From The Editor | September 27, 2016

Top (Secret) Quality Concerns For Selecting CMOs: How Important Are Records?


By Louis Garguilo, Chief Editor, Outsourced Pharma

Top (Secret) Quality Concerns For CMOs: How Important Are Records?

Five experts go undercover to prioritize a secret top-ten list of quality topics for Pharma and Bio sponsors selecting contract development and manufacturing organizations (CMOs). After weeks of discussion, they select a conference venue with a room chockfull of drug industry sponsors and service providers to unveil their work.

What they aren’t aware of is that the audience will have its own stab at the list. An app downloaded to mobile devices allows them to select their personal preference from among the topics presented.

When the two lists are compared for all to see … well, let’s just say a quality quandary is exposed.

Here’s the experts list in order of importance, with the audience’s selections in parentheses at the end of each item. Do you spot the anomaly?

What do you see as the top quality/regulatory issue when outsourcing?

1. Quality culture or culture of quality (1)

2. CMO commitment to FDA vs. client’s quality needs (3)

3. Success metrics for CMOs and clients; reconciling win-win paradigm (tied for 5)

4. Agency inspection and client involvement; during and after (tied for 6)

5. Back to basics: CMO’s track record of GMP manufacturing (4)

6. CMO’s mechanism for introducing new product into facility (tied for 5)

7. CMO’s interpretation of GMP readiness for analytical methods (tied for 6)

8. QMS requirements not designed for outsourcing model (tied for 5)

9. Quality records – batch records; lab records (2)

10. Qualifications of CMO subcontractors/vendors (tied for 6)

I’m sure you see it: Something’s cooking with those ubiquitous quality records, the ones the industry often describe as the backbone of cGMP compliance.

Fortunately, all this leads to an elucidation sponsors and CMOs everywhere should hear.

Is It Really A Matter Of Record?

Faced with the audience’s placement of quality records much higher up the list than did her experts, our moderator defects to the resistance.

“Interesting,” says Julia O’Neill, Principal, Tunnell Consulting. “I was also one who voted for quality records.” The room falls silent; she continues. “I’ve been in a lot of discussions about ‘quality culture,’ and how to measure it. But from my point of view, the proof is in the documentation.”

Some of the experts scribble notes to themselves. O’Neill pushes on: “If an outfit you’re working with, whether it’s a CMO or any other stripe, have the records that you need in good order, then you know they’ve got some semblance of a quality culture. And by quality culture I do mean GMP. They can talk all they want, but I want to see the documents.”

One panelist leans into his microphone just ahead of the others, all seemingly eager to respond.

“You’re right,” says Bikash Chatterjee, President and CSO, Pharmatech Associates, in a measured tone. “You do have to look at the key elements that need to be there from a GMP perspective. But the devil is in the details.

“Think of quality as a process, and all high performing business processes have the same characteristics. When you look at folks that have a fully compliant quality structure, versus those that have a culture of quality, you see the difference.

“In the first case, you see institutionalized governance and oversight. A CMO may faithfully track CAPAs [corrective and preventive actions] and deviations for a quarterly report. But when you ask what do you do with that, they say, ‘We discuss it and meet the next quarter to see how we’re doing.’

“A company with a culture of quality uses that data to actively design their remediation programs, to ensure they can anticipate, and stay ahead of the curve. For CMOs that are extremely successful, it’s a leading indicator.

“Documentation is a key component, but how do you use it? The difference between ICH Q 9 and Q10 guidance? It’s that quality is involved in the scientific element. That means quality folks understand how the process, oversight and control philosophy ensures the product will work. Not to make sure that forms are fully filled out before proceeding to the next step.”

He barely finishes when E.J. Brandreth, VP Quality, Inovio Pharmaceuticals, jumps in.

“Of course quality people embrace their quality system. But the question is how much does the manufacturing group embrace quality. Are they on the same page? You’ll see that in the documents where deviations or CAPAs are late. Quality tells the engineers they’ve got to turn that in, but it isn’t important to them. So yes, you’ll see it in the documents, but the point is at the good CMOs – and good clients – the production people care about quality as much as the quality people.”

Keith Hall, VP Operations, Vical, finishes this point:

“I’d add that this type of quality-culture organization has to start at the top. It can’t be something that the guys at the bottom are trying to bolt up, so to speak. If people see the heads of quality and production working together, and having a common culture and message, it filters throughout the workforce.”

Next Roy Musil, Sr. Director Quality, Juno Therapeutics, takes his opportunity:

“It reminds me of an inspection I was involved in, where a particular inspector said to us: ‘Your change control system is fine – you have all the right elements – but I’m concerned about your control of change.’

“In other words, it’s fine if the documentation is there, but how is that organization managing change on a day-to-day basis? If you see documentation for a major change that all lines up, but the timing doesn’t seem to make sense – something should have been planned months or a year ao – you know something was going on behind the scenes. These types of things speak to an organization’s maturity, and culture of quality.”

Ought We Talk About Audits?

The first response from the audience concerns auditing CMOs (but ends up leading us right back to documents):

“I’d like advice on the qualification audit before a contract is signed. It’s difficult to assess the quality you’re going to get based on this audit. Anybody can have pretty systems. All the documents could be in place.”

Brandreth responds first: “Yes, CMOs get really good at hosting audits. The documents they show you have been looked at dozens of times. If everything is perfectly smooth, and it feels staged instead of honest, that might speak to how well they can host an audit, and not really what’s happening at the company.

“The best evaluations come from the discussion with the people at the audit. Interview the manufacturing people. When you look at the maintenance SOP, ask for the maintenance people. If they have a chip on their shoulder, or the quality people are bickering about something, that’s the tip of the iceberg.”

Chatterjee jumps back in: “If you use a fair number of CMOs, measuring the results of your qualification audits versus your actual performance is a good way to understand if you need to tweak your audit process to be more in line with what your actual organization’s needs are.”

His final comment seems to bring the room together: “Think of it this way: You’re not the first person to make a request to look at a quality document. CMOs have constant requests. If they’re going to work with clients, they should have figured out how to accommodate requests in a way that maintains confidentiality, but allows you to get into those particular systems. If they can't, that’s a red flag. You can start to piece together the quality documents and the culture.”


* E.J. Brandreth, VP Quality | Inovio Pharmaceuticals; Keith Hall, VP Operations | Vical; Roy Musil, Sr. Director Quality | Juno Therapeutics; Bikash Chatterjee, President and CSO | Pharmatech Associates; Julia O’Neill, Principal | Tunnell Consulting (Moderator)