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.

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More than 25 years of expertise

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 customer project.

Flexible scaling of extractables

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.

Comprehensive extractables profiles

Sartorius provides reliable extractables profiles, identifying all relevant chemical entities. We have identified more than 95% of all compounds across the Sartorius consumables portfolio.

Optimized turnaround

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.

Reduced validation costs

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

Evaluate Your Extractables Risk 

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 customer 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 our customer’s unique 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 

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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 

Multiple*: Aqueous,
high and low pH, pure organic solvents 

Number of formulations

1

1

Rationale for chosen comparison solvent
(based on customer formulation) 

 

 

Scaling of extractables results according
to customer process  

 

 

Conclusion on further validation steps (if any) 

 

 

Risk classification of process step (USP <1665>)

Optional

Optional

Safety evaluation  

Optional 

Optional 

Request a Risk Evaluation

Request a Risk Evaluation

*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.

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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. 

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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). 

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Extractables Information

Comparison of Extractables Protocols 

It is Sartorius’ goal to provide our customers 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

  • HPLC-PDA/MS (APCI, ESI, +/-)
  • ICP/MS
  • GCMS-DI
  • GCMS-HS

+ (TOC, pH, NVR) 

BPOG
+ Ion Chromatography  

Solvents* 

  • 50% ethanol
  • 0.2M KCl, pH 3 
  • 0.1M phosphate buffer, pH 10
  • 50% ethanol 
  • 0.5N NaOH 
  • 0.1M H3PO4
  • WFI 
  • 100% ethanol 
  • 1M NaOH 
  • 1M HCl 

+ BPOG 

Timepoints* 

1:
24h, 7 and 21 days 

1-3**:
24h, 7, 21 and 70 days 

1-3**:
24h, 7, 21 and 70 days 

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

 

Request Extractables Guides

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

Request Extractables Guides

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

Request Extractables Guides

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

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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

Request Extractables Guides

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

Request Extractables Guides

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

Request Extractables Guides

SU Component | Product

Pre-treatment

Report ID

Extractables Approach

Sartobind® Capsules (S | Q | STIC® | HIC)

preconditioned

SK-5702

Sartorius Extractables Approach

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Featured Resources

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Webinar: Confidence® Extractables Assessments powered by ExS...

Learn how Confidence® Extractables Assessments, powered by the Extractables Simulator, help you ensure patient safety and product quality.

Watch Webinar
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Mastering Extractables Scaling for Complex Assemblies with Just a Clic...

Sartorius developed the Extractables Simulator to transform E&L validation from a purely empiric to a software-supported approach.

Read Blog Article
White Paper

Sartorius Extractables Simulator: Simplifying E&L Through in-Silico Modeling

PDF | 1.3 MB
Article

Development of a Standardized Extractables Approach for Single-Use Components

PDF | 7.6 MB

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Request Extractables Guides