USP Announces Monograph Revisions List and Postponed Publication of General Chapter <1226>

October 13, 2005
Pharmaceutical Technology Editors

ePT--the Electronic Newsletter of Pharmaceutical Technology

USP Announces Monograph Revisions List and Postponed Publication of General Chapter <1226>

During its annual scientific meeting late last month, the US Pharmacopeia (USP) announced plans to post on its Web site (www.usp.org) a list of monographs that require improvement. A small segment of the list of monographs that require stability-indicating assay procedures for steroids has been posted on the site. A complete list, scheduled for posting by the end of the year, will call on the industry to submit improved procedures for monographs where deficiencies have been identified. “In most of the cases, USP has identified where the deficiencies are. Most likely, the industry has developed alternative methods that are better than those in the USP,” says Lokesh Bhattacharyya, PhD, director at USP’s Noncomplex Actives and Excipients Department of Standards Development. “These methods have been submitted as alternative methods to FDA for appropriate approval. Now, we are just asking [these companies] to submit them to us.”

USP already has made available a list of approximately 800 high-priority new monographs for drug substances, drug products, and excipients. “We’ve received a good response on these,” notes Bhattacharyya. He says the list will be updated approximately every three months and will indicate which monographs have been received. “Industry now has a clear idea about the monographs we are most interested in.”

At the annual meeting, USP also announced postponement of the publication of General Chapter <1226> “Verification of Compendial Procedures.” The chapter was intended to provide guidance on 21 CFR part 211.194(a)(2), which states “The suitability of all testing methods used shall be verified under actual conditions of use,” in efforts to promote a more uniform approach to suitability testing.

Karen Russo, associate director of Monograph Acquisition and Infrastructure for USP, presented the proposed verification process, including tables of data elements for verification of dosage forms, drug substances, and excipients, which are similar to those in General Chapter <1225>. USP acknowledged this verification represented “the minimum set of requirements” and more stringent requirements will depend on the intended use.

Since General Chapter <1226> was published earlier this year (Pharmacopeial Forum31 (2), 555–558), USP has collected “a significant number of comments,” including those voiced at the annual scientific meeting. During the meeting, industry participants expressed their concerns over the stringent requirements and the applicability of the proposed chapter. A representative for Big Pharma companies pointed out that the chapter “sounds like an SOP” and that the guideline should not be intended for retroactive application. Meanwhile, representatives from contract analytical laboratories voiced concern over the “unreasonable” burden that could result because of the large number of testing performed by them under “actual conditions of use.”

USP representatives at the meeting noted USP has been receiving questions from several companies, including pharmaceutical and biotech companies, on the issue of the verification of compendial methods. Indeed, the chapter was developed in response to the large number of questions USP staff received. The challenge is how to develop the requirements without interfering with the good science already established.

According to Bhattacharyya, the comments received during the annual scientific meeting and the ones received previously will be forwarded to the General Chapter Expert Committee, which is responsible for this chapter. The committee will review the comments and consider revisions. The revisions then will be published in the Pharmacopeial Forum and additional comments from the industry would be welcomed. “At some point it will become official,” says Bhattacharyya, “but it is unlikely that it will become official on January 1, 2006 or in the first supplement to USP 29 published in April 2006.”

–Maribel Rios