CHPA Guidance Gives Structure To OTC Monograph Product Stability Testing

A CHPA working group will convene within the next few weeks to discuss plans to update a guidance on Stability Testing for OTC monograph drug products by addressing changes that occur to the products.

The additional guidance would detail the required adjustments to stability testing for monograph products that undergo formulation, flavor, excipient or packaging changes.

Stability testing takes place in order to evaluate the product, as well as determine its expiration date.

The guidance would be an extension of the group's final guidance on OTC monograph product stability testing, which was published by the Consumer Healthcare Products Association on Oct. 8. Two members of the working group - McNeil's Kevin Bradley and group chair Karen Lucas of Pfizer - spoke about the development of the guidance during CHPA's Manufacturing Controls seminar in Parsippany, N.J. Sept. 30.

Guidances on stability testing - the testing of primary product batches that takes place before the drug goes to market - are lacking for OTC monograph drugs, Lucas said. She added: "though there are numerous guidances for NDA and ANDA products that address stability related issues and requirements, things are not so well-documented for the OTC monograph products."

CHPA was approached in August 2002 about the lack of guidance for monograph products, and the association authorized the formation of a 10-person working group in May 2003. A draft of the guidance was published in June 2004. The recent final version incorporates comments that were submitted by six CHPA member companies.

A variety of existing stability testing programs within the industry led the working group to believe it was necessary to establish one process for the whole industry to follow. "Our aim and ambition was to have clear stability requirements while leveraging science and our experience," Lucas said. Many of the existing programs are considered inadequate, Lucas noted. In addition to the wide range of existing programs, a number of companies do not have formal stability testing programs at all, she said.

The inadequacy of the programs is evidenced by a series of citations from the agency in recent years. From 1997 to 2003, the number one reason for OTC companies to receive warning letters was "failure to establish a written stability program," while the number two reason was "failure to follow a written stability program," Lucas said. She maintained the primary reason for recalls by OTC companies during the same time period was cited as "data does not support labeled expiration" - an occurrence caused by not having a written stability program.

Guidances for Rx drugs tend to be updated more often, since those drugs deal with new chemical entities, Lucas said. "But then when you get to the OTC world...the guidance is a little outdated."

Due to an absence of an updated guidance, most companies currently follow the ICH (International Conference on Harmonization) Q1A guidance, because it "represents the most conservative set of stability requirements." However, since OTCs do not require as much testing as stipulated under ICH Q1A, many companies are not strictly following it, leaving themselves at risk for non-compliance.

The guidance would lower the regulatory risk by creating a science-based approach, Bradley said. The resulting "level playing field" also would benefit industry, since the practice of everyone followed different guidances would be avoided, he said.

The guidance will give companies the opportunity to reduce the amount of stability testing required prior to launch in the U.S., Bradley maintained. It also will allow businesses to increase efficiency and plan more effectively.

However, some potential risks associated with having a guidance include that it "could serve as a starting point for FDA to eventually over-regulate the OTC industry," Bradley said. Additionally, the guidance could decrease the flexibility of some CHPA member companies' not already meeting minimum standards.

Industry's acceptance of having a guidance at all is questionable, Bradley said, since some drawbacks do exist.

In its upcoming meeting, the working group also will discuss ways to increase awareness about the guidance, Lucas said.