MPMN_Medical Product Manufacturing News

Medical Product Manufacturing News, March/April 2015

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q m e d . c o m / m p m n M e d i c a l P r o d u c t M a n u f a c t u r i n g n e w s M a r c h / a P r i l 2 0 1 5 2 3 detecting Toxicity the first matter of concern to orthopedic device companies relates to a sentence in the fda guidance document that has to do with endotoxin testing. "the endotoxin is a specific pyrogen from gram-negative bacteria. it is found in their cell walls and is not removed from products with sterilization," rollins says. "it is a critical element of cleanliness to remove pyrogens from medical devices, especially ones that have vascular system, ocular, neurological or cerebral spinal fluid contact. Many medical device companies in the cardiovascular, drug-delivery, and neurological fields have always tested for it. But for many orthopedic companies, this is new," rollins explains. in the past, fda's thinking was that a device had to be in the vascular system to be covered by this rule. the latest draft guidance though, instead of saying vascular contact, cerebral fluid, and all of those normal contacts, states: "implants, as well as sterile devices in contact directly or indirectly with the cardiovascular system, the lymphatic system, or cerebrospinal fluid (csf) (regardless of duration of contact), and devices labeled as 'non-pyrogenic' should meet pyrogen limit specifications." Most orthopedic companies don't do this test right now. "the first comma in that sentence suggests that all implants that directly or indirectly contact the patient in this manner must conform to device guidance for bacterial endotoxins and the limulus amebocyte lysate (lal) test," rollins explains. the potential impact of this draft guidance, if it means that orthopedic companies must do this test, is that they would be required to do it for every lot. "we are checking with fda to make sure that is their intention," rollins notes. "But we still haven't heard back." he adds that the agency might weigh in on the matter in the months to come. questions Related to FdA's G95 the other thing that could be of concern for orthopedic device makers is a chart that has long been a part of fda's g95-1 memorandum, which relates to the iso 10993 standard. the idea of g95 is that you look at the contact type of your device and the duration in a standardized matrix, and it tells you what kind of biocompatibility test to conduct for the medical device. it helps you plan based on which considerations have to be used for that device to be tested, rollins says. there were a number of test categories pertaining to this that fda considered optional. "that means if i am an fda reviewer and i am not familiar with your material, or i am suspicious or concerned in any way, i can require those types of tests beyond the guidance matrix," rollins comments. But the most recent relevant draft guidance would not view such categories as optional but require that device firms justify why they are not doing them through a formal, documented risk assessment. "for instance, if i have a device with limited contact to circulating blood, genotoxicity testing has been traditionally optional. But now, we see fda asking manufacturers to either justify why they didn't do those tests or to do them," rollins says. another good example from orthopedics is a delivery device for a screw or a surgical tool. "it could be an external communicating device used for less than 24 hours that could have an optional pyrogen test for toxicity," rollins remarks. traditionally, orthopedic device firms haven't used this pyrogen test for such parts, which are often made of materials such as PeeK, stainless steel, or titanium. But as a result of the new guidance, device firms would either have to do them or justify why they are not doing them. on the positive side, fda is putting greater emphasis on risk assessments for materials based on scientific principles. a couple of years ago, the agency viewed the risk assessment process as a sort of checklist of tests. "But now, in the latest draft document, it says that it is not a checklist; these are the categories you have to consider, but you don't necessarily have to test for them," rollins says. "You could address them through evaluation of literature, chemical and material characterization, and other means to evaluate risk and address it other than just biocompatibility testing." this is good news for many orthopedic firms, since most of their products are made from such well-known materials as titanium or stainless steel using standard manufacturing procedures. orthopedic firms are often able to justify the lack of testing based on these factors and on a documented understanding of their device cleanliness. Examples of residual materials commonly found on medical devices following manufacture that may induce unwanted toxicological risk.

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