Schoneker (Colorcon): In the food industry, there's a guideline on acceptable filth that specifically states how many insect parts are okay, how
many wings are okay, and how much dirt can be present. Now we don't necessarily want to go there in the pharma industry, but,
again, the concept that FDA can't find a particle to be acceptable is not true. FDA on the food side has been saying that
for decades, and a certain amount of particles, if you will, is the reality. We just need to figure out for our industry what
we can do in a reasonable way.
PharmTech: Can you provide some insight into the pending IPEC guideline on atypical visible particles in excipients and its goals?
Van Meter (IPEC): We have a subteam in which excipient manufacturers are looking at what a responsible manufacturer in full GMP compliance
would need to do to provide a high degree of assurance to customers (excipient users). The manufacturer needs to be able to
tell the customer that it has the issue under control, that it has minimized the particle occurrence to the greatest extent
possible, and that it can communicate with them about this topic.
The next phase of our plan is the user phase. Users will need to have a subteam where they look at issues such as, 'What do
we do upon receipt? If we see a black particle, do we automatically reject?' And in some cases, users will need to re-examine
their decision-making procedures in this regard.
Ultimately, we hope to bring together the responsible manufacturing point of view from the maker's side and the responsible
acceptance procedures on the user's side, all with the focus on patient safety. Once we have what we consider a good guideline,
we hope to sit down with FDA and review it with them to gain acceptance and move forward.
Schoneker (Colorcon): To be clear, from the point of the IPEC Executive Committee, this guideline is not meant to give manufacturers the ability
to avoid high quality standards. If you have a belt that is shearing pieces into the product—the resulting specks are not
inherent. That problem needs to be fixed and GMP practice must apply.
PharmTech: The IPEC guideline may suggest taking a customer complaint about specks being found in excipient materials and using that
complaint to perform a risk assessment. Can you provide some more detail on what's planned?
Van Meter (IPEC): The way that we think a good manufacturer should behave in this regard is that you need both a feed-forward and a feed-back
risk assessment. The feed-forward risk assessment involves having documentation of the process that details where these types
of particles may be formed. Then a company can perform a review or a mitigation when they are found. We also want a feed-back
risk assessment, which means that when a manufacturer gets a customer complaint, you can take the particles, analyze them,
and look back in the manufacturing process to see where the particle may have been generated. That risk assessment should
then be updated as necessary.
In addition, I'd like to make a comment about testing and how we can learn how to mitigate some of these issues. We get asked
all the time about whether our sample plan covers visible particles. The answer is, you sample, and you evaluate your samples
for particles of any kind that would be atypical. However, when you're looking at a performance level, even if you're generating
off-color particles, in many cases, you're looking at performance levels of 6, 7, 9 Sigma, and beyond. So anything that you
can grab a sample of, you can ensure yourself that if you have an off-color particle that may end up in a final product, you're
going to catch it.