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janmacek ☆ Czech Republic, 2015-02-13 11:57 (3685 d 04:45 ago) Posting: # 14413 Views: 12,629 |
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Dear colleagues, the Guideline on bioanalytical method validation states in chapter 4.1, Reference standards "Suitable reference standards, include certified standards such as compendial standards (EPCRS, ..." We have bought such a European Pharmacopoeia Certified Reference Standard (EPCRS) from EDQM, but we were very surprised that they 1) do not provide a certificate of analysis for these standards, 2) do not indicate their expiry date and 3) they even do not specifiy the content of the compound in the standard (in some cases). They only state "If a CRS has no assigned content, this should in no case be interpreted as if the content were 100 per cent." This seems very funny to us - a reference standard with no declared content  . But, more seriously, we have to work with it. Of course, we all know that for bioequivalence studies with relative measurements the purity of the reference standard is not critical, but auditors usually have not the same opinion.Have you any experience with these European Pharmacopoeia Reference Standards? If so, how did you solve the above problems? Have a nice day. Jan |
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ElMaestro ★★★ Denmark, 2015-02-13 12:51 (3685 d 03:51 ago) @ janmacek Posting: # 14414 Views: 11,444 |
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Hi JanMacek, ❝ Have you any experience with these European Pharmacopoeia Reference Standards? If so, how did you solve the above problems? How silly, I wasn't aware: "The Ph. Eur. does not provide any certificate of analysis for the European Pharmacopoeia substances." I wonder if the standards have any use at all for BA/BE GLP analyses then. I hope you'll get some answers here. — Pass or fail! ElMaestro |
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Helmut ★★★   Vienna, Austria, 2015-02-13 15:13 (3685 d 01:29 ago) @ ElMaestro Posting: # 14416 Views: 11,532 |
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Hi ElMaestro & Jan, ❝ I wonder if the standards have any use at all for BA/BE GLP analyses then. GLP? Interesting to read in the OECD Principles on Good Laboratory Practice, Section II 4.4.: Chemicals, reagents, and solutions should be labelled to indicate identity (with concentration if appropriate), expiry date and specific storage instructions. Information concerning source, preparation date and stability should be available. The expiry date may be extended on the basis of documented evaluation or analysis. (my emphasis)May we conclude: If the concentration is not given = not appropriate = don’t worry = still in accordance with OECD’s GLP? Strange. On the other hand Section II 6.2.2. For each study, the identity, including batch number, purity, composition, concentrations, or other characteristics to appropriately define each batch of the test or reference items should be known. — Dif-tor heh smusma 🖖🏼 Довге життя Україна! ![[image]](https://static.bebac.at/pics/Blue_and_yellow_ribbon_UA.png) Helmut Schütz ![[image]](https://static.bebac.at/img/CC by.png) The quality of responses received is directly proportional to the quality of the question asked. 🚮 Science Quotes |
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Ionsource ☆ Pakistan, 2015-02-16 09:04 (3682 d 07:38 ago) @ ElMaestro Posting: # 14426 Views: 11,199 |
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Hi ElMaestro & HS! I thought I was the only one not aware of the reason why EDQM doesn't provide CoA etc. In fact we were once badly criticized by an auditor for not knowing how to get CoA from EDQM. We learned the lesson and only purchased from USP since then. But please guide us to the solution. |
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Ohlbe ★★★ France, 2015-02-13 16:49 (3684 d 23:53 ago) @ janmacek Posting: # 14419 Views: 11,406 |
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Dear Jan, ❝ [...] "Suitable reference standards, include certified standards such as compendial standards (EPCRS, ..." ❝ [...] they 1) do not provide a certificate of analysis for these standards, 2) do not indicate their expiry date and 3) they even do not specifiy the content of the compound in the standard (in some cases). Well, can it really be called a certified standard then ?  — Regards Ohlbe |
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nobody nothing 2015-02-13 20:22 (3684 d 20:20 ago) @ Ohlbe Posting: # 14420 Views: 11,365 |
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...by all means: No. Even Kafka could not have invented such a clusterf*ck... But face it: We live in times where your telescreen, eeeh TV is sending all the voice data it can get to someone on the internet and the manufacturer advices not to talk anything private in front of this machine. In your livingroom.. So world has gone crazy, anyways. — Kindest regards, nobody |
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ElMaestro ★★★ Denmark, 2015-02-14 00:00 (3684 d 16:42 ago) @ nobody Posting: # 14421 Views: 11,300 |
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Hi all, ❝ So world has gone crazy, anyways. Agreed. I wonder what the use of the products from EDQM is at all? If they don't come with a CoA they aren't useful for anything quantitative in a regulated manner such as medicines. Perhaps they'd be useful for qualitative purposes - identification and such. You do an IR spectrum or whatever on it and hope it contains more than trace amounts of the stuff you are interested in - I mean that the spectrum you get is not too influenced by whatever is also in the sample in amounts you have no clue about and of which EDQM is silent. While I do not like to resort to any degree of harsh words, yes, I must say it does seem to be a kind of clusterf#ck this one. Will we in the future be expressing our concentrations as 30P ng/mL where P is an unknown purity coefficient? Come on, EDQM, you can do better than that. You value, first and foremost, public health, scientific competence, integrity, objectivity and respect for the fundamental principles of the Council of Europe, so perhaps you can offer to use a tiny bit of that competence to give your costumers a CoA? At USP they must be having a great laugh. Now if you'll excuse me I'll go back to my living room and tell my tv some deep secrets. — Pass or fail! ElMaestro |
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ElMaestro ★★★ Denmark, 2015-02-14 00:18 (3684 d 16:23 ago) @ ElMaestro Posting: # 14422 Views: 11,415 |
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Hey........thinking loud here: To do GLP you are responsible for your subcontractors. You can be nailed -and nailed badly!- for not having an audit programe in place for them, even if the OECD guideline is not overly clear about vendor oversight. So, how would EDQM react if you tell them you are going to audit them? It would be a perfectly reasonable routine activity for any company buying a standard from them. Probably such an audit might shed some very relevant light onto why products produced by EDQM are of unknown quality. I'll be happy to do it on behalf of a client — Pass or fail! ElMaestro |
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nobody nothing 2015-02-14 13:49 (3684 d 02:53 ago) @ ElMaestro Posting: # 14424 Views: 11,315 |
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I join you! Extra rates, I swear! — Kindest regards, nobody |
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janmacek ☆ Czech Republic, 2015-02-16 13:59 (3682 d 02:43 ago) @ Ohlbe Posting: # 14428 Views: 11,150 |
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Dear Ohlbe, I could imagine that the primary standard does not need a certificate of analysis and the content of the substance is given simply by the assigned value. This would resemble the previous definition of a length unit meter, which was specified as a length of prototype meter standard stored in France. In most cases, the EDQM specifies at least this assigned value. But recently we have bought a standard of perindopril tert-butylamine and in this case no assigned value is specified. Generally it seems me that the EDQM did not cooperate well in this case with EMA. The Guideline on bioanalytical method validation specifies the EPCRS as a first choice, but EDQM states that "The EDQM Reference Standards are established exclusively for the intended use(s) described in the official texts of the Ph. Eur.". These statements are contradictory and should be harmonized. Best regards, Jan |
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janmacek ☆ Czech Republic, 2015-07-15 11:28 (3533 d 06:14 ago) @ janmacek Posting: # 15084 Views: 10,057 |
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Hi all, I asked EMA on this problem and after two months they responded that they consider updating the guideline on bioanalytical method validation. They really did so by eliminating the reference to European Pharmacopoeia Certified Reference Standards, EPCRS (see EMEA/CHMP/EWP/192217/2009 Rev. 1 Corr. 2) and the problem is thus solved. In the future studies the EPCRS cannot be used anymore. Best regards, Jan |
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ElMaestro ★★★ Denmark, 2015-07-15 12:35 (3533 d 05:07 ago) @ janmacek Posting: # 15087 Views: 10,042 |
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Dear janmacek, ❝ They really did so by eliminating the reference to European Pharmacopoeia Certified Reference Standards, EPCRS (see EMEA/CHMP/EWP/192217/2009 Rev. 1 Corr. 2) and the problem is thus solved. No, one problem is solved, but the problem is not. ❝ In the future studies the EPCRS cannot be used anymore. And this is the real problem. The fact that an ECPRS product is not accompanied by a CoA specifying its purity probably only relates to the fact that it is difficult. It certainly would otherwise be both relevant and highly useful and appreciated by companies traditionally relying on reference standards. — Pass or fail! ElMaestro |
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