When must you write an SOP for a USP method?

[MestizoJoe]

Hi,

I was wondering when exactly is an SOP needed for a USP method.

Specifically, there is a method I will use now for lidocaine assay, but it is a titration (Lidocaine HCl 2% Jelly). I have never used an in house method to run the exact USP test for a titration (not an autotitrator).

I thought we skip writing our own protocol for titration because there is no electronic instrument or software or anything like that. Is there a more specific reason? I'm asking because a director is trying to get me to write protocols for this and another titration and I know I dont have to.

I did write a protocol for an HPLClidocaine assay, but there we have the HPLC instrument.

[JGK]

When using Published methods like those from the USP it may not be necessary to have it in SOP form (unless your internal documentation system demands it). However, many of these "official" methods are worded fairly vaguely and are subject to many possible interpretations. We always found it useful to have a method guide associated with the official text where analysts could add notes which enabled the assay to be performed to an acceptable standard consistently.

[KM-USA]

When using Published methods like those from the USP it may not be necessary to have it in SOP form (unless your internal documentation system demands it). However, many of these "official" methods are worded fairly vaguely and are subject to many possible interpretations. We always found it useful to have a method guide associated with the official text where analysts could add notes which enabled the assay to be performed to an acceptable standard consistently.

Where I work it's the opposite. While I agree that many/most of these "official" methods are worded fairly vaguely and are subject to many possible interpretations, the folks here are terrified of doing anything that is not specifically allowed in the USP or FDA in writing.

So here we have test methods that simply state: "use the assay procedure in the current USP Official Monograph", so then analysts at every location can scratch their heads.....

I cannot agree with this strategy; too many USP assays are obsolete, confusing, or worse. For example: for your lidocaine hydrochloride assay (extraction after neutralization with ammonia, followed by titration with acid), do you assay in singleton? Duplicate? Triplicate? If duplicate or triplicate, how precise must the determinations be to agree?

Is such procedure the best modern science has to offer? Sad.

Are you standardizing your acid titrant? How often? In singleton? Duplicate? Triplicate? If duplicate or triplicate, how precise must the determinations be to agree?

[MestizoJoe]

Thanks for the comments. I was planning on performing the titrations in triplicate. As for the precision I think less than 5% is good but I see how not having an established limit might be trouble some.

As for the acid standardization, we will be trusting the vendors CofA. I may perform the assay on a USP ref std instead of standardizing the acid as a check.

[KM-USA]

As for the acid standardization, we will be trusting the vendors CofA.

My supervisor says for cGMP assays the FDA expects all titrants to be standardized before use (no matter how well one trusts the vendor).

Anyone know whether the FDA accepts using certified titrants as is?

[shaun78]

Anyone know whether the FDA accepts using certified titrants as is?

If you purchase VS solutions and use them within 2 to 4 weeks (I forget the exact time; I think either the bottle or C of A states the time allowed to be opened before restandardization) of first opening; yes.

[KM-USA]

Anyone know whether the FDA accepts using certified titrants as is?

If you purchase VS solutions and use them within 2 to 4 weeks (I forget the exact time; I think either the bottle or C of A states the time allowed to be opened before restandardization) of first opening; yes.

Shaun78 - do you have an official reference source for this?

I've talked to several manufacturers of volumetric solutions. All the manufacturers can certify is that they've documented stability to (1) when the container is first opened or (2) the listed expiration date, nothing more. They do not state that such solutions can be used directly for cGMP assays; and I believe that even goes for such volumetric solutions that even state USP on their label. So an official reference would be great.

Our supervisor wants all such solutions standardized here at time of use. Of course that assumes that the primary standard KHP is of stated quality, etc.....

[LC_labrat]

I looked up a CofA for 0.1 N volumetric HCl,the manufacturer specifies the standardization is traceable to NIST and specifies the standard reference material that was used. It also states it is suitable for use in ACS, USP and NF compendial methods. The vendors may not have documentation for the expiry of the standardization, or it might be on the bottle. It might be worth the time to perform a study on the standardization expiry, depending on how quickly you use the reagent. FDA does not provide guidance for these type of details, one size does not fit all. It's a risk based assessment, most conservative-standardize prior to use.

[Johnny Rod]

Would they take a different view whether you're doing in-process or intermediate testing vs. raw materials or final product testing? Historically they're spectacularly inflexible but I thought these days they were becoming more comfortable with risk-based approaches.

I agree with the comments above supporting writing your own SOPs, you can also use these for training, but also some busy labs use a large range of methods so having a concise method to pull out and use is a good thing on various levels.

[Tarapan]

It really depends which standards you wanna follow (Local authority, ISO etc) but during one of our training at a neighboring country regulatory authority lab on this subject this is what our lecturer has to say:

The compendial methods (USP, BP EP) are guidelines and therefore you will still need to write the SOP/ work-instructions based on your laboratory's set-up.

Tarapan