Disposable Technologies and the Question of Leachables and Extractables
In the 1967 film "The Graduate,'' Mr. McGuire offers one word of advice to Dustin Hoffman's character, Benjamin Braddock - "Plastics."
A prophetic statement indeed. Since then plastics have found their way into every corner of our modern lifestyle. From the packaging our foods and beverages come in to the vehicles we drive, plastics are everywhere, and we have come to take their benefits and convenience for granted.
Slow to adapt to the benefits of plastics is the pharmaceutical industry. Reluctant to change and heavily invested in stainless steel, it is only recently that the industry has begun to see the benefits of using plastics in the form of single-use and disposable equipment.
However, recent reports of problems with plastic products containing Bisphenol A, commonly abbreviated as BPA, has put the use of plastics that are in contact with products consumed by people under the microscope.
The main issues of concern for pharma and biopharma companies that are using disposables are leachables and extractables. Extractables are defined as compounds that can migrate from a material into a solvent under exaggerated conditions of time and temperature, whereas leachables are compounds that actually do migrate into a drug product formulation under normal processing conditions.
It's important that end-users exercise due diligence when selecting equipment with disposable/single-use product contact parts such as this bioreactor line. While many vendors offer extractable and leachable reports for their equipment, end-users have to make sure that their product has no reaction with the disposable equipment. (Photo courtesy: Finesse Solutions)
To find out more about the use of disposables and the current emphasis on extractable and leachables, Pharmaceutical Processing spoke to experts at several companies that supply disposable/single-use products to the industry for their views on the issue.
The Big Push For Information
“People are worried about extractables and leachables,” says George Moyer of Broadley-James (www.broadleyjames.com). “There has been a huge void of information on extractables and leachables; but in the last 12 – 24 months vendors have become more adept at providing turnover packages to end-users and they (turnover packages) have become very comprehensive.”
Moyer states that early adopters of disposable technologies have forced vendors to provide full disclosure of all extractable and leachable data. But, he adds, “The end-user has the responsibility to make sure the products are appropriate for their use. They must perform due diligence. The end-user has the responsibility to demonstrate that the product has no reaction with the disposable equipment.”
“We are absolutely seeing a big interest in extractables and leachables,” says Marcia Coulson of Eldon James (www.eldonjames.com). “The use of disposables is on a sharp rise,” she continues. Coulson says companies are looking for products that are non-animal derived and don’t have oils or plasticizers.
“Everyone wants to be ‘clean and green’," she says. In particular companies are very concerned about the release of harmful toxins when disposable products are incinerated.
Laura Okhio-Seaman at Sartorius Stedim Biotech (www.sartorius-stedim.com) says that when disposables were first implemented in the industry there was very little interest in extractables and leachables, but now it's the big “rage” "Companies are more aware of product and process interaction now and were not really aware of it before,” she says.
Okhio-Seaman adds, “There are more aggressive products being produced now. Testing for extractables and leachables is very important for products such as injectables; companies have to account for toxicity.” Companies have to take into account things such as stabilizers and adhesives says Okhio-Seaman. “Something as simple as a label on a bag can cause problems.”
Arkema’s (www.arkema.com) Bill Hartzel says extractables and leachables are still a big concern to end users. “Every product has extractables” says Hartzel, “even stainless steel.” Hartzel says that since stainless steel has been around for a long time, processors know what’s coming out. “In many cases these new materials present an unknown, you must due an extractable/leachable profile to know what you are dealing with.”
All bag contact parts in this single-use bioreactor are Class VI tested. (Photo courtesy: Broadley James Corporation)
“Extractables and leachables are manageable issues.” Says Barbara Paldus of Finesse (www.finesse.com). “It is imperative to select materials known to not have leachable or toxicity problems,” she adds. “If you have a product that requires a new type of material, this material must be tested, which is a fairly routine process. Expensive? Yes. Time consuming? Yes. But once that product is proven, certified and documented, QA/QC can sign off on it.”
John Boehm, Colder Products, (www.colder.com) agrees with his colleagues. “There has been a ‘big scare’ recently in regards to leachables and extractables,” he says. “As recently as five years ago end users didn’t know the difference between leachables and extractables, or what to ask for when selecting products.” End users now have a better understanding of the issues says Boehm. “Major industry suppliers do extractable profiles on their materials, but it is up to the end user to decide what products work best with the products they are processing.”