The High Life And Times Of A Qualified Person (QP) In Europe

By Louis Garguilo, Chief Editor, Outsourced Pharma

To operate as a QP and release batches, you must be appropriately qualified, trained, accepted by the relevant competent authority in the European Union, and named on a site’s authorization.

According to Nollaig Buckley, a Qualified Person (QP) for some 22 years, you also need a dose of creativity.

Here’s a real-world example she provides.

“A U.S. drug sponsor had about five patients left to dose to complete a clinical trial here in Europe. They needed a small amount of material to finish dosing. While there were units of a batch located at the EU clinical trial sites, these were about to expire."

Without consulting the QP [Buckley], the sponsor had ordered the manufacture of new units to replace the expiring units. But the manufacturing was at a site different from that named in the dossier. The sponsor also adjusted the manufacturing process to accommodate a smaller batch size.

"Moreover," she continues, "known to me but not the sponsor,  there were compliance issues at the new – unauthorized – site!"

The replacement batch processing records were presented to me, but I wasn't going to release that batch."

They responded, ‘Why? The other batches for the trial were released. Our company's going down if we don't finish this clinical trial.’

"Rather than take an entrenched position, Buckley  asked questions.

Regarding the material in the EU clinics right now, when does it expire? Is the batch at the EU clinics being studied for stability? Can you get your hands on those stability samples and test against the stability protocol?

“The plan was to see if we could extend the shelf life of the existing and available units. Additional stability was generated so an extended shelf life, and a new expiry date, could be supported. The units were already available at the clinics to get their expiry date updated.

They got their product. Patients got dosed. Happy days.”

After a contemplative pause:

“Honest to God, you must be creative. I guess that sort of individual skill is helpful. I'm a troubleshooter. That's what I love.”

The QP Is Born

When I ask Buckley if her career path to becoming a QP was typical, she replies, “In my day, few people knew much about this guild. When I was in college in the mid-80s, I had never heard of a QP.”

In fact, the European Union only introduced the concept of the QP role in 1975. The importance of the role was emphasized through what is designated EU Directive 2001/83/EC. This set the requirement that Qualified Persons (QP) must officially release (or reject) medical materials imported into or produced in Europe.

Buckley earned degrees in Industrial Chemistry; her first industry job was in process development at a pilot plant. “I had a technical role focused on lab-based synthesis, and all of that. I loved it.”

“But I was ambitious,” she appends with a smile.

She found herself interested in the finished-product side of the industry.

Buckley joined an "innovative Irish company called Elan Pharmaceuticals."

“They were paving the way for reformulation of existing authorized products, so finding new indications, et cetera. They were essentially a CDMO but did own some products.”

She took on a technical services role, for example working on scale-ups and validation.

“You learn what quality means when you're in such a position,” she says. “And perhaps because of my natural ‘negative bias,’ I was able to see things that are wrong, or that could go wrong.”

This was also Buckley’s first introduction to the QP role.

“I saw that the QP we were working with was a decision-maker. I thought, ‘I have no problem making decisions.’

“Decision-making is not everybody's thing, but I like people coming to me with an issue and asking, ‘What do we do here?’

“I instinctively get thinking, ‘What do the regulations say? What are we allowed to do?’ We need to make judgements on potential gaps in our compliance versus patient needs.

“I saw that a creative QP is judging circumstances and suggesting solutions.”

Time To Train

Typically, a pharmacist or a medical doctor in Europe, for example, is deemed  eligible to become a QP. Buckley, though, needed a “conversion course.”

There was a single course offered in Ireland (late 1990s) for getting qualified to be a QP, and she took it.

Next, as we detailed in part one, she needed to get named on a manufacturing site’s authorization as a QP.

“I had to approach an authorized site and convince them I’m worth training in their systems, and should be named as one of their QPs,” she explains.

She did, they agreed, and she says, “I've been working as a contract QP ever since.”

Today, Buckley is the experienced trainer of want-to-be QPs. She creates custom courses for her CDMO and sponsor clients, leveraging years of experience dealing with investigational medicinal products.

She says CDMOs and sponsors outside (and some located in) Europe still do not understand or anticipate the complexities of getting their materials released in Europe. (see part one)

“Sponsors go to the CDMO expecting to be educated,” she explains. “Unfortunately, in too many cases, the CDMO isn’t in a position to do that.”

This is exacerbated when the CDMO is not based in Europe, but exporting there for a client’s clinical trials. CDMOs are focused on getting the batches manufactured, not particularly getting those batches into the EU, which as per above,  involves the authorized site responsible for importation, and QP certification.

“QPs,” Buckey says, “end up surprising the sponsor with documentation requests. It can be a stream of QP requests, and the sponsor passes them on to the CDMO.”

For example, the EU has new requirements around the manufacture of sterile products, such as filter-integrity testing now required for the sterilizing filter both before and after use.

U.S.-based CDMOs may not know this, and only undertake post-use testing.

“Now the QP is asking for the risk assessment that justifies the approach … and the list of additional needs goes on.”

Buckley concludes:

“We need to train the CDMOs and the sponsors. Too many batch releases get delayed. With prior training from a QP, everybody wins – including patients.

“And I can rest at night assured I have met my legal obligations. Although I do enjoy having to get creative.”