Is making pharmaceuticals offshore more problematic than in the US? A new study suggests the answer is resoundingly 'yes.' Even drugs made in offshore plants run by US drugmakers pose a greater quality risk than those manufactured on the mainland, according to the study in the Journal of Operations Management.
For instance, the study found drugs made in plants in Puerto Rican that are owned by US drugmakers were more likely to have quality problems than those made by the same drugmaker at a similar plant in the US. "This finding persists above and beyond potentially important factors, such as geographic distance and the local population's general and industry-specific skills," the researchers wrote.
The findings accounted for many of the alternative explanations about why offshore plants may have lower quality than those on the US mainland, and also underscores the need for the FDA to maintain a focus on inspecting plants that are not based in the US. The agency has been attempting to step up its scrutiny of overseas plants ever since the heparin scandal a few years ago (back story).
"We believe the quality differences we found in Puerto Rican plants were driven by challenges in transferring knowledge from headquarters to the plant, due to cultural differences, primarily differences in language and values,” John Gray, the lead author and an assistant professor of operations at Ohio State University’s Fisher College of Business, says in a statement.
The researchers used FDA inspection reports issued between 1994 and 2007 concerning 30 plants based in Puerto Rico and the mainland US that make both over-the-counter and prescription drugs. The researchers then asked four independent experts - one worked in the FDA for 34 years and the other three had "extensive" experience working in quality control for major US drugmakers - to create a scoring system based on possible inspection outcomes. Then they created a tool for measuring risk.
One possible interpretation is that, for all the concern about risk associated with plants in Puerto Rico, overseas plants may be problematic, since workers and plants in Puerto Rico most likely have a good deal in common with similar mainland operations. “Facilities in more distant, less developed countries may face even greater obstacles to quality control than what we found in Puerto Rico," says Gray (you can read the abstract here).
The study notes, by the way, that even "household" brand-name drugmakers with "long histories of operating in an industry - where quality is critical and regulation is intense - have been unable to achieve the same levels of quality risk in their offshore locations, on average, as they have in their onshore plants. Examples include GlaxoSmithKline, Johnson & Johnson, Bristol-Myers Squibb and Baxter (see here, here, here and here).
8 Comments
Maybe more oversight would help fix the alleged problem. Simple enough!
Sounds simple, but it's not that simple. Oversight in other continents require more resources and creates dispersion and communication gaps.
Steve Knows is correct. Have independent testing labs QC test all lots imported into the United States. With failed lot numbers rejected entirely.
That would take care of Kevin's concern by forcing QC compliance onto the manufacturer where it belongs.
Steve and Steve -
It's not that easy - can't test quality in. Testing a small percentage of tablets can't assure the quality of the entire batch without quality management and QbD and quality systems at the manufacturer. Make no mistake though that there are significant issues in the US (see J&J PA facilities) as well. And, the facilities in PR that are referenced have the same amount of oversight as a mianland US facility - they are subject to the same laws as US state facilities -there is an FDA office on the island. Much different paradigm than a facility in China.
Linda: fully agree that you "can't test quality in". You can test a higher proportion of each batch (where the meaning of that term has to be carefully monitored) and raise the stakes by requiring rejection of entire batches for a failure.
You have to test a large enough fraction of each "batch" to achieve your desired probability of not letting bad stuff through (however "bad" is defined). If the manufacturing process is less stable (as it is likely to be in overseas facilities), then a higher proportion of each batch must be tested.
But . . . testing more costs more money, and raising the stakes (entire batch gets trashed = some financial loss (although, ironically, they can probably still sell it overseas)) increases the incentives for corruption in various forms.
Oversight/quality control is just what it describes. If the company pays more attention to the details and [surprise] spot checks, it would make a better and more profitable operation.
Side comment: The patient expects to get what it pays handsomely for. It's called dependability.
I have experience with FDA auditors in PR and they are notorious for being extremely conservative and thorough, rightfully so. I wonder how much closer in quality the mainland-based facilities would be deemed, if those same inspectors audited them.
All of the auditors that have come through our facility (based in the Midwest) have been conservative and thorough. They all get the same training, but not all auditors are created equally. We are seeing a lot of younger auditors that seem to be trying to make a name for themselves.
If your product is based on strong process validation, you should not have to test fractions which would be more apt with a product with either. Lot of process drift or weak process validation.
A strong internal auditing and QA group definitely helps as well.