Challenge may be to R&D staff, not just QA/QC, says Mallinckrodt exec.

PHILADELPHIA -- FDA has been trying to get the pharmaceutical industry to implement PAT as a means of applying real-time QA/QC instead of testing and validating batches after the fact, but the real challenge to PAT acceptance might not just be with QA and QC staff, but R&D personnel.

So says Vishal Gupta, Ph.D., a senior research investigator at Tyco Healthcare Mallinckrodt in St. Louis, who told CPT's conference here Oct. 1:

"It's going to be a big learning phase for all of us, understanding how exactly R&D can apply PAT, and it will be important that everybody is on the same page."

Gupta pointed to PAT's potential for anticipating future changes based on past trends. One problem is that the industry lacks one good, reproducible method for the scale-up process.

"We also don't really have a good tool in R&D to predict what will happen to the product in terms of physical process attributes," he said. "It would be nice to eventually have a PAT type of instrument that's a good predictor of change from R&D. As an industry and as scientists, we need to bring in technologies maybe from other industries that are effective predictors of change."

Gupta, who contended that Abbott Laboratories is ahead of the curve with its use of PAT, said other big pharma companies would like to "get it right the first time," too. He argued that PAT can make pre-validation batches "right the first time," as well as save time and money for companies that employ it.

"PAT is merely a fancy word in my opinion that we have started using recently, but there is nothing new about it," Gupta argued. "People in other industries have been using these techniques for years. It's just now they have a name and they are under one umbrella."

Moving away from a model that tests the product at completion, PAT ensures that the quality is built in. Gupta said: "Once validation is done and the product is manufactured or is in production on a regular basis, most of that testing is never repeated, so what we rely on is a representative sample. The vision of PAT is that if we can employ some of these tools during processing at different unit operations, then we have quality built in at every step."

For Gupta, PAT's biggest advantage is its "closed-loop approach" that allows quality control to be monitored in real time. In this way PAT can be an extraordinary time-saving device. "We are spending too much time now doing off-line testing and shuffling paperwork for compliance procedures. If quality is built in, maybe we can reduce the time it takes to complete a batch." Although PAT has not yet obviated the need for off-line testing, that should be one of its primary goals, says Gupta.

"When you're testing the feasibility of different approaches you make your batch and give it to the analysis department; you wait for testing to come and then you move forward. But if we have a PAT procedure in place, then we can have results on the fly, with no hold time for parallel processing."

Another advantage to using PAT is that its testing procedures are non-destructive. "One of the ironies now is that when we test a sample, the usage form is destructed [sic] and we can't use it later for root cause analysis." PAT may also improve health and safety of employees by allowing testing to be conducted with less exposure to dangerous compounds, he added.

Currently, PAT is being used on a per-product basis, rather than as a platform technology, and Gupta would like to see that change. According to Gupta, most companies are already using PAT to a greater or lesser extent. "Now it is common in production to have little cameras photographing clumping or anything unusual in the formulation. This is a form of qualitative, if crude, PAT."

He also said PAT is not just for big pharma companies, but small-to-medium-size firms.

"Everyone is a stakeholder in the process. Everybody needs to be at the same level on what they're going to do with this technology."

However, he warned that, from his personal experience, companies that are behind with PAT would do better to adopt just a few techniques at a time, keeping a narrow focus and slowly developing necessary resources to further expand PAT technology.