With 14,350 U.S. restaurants selling more than 100 different menu items, even slight changes to McDonald’s Corp.’s supply chain can cause headaches.

So the fast-food giant MCD, -1.03% has been planning extensively for its shift to chicken made from birds raised without antibiotics that are important to human health, though work remains to be done on issues like labeling and marketing, said Marion Gross, senior vice president of McDonald’s North America supply chain.

“Because of our scale, we have to plan well in advance and very thoughtfully,” Gross said in an interview. “It is limiting if we don’t.”

Whether it is baby carrots for Happy Meals or cucumbers in salad wraps, it can take years for McDonald’s to secure enough supply for new ingredients, and the company has struggled in the past with menu changes that can lead to shortages.

Gross said the last major change McDonald’s made to its chicken was moving to all white meat for its McNuggets in 2003, but that was simpler. Antibiotics include various types of medicines that are used differently. McDonald’s had to decide what level of reduction it wanted, then work with its suppliers on changing practices at their hatcheries and among the farmers they contract with to raise the chickens.

McDonald’s is best known for its burgers, which it isn’t changing. Nearly a fifth of McDonald’s menu items contain chicken, and its sells billions of dollars of the products every year in the U.S. The company doesn’t disclose exact figures. Research firm Technomic Inc. says McDonald’s is the biggest single restaurant customer of Tyson Foods Inc. TSN, -2.69% , which is the largest U.S. chicken producer. McDonald’s has said it buys 400 million pounds a year of chicken from another supplier, Keystone Foods, a unit of Marfrig Global Foods SA.

An expanded version of this report appears at WSJ.com.