$re = '/,(?!\s+and\b)(?=[^,]+$)/mi';
$str = '1, 2, 3, 4
1, 2, 3, and 4
1,2
1234';
$subst = ", and ";
$result = preg_replace($re, $subst, $str);
echo "The result of the substitution is ".$result;
Please keep in mind that these code samples are automatically generated and are not guaranteed to work. If you find any syntax errors, feel free to submit a bug report. For a full regex reference for PHP, please visit: http://php.net/manual/en/ref.pcre.php