Bacterial Endotoxin Testing Services
Our bacterial endotoxin testing services laboratory can support you with performing your critical tests to help streamline the process to final product release. By partnering with Charles River, you can be confident that our experienced specialists can help improve the compliance and efficiency of your endotoxin testing program and help you to achieve control, consistency and precision in your laboratory.
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Hints and Tips for Ensuring a Successful LAL Product Validation
Whether you’re new to endotoxin product validations or just need a refresher, this webinar will provide you with information on the steps necessary for LAL product validation, how they’re different for gel-clot and kinetic methods, and product validation examples following guidance from the USP and EP.
Routine endotoxin detection for non-release applications*
The bacterial endotoxin testing services performed by Charles River uses customer-requested methods for submitted samples. Our optimized formulations provide increased sensitivity, greater linearity, and superior interference resistance. Endotoxin testing formulations are offered with a comprehensive range of buffers and accessories, providing numerous options for resolving interferences with difficult to test products.
Product validation – one and three lots*
Before performing product release testing, Charles River offers validation testing for up to three product lots.
Product release testing**
Charles River can be your partner during this crucial part of ensuring drug product quality and safety. Regulatory bodies such as the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) require lot release tests for each biopharmaceutical batch.
Charles River can test your product for stability after exposure to a variety of environmental factors such as temperature, humidity and light.
Charles River offers depyrogenation validation testing from oven validation to stopper washing endotoxin reduction using specifically contaminated articles to verify a 3-log reduction in endotoxin content.
Charles River can create and facilitate training courses on LAL to meet your specifications.
SOP and protocol writing
Charles River offers SOP and protocol writing assistance to help our customers create a procedure specific to your operation including the activities necessary to complete tasks in accordance with your standards and regulations.
Routine endotoxin determination, non-regulated, any method*
- Endosafe® cartridge technology
- Gel-clot - Specific sensitivity requests can be met with ranges that include 0.015 to 0.25 EU/mL for gel-clot.
- Kinetic chromogenic - Specific sensitivity requests can be met with ranges as low as 0.001 EU/mL for the kinetic chromogenic method.
- Kinetic turbidimetric
TS700 Service Code Product validation – 3 lots TS203 Product validation – 1 lot TS201 Product release testing** - Quality agreement available with this testing TBET1 Stability testing** - Quality agreement available with this testing TBET1
Service Code Device extraction preparation or special sample preparation such as heat treatment*** TS700E Depyrogenation validation (≤ 10 vials) TS203 Depyrogenation validation (> 10 vials) Inquire when >10 vials On-site training† TS400 SOP and protocol writing TS800
Endosafe® LAL proficiency testing program: For schedule information, email [email protected], or contact us at +33 (0) 474 72 28 53.
*Includes methods development and sample preparation.
** Product validation must be completed prior to finished product release or stability testing.
*** If Charles River prepares the extraction or treats the sample, there is an additional price per sample.
† Travel expenses additional.
- AVAILABLE METHODS
FRANCE SITE ISO ACCREDITATION
ISO 9001:2015 concerns all of the activities carried out at the Charles River Endotoxin Microbial Detection site in Ecully (Lyon), France, as defined by the sale of material, equipment and reagents, provision of services, and training related to carrying out tests in laboratories in the field of endotoxin detection and microbial identification.
About ISO 9001:2015
ISO 9001:2015 sets out the criteria for quality management systems. It can be used by any organization, large or small, regardless of the field of activity. In fact, ISO 9001:2015 is implemented by over one million companies and organizations in over 170 countries. The standards outlined in ISO 9001:2015 are based on a number of quality management principles, including a strong customer focus, the motivation and implication of top management, a process-oriented approach and continual improvement. Using these standards helps ensure that customers get consistent, quality products and services.
In order to comply with federal and international regulatory requirements, you must work with a partner that does the same. Our corporate compliance program assures clients, management, and regulators that our work meets your expectations.
Frequently Asked Questions (FAQs) About Endotoxin Testing Services
What regulatory documents apply to bacterial endotoxin testing?
In the US, the main guidance is found in the FDA's Guidance for Industry: Pyrogen and Endotoxins Testing: Questions and Answers.
Much of the information contained in the original 1987 FDA Guide is now covered by USP chapters <85>and <161>, as well as ANSI/AAMI ST72:2019, which is referenced in the latest guide from 2012. While the 1987 FDA Guide has been retired, some of the information is not covered by more current guidances so it is still often cited. The United States Pharmacopeia chapters <85> and <161>, and ANSI/AAMI ST72:2019 are not regulatory in themselves, however the 2012 guidance document specifically references them as accurate. USP is harmonized with the European Pharmacopeia and the Japanese Pharmacopeia, so they present the same overall information.
Do I need to validate the LAL endotoxin testing method?
The LAL endotoxin testing methods of Gel-Clot, Kinetic Turbidimetric, and Kinetic Chromogenic are considered compendial, validated methods, so the method itself does not need to be validated as would an alternative method. Suitability tests, known collectively as a Three Lot Product Validation should be completed to assure suitability of your product to the chosen method and dilution.
What are the acceptance criteria for my LAL endotoxin test assay?
The acceptance criteria for LAL endotoxin testing assays are as follows:
Gel-clot Endotoxin Test – The labeled sensitivity of the LAL reagent must be verified by obtaining an endpoint that is with 50-200% of the labeled sensitivity using endotoxin standards. The Negative Water Controls must be negative. For samples, the endpoint correlating to the sample’s endotoxin value must be below the sample’s endotoxin limit, and Positive Product Controls must be positive.
Kinetic Endotoxin Test – The correlation coefficient (R-Value) of the standard curve must be greater than the absolute value of 0.980. The Negative Water Controls must contain less endotoxin than the lowest tested endotoxin standard. For samples, the endotoxin value must be below the sample’s endotoxin limit, and the Positive Product Controls must recover between 50-200% of the spiked endotoxin.
Which LAL endotoxin test method is best for my product(s)?
Gel-clot, Kinetic Turbidimetric, Kinetic Chromogenic, and Endosafe® cartridge technology (which falls under the Kinetic Chromogenic category) are all considered compendial endotoxin test methods, validated methods for LAL endotoxin testing of any product.
Specific suitability studies should be performed to show that the chosen endotoxin testing method is appropriate for your specific products. Although not always the case, as a general rule, colored samples will show less interference to the Kinetic Turbidimetric assay, and turbid or cloudy samples will show less interference to the Kinetic Chromogenic assay. Neither color nor turbidity would affect the Gel-clot endotoxin test method.
How many replicates of the Negative Water Control, Standard Curve, Negative Product Control, and Positive Product Control do I need to run with my endotoxin testing assay?
Gel-clot Endotoxin Test– For a reagent qualification, the Standard Curve and Negative Water Control should be run in quadruplicate. For a routine assay the Negative Water Control, Standard Curve, Negative Product Control, and Positive Product Control may be run in duplicates.
Kinetic Endotoxin Test – For a reagent qualification, the standard curve and Negative Water Control should be run in triplicate with average replicates turned off. For a routine endotoxin test, the Negative Water Control, Standard Curve, Negative Product Control, and Positive Product Control may be run in duplicates, or in the desired number of replicates.