Warning letter emphasizes need for quality agreement with contract manufacturer

31-May-2017 - Last updated on 01-Jun-2017 at 14:42 GMT

A recent FDA warning letter reinforces the idea that a quality agreement that covers all aspects of a contract manufacturing relationship—including the documentation aspect—is really a must-have for GMP compliance.

In the warning letter that FDA sent to VitaPurity Corporation, which is based in Central Point, OR, the GMP compliance deficiencies noted revolved around that company’s relationship with its contract manufacturer. Long familiarity with and confidence in a contract manufacturer might be all fine and good, but it does not substitute for documented procedures to assure that the products that come in to the brand holder’s facility meet specifications.

“You state that you assume your contract manufacturer is responsible for preparing a master manufacturing record, exercising quality control functions, and verifying that the finished products meet specifications. You state that you assume your contract manufacturer is complying with 21 CFR Part 111 because you are unaware of any problems at the plant,” the letter reads.

“You state that you do not have a written agreement with your contract manufacturer, and have not performed any audit or engaged in any other activity to determine the acceptability of the manufacturer to manufacture your dietary supplement products, or to ensure the quality of the dietary supplements received and that the products are packaged and labeled as specified in the master manufacturing record,” the letter went on to say.

Quality agreement ends finger pointing

A quality agreement with a contract manufacturer is one of the things that an FDA inspector would look for when delving into the operations of a brand holder, said Larisa Pavlick, vice president of regulatory and compliance for the United Natural Products Alliance. Before coming on board with the organization last year Pavlick spent a number of years as an FDA inspector working out of the Denver office. She said in her experience things changed around 2013, because so often when inspectors were looking at operations on the brand holder side, or conversely were inspecting a contract manufacturing operation, fingers got pointed both ways when questions were raised about who was responsible for what when it came to maintaining master manufacturing records, batch products records, etc. The answer came to be: The buck stops with the brand holder, but both sides have obligations in the GMP responsibility chain.

“During my time at FDA this idea kind of evolved, because somebody has to be clearly responsible for the quality of the product,” Pavlick told NutraIngredients-USA.

Agreements with contract manufacturers would cover the basics of commerce: what product is to be made, with what ingredients, when it is to be delivered and at what cost. What is really critical for full GMP compliance would be a separate quality agreement that would lay out in detail the procedures for making sure that product is what it is supposed to be, and that it will turn out that way every time. This would cover the master manufacturing record, the batch production records, finished product testing, and in particular the procedures for verifying that all of the above is up to snuff.

“I would always ask a brand holder who is responsible for releasing the product, and that is mentioned in this warning letter as well,” Pavlick said.

Interplay between parties

Pavlick said that the quality agreement could allow for some reasonable interplay with a contract manufacturer as to how the master manufacturing records and batch production records are structured. It is not necessary, in other words, for a brand holder to impose a specific set of documents in order to comply with GMP regulations.

“The contract manufacturer would likely have their own procedures. They might say, we know how to run a tableting press. We know how to run a mixer,” Pavlick said.

But even with such a quality agreement in place, if the brand holder is releasing the product to interstate commerce, it is incumbent on that party to have a procedure in place to make sure that the products meet specifications. “We’ve never had a problem with them. Their stuff always meets spec,” is not a GMP-compliant procedure.

“The rule doesn’t say you have to do chemistry on every lot, but you do have to define a procedure. You could say we’ve weighed the product, we’ve looked at it visually, and so forth," Pavlick said.