Extractables and Leachables Testing - Confidence®
Releasing Potential Leachable Impurities From Your Biomanufacturing Process
The importance of extractables & leachables testing has grown with increased utilization of single-use systems. Hence, E&L testing is a regulatory requirement to demonstrate that leachable impurities from plastic materials used in the processing of a medical product don’t interfere with the active pharmaceutical ingredient, ensuring patient safety.
Sartorius has been a leader in the field of extractables and leachables since 1996, which means we bring deep understanding of the science of extractables to every project.
The Extractables Simulator from Sartorius is unique in the industry. It provides scientifically accurate scaling data for Sartorius products and assemblies, making it possible to provide quantitative data for all product sizes, from development to large process scale.
Sartorius provides reliable extractables profiles, identifying all relevant chemical entities. We have identified more than 95% of all compounds across the Sartorius consumables portfolio.
Thanks to our Extractables Simulator, we can offer rapid provisioning and rapid turnaround of extractables validation. Even with calculations made on complex assemblies, data can be available in less than 1 week. 10 weeks for extractables or leachables testing.
Cost reduction of 80% in the assessment creation. More savings in comparison to analytical testing.
Extractables Simulator: Replace Physical Testing With Predicted Results
The Extractables Simulator (ExSim) is an important internal tool that supports our Confidence® Extractables and Leachables services and paves the way for the future of validation. It is a qualified software platform that scales extractables data for Sartorius products and assemblies and predicts the total amount of extractables based on your process:
- Scaling algorithms for short and long contact times
- Thousands of combinations and assemblies possible (including CTOs and ETOs)
- Fast retrieval of legacy and calculation data
- A reliable source for up-to-date extractables data, substance data and toxicological data
How We Help You to Succeed?
Sartorius has been a leader in the field of extractables and leachables since 1996, which means we bring deep understanding of the science of extractables to every project.
Our Confidence® experts will perform an E&L risk assessment to evaluate the applicability of the extractable profile data (EU GMP Annex 1) and guide you through the entire validation process.
The scope/effort for extractables and leachables testing correlates with a risk-based approach considering the uniqueness of each development scenario.
Our E&L risk assessment strategy considers:
- The proximity of a process step to the patient
- The consumables used
- The product and the process parameters
- The drug development phase
We provide the right validation for all products in the process chain, including single-use systems, container closure systems, and filters.
Confidence® E&L Portfolio
In addition to consumables, Sartorius provides extractables guides, which present the methodologies and results of in-house extractables and leachables studies for all of our products and identify virtually all extracted compounds (more than 95% for the whole Sartorius consumables portfolio). Each is a quality-controlled and approved document that can be used to qualify design and installation qualification and to determine the need for leachables testing.
The guides provide:
- Identification of all relevant extractables
- Extractables quantification
- Extractables toxicological information
With an Extractables Assessment, substances found in the standard extractables analyses under reasonable worst-case conditions can be evaluated for individual customer processes. This provides you a comprehensive understanding of, and confidence in, the Sartorius components used in your processes. This risk assessment — informed by our proprietary Extractables Simulator (ExSim) platform, which predicts the concentration of extractables for single-use systems and assemblies and scales data appropriately based on process needs — is the comprehensive first step of your validation
Extractables Assessment, basic |
Extractables Assessment, complex |
|
|---|---|---|
Number of devices |
1 |
> 1 |
Number of solvents |
2 |
Multiple*: Aqueous, |
Number of formulations |
1 |
1 |
Rationale for chosen comparison solvent |
|
|
Scaling of extractables results according |
|
|
Conclusion on further validation steps (if any) |
|
|
Risk classification of process step (USP <1665>) |
Optional |
Optional |
Safety evaluation |
Optional |
Optional |
*If available for selected device/assembly
Note: Any third-party product evaluation (not standardly used by Sartorius) is automatically categorized as complex.
Besides our Extractables Assessment, we also offer Extractables Studies to identify and avoid potential leachables to your final drug product. Extractables Studies are just what you need during the selection of appropriate packaging materials or processing equipment, e.g. during drug product development. It is the perfect fit for you if the temperature, timepoints, or solvents recommended by the Sartorius approach do not suit your purpose. We create extractables data according to your individual requirements.
As part of Confidence® Extractables and Leachables Services, our team provides complete leachable analyses — including leachables screening analyses or special leachables target analyses — if more detailed investigations are required. In these analyses, we test for compounds present in the actual medical product. Using our specifically evaluated and qualified methods, we can detect leachables known to be found in consumables in nearly all complex pharmaceutical solutions.
Our Safety Evaluation takes assessed extractables or leachables results coming from an Extractables Assessment or study or a leachables testing and correlates the data to the patient situation. Knowing a patient’s medicament application, we can calculate the possible daily intake of potential leachables against dedicated exposure limits, such as the permitted daily exposure (PDE) rate or the threshold of toxicological concern (TTC).
Extractables Information
Comparison of Extractables Protocols
It is Sartorius’ goal to provide you with the most comprehensive extractables data possible to simplify their process qualification and validation. To meet not only regulatory requirements but also individual preferences, we apply key Extractables protocols to our consumables: Sartorius Standardized Extractables Approach, USP <665> Draft and BPOG.
USP <665> (draft) 1 | BPOG 2 | Sartorius Approach 3 | |
|---|---|---|---|
Analytical methods | Described in USP <1663> Broader scope in method selection |
+ (TOC, pH, NVR) | BPOG |
Solvents* |
|
|
+ BPOG |
Timepoints* | 1: | 1-3**: | 1-3**: |
All approaches consider pre-treatments, are component-based, and focus on fluid contact | |||
1. United State Pharmacopoeia DRAFT <665> Polymeric Components and Systems Used in in the Manufacturing of Pharmaceutical and Biopharmaceutical Drug Products, 2020
2. Weibing Ding et al. “Standardized Extractables Testing Protocol for Single-Use Systems in Biomanufacturing”, 2014; updated version: "BioPhorum Best Practice Guide For: Extractables Testing of Polymeric Single-Use Components Used in Manufacturing" BioPhorum 2020
3. Pahl, I.; Dorey, S.; Uettwiller, I.; Hoffmann, C.; Priebe, P.; Menzel, R.; Hauk, A. Development of a Standardized Extractables Approach for Single-Use Components - General Considerations and Practical Aspects. Bioprocess Int. 2018, 16 (10)
*Solvents vary for products. WFI and pure ethanol always included.
**Depending on the component
Extractables Guides
SU Component | Product | Pre-treatment | Report ID | Extractables Approach | |
|---|---|---|---|---|
| Flexsafe® 2D & 3D Single-Use Bags | gamma irradiated | SPT5728 | Sartorius Extractables Approach | |
| Flexsafe® 2D & 3D Single-Use Bags (film) | gamma irradiated | 2396284 | BPOG | |
gamma irradiated | 2610240 | Sartorius Extractables Approach | ||
| Flexboy® Bags | gamma irradiated | SPT5723 | Sartorius Extractables Approach | |
| Celsius® Bags | gamma irradiated | S--5710-e | Sartorius Extractables Approach | |
| Flexboy® & Celsius® Bags (film) | gamma irradiated | 2396285 | BPOG | |
Flexel® Bags | gamma irradiated | SBT5703 | Sartorius Extractables Approach | |
Flexel® Bags (film) | gamma irradiated | 2577216 | Sartorius Extractables Approach | |
SU Component | Product | Pre-treatment | Report ID | Extractables Approach |
|---|---|---|---|
Flexsafe® Pro Mixer | gamma irradiated | 1000074440 | Sartorius Extractables Approach |
Flexsafe® RM | gamma irradiated | 2436792 | Sartorius Extractables Approach |
Flexsafe STR® Single-Use Bioreactor 50 - 2000 L | gamma irradiated | 2540178 | Sartorius Extractables Approach |
Flexel® Bags for LevMixer® and Magnetic Mixer | gamma irradiated | SBT5706 | Sartorius Extractables Approach |
Flexsafe® Bags for LevMixer® and Magnetic Mixer | gamma irradiated | 1000051103 | Sartorius Extractables Approach |
| OctoPlus FF® | gamma irradiated | 1000049369 | Sartorius Extractables Approach |
kSep® Consumables (Ksep® 400 or 6000S) | gamma irradiated | 2434823 | Sartorius Extractables Approach |
SU Component | Product | Pre-treatment | Report ID | Extractables Approach |
|---|---|---|---|
TuFlux® SIL | gamma-irradiated | autoclaved | 2565834 | Sartorius Extractables Approach |
gamma irradiated | 2607533 | BPOG | |
autoclaved | 2607531 | BPOG | |
TuFlux® TPE | gamma-irradiated | autoclaved | 1000049331 | Sartorius Extractables Approach |
| Opta® SFT | gamma-irradiated | 2692756 | Sartorius Extractables Approach |
SU Component | Product | Pre-treatment | Report ID | Extractables Approach |
|---|---|---|---|
Sartopore® Platinum | gamma irradiated | autoclaved | 2541222 | Sartorius Extractables Approach |
gamma irradiated | 2396281 | BPOG | |
Sartopore® 2 | gamma irradiated | autoclaved | 1000049331 | Sartorius Extractables Approach |
gamma irradiated | 2396283 | BPOG | |
Sartopore® 2 XLM | gamma irradiated | autoclaved | SPK5823 | Sartorius Extractables Approach |
gamma irradiated | 2396282 | BPOG | |
Sartopore® 2 XLI | gamma irradiated | autoclaved | SPK5822 | Sartorius Extractables Approach |
Sartopore® 2 XLG | gamma irradiated | autoclaved | SPK5821 | Sartorius Extractables Approach |
Sartobran® P | autoclaved | 100002449247 | Sartorius Extractables Approach |
Sartolon® | autoclaved | SPK5729 | Sartorius Extractables Approach |
Sartofluor® GA | autoclaved | 2461994 | Sartorius Extractables Approach |
SU Component | Product | Pre-treatment | Report ID | Extractables Approach |
|---|---|---|---|
| Sartoguard PES | autoclaved | SPK5824 | Sartorius Extractables Approach |
Sartoguard NF | gamma-irradiated | autoclaved | 2643919 | Sartorius Extractables Approach |
Sartoguard GF | autoclaved | 2614404 | Sartorius Extractables Approach |
Sartopure® PP3 (0.45 µm) | autoclaved | 2552579 | Sartorius Extractables Approach |
Sartopure® PP3 (0.65 – 3 μm) | autoclaved | 2544688 | Sartorius Extractables Approach |
Sartopure® GF Plus | autoclaved | SPK5780 | Sartorius Extractables Approach |
SU Component | Product | Pre-treatment | Report ID | Extractables Approach |
|---|---|---|---|
Virosart® Media | autoclaved | 2494649 | Sartorius Extractables Approach |
Virosart® HC | autoclaved | SPK5790 | Sartorius Extractables Approach |
Virosart® Max | autoclaved | 2654263 | Sartorius Extractables Approach |
Virosart® CPV | autoclaved | SPK5773 | Sartorius Extractables Approach |
Virosart® HF | autoclaved | 2641986 | Sartorius Extractables Approach |
SU Component | Product | Pre-treatment | Report ID | Extractables Approach |
|---|---|---|---|
Sartocon Hydrosart® Microfilter | preconditioned | SPC5714 | Sartorius Extractables Approach |
| Sartocon Hydrosart® Ultrafilter | preconditioned | 2605184 | Sartorius Extractables Approach |
| Sartocon® PESU Microfilter | preconditioned | SPC5715 | Sartorius Extractables Approach |
| Sartocon® PESU Ultrafilter | preconditioned | 2682084 | Sartorius Extractables Approach |
SU Component | Product | Pre-treatment | Report ID | Extractables Approach |
|---|---|---|---|
Sartobind® Capsules (S | Q | STIC® | HIC) | preconditioned | SK-5702 | Sartorius Extractables Approach |
