Your question is a bit ambigious. Do you want to

1. create a new file with no comments
2. load the file into memory and strip the comments before further processing

?

variant 1:

open (my $in, "<", $ARGV[0]) 
    or die "in: $@";

open (my $out, ">", "$ARGV[0].new") 
    or die "out: $@";

while( my $line = <$in>)
{
    print $out $line
        unless $line =~ /^#/;
}

close $in;
close $out;
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variant 2:

open (my $in, "<", $ARGV[0]) 
    or die "in: $@";

my @lines = grep { not /^#/ } <$in>; #<> here in list context, therefo
+re no explicit loop
[download]

Note that you cannot erase a line from the middle of a file, you will always have to write a new one. But you already knew that, didn't you? ;-)