From The Editor | April 1, 2019

Solutions Needed For Automated And Analytical Services In Fill Finish

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By Louis Garguilo, Chief Editor, Outsourced Pharma

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When it comes to fill finish services provided by CDMOs, two items high on biopharma executives’ wish list are increased analytical and testing capabilities, and automation to replace manual product-line inspection.

The CDMOs have some thoughts on these as well.

These specific challenges were revealed in a recent Outsourced Pharma editorial. This CDMO response follows some earlier comments (part one is here).

Respondents include these chief executives of CDMOs:

  • David Enloe, President & CEO, Ajinomoto Bio-Pharma Services
  • Stephan Kutzer, President & CEO, Alcami Corporation
  • Vivek Sharma, CEO, Piramal Pharma Solutions
  • Tae Han Kim, President & CEO, Samsung Biologics

Analyzing Analytical Services

The implication from biopharma is that CDMOs are dragging their feet when it comes to implementing beefed up analytical services to support fill-finish programs.

The CDMOs, it turns out, couldn’t agree more – nor heard the cries more clearly – for a widening of analytical-support services.

What they don’t agree with is that the service providers aren’t responding to those needs as best they can. Here’s how one CDMO CEO sees it:

“It’s interesting. I read through that. But it’s actually something we took into full consideration when creating our company. We do the development of the processes, the tech transfers, the analytical work, the release testing, and the formulation work. Our integrated offering addresses exactly this challenge, which I have personally seen over the last 20 years, where five or six different CDMOs specialized in certain areas, such as Lonza does API, Eurofins analytical work, and Patheon the drug product, for example.

“The amount of knowhow that gets ‘lost in tech-transfer translation’ leads to problems and makes the whole process bumpy. That’s why customers are saying you’ve got to have an integrated offering. Particularly for smaller customers, when a CDMO releases a batch, you have to understand what you’re looking at, any complications, as well as develop an analytical synthesis or analytical-release protocol exactly fitting the way you have developed the product.

“Drug development and manufacturing is in fact moving towards that. We see Cambrex, and Thermo Fisher buying other companies – including Patheon. Specializing only on manufacturing doesn’t do very good anymore.

“So the trend is integrated services, including the analytics. There will remain stand-alone testing labs for environmental and non-process-related needs, absolutely. But anything that has to do with pharmaceutical manufacturing is more in the hands of a manufacturer.”

Another respondent informed me of this:

“Analytics are often among the most complex portions of the tech transfer process. For CMOs, investment in a laboratory that can handle over ninety-five percent of all possible methods is cost prohibitive. Nonetheless, we’ve justified a larger investment in analytical capability by also making a stand-alone analytical service business to support release testing into Asian markets, for example. This strategy justifies higher investment in equipment and people to ensure we can manage tech transfers across nearly all methods.”

Finally on this subject:

“I assure you if the dollars worked for the biopharma customers themselves, those analytical services would already be provided in-house.

“This needs to be a team effort. For example, we have a drug-substance customer who put enough emphasis on its batch-release turnaround times that it invested in us hiring dedicated, incremental personnel to ensure their timelines would be met. It’s been a fantastic partnership. We’ve shown a marked decrease in turnaround times, and an increase in expertise with their product. They’ve been willing to pay for that in a way everybody can be happy with the relationship.

“Unfortunately, it’s still a novel approach.”

Visualizing Visual Inspections

Regarding visual inspections for products in development and manufacture, there’s a distinct disconnect between what the biopharma customer wants, and the service-provider reality.

“We understand visual inspection is a major challenge facing the industry,” says one CDMO CEO.

“But here’s the real challenge: If I looked at our fill schedule for the next month, it might require 30 different vial or syringe configurations. Automated inspection equipment has traditionally been dedicated to any one of those myriad configurations.

“In other words, we wouldn’t need two visual-inspection automated machines, we would need dozens. Each would cost well in excess of a million dollars. Now, if a client wants to partner, and it’s important enough for the client to be automated in that area, perhaps it would be important enough for them to give volume commitments over time, and/or co-invest in that automated equipment. Our margins aren’t supporting us investing in every what-if configuration of automated inspection.

“That being said, yes, we’re working on the best ways possible to automate our visual inspection process.”

However, as this CEO intimates, the devil is in the equipment and technology details: for the most part, it doesn’t exist.

“Overall, new technology and equipment is entering fill finish. The next piece of equipment we are putting in – actually in fabrication now – is a newer, nested configuration. It’s a multi-purpose production line agnostic to type, vial, syringe, or cartridge. You feed in pre-sterilized units, and whatever you send down the line is filled. Suddenly, that one line can do vials on a Monday and syringes on a Tuesday.

“So now we need to get there with our automated visual inspection equipment as well. Equipment that can automatically inspect a 2ml vial on Monday and a 5ml vial on Tuesday has not existed in the past.”

Therefore, at this point in our outsourcing history, while biopharma nor CDMOs have solutions, it appears to the CDMOs that customers are saying, “We need to get to visual inspections, and the onus is on you to figure it outand pay it forward.”

Contributing Trends

At the same time, the above realities collide with another trend in outsourcing.

“The pressure on the biopharmaceutical-customer base is to have fewer but deeper CDMO relationships. One of the larger pharma companies in the world recently told me they’re under edict to reduce the number of relationships they have from 1,200 to 400!

“The only way they’re going to do that is by getting rid of specializations. Therefore, I believe the next step will be the realization, ‘For us to work more deeply with you, we’re willing to invest some capital – either dedicated wholly or in part to us – and truly work to ensure we’re getting what we want produced in the most modernized and acceptable manner available.’

“Customers have to understand CDMOs just can’t make that investment on every one of their programs.”

Separately, “Annex 1” in Europe is a challenge regarding global fill finish services.

“This entire Annex One draft, I believe, is a first try to somehow get us more organized. Once we do get technologies that can do the visual testing and inspection, and go from the variables of the human eye to laser scanning or whatever that might be, we can finally get to a point where we have comparable results. Standardizing is the biggest move we are seeing now. I fully agree with our customers it’s a challenge, and we need to do this.

“You know, the CDMO industry is trying to come up with something. It will take a bit more time – from technical development, equipment and testing points of view – to improve what we have today. Millions and millions of dollars have been blocked because of this visual inspection challenge. It has to change. We don’t have a solution yet.”

Here’s an idea – and perhaps the largest take away from all three of our editorials:

How about drug sponsors and service providers share both the visions and investments needed to meet increasing fill finish needs. That shouldn’t be so hard to see or analyze.