foo.*bar
\w+\d+\s+\d+:\d$

##</code><code>##

my @skips = get_skips(); # However you get them
my $skip_regex = join '|', map { "(?:${_})" } @skips;
while ( <BIG_FILE> ) {
    next if /$skip_regex/;
    # Now you've checked everything.
}