Chemical Characterization

The WuXi AppTec Advantage

WuXi AppTec is committed to complete characterization and built a Chemical Characterization Center of Excellence to prove it.

11 years ago we built a lab and a chemistry program based on one unique foundation: That complete identification is the expectation. The same commitment holds true today. This identification is not an “add on” service for our team, as we believe the reason for extractables and leachables studies is to identify potential risk—a standard that cannot be upheld with an incomplete chemistry report.

E/L studies are a journey. While each path may start at a different place (combo products, container closure, SUS), the goal is to identify what may migrate out and evaluate the risks of exposure to those compounds. Extractables are compounds that are extracted or “pulled” out of the product with strong solvents. In pharmaceuticals, typically an acid, a base and an organic solvent is used. Leachables on the other hand, are compounds that are allowed to leach or “migrate” out of the product using less harsh extracts — oftentimes drug product or physiologically relevant solvents. And in pharmaceuticals, drug product is often used as the extract.

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Evaluating Single-Use Systems (SUS) Using a Risk-Based Approach

Today’s vast majority of drugs are manufactured using plastic bags, tubing, bottles, connectors, pumps, sensors, filters, valves, and more. The advent of plastic SUS has improved product quality, streamlined operations, and reduced production costs. But chemicals within that plastic may contain contaminants that could raise safety concerns to patients.

Regulators are Taking Notice

China is the only country with regulation requiring E/L for SUS; global regulatory bodies are asking for, even expecting, this testing be conducted. The EMEA, ICH, CFR and U.S. FDA have alluded to the importance of biomanufacturers to take a risk-based approach to evaluate these systems. Thus far, most regulators have stopped short of requiring E/L testing and a toxicological risk assessment for SUS, but biomanufacturers should know that it is coming.

BioPhorum Operations Group (BPOG) created a comprehensive set of guidelines for full E/L testing on SUS. BPOG revised its guidance in 2020 but remains the industry’s most rigorous extraction matrix used today. 

Creating a successful test plan that supports safety and achieves regulatory approval requires a strong partnership and continued collaboration between chemists, toxicologists and biomanufacturers.

A Risk-based Approach for SUS

In the absence of formal regulatory guidance, forward-thinking biomanufacturers should be developing risk-based approaches to evaluate their SUS. Adopting a risk-based approach means focusing on five factors that could potentially inhibit cell growth and/or jeopardize patient safety. These factors include:

  • Proximity. How close is the plastic tube, bag, valve, filter etc. is to the final biologic product?
  • Duration. How long are biologic products in contact with disposable plastic components?
  • Contact area. How much plastic surface area is in contact with the biologic product?
  • Type of plastic. Plastic components with greater flexibility generally present greater risk than inflexible components.
  • Dose and route of exposure. How will patients encounter the biologic product and how much will they use?

Changes are on the Horizon

Recently, U.S. Pharmacopeia (USP) approved the revision of two new chapters (665/1665) on production equipment and patient safety for polymeric components and systems used in biomanufacturing. The new USP guidance provides clear expectations for what biomanufacturers using SUSs can expect from the regulatory body in their chosen market.

USP <665> specifically demonstrates harmonization with BPOG’s 2020 guidance, including similar or identical component names, categories and testing time points. The USP chapters are a step forward in finalizing and clarifying regulators’ expectations around fluid-contact equipment in biomanufacturing. The risk-based approach also helps manufacturers prioritize which data they
need to present to achieve regulator y success.

With the new USP regulations, regulator y bodies have the prerogative to ask manufactures to provide whatever data they would like to see. Neither USP nor BPOG possesses enforcement capabilities—their guidance is recommended, not required. On the other hand, the U.S. FDA can enforce its regulations by rejecting device submissions. Biomanufacturers should know that the agency has stated that any primary packaging component that is, or may be, in direct contact with a dosage form needs a toxicological risk assessment. This is a clear indication that the U.S. FDA will likely follow USP ’s lead and make chemical characterization followed by a TR A the standard for SUSs and their componentry.

Analytical Chemistry for E&L Studies

We use multiple analytical techniques to help uncover the full range of extracted chemicals associated with your SUS.

  • Inductively Coupled Plasma-Mass Spectrometry to identify elements and metals [ICPMS].
  • Gas Chromatography-Mass Spectrometry and Headspace Gas Chromatography-Mass Spectrometry to identify volatile and semi-volatile compounds [GCMS & HS-GC-MS].
  • Liquid Chromatography-High Resolution Mass Spectrometry, such as LCMS QToF, to identify semi-volatile compounds to non-volatile compounds [LCMS].
  • Ion Chromatography (IC) is sometimes required for the evaluation of ionic contaminants.
  • Full identification of the chemicals is required, and unknowns must be treated as worst-case scenarios. WuXi AppTec is the industry leader in identification, and our chemistry program was built knowing that chemistry data alone—without a toxicological risk assessment—is not enough to support safety.

Multiple analytical techniques aid in uncovering the full range of extracted chemicals associated with your product. Regulatory bodies are looking for this as part of the assessment of risk associated with your product.

Identification of compounds is extremely important for a toxicologist to accurately assess risk. While identification using some analytical methods is relatively straight-forward, identification of compounds from LC-MS can be challenging, as no commercial databases exist. With today’s devices that include polymers and plastics, LC-MS is an analytical method that tends to yield more chemicals – which means laboratories must tap into their experts to make the identification; a significant resource commitment. WuXi AppTec’s Chemical Characterization lab is the only lab committed to complete characterization as part of our standard service—a commitment we refer to as “Unknowns are Unacceptable.”

We have a long-established reputation for a commitment to complete identification – to our customers – and regulatory bodies. And find ourselves regularly helping customers with their regulatory challenges as a result of work from labs that are not committed to complete characterization. 

We have developed a proprietary LC-MS database of more than 6,000 compounds. And we maintain a LC-MS library of more than 700 compounds verified through reference standards, as well as a team of expert scientists who can elucidate compounds not listed in either database. This makes WuXi AppTec’s LC-MS capability significantly more efficient and accurate than our competitors.

Analytical Chemistry

Full characterization of all chemicals is required for an accurate assessment of risk, and it is our goal to identify all of the potential chemicals that could come out of your product. Utilizing multiple analytical methods, our team of chemistry experts works tirelessly to understand your materials, process and product to detect a full range of organic, semi-volatile and volatile chemicals, providing you with the data you need to make informed decisions and meet current regulatory requirements. These are some other techniques that are used:

  • Fourier Transform Infrared (FTIR) Scan: A type of infrared spectroscopy in which the sample is subjected to all the wavelengths in the region of interest at all times, instead of only a small portion at a time.
  • SEM-EDS – Elemental Analysis: Used to determine the presence of trace metals by atomic absorption spectroscopy.
  • UV/VIS Spectrophotometry: Refers to absorption spectroscopy or reflectance spectroscopy in the ultraviolet-visible spectral region or light in the visible and adjacent ranges. The absorption or reflectance in the visible range directly affects the perceived color of the chemicals involved.
  • Particulate Matter Light Obscuration Method – Medical Device Extraction: Involves extraction of the medical device in water followed by analysis of subvisible particulates using a light obscuration particle counting method.

Safety Assement / Toxicological Risk Assessment

Assessments are conducted to identify potential risk to patients from the chemical constituents of the product.

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Expertise and Experience Matter

Leaning on our globally-recognized experts means you will gain insights from a team that is actively involved in the international standards committees, including knowledge about upcoming standards changes and how different regulatory bodies are interpreting those standards.

6,000+ Materials Characterizations

We’ve completed more than 6,000 materials characterizations for device and biological manufacturers.

Speak With a Chemical Characterization Expert

about your upcoming project to see how we can help you