This means that excipient companies will need to share a lot more information about their process and their material residual
levels than they had previously. "Some small pharma companies and generics houses haven't really talked to their suppliers
about how these materials are made," says Schoneker. "These companies then have to scramble to get better information from
their suppliers than they had done in the past."
The problem that arises is that companies tend to develop exhaustive, sometimes irrelevant, questionnaires for their suppliers.
"Suppliers are getting different questionnaires from every customer and asking different questions—some are reasonable and
some about issues that don't really matter," says Schoneker. "You have to have this balance. How do you share information
in a reasonable way so that you get what you need without putting the excipient supplier in a situation where they are having
to do a huge amount of work to supply their customers with information they consider confidential?"
IPEC is working on excipient qualification guidelines, which focus on technical and GMP qualification and information and
understanding how much information companies need to meet the requirements. IPEC's Excipient Information Protocol has a section
on residual solvents and discusses the need for the supplier to incorporate the key information that is needed to use the
material and meet the residual solvents guideline.
The effect on OTC manufacturers.
Some over-the-counter (OTC) products also may fall under the USP ‹467› requirements. "A lot of these issues are always positioned in terms of Rx-type products, but there is a whole other
business area that often gets overlooked," says Tine Engel, PhD, principal scientist at The Procter & Gamble Company (Mason, OH). In general, OTCs contain a lot more excipients and ingredients because consumers are interested in taste,
mouth feel, and so forth, which require additional nontherapeutic ingredients in formulations.
OTC products with USP monographs fall under the requirements in USP ‹467›. Other OTCs may be approved under an NDA or ANDA but do not have a USP monograph. "In these cases, we will probably continue to apply the ICH Q3C guideline," says Ouderkirk.
Engel and other OTC analysts largely support the USP ‹467› changes. "I think they are good rules. The fact that USP has harmonized with ICH means we don't have to make up different rules for products that we sell at different global locations.
What people may not realize is that we are working with a lot of different materials and at bigger quantities. It takes more
raw materials to make a tube of toothpaste than a pill. And we do have to be very careful to set up good systems because normally
consumers are more exposed to many of our products. You may take a pill once a day, but you brush your teeth two or three
times a day. Any additional testing that is required hits us doubly hard. Of course it is very important to protect the safety
of the consumer, but we need to do it in a way that isn't going to put OTC companies out of business."
Manufacturers that choose not to pay close attention to the requirements may undergo costly consequences. "One of the things
we see almost every time a USP revision comes out is that there is always a group of products that have been tested according to an older version of USP, and then if they don't immediately employ their (raw) material in the manufacture and it sits in a warehouse while the USP changes, they all of a sudden are stuck in a situation where they are trying to use material that is now out of spec," says
Dr. Jon Brice. If a manufacturer tests its raw material according to a USP monograph, uses it in manufacture and then USP changes, the company is grandfathered in. However, if a company tests its raw material and then the material sits in storage
and during that time the USP changes, then they simply can't use that material in manufacturing because the company must test according to the USP that is in effect when manufacture begins and must retest.