I apologize, I dropped by mistake a paragraph, here is the full specifiedd explanation, I'll be here to explain and specify more if necessary, I know there a couple of members with background in chemistry here -
I'll try to explain in clear English the scientific description and terms in the attached document, sorry in advance - my English is not perfect
The first 4 paragraphs are a brief of the manufacturing process
The 5th paragraph discusses the quality assurance testing, and is the most interesting and relevant part to us -
When extracting proteins such as GH they have a tendency to create isomers - what I refer to is that 2 GH molecules or more are folded together, this form of the GH is biologically not active.
The first graph shows a the desired size which confirms the appearance of the product as a monomer (one GH colecule seperated and biologically active).
The second set of graphs is a HPLC prints of the set of analysis along the manufacturing process. As you may learn from the peak (or actually peaks) the GH when extracted from the bacteria contains several impurities (step1), mostly other proteins, and along the advanced purification process (step2+3) a purity GH of 98%+ is achieved (step4)
Another test which is mentioned is called LAL test, as described by USP/otherPharmacoepial and check the present of toxins and pyrogen to confirm the product is safe for injection, I didn't include it, and is done by another independent lab, there is simply no use to have such equipment in our facility, we just check per batch and pay like 80usd per test.
Now we go to the biological assay tests - these tests are unique to such peptides as GH and also called in vivo tests -
GH is a very delicate molecule. Slight harm in its 3 dimensional structure may harm its biological effect. For instance the the minor change in the slightest angle of the binding are to the receptor may prevent activation of the receptor. A very precise, careful purification process we developed to sustain the GH in its active form, which we confirm by the biological assay test.
The USP defines certain protocol to asses the biological effect of GH. In a nutshell it tests the effect of GH which is injected by certain protocol to mice, which their hypophiza is removed, and check along 3-6 months their liner growth (and other parameters). This is quite complicated clinical trial.
In our facility we use more advanced biological assay tests - we check the prolifiration of human cells under exposure to the GH in the product. this is currently the ultimate test, as it test directly the interaction of the GH with target receptor and quantifies its direct clinical effect.
When mice are injected with GH there are more factors are involved in their growth, like nutrition, genetic parameters, enviorment influence etc', of course the test tries to isolate the effect of GH by giving similar nutrition etc' to the mice, but as you understand it can't eliminate 100% such conditions.
In the biological assay.
In this Specific test the Somastim was fond to be about 6% more active then Saizen, but he clearly says that the statistical difference is not significant - and as u may see the graphs are quite identical.
This brings us to the serum tests which many relies on as an indication. (GH an IGF1 serum tests)
- Serum GH tests confirm the present and quantity of GH in the product. It's certainly not an indication to its clinical effect. It's a good start as it confirms that what the label declares is there, but it's certainly not the whole picture - it confirms the present of GH in the blood, but it certainly doesn't check biological activity of the GH - it doesn't check the form of the GH (monomers which is the active biological form) and not it's intact 3 dimensional structure)
- IGF1 serum tests clearly gives a valid indication to the clinical effect of the GH, but the results may widely vary as the IGF secretion (mainly in liver, as well as kidneys) depends also on many other factors such as nutrition, other hormonees like sex hormones, stress hormones insulin and glucagon, so the numbers this test brings are not an ultimate measure.
This is the significant of the biological assay in vivo tests
