FDA Outlines Upcoming Regulatory Changes And Urges Industry To Be Proactive And Transparent
By Trisha Gladd, Editor, Life Science Connect
In a keynote session at Pack Expo 2014, Ricki Chase, director of investigations for the FDA’s Chicago office, opened her presentation with a reference to the 2008 recall of heparin due to adulterated stock of raw heparin imported from China. In doing so, she reminded the audience of not only the vulnerability of pharma’s supply chain but also the ability of both industry and regulators to prevent tragedies such as this example, which claimed 81 lives. “We had to ask ourselves—how did that happen? How did we miss it, and where was it missed?” says Chase. “It caused us to step back and say, ‘We have to do a better job,’ not just the agency, but also the industry. We have to ensure there's global supply chain integrity and product integrity at every step, from cradle to grave.”
There are many ways the pharmaceutical supply chain can be infiltrated—counterfeit drugs, intentional acts, cargo theft, diversion. However, solidarity, collaboration, and consistency are surefire ways to combat these threats and protect the consumer. And no player is too small. As Chase walked the floor of the largest packaging and processing trade show in North America, she described how excited she was about what vendors had to offer. Each one presented a new solution to consider for manufacturing practices, and as Chase described them, they are each a small piece of the puzzle, yet an integral one. “We can make labels that have holographic images on them,” she says. “We have barcode readers that we can put on pharmaceuticals. We have containers and closures that we can design to be tamper-evident and can be uniquely identified so that we can detect them as counterfeits. There's a lot that we can do together to ensure that product and supply chain integrity is being maintained.”
To start at the “cradle,” or the beginning, Chase says we have to go all the way back to the raw material provider, not just the manufacturer of the finished drug product. Her explanation is simple – “If you touch the product, you are responsible.”
A Global Market Requires A Global Solution
The complexity of the industry’s supply chain presents numerous challenges in achieving product integrity. One of the biggest of those challenges, globalization, is one both industry and regulators face in this spider web of supply exchange. Currently in the U.S., 40 percent of finished drug products and 80 percent of all active pharmaceuticals are coming in through import status. What this means is the U.S. market is really a global market, and that requires a global solution in order to holistically address product and supply chain integrity. “It no longer seems fair or right, practical, or prudent to focus only on the domestic market,” says Chase. “We must raise the level of expectation for our foreign providers and our foreign partners to ensure they have the same type of both standards and expectations as those in the domestic market. It keeps you competitive, and it's good for everyone.”
To achieve this, Chase says industry needs better coordination with foreign counterparts, which she notes as one of many things the FDA is working on through a multitude of harmonization projects. She specifically cites work with PIC/S, an effort of both the Pharmaceutical Inspection Convention (PIC) and the Pharmaceutical Inspection Co-operation Scheme (PIC Scheme) working in parallel. “We're looking at recognizing each other's standards, and trying to come up with a global standard that we can all agree on in order to ensure that no matter where the product comes from, it's safe for human consumption,” she explains. “It has long been that we have focused on the domestic market. We're looking now to level the playing ground between foreign and domestic manufacturing and contract manufacturing obligations.” She urged the audience to understand the importance of sharing information with foreign counterparts, which allows us to detect problems before they exist and to make sure we're working towards securing the safety of every individual, not just those in the United States.
In addition, she says the FDA is working to recognize foreign government inspections, which adds protection to the consumer in the face of limited resources. “We are understaffed and undermanned,” says Chase about the FDA. “We can barely keep up with the capacity, so we have to find ways to leverage with our government partners in other countries to recognize each other’s work,” a move she says would alleviate multiple inspections by multiple agencies. She also adds there will be greater penalties for counterfeiting and intentional adulteration, and the FDA will now have a greater regulatory authority beyond just stopping importation.
Supply Chain Stakeholders Face Upcoming Regulatory Changes
Diligence on behalf of the industry is imperative, and to ensure each stakeholder is being held accountable, Chase reviewed several upcoming changes heading industry’s way through regulatory legislations, such as the Food and Drug Administration Safety and Innovation Act (FDASIA) and the Drug Supply Chain Security Act (DSCSA). Beginning with excipient manufacturers, she said “As an excipient manufacturer, you will be required to list and notify us of what the excipients are that you’re manufacturing, to whom you are supplying them, and for what intent and purpose,” she warns. “No longer will you fly under the radar and only be subject to an audit, or lack of audit, of the person you are supplying.”
In regard to manufacturers of finished drug products or APIs, Chase explained that the two-year statutory obligation for investigations by the FDA is going to be a thing of the past, and instead, the focus will be on companies or individuals who need their assistance and technical expertise for guidance. “No more will we conduct our work by revisiting firms which have demonstrated a culture of compliance and a culture of integrity, and a willingness to do everything in their power to make sure that the product that they produce is safe and effective,” Chase says. “We will focus the attention where it needs to be focused until we are rest assured that there is product integrity at all levels.” The goal, she explained, is to work with them as team members, not as a regulator with a big stick.
According to Chase, an area frequently overlooked is the responsibility of those supplying contract services. She references the finger pointing that can happen in these situations when something goes wrong, and the lack of responsibility taken by manufacturers who assume it’s the contractor’s responsibility if something on their end goes wrong. Again, she reiterates it is the responsibility of everyone who touches the drug to maintain its integrity.
In the case of distributors, Chase says they will also be held accountable. It used to be that once a case reached the distribution center, everything was assumed as moving along its intended path. However, more transparency will be necessary to ensure this is definitely the case. “We have to know what's on the pallet, what's in the box, what's in the bag in the box, and what's in the bottle,” she explains. “We have great tools and imports to detect counterfeit drug products, but it's very difficult, once they get up to the open market. We don't really have a staff with the force to go out to every pharmacy, or to supply a CD3 unit, which detects counterfeit drug products to every pharmacy, so that they can just double check, as a reassurance, before they dispense that to the patient.”
By enforcing stronger regulations around product safety, the FDA is ensuring industry stakeholders have bigger eyes and ears when it comes to safeguarding the supply chain. It’s this participation from the industry as well as their feedback when legislation is open for comment that helps the FDA do its job better. “Regardless of what role you play in the supply chain, it's your opportunity to do better and to make it better. We have to continue to work towards harmonization and closing the gaps in our regulatory standards,” she says. It’s her opinion that companies should view this as corporate responsibility, since millions of dollars are lost when something does go wrong. Chase adds, “If for no other reason than the regulations say you must and that you shall, do it because it's smart business.”
Finding A Balance With The Paper Tiger
It’s not uncommon to hear the FDA being referred to as “the paper tiger,” a term used to describe something that seems threatening but is ineffective and unable to withstand challenge. Chase admits the FDA does indeed like paper, citing the process of 483s—a process that includes the notice itself, a reminder notice, a response saying they got a company’s response, additional letters, an untitled letter, and then a response to the company’s untitled letter response. However, she adds, “We love paper and we will kill you with paper, but does it really change anything? It really doesn’t.” While a warning letter may pack a heavy punch for a larger company, because this would not be viewed favorably by stakeholders, it does not carry a lot of weight with a private company. Chase says a better solution is to stop pushing that paper and push the “right” kind of paper, such as a guidance document, resource, educational tool, or even advice. “We need to make sure you understand what we need, and we need to understand your limitations, so we can figure out together how to make it right,” she explains. “It's the most cost-effective solution for everyone involved, and in the end, it gets us where we all want to be; not pushing paper at each other, but talking to one another and being true partners in safety for the American public.”
She also says it’s important that a balance is reached between what the FDA is able to achieve and what the public expects them to achieve. When the FDA does intervene or pass new legislation, companies negatively perceive it as being told how to run their business; however, when something goes wrong in pharma, such as the heparin debacle, the first question people ask is, “Where was the FDA?”
Although they are stuck between this rock and a hard place, Chase says, in addition to their work with PIC/S, the FDA is continuing to make steps toward leveraging their resources. “Our balance is figuring out how to address our program needs, our resource needs, and making sure that we’re making good decisions and putting our resources where the highest risks are,” she says. “We are focusing our efforts on training and outreach to targeted markets through FDA’s foreign offices in China, India, Latin America, Europe, the Asia Pacific, and South Africa. That is our effort to educate, to train, to leverage, to share, and to make sure we're protecting the global market.”
Chase adds that the Program Alignment Group (PAG), created by FDA Commissioner Dr. Margaret A. Hamburg in September 2013, which matches investigators to their trained field, breaks down the communication barriers within the agency and holds the FDA to the same expectations as industry: better communication, better quality systems, and more technically-trained individuals doing the job. “When that investigator walks into your facility and you're doing, for example, a sterile injectable LVP, they are the expert in LVPs and you can rest assured that they know what's going on,” she says about the program that focuses an individual on one program (and possibly also a sub-program) rather than multiple areas across industries.
Finally, Chase urges the audience to not just focus on product integrity, but also personal and corporate integrity. “Everything you do comes down to an opportunity to fail to protect the public health. Find your problems. Look for them. Challenge your systems and be proactive. Don’t let money be the driver. If you let money stop you from doing something, eventually your money will go away because a mistake will be made.” She continues, “Be proactive. Be suspicious. Trust, but verify. Be diligent, and most importantly, be transparent. Be a part of the safety solution in partnering with the Food and Drug Administration to make sure that all products are safe and effective for their intended use.”