Plan early to avoid late attrition !
Stem cell therapies (SCTs) are heralded as the cure of the future for a large range of ailments that remain untreatable in the current therapeutic setting. Together with gene therapy and tissue engineering they represent the so-called ATMPs (advanced therapy medicinal products).
The set standard for this class of therapeutic products is cGMP, no way around this. The European regulation is extremely clear : “All medicinal products for human use … are to be manufactured in accordance with the principles and guidelines of good manufacturing practice.” (Commission Directive 2003/94/EC). In the US, the Code of Federal Regulations, CFR parts 1270 and 1271, sets the requirements for donor selection and cGMPs for Cellular and Tissue-Based Products (HCT/Ps).
GMP by itself is no guarantee for efficiency but
1) GMP ensures that the cell preparations are produced in a standardized manner according to validated SOPs in order to contain batch variability and to allow for seamless technology transfer and
2) and most importantly, GMP sets also the safeguards for the patient’s health.
Regarding the latter, besides obvious risks of contamination by all sorts of infectious agents, a major health threat consists in potential allergic reactions to xenogeneic protein. Presence of anti-calf serum antibodies in blood of patients treated by MSCs expanded in FBS-containing medium have been reported; also, severe anaphylatoxic reactions after administration of other cellular products prepared with FBS are not uncommon.
In view of all of the above, in order to obtain ‘clinical grade’ cell therapies, the complete manufacturing process has to be GMP-compliant, from procurement, harvesting, testing, processing, preservation, storage to distribution after release criteria are met. To date SCTs have never been beyond the ‘research grade’ which restricts their clinical usefulness for only short and limited studies, approved on a case-by- case basis, and this only if it can be demonstrated that there are no residual animal products of any kind left in the final cell preparation, a daunting task. Hence it is clear that research grade cell lines are not fit for widespread human therapies.
The assertion that it is possible to apply GMP to animal components if no better options are available has become a challenging stand. And even as use of adequately controlled bovine sera is still allowed, it won’t be for long as regulatory standpoints will predictably adapt to technical progress in cell culture technology.
‘Research grade’ cell therapies, originally created using animal products for research may still be converted to clinical grade, but this only after a long and laborious vetting process, spanning over numerous passages during which attrition issues can put the whole process at risk.
To put an end to all these considerations, today all GMP-related constraints can be easily addressed by implementing sound and validated SOPs that should be built on a completely defined cell culture process. This includes operating chemically defined, GMP-quality, xeno-free culture and cryopreservation media containing no animal-derived substances, as well as GMP-quality recombinant enzyme versions and extracellular matrix components for cell attachment and spreading.
A perfect completion along these lines is exemplified by the achievement of Peter Braud’s team from King’s College, London, January 2012 (see http://www.nature.com/news/stem-cells-that-are-pure- enough-for-the-clinic-1.9566 and http://dx.doi.org/10.3109/14653249.2011.623692 for the full article).
Recently I discussed with a scientist who is performing cell culture for many years, that using serum in a cell culture medium is very unnatural.
What is the case? In no living, healthy body cells are ever in contact with serum. Serum doesn’t exist in the body of animals and humans. The blood cells like the lymphocytes are in plasma.
Serum arises by clotting of the blood. The platelets and clotting proteins form a blood cloth clot. The moment this happens the platelets secrete an enormous amount of factors into the serum, called platelet lysate.
What is the impact of these factors on the cells growing in a medium with FBS?
This way a lot of these platelet lysate factors encounter those cells that are normally not a target for these factors, a phenomenon that would never happen in their normal natural surroundings, the body. A situation in which cells come into contact with serum with all those factors in those amounts exists only in cases of extreme traumatism, or even more terrible.
But, the non-blood cells, do never come into contact even with plasma under normal circumstances. Those cells are surrounded by the extra-cellular fluid matrix, which contains much less proteins and growth factors then plasma does. Cells should normally produce themselves most of the factors they need.
Therefore if you want to approach the natural growth surroundings for cells you should not use serum, but a protein poor alternative, containing no or only a few growth factors. This way you stimulate the cells to become autocrine-competent and thus to become more productive.
MORE >2012 might be the year were the cell culture world as we know it will change; new concepts are not only introduced over the past years but a few market dynamics seem to come together. The use of FBS is not only seen as a product that brings certain problems that can be overcome.
More and more it becomes clear that having a future proof scientific research, sustainable if you will, is not anymore based on techniques that once will be outdated.
Anyone that is doing research that will finally end up in any form in use for humans should from scratch start with a clean approach.
Medication will increasingly be based on biopharmaceuticals rather then chemicals. Production will depend on cell culture more and more.
Are you working in this field? Then we would like to invite you to join the discussion; let us know what you think this Life Science world is going to and what role it will play.
MORE >We are kicking off! At this moment we have produced over 1000 samples of our XerumFree™ serum replacement. They are available for testing to everyone who is interested in changing from FBS to serum free.
Extensive quality control is being carried out right now, but for people interested that cannot wait we have samples available now. It is the sterile version; functionally the same as the GMP version we will introduce in the coming months. Further down the road we have planned a stem cell version that basically is the same.
Mid october we will have a booth at the BioTechnica 2011 in Hannover. So if you want to visit us ; you can!
End of next week we will bring live our completely new website and introduce our new logo (as you can see partly in the header).
So it seems we are getting alive! Join us in changing to XerumFree™!
MORE >These days it is common practice to test cosmetics without the use of animals. This is stated by most manufacturers of the famous brands on the package, to assure the consumer.
There is however one aspect of this that is often hidden and that is that most of these companies has a part of the production or testing where fetal bovine serum is used amongst other animal deriviatives.
Is this common practice on purpose, do they know or do they care?
Anyhow, it is not necessary anymore as alternatives ar available, and from a growing list of suppliers, used by selected test laboroties.
MORE >The discussions on the use of fetal bovine serum generally come to a few different aspects: ethics, production, and science, let’s sum up some of the arguments:
I – ethics
Not everyone seems to now how serum is “harvested” and hardly anyone saw pictures from the actual proces. But if you know, you would like to seek an alternative also. The serum is won from blood from unborn calves and sucked out of their hart while they are still alive in the uterus. With a synthetic serum replacement this is of course not the issue.
II – production
In the actual process there are a lot of advantages by using serum-replacements. The big question mark for FBS is the actual contents; we simply do not know. So we need various steps to ensure there are no influences and traces of FBS: some advantages include:
1. Improved reproducibility of results from different laboratories and over time since variation due to batch change of serum is avoided.
2. Easier downstream processing of products from cultured cells.
3. Toxic effects of serum are avoided
4. Biassays are free from interference due to serum proteins.
5. There is no danger of degradation of sensitive proteins by serum proteases.
6. They permit selective culture of differentiated and producing cell types from the heterogenous cultures.
III – science
As we do not know what is in FBS we cannot tell what (in a positive or negative result) was the precise benefit of the process or the material used. Or was it due to FBS? With a synthetic replacement we do know, and we can deduct various stable, know factors.
This blog is about serum replacements, as we believe that fetal bovine serum based cell grow media should be replaced. There are a lot of reasons for this: technological, ethical and production related. What ever reason is yours we have a product coming to the market soon (september 2010) that will replace fetal bovine serum (FCS or FBS) for most general purposes.
But this blog is not advertising; we want to give insights in the market, the alternatives, the directions towards a sustainable solution etc. And we would like to ask you what your opinion is about these subjects. So please comment, follow us on twitter and discuss with us the new era of cell growth.
MORE >To our pleasant surpise we have quite some visitors to our website, blog and twitter. And we do agree; we could do a bit more. As you know there are always alot of excuses, but in this case we are working day and night to prepare everything for the launch of our products. With that launch we will improve our our online presence, so please hold on.
But we also received requests for information and background of the products. Therefor we decided to make an “in-between” website. It’s simple, straight forward and limited.
So, the next time you visit our temporarily site; it’s not perfect, but is its up and running!
MORE >The Naked Cell develops, manufactures and markets the first broad spectrum serum replacement that is completely animal-free. Besides that The Naked Cell is the first company ever with a 100 % sustainable portfolio and has no animal unfriendly products. We produce for biopharmaceutical formulation, life science research, bioprocessing, stem cell & regenerative medicine and diagnostics.
MORE >It has been a while since our last announcement to start in 2011 with our Xerumfree™ range, and now we can confirm that TNC will go live june 1st and that the products will be available in large quantities late this summer.
After finalizing a contract for financing, The Naked Cell is now ready to start rolling out it’s strategy and to bring our Xerumfree™ products to market. We plan to start joining the major trade shows as of september and our blogging will become a regular habit from then.
So, stay tuned for the world’s first universal, animal free serum replacement!
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