As more excipient and drug-product manufacturers operate globally, the use of harmonized monographs will increase. Presently,
a majority of stakeholders use the most stringent test method, specification, or acceptance criteria for compliance, or may
also test for the same attribute using another pharmacopeial analytical procedure, resulting in redundant testing of the same
attribute. Drug-product manufacturers would like the option of using a specification (test for an attribute, analytical procedure,
and acceptance criteria) for a drug substance or excipient from the current edition of the British Pharmacopoeia (BP), PhEur, or JP monograph as part of the specifications in a drug application. This approach would facilitate the use of test methods where
the analytical procedure and acceptance criteria in the BP, PhEur, or JP monograph are equivalent or superior to the analytical procedure and acceptance criteria in the corresponding USP–NF monograph. This option would be helpful for both drug substance and excipient monographs.
The workshop discussed the effective use of harmonized monographs. Excipient and drug-product manufacturers envisioned two
ways going forward: full harmonization or mutual acceptance of the other pharmacopoeias by the regulators. As stated in USP
General Information Chapter ‹1196› "Pharmacopeial Harmonization":
A pharmacopeial general chapter or other pharmacopeial document is harmonized when a pharmaceutical substance or product tested
by the document's harmonized procedure yields the same results and the same accept–reject decision is reached.
Further details of ongoing effort and activities by the Pharmacopoeial Discussion Group (PDG) and ICH on this subject
can be found in the ICH Step 2 document, "Q4B Regulatory Acceptance of Analytical Procedures and/or Acceptance Criteria (RAAPAC)"
available at FDA's website (22).
The closing questions and comments of the workshop observed that one word in CFR 211.84 that causes confusion is the use of test instead of a term such as evaluate. It was pointed out that excipient manufacturers are not going to perform every compendial test on samples of finished material
if it is not necessary to perform such tests to demonstrate control of their processes and adequate product quality. Also,
there is no requirement for excipient manufacturers to perform compendial tests on finished material as a release test. It
apparently was not understood that the CGMP regulations in 21 CFR Parts 210 and 211 apply to manufacturers of finished dosage forms and not to the manufacturers of excipients. As such, the
requirements in 21 CFR 211.84 do not apply to excipient manufacturers. Nevertheless, excipient manufacturers should have appropriate control processes
in place along with sufficient testing and measurement to ensure that each finished lot of excipient meets all of its quality
Using ICH Q4B harmonized compendial procedure published in USP–NF or its supplement, with a future implementation date.
When a new compendial procedure or a general chapter is published in USP–NF or its supplement with a future implementation date, an excipient manufacturer or a drug-product manufacturer may begin voluntarily
use of such new procedure or general chapter before the published implementation date. In general, FDA has not objected to
such a practice. In other words, before the implementation date of a published harmonized procedure, either the current official
procedure or the new harmonized procedure may be used for testing. However, after the official implementation date of an ICH
harmonized new procedure or a USP–NF general chapter (specifically, those numbered between ‹1› and ‹999›), the new procedure becomes effective and enforceable