From The Editor | September 28, 2018

Levels Of Risk Severity In Biopharma's Global Outsourcing


By Louis Garguilo, Chief Editor, Outsourced Pharma

Levels Of Risk Severity In Biopharma’s Global Outsourcing

It’s unanimous across this panel of international biopharma outsourcing experts: global playing fields are uneven, the players unequal, and supply-chain risks imbalanced.

Perhaps this was best laid out by Kenneth Wexler, Senior Quality Assurance CRO Manager for Global Quality and Compliance, Boehringer Ingelheim Pharmaceuticals. Wexler has years of experience conducting global site visits and audits, negotiating international quality assurance agreements, and onboarding CMOs in countries around the world for development of new drugs.

When it comes to quality and “GMP mindsets” at CMOs in various countries or regions, he says, “We tend to select what we view as globally-oriented CMOs with a robust understanding of compliance. We still view that many of these are located in Western Europe and the United States.” He adds: “Of course it can depend on what the supply chain needs are, but the quality risks can be more severe in other countries.”

Wexler, though, is careful not to paint with broad brush strokes. “There are certainly differences within countries, so it is hard to generalize. There are excellent CMOs in weak countries. It’s the same here in the U.S. – we’ve had fraud and corruption here. It’s not black and white, but it is a risk assessment.”

This lingering delineation between the U.S./Europe and “others,” prompts Patrick Guertin, Global Technical Manager, GE Life Sciences’ Fast Trak Services – an organization responsible for process development, tech transfer and cGMP manufacturing of biomolecules – to interject a question of drug-sponsor motivation.

“There’s definitely a difference throughout the world,” he iterates. “If you are Western-based, and contemplating outsourcing offshore, you have to ask yourself, ‘What is my real motivation for this decision?’”

So Outsourced Pharma readers, “What is your motivation?”

Is it specific to costs or pricing? Is it in the quest to acquire more secure sources of material, to better the quality of your products, to serve those foreign markets, and/or to serve patients in the long run?

Guertin believes some drug sponsors perceive that “regulatory compliance is lesser in other countries, so there may be an easier path forward for programs.” However, he advises, there are pros and cons to different levels of regulatory and compliance expectations. “I think that to stay within the highest level of compliance, regardless of whether it’s coming from the relevant regulatory body, your internal organization, or in fact your CMO, is the highest order of business.” In other words, meeting the most stringent standards of quality, and supply-chain security is, a business and moral imperative to meet the needs of patients.

Vimal Gandhi, Procurement and Supply Chain Executive at AstraZeneca’s biologics division in Medimmune, has held roles across R&D and operations, supporting vaccine manufacturing, biologics development, and the launching of biosimilars. He, too, has given this subject much thought. “New biopharma companies appear to be popping up every day, especially in the China regions. How can they so quickly achieve the level of GMP maturity that we [Big Pharma in the West] must have, and are expected to consistently maintain?” he asks.

“CDMOs may advertise GMP compliance, because they’ve had the certifications and sign-offs,” Gandhi continues. “However, it’s likely they could have just emerged from an ISO or GLP environment. They have yet to prove consistent GMP performance with metrics. Audits and FDA reviews still need to be undertaken. We must continue to be cautious and deliberate to not just accept the term ‘GMP,’ and perform our own due diligence. Many of these new companies seem too good to be true; unfortunately, that’s exactly right. Many don’t yet have the right skill set or experience level. Many key leadership positions are less-experienced people recruited from outside of China. How well do you think that will work when investigating deviations and root cause, and addressing regulatory questions?”

He finishes here: “Don’t get me wrong, they have come a long way, but you have to be aware of what you’re really getting into.”

Culture As Limiting Or Advantage

Can culture itself be a risk factor?

“Countries have different ethical, cultural, and hygiene standards, as well as varying financial and business practices,” says Wexler. “They may look at fraud differently.” He, though, again adds that a sponsor must also stay diligent when sourcing from U.S. and European CMOs.

If any reader doubts this, read just this one press release from the FDA on a Florida contract manufacturing facility – now closed down and in bankruptcy – caught manufacturing pesticides and drugs in the same equipment.

Guertin turns the lens of limitations around to examine the idea of cultural advantages. “When outsourcing, you need to contemplate R&D, pre-clinical, and GMP. Various countries have strengths in certain areas. For example, India is strong in the vaccine R&D space. You need to look holistically, and include government regulations, the organization’s policies, and the skill set you’re drawing from.”

Regarding the improving of that worker skill set within any culture, Guertin suggests establishing “structured training programs, whether they are here in the U.S. or harmonized and operated in other countries.” While there is an associated expense, he believes it’s worth the investment. “It’s for the betterment of the product quality, and ultimately the patients, but also specific to the personal growth of the staff. It’s a continuing skill-set expansion that will pay dividends for everyone involved.”

Trust Your Gut … And Nose?

For Gandhi, it “comes down to the trust factor.” However, his trust factor is of his own internal thought process. Maybe we could call it a practiced “gut check,” or as an attendee at the conference said – a bit less delicately – a “smell test” applied to auditing for the selection of global CDMOs.

“Get on the plane and visit them; you must do your own due diligence,” says Gandhi. “Do you come away feeling a high enough level of comfort that you are willing to put your name behind this selection, and make this recommendation to your company? That ultimately is my decision point. In all honesty, rarely have I felt like that when I visit a CMO in the Asia-Pacific region.”

There’s also what we might call the “FDA test.”

“When you’re filing for a new submission with a CDMO that might not have the greatest credibility with the FDA,” Gandhi explains, “you’re jeopardizing your launch, and ultimately your company’s reputation. I ask myself, ‘Will the FDA feel comfortable with this company, or end up questioning everything?’ Some people might call it being risk-averse. I see it as ensuring our CMO follows the same core values we do. In the end, it’s about the safety of our patients. For one example, because of such concerns, AstraZeneca has drastically limited its manufacturing footprint in India for now.

Finally from Gandhi: “Simply stated, if I walk onto a CDMO site and need to work hard to convince myself this company is in fact good enough to meet our quality standards, that tells me I should not be wasting my time. I do try to go in with a positive attitude, but fundamentally, my approach is to find reasonable excuses to not work with them. I’d rather have the expectations set high, and try to pick them apart. It’s an easier approach, and safer. If in the end I can’t come up with reasons not to work with them, then the process worked!”


Based on the Outsourced Pharma Philadelphia 2018 conference session: “Regulation 'Round The World: How To Navigate International Outsourcing.” Panelists were: Vimal Gandhi, Director, Global Biosimilar Operations & Strategy | AstraZeneca; Kenneth Wexler, GMP Quality Assurance | Boehringer Ingelheim; Patrick Guertin, Global Technical Manager | GE Healthcare; Kelly Waldron, Senior Consultant | ValScource (Moderator)