Hi everybody,
I have some questions about product release (medical devices) concernig pyrogen test. So....After a years of pyrogen testing (rabbit) on each lot we will not be able to do it after the october pass. I search through Iso 13485, MDD and also ISO 10993 series of stand. and tried to find is it obligatory to do pyrogen test on each lot?
I red something about LAL test, do anyone knew how to perform it (pyrogen free water, pyrogen free equipment, laminar flow etc.)?

Thanks for any help!
Tomislav

Hi everybody,
I have some questions about product release (medical devices) concernig pyrogen test. So....After a years of pyrogen testing (rabbit) on each lot we will not be able to do it after the october pass. I search through Iso 13485, MDD and also ISO 10993 series of stand. and tried to find is it obligatory to do pyrogen test on each lot?
I red something about LAL test, do anyone knew how to perform it (pyrogen free water, pyrogen free equipment, laminar flow etc.)?

Thanks for any help!
Tomislav

Hi Tomislav,

Welcome to the Cove :bigwave:

The United States Pharmacopeia (USP) has recognized the Limulus Amebocyte Lysate (LAL) method as the official method for carrying out the Bacterial Endotoxins Test. The rabbit pyrogen test may be used only if a product is incompatible with the LAL test.

Limulus amebocyte lysate (LAL) is an aqueous extract of blood cells (amebocytes) from the horseshoe crab, Limulus polyphemus. LAL reacts with bacterial endotoxin or lipopolysaccharide, which is a membrane component of gram negative bacteria. This reaction is the basis of all three LAL test methodologies viz. gel-clot, turbidimetric, and chromogenic.

Gel-clot Method

The gel-clot method is the simplest and most widely used LAL test. The gel-clot test is the compendial method. It is the only endotoxin test fully described in the United States Pharmacopoeia (USP) and many other pharmacopeias. You could use other methods as alternatives also.

Turbidimetric Methods

As the concentration of insoluble coagulin increases during the LAL reaction, the turbidity of the reaction mixture increases. The rate at which turbidity increases is related to the endotoxin concentration in the sample and is the basis of the Turbidimetric methods.

Chromogenic Methods

Chromogenic methods utilize a synthetic substrate which is added to the lysate. When chromogenic LAL reagent reacts with endotoxin, the cascade is initiated and clotting enzyme is activated as in the other methods. The reactions proceed more rapidly at higher endotoxin concentrations.

Refer FDA document - Validation of LAL Test as an end product Endotoxin Test for Human and Animal Parenteral Drugs, Biological Products and Medical Devices (http://www.fda.gov/cber/gdlns/lal.pdf).

You could refer to USP General Chapter 85 < Bacterial Endotoxin Test > for more detailed methodology on how to perform this test.

Ajit,

Great information and a great link provided. I quickly scanned through the document but didn't see the answer to the OP question about performing on every lot. Any thoughts there?

Ajit,

Great information and a great link provided. I quickly scanned through the document but didn't see the answer to the OP question about performing on every lot. Any thoughts there?

I would say that is purely based on the specifications that are defined for the Raw Materials / Finished products.

We had another good discussion thread Endotoxin testing - Raw materials and components of a Class III medical device (http://elsmar.com/Forums/showthread.php?t=19658)that can be referred.

Hi everybody,
I have some questions about product release (medical devices) concernig pyrogen test. So....After a years of pyrogen testing (rabbit) on each lot we will not be able to do it after the october pass. I search through Iso 13485, MDD and also ISO 10993 series of stand. and tried to find is it obligatory to do pyrogen test on each lot?
I red something about LAL test, do anyone knew how to perform it (pyrogen free water, pyrogen free equipment, laminar flow etc.)?

Thanks for any help!
Tomislav
Hii ... Greetings from Somashekar.
I do not know what type of medical device you refer to, however what we do is that we have decided on a lot size and this quantity is always taken up and processed in agreement with the customer. The device concerning us falls under the USP < 20 EU per device catagory. We have a method of assessing the quality of water used in the device processing daily at the beginning of the work by the std LAL gelclot test using the ACC make quick test kit. The process water is certified good when this test passes. Having done this, and progressing further, when the lot quantity is ready for release, the customer picks random samples and the same are identified and sent which are subjected to testing by LAL (Turbidimetric Methods) on the pooled sample, and on the success of this, the customer authorizes the lot release. Its successful and well controlled and this process is established since last 3 years....
Hope this input gives some lead to your question sir.
Regards
Somashekar

Hi to all!
Thank you and I apologized for so late answer...I were on vacations.
Still I’am not sure about product release (EU market). We are producing class I sterile and class IIa and if I try to logically think about pyrogen test on nelaton catheter (for example) there are no rational/regulatory explanation why to do test (intended use and some risk assessment are not giving the answer) on each lot. Maybe for administration set (infusion) and transfusion sets are rational to do on each lot regarding to FDA (devices in contact with circulating blood or cerebrospinal fluid) but still I couldn’t find any documents that will mention this.
Ones more I go through MDD, ISO 13485 and GMP (Japan and US) there were no requirements (or I didn’t recognise) for testing pyrogen on each lot.

Tomislav.

For FDA Class II devices the general requirement is that all patient-contact product materials be ISO10993 biocompatible. Non-pyrogenicity is a baseline ISO10993 requirement, so that would apply to all released product. The normal assumption is that materials need be tested only once to qualify them for continued use. This of course assumes that the materials are consistently biocompatible and that the processing does not change their biocompatibility.

If those latter assumptions were not correct, I can understand a self-imposed requirement for batch testing, perhaps incorporated into a 510(k) as a means of finessing what might otherwise be a barrier to FDA approval.

Otherwise, I'm not familiar with a specific FDA requirement for batch pyrogenicity testing of devices for which general materials biocompability has already been established.

Thanks Miregmgr!
It is very resonable to do pyrogen test, as you said, only in case if process can influence on biocompatibility issue.

Best regards!
Tomislav