Standardized Extractables Testing Advances Single Use Adoption

By now, the single-use community is certainly no stranger to the word “standardization.” While the technology itself has gradually matured, it is still a challenge to implement in a facility because users are not able to make an accurate assessment and comparison of single-use systems/components from supplier to supplier. There has been some progress in the area of design standardization, but suppliers and end users continue to strive to reach common ground when it comes to extractables testing.

At the end of last year, the Standardized Extractables Testing Protocol For Single-Use Systems In Biomanufacturing was released. This guidance document was authored by five members of the Biophorum Operations Group (BPOG) and was the first effort to standardize extractables testing procedures among suppliers. However, since its release, there have been some questions and discussions about how to effectively implement the protocol.   

A Step In The Right Direction

Understandably, suppliers want to make sure the correct solvents are being tested under the appropriate conditions. And there are varying opinions as to what is “correct” and “appropriate.” Dr. Weibing Ding, a principal scientist in process development at Amgen and one of the authors of the protocol, says one frequently asked question is why the BPOG authors decided to test the six solvents that they did. “The choosing of the six solvents was based on the biomanufacturing processes,” he explains. “For complex protein solutions, there are surfactants, salts, organic excipients, and water with high, low, and neutral pH. These six solvents effectively represent all these components. For these who read the PDA Technical Report 66, these six solvent types are also called out in that document. Obviously, if the intended use of a SU component does not involve process fluids that need to be simulated by all six solvents, the suppler may justify and choose a subset of these solvents based on the targeted applications.”

The authors of the protocol are confident their work is thorough. “This protocol was generated based on the input from hundreds of scientists and engineers from end users, suppliers, and independent testing labs in a two-year timeframe,” says Dr. Ding. “It was application- and science-based and very well thought out.”

The protocol is certainly not the end of this effort, but implementing a science-based and application-oriented standardized extractables protocol is a good start. Establishing a foundation to build from would facilitate the implementation of single-use technology (SUT) and increase adoption. “Think about the future,” says Dr. Ding. “This is where the industry should be in five years. We all know that changes in order to bring new concepts are always hard in the beginning. But in the end, less uncertainty about extractables from SUS and shorter time to manufacture biological drugs will benefit the industry (both suppliers and biopharmaceutical manufacturers), and most importantly the patients too.”

Redundant Testing A Waste for Both End Users And Suppliers

In today’s world, suppliers are testing equipment according to their own companies’ practice, but there is inconsistency when it comes to the test solvents, conditions, analytical methods, and method qualifications they use. Because of these differences, along with inadequate identification and quantitation of compounds extracted, end users cannot use the test reports and often have to perform their own extractables study when they receive the equipment. Leachables evaluations assess the potential risks of the disposable components they use in drug product manufacturing, and extractables data is usually used as a reasonable worst case to assess potential leachables. Therefore, extractables testing data provided by an SUT supplier must be sufficient enough for the end user to perform an adequate assessment of risks.

It is a time-consuming process for end users to conduct their own extractables studies in order to generate sufficient extractables testing data. If both end users and suppliers are performing testing, this is a significant waste of time, effort, and money. “Testing by both sides delays the implementation of SUT in biomanufacturing, and in turn, results in an elongation of time to patient,” notes Dr. Ding. “In addition, this results in the same components being tested multiple times by many end users instead of by supplier doing it once and doing it right. This (redundant testing) is the current situation. The standardized extractables protocol provides a platform and fills in this gap. The industry needs suppliers’ understanding and cooperation to change this.”

There are also other benefits to suppliers if they use the standardized protocol. One is that it creates a level playing field among those suppliers using it, regardless of the size of their company. Another is that by using the standardized protocol to test the SUT components prior to marketing them, suppliers would know what kind of extractables would be potentially leaching to end users’ process stream. If they see any red-flagged toxic compounds, they could perform a root cause analysis and make continuous improvement to the quality of their products.

They may differ in opinion on these issues, but suppliers and end users are all on the same mission. They are partners and share responsibilities and accountabilities to the safety of the patient. Therefore, standardizing extractables testing wouldn’t just advance the single-use industry but also patient commitment and the quality of drug development provided to them.