D. They have to predict which strains of flu will become active months before the flu season begins.
The text states, "Creating a flu vaccine is a bit of a guessing game, because the shots take months to manufacture. Each year in February, the World Health Organization (WHO) tries to predict what viruses may be circulating the following winter, a process that can change as bugs mutate. " This supports the answer that a challenge for vaccine makers is determining which strain of the flu must be targeted in order to prevent its spread.