina's manager, has claimed that the negative result was due to a power drink.
Scotland's Willie Johnston also took an early flight home from Argentina in 1978 after he was found to have taken a banned stimulant. He also said it was inadvertently taken.
"Negative results would be nice. The chances that we'll have a positive are slight. We'll just have to see," Van der Merwe said.
FIFA regulations demand that two players from each side give a urine sample, and if requested, a blood sample, after every game. It can also carry out spot checks.
The samples will be delivered to the lab in this city on the plains of central South Africa by road. FIFA wants to get the results back within 24 hours.
"It's going to be hard. We'll be working right through to get the results," Van der Merwe said.
CLEAN SHEETS
He has a team of eight assistants, who will work off the WADA (World Anti-Doping Agency) list of banned substances.
The samples are first taken to a preparation room, then passed through an array of machines for computer analysis.
According to FIFA, anabolic steroids are not a big problem in world football, showing up in only 0.3 per cent of tests. Use of recreational drugs such as cocaine and marijuana show up more frequently.
But of 33,000 tests done by FIFA in 2008, only 75 led to sanctions, FIFA said in a statement.
The test results during the World Cup will be highly secret. It will be up to FIFA, not the laboratory, to announce any problems, van der Merwe said.
The South African scientist has a lot of experience in such work for big sporting events. His laboratory handled the doping tests for the 1995 Rugby World Cup, which was famously won by South Africa who were also hosts then.
It also worked on the Confederations Cup held in the country last year, when the tested players all had clean sheets.
"That was a nice trial run working with FIFA, he said. "It's a big honour for the university, and we're looking forward to be part of the World Cup.
"I like sport in general - but I'm more a rugby fan," he added.
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