tag:blogger.com,1999:blog-5251734313338196429.post5193818850297787145..comments2024-02-27T04:00:13.116-08:00Comments on Cell Therapy Blog: Are some cell counts too good to be true? Why some companies' product data may mislead.Lee Bucklerhttp://www.blogger.com/profile/05830444908952419444noreply@blogger.comBlogger5125tag:blogger.com,1999:blog-5251734313338196429.post-61458973340924942052012-10-30T22:06:16.751-07:002012-10-30T22:06:16.751-07:00The problem is that the manufacturing & qualit...The problem is that the manufacturing & quality processes do not check the actual accuracy of the counting method. The quality protocol may start with " We take a sample of 10.000 cells, we seed it and make it grow for XX hours..". The process will take good care that all the steps are properly taken.. but it will not ensure that the initial 10.000 cells are exactly 10.000 (or 8.000, or 6.000)<br /><br />I wrote an article about<br /><br /><a href="http://www.celeromics.com/en/resources/Technical%20Notes/counting-chamber-error/counting-chamber-error.php" rel="nofollow">Errors in Cell Counting</a> which explains the problem of cell counting using manual method. Without the proper care, automated systems like the one described on the report, or flow cytometers can be much worse.. <br /><br />Oscar Bastidas – <a href="http://www.celeromics.com" rel="nofollow">Celeromics Cell Count Devices</a>Oscar Bastidas - Celeromics Cell Counting Deviceshttp://www.celeromics.comnoreply@blogger.comtag:blogger.com,1999:blog-5251734313338196429.post-56065683542308881512012-09-12T21:33:53.293-07:002012-09-12T21:33:53.293-07:00I didn't know taking medicines or drugs can be...I didn't know taking medicines or drugs can be this dangerous. It is indeed very important that manufacturers should have proper guidance and rules in terms of dissemination of their products.heidihttp://coghlincompanies.com/cogmedix.phpnoreply@blogger.comtag:blogger.com,1999:blog-5251734313338196429.post-14195501684777096172012-08-31T08:51:07.871-07:002012-08-31T08:51:07.871-07:00(continued from above)
It could be said this blo...(continued from above)<br /><br /><br />It could be said this blog demonstrates that where a point of care device is actually making a medicinal product, e.g. non-homologous use of minimally manipulated cells, regulation of devices is probably not the right regulatory mechanism, or would need changes. Many of these devices are evolving further to the point they can more than minimally manipulate the cells, which poses all sorts of problems since the legislative framework didn’t anticipate this.<br /><br />Trying to be optimistic, minimally manipulated autologous cells used homologously are unlikely to do you any real harm, but they made do you no benefit either. Cell dose accuracy doesn’t’ normally appear to be critical, quite wide doses often show little measureable difference in clinical effect; but dose responses are seen. However, the differences observed are quite likely to alter the benefit, although it does say the claims are 10 fold higher than most published values, so the method is probably equivalent – just the user might dose differently as a result – but then has anyone done dose-finding studies anyhow? <br /><br />There is a general attitude in cell transplantation that more is better, give as much as you can: so here that would probably result in the same dose being given in reality (although assumed to be 10x). For a medicinal cell therapy this would be completely unacceptable, but then the cell content method would need to be thoroughly validated – it is hard to believe any validation was undertaken for the cellorometer and SVF.<br /><br />Very interesting, and a little worrying, especially that device regulation may not be adequately evaluating analytical functions.<br /><br />______<br /><br />Christopher Bravery of Consulting on Advanced Biologics (London) www.advbiols.com<br />Lee Bucklerhttps://www.blogger.com/profile/05830444908952419444noreply@blogger.comtag:blogger.com,1999:blog-5251734313338196429.post-51841531703899615732012-08-31T08:48:36.717-07:002012-08-31T08:48:36.717-07:00Unfortunately Christopher Bravery (regulatory cons...Unfortunately Christopher Bravery (regulatory consultant extraordinaire) was unable to post the entirety of his comment so he emailed it to me. With his permission, it appears below in two parts (a very worthy and worthwhile response).<br />___<br /><br />Interesting story, and some lessons to learn in there regarding appropriate methodology and the need for validation (seems unlikely this was undertaken correctly, if at all).<br /><br />However, some comments/perspectives and minor corrections. <br /><br />Firstly, actually the ingredients of medicines are stated (in the EU at least, but equivalent information is available in a slightly different form in the US) in the summary of product characteristics (SPC or SmPC in the EU) lists all excipients (not amounts) and the amount of the active substance/s is included. So not all the ingredients (raw materials) that are used to manufacture the medicine, but those present. There are of course residual raw materials (impurities), but these have to be controlled, as low as possible and shown to be demonstrated to be acceptably safe. <br /><br />Sometimes there is mention of materials used in the manufacture, where these might be important to know clinically, for instance the Apligraf label states “Product manufacture also includes reagents derived from animal materials including bovine pituitary extract.” Indeed I might argue the information provided is more reliable than for food.<br /><br />Although in broad terms it is correct that most medicine active substances are very pure (although the final product may not be due to necessary excipients), it is not perhaps as uncommon as might be implied here that active substances are heterogeneous and poorly defined; good examples are medicinal blood products e.g. normal human Ig, polyclonal antisera etc. I’ve come across a fair number of other complex and difficult to define biologics – they are as big a headache as cell products.<br /><br />What your discussion does pull out is the difference between a medicine and a cell or issue transplant (GTP’s only), because a transplant is minimally manipulated and used for the same essential function, it is an extension of surgery and left to the judgement of the surgeon. The public health concern (GTP) here is not practice of medicine (surgery) but protection of the donor and control of disease transmission – so donor consent, appropriate donor (adventitious agent) testing, and suitable facilities for any minimal manipulations. So legally there is no need to perform extensive testing on the cell transplant; and in general terms where is the risk? <br /><br />Of course this also means no assessment of efficacy/effectiveness is mandated, this is left to practice of medicine to decide whether they undertake trails or not – or the device manufacturer if they are selling a device (may be required for device registration too of course). Which I guess brings us to the device, here the approach to regulation doesn’t appear to require detailed characterisation of the result, but you would have thought it would evaluate the ability of a cell counting device to count cells accurately. <br /><br />I’m speculating now, and I confess to having some prejudices here, but I think this could have resulted from the tendency to regulate devices through standards, meet a set of standards and the device is fit for purpose. Standards work where things are predictable, and only if the scope of their use is carefully defined and adhered to. <br /><br />So if they followed a standard for the cell counting system that didn’t anticipate micelles, they could well have complied with it. Which loops us back to the lack of need for characterisation for the biological material being processed. So perhaps a flaw in the system, although in this situation the responsibility lies with the surgeon and/or the device manufacturer where the regulation does not cover this.<br /><br />(continued below)<br />Lee Bucklerhttps://www.blogger.com/profile/05830444908952419444noreply@blogger.comtag:blogger.com,1999:blog-5251734313338196429.post-86407707064557902192012-08-31T01:56:08.610-07:002012-08-31T01:56:08.610-07:00Trying to be optimistic, minimally manipulated aut...Trying to be optimistic, minimally manipulated autologous cells used homologously are unlikely to do you any real harm, but they made do you no benefit either. Cell dose accuracy doesn’t’ normally appear to be critical, quite wide doses often show little measureable difference in clinical effect; but dose responses are seen. However, the differences observed are quite likely to alter the benefit, although it does say the claims are 10 fold higher than most published values, so the method is probably equivalent – just the user might dose differently as a result – but then has anyone done dose-finding studies anyhow? There is a general attitude in cell transplantation that more is better, give as much as you can: so here that would probably result in the same dose being given in reality (although assumed to be 10x). For a medicinal cell therapy this would be completely unacceptable, but then the cell content method would need to be thoroughly validated – it is hard to believe any validation was undertaken for the cellorometer and SVF.<br /><br />Very interesting, and a little worrying, especially that device regulation may not be adequately evaluating analytical functions.<br />Christopher Braveryhttps://www.blogger.com/profile/00294327680328137059noreply@blogger.com