From The Editor | May 4, 2015

Not a Sterile Debate On Aseptic Services Crunch

By Louis Garguilo, Chief Editor, Outsourced Pharma

Louis Garguilo

In 2012, a report from the U.S. Congress Committee on Oversight and Government Reform was clear on whom to thank for a growing aseptic services crisis. Allow me to paraphrase from the report, poignantly titled, “FDA’s Contribution to the Drug Shortage Crisis”:

“Patients confront an unprecedented shortage of critical drugs, causing inferior treatment regimens, interruptions in care, higher health care costs, and even premature death. The crisis was largely sparked by the FDA’s regulatory activity that effectively shut down 30% of the total manufacturing capacity at four of America’s largest producers of generic injectable medications. Of the 219 drugs listed on the American Society of Health System Pharmacists (ASHSP) shortage list, at least 128 – 58% of the list – were produced by at least one facility undergoing FDA remediation…”

Well, at least it wasn’t the usual circuitous government syntax. But should we hang that level of blame in the FDA’s closet? Subsequently, legitimate concerns for patient safety, and the initial impetus for remediation, garnered more attention.

Most recently, driving the aseptic services sector is positive news, but with a side effect: the breakthroughs in biologics and biosimilars, immunotherapy, therapeutic vaccines and virus production, and other increasingly complex products, are enabling the creation of exciting new drugs and therapies … all requiring more aseptic services.

The government report above deals primarily with a shortage in generics that have been on the market for decades. Today, we confront a brave, new world of medicines, and as we will see, one that can hinge on the right capacity and perfect safety compliance in aseptic facilities. This new frontier is being opened by the largest drug manufacturers as well as virtual biotechs. And it offers a high risk-reward opportunity for aseptic service providers working with drug innovators. In fact, in a recent survey, two-thirds of sponsors who outsource indicate they are looking for “injectable development support” from CMOs.

Aseptic All Around

Two main components spurred the capacity crunch that led to shortages of some common, large-volume injectables, and the concerns around current and future capacity to produce new products.

The first component is safety, and therefore compliance. The second is the new types of drugs/therapies on the market, and those just behind them in development, all requiring aseptic services. Many in the industry – and public at large – point to the breakthrough vaccine Gardasil as an usher of this new era. What’s certain is aseptic capacity concerns are as much on the minds of those in the bio/pharma industry as any other subject.

In a recent conversation for an upcoming Life Science Leader magazine feature, a VP of pharmaceutical manufacturing operations at a Big Pharma said he constantly evaluates not only whether there’s the requisite capacity for aseptic production, but also whether there’s the right capacity. “It’s crucial to have capacity, but up-to-date capacity,” said this manufacturing executive. “Will we be contemporary in the future?” is the leading question in an era of accelerating changes in production for new drugs and technologies.

Marco A. Chacón, President & CEO at Paragon Bioservices, Inc., who counts as many biotech as pharma customers, echoes this focus on the right capacity. He’s investing in his facilities to stay ahead of customers who are developing new vaccines, oncology drugs, and immunotherapies. Chacón knows the common denominator for all these new drug categories requiring aseptic standards. “At the end of the day, you are dealing with injecting a human being. You have to ask would I inject myself, or my own child, with this product, and the answer better be yes.”

Perhaps the FDA could have had a better implementation when it started cracking down on aseptic facilities. On the other hand, we owe the agency a nod of approval for getting in front of growing issues, more closely monitoring compliance, and yes, for tightening requirements to better guard patient safety.

A Real Lack Or Just Concern For Current Capacity?

Aseptic service provider Lyophilization Services of New England, Inc. (LSNE), recently completed a successful FDA Pre-Approval Inspection (PAI) at its facility in Bedford, New Hampshire, to manufacture a commercial drug product for U.S. distribution. “This is the culmination of years' worth of preparation and diligence,” said CEO Shawn Cain. Statements like this remind us of another contributing factor to concerns of aseptic services capacity: The high barrier to entry. This barrier exists for new companies, established providers thinking to get into the business, and current aseptic service providers looking to expand capabilities (like both LSNE and Paragon). It also applies to BioPharma itself, who instead of adding internal aseptic capacity, will continue to rely on outsourcing.

“The compliance bar has risen for good and bad,” comments LSNE’s VP of quality, Tom McGrath. “The financial investment, skill set and time period needed to build a compliant facility are so daunting that few will undertake the task. Few organizations of any size – including pharma – will bring a facility up without an existing book of business. It’s a big leap of faith.”

As a result, McGrath says, “My feeling is there is not enough capacity, at least in terms of current idle capacity out there, both at sponsors and providers.”

On the provider side, McGrath divides the industry into two main categories: smaller “boutique shops,” and the large “commodity” manufacturers. He says few CMOs can really fit in the middle of those two right now. “That’s important,” he says, “because Big Bio and Pharma are increasingly looking for providers to handle early, limited capacity for development and clinical trials, and also grow with them to millions of units a year if they get to commercial.”

It’s a tough middle ground to fill. Sponsors want a current commitment should more capacity be needed in future, but don’t want to “own” the capacity. This isn’t a unique circumstance, and a major reason for outsourcing in the first place. However, given capacity concerns and increasing demands, sponsors and providers would do well to work this dynamic out particularly for aseptic services.

Finally here, McGrath says compliance risk has escalated to the extent it impacts the RFP process between sponsors and providers. First is the question of capacity – the right capacity – often determined by lyophilization capabilities – and pricing is always a main factor. “But since 2008 [when the FDA started focusing on aseptic service facilities], the biggest factor might very well be compliance, and your track record with the regulatory bodies,” he says.

True Around the World

The concerns surrounding aseptic services are global. From the U.K., for example, we hear recent comments like these from service provider Aesica, who though a small player, decided to leave the aseptic market after an inspection by the UK’s Medicines and Healthcare products Regulatory Agency (MHRA). “What we hear now from the market,” said Ian Muir, Managing Director - Finished Dose at Aesica, “is there is limited capability for early stage development steriles in the UK … The market has gone from a position where there were quite a number of players to very few.”

Some Pharma leaders say privately that while oversees markets are growing in importance, safety and compliance concerns give pause to utilizing aseptic services for innovative drugs and therapies in countries outside the U.S. and parts of Europe.

In the meantime, academic researchers around the world, government-based health organizations like the NIH, the regulatory bodies themselves, and indeed entire national healthcare systems, all join the biopharma industry in looking increasingly to getting these new drugs and therapeutics to patients. For the most widespread success, progress must be matched by the safe, compliant, and “right” capacity in aseptic facilities, both internally at manufacturers, and externally at providers. This will also require a high level of cooperation and partnerships between the two.