Changes Affect Clinical Trials

By Marie Redding
Freelance Writer

Clinical trials are a critical step in the approval process for new drugs. Every detail is preplanned and closely monitored during the trial. Packaging plays an important role and can have an effect on patient compliance as well as the outcome of the trial.

FDA’s Center for Drug Evaluation and Research (CDER) continues to look for ways to improve the drug approval process, and recently presented a seminar in which some of the issues surrounding clinical trials were discussed.

The need to ensure the quality of trials is one issue addressed by FDA. Another is globalization. As pharmaceutical companies look for solutions to these issues, suppliers are developing ways to offer better solutions for their customers.

The Slow Approval Process for A New Drug

Even with the intense research that goes into drug development, and the extensive preparation when setting up a clinical trial, many new drugs never see approval. The overall success rate for drugs moving through clinical trials to FDA approval has been just 1 in 10, from 2003 to 2010. In prior years, the rate of drug approvals was 1 in every 5 or 6. This was reported in a study released on February 14 by the Biotechnology Industry Organization.

“There is definitely a debate within FDA—do they speed up the approval process or do they require companies to conduct studies to cover all possible safety scenarios?” asks Frank Lis, vice president and general manager, clinical supply services, Catalent Pharma Solutions (www.catalent.com).

“FDA is being very conservative. They know they will see bad press if a drug is approved quickly and later find issues regarding its safety. But you don’t hear criticism when a drug’s approval is delayed for two years. And it may be an oncology drug, where 5000 lives could’ve been saved if it were approved more quickly,” says Lis.

Christoph Hammer, CTO, Dividella AG (Grabs, Switzerland), part of the Körber Medipak Group, may have a solution for shortening the time-to-market for a new drug: using the same package for trials that will be used to market the product. 
“If the same type of package was used for both the trial and the commercial phase, it would save money and time in the long term because there would be no need for a redesign after a drug is approved,” says Hammer.

“The packaging would just be scaled up from the trial,” he adds. “We’re not seeing this happening yet, but we have some customers who believe that it would be more economical,” adds Hammer.

The Need for Automated Solutions  

Clinical trials are becoming larger, which is slowing down the drug approval process even more.    

“FDA is requiring larger studies to collect better data concerning the safety of new drugs,” says Lis. “Years ago, you may have had 2000 patients for a cardio study, for example. Now, you may have up to 10,000 participants. This is not new, however, and has been happening for several years,” says Lis.

Larger clinical trials may mean the packaging process might soon be automated.

“As studies become larger, manual operations won’t work anymore,” says Hammer. “Production will either be too slow or too expensive,” he adds.   

Besides speed, there are other benefits automated production would provide. “Automation can provide consistent quality with less error. You will have the ability to log certain events. Better quality control may contribute to a more successful trial, which may even lead to a faster approval process for a drug,” says Hammer.   

Hammer says that down the road, automation may be the solution for larger companies, but smaller companies might not be able to justify the investment.

“It needs a certain number and volume of trials. This can be the case if various objects, such as blisters, syringes, or vials can be handled on the same machine,” says Hammer.

The Dividella NeoTOP carton provides such a platform. “We are seeing this happening already. Dividella’s had a number of recent requests for quotes for machinery,” says Hammer.

Catalent Pharma Solutions has also been suggesting automated solutions to its customers.

“We’re doing several things differently now in an effort to reduce timelines and costs, so we can pass that savings onto our customers,” says Lis.

For instance, Catalent uses 2-D bar codes when assembling patient kits for clinical trials.

“We put a bar code on the product itself as well as on the kit’s label, and check the kits using a scan assembly process. Normally, random manual checks would be done to ensure the right products are in the kit, which is much more time-consuming,” says Lis.
Implementation of this system has increased Catalent’s productivity by 60 to 70%.

The supplier also has new equipment for applying booklet labels onto vials and syringes, which was normally done manually. Catalent is also using camera systems to inspect label text after printing.

“We’ve invested a lot in our new equipment, including software and computer systems for the scan assembly process, but the payback will be worth it in the long run. It will reduce costs for our customers, while ensuring quality,” says Lis.

Trials Go Global, Need Logistical Solutions

Clinical trials are being conducted more frequently on a global scale.

“We’re seeing a lot of clinical programs being held in the Pacific Rim,” says Lis.

Many clinical trials are being done in India and Asia because it is economical to do trials there, and the wide range of patients to pool from is attractive, according to Lis. 

“Asia is a huge market. A lot of pharmaceutical companies want to develop a drug in countries such as China, because later on, commercializing it there will be easier,” says Lis.

Along with the benefits of setting up trials overseas, logistical problems arise. The logistical issues of setting up a trial in another country might affect the rate at which a drug can move through the clinical trial phase to approval, and then commercialization.
“There are huge challenges when doing trials in different countries. Shipping is a big issue,” says Lis. “Regulatory issues and the requirements for setting up a study in each country must be understood. The proper documents must be filled out, and you have to be able to estimate how long everything will take,” he adds.

Suppliers are devising ways to help customers simplify and expedite the clinical process at all stages—from packaging to shipping. More pharmaceutical companies are partnering with contractors who can help establish packaging and distribution channels in other countries. Having a partner based in the country where the trial is being conducted can be a tremendous help with customs and paperwork, since these companies keep up to date on current regulations within that country.

Catalent works with its own global trade organization in the United States, which has a regulatory arm designed to provide assistance with these types of issues. The supplier has also partnered with a number of depots in Asia and India, to help facilitate shipping and paperwork. “We’ve audited these facilities to make sure they’re compliant,” says Lis. 

Ropack (Montreal, Canada) is another supplier helping sort out the logistics of setting up trials in other countries, but its expertise lies in helping United States and international companies conduct trials in Canada.

Although the rate of clinical trials being done in Canada may not be as high as the expansion to other countries has been, it is still an important market for the U.S. pharmaceutical industry.  

“Clinical trials in Canada represent such a small niche that these methods and shipping costs haven’t come under scrutiny before, but now companies are realizing that by making the logistics more efficient, a lot of money can be saved. We simplify the process so that trials can still be done in Canada economically,” says Paul Dupont, director of business development, Ropack.
Business has increased dramatically for the supplier during the past year.

“Many of the top clinical trial service providers have contacted us over the past year, audited our facilities, and signed service agreements,” says Dupont. The company is currently a partner for the four major global clinical trial groups, which all want
to establish a distribution depot in Canada.

Certified by both FDA and Health Canada, Ropack can be listed as the packager on paperwork. “Since we’re already on record as one of the packagers, it’ll be an easier path to distribution once the drug is commercialized,” says Dupont. 

Ropack is approved for controlled substances and can handle drugs that are time, temperature, and humidity sensitive. If a trial involves a temperature-sensitive drug, then a company will send a refrigerated pallet to Ropack, which will send individual coolers to clinics. “This amounts to a huge cost savings,” says Dupont. 

Besides being more economical, using a company such as Ropack can ensure the safety of the shipments. “The shipments are fully controlled and limited to just one destination in Canada, which offers a lot more security,” says Dupont.

For example, if there are 50 trials happening in Canada at one time, Ropack will receive all the kits, ship them to each clinic, and collect them back. Proof of signature traceability—all the way back to the doctor—is also provided.

This is a model that works all around the world, and there are many companies providing this type of shipping and distribution services for clinical trials.

Looking Ahead

What new trends are affecting packaging for clinical trials? Some suppliers are seeing an increase in oncology drugs being tested.

“More sterile applications, such as oncology products, tend to be in vials rather than packaged as oral solids,” says Lis.

“We’re also seeing a lot of refrigerated products, which need to be in prefilled syringes, or vials with labels, so we’ve been investing in that type of equipment,” says Lis.