During a recent class I taught at University of California, Berkeley in their Quality and Compliance postgraduate certificate program, a question came up from one of the attendees that mirrored very closely observations I have made in audits over the years. And that question was “do we have to validate compendial methods we use in testing our commercial products?”

That question is, on the surface, very simple. And the answer is no. Neither the FDA nor the EMA requires us to validate compendial tests that we use with our products. But the answer actually has another layer to it which people do not venture too often to address.

While we do not have to validate a compendial method we use with our products, we must demonstrate that it works for the application with our product. ICH Q7 describes in section 12.80, this point clearly.

Analytical methods should be validated unless the method employed is included in the relevant pharmacopoeia or other recognised standard reference. The suitability of all testing methods used should nonetheless be verified under actual conditions of use and documented

Thus it is clear that while formal validation is not required, we must demonstrate that it works for our product for the intended purpose. This is very clearly shown in the original form 483 issued to Chiron Corporation for their flu vaccine product plant in UK in October 2004 that resulted in issuance of a warning letter in December 2004. They were cited for a lack of data to support the use of the USP sterility test for their product. Their response was clearly adequate since it was not cited in the warning letter. This action took them off the market in the 2004 flu season for their flu vaccine product

Many times on audit I have reviewed specifications and seen that compendial methods are used for a variety of tests including sterility, endotoxin, particulates and others. My first question is usually to ask for the data to support use of the method for their product. At least 9 out of 10 times, I get blank stares followed by the statement, “we don’t have to validate compendial methods!” I agree with them but follow on with the statement, “I know, but where is the data to support usage of the method?” They often look puzzled still but cannot provide any data. Too often, I believe, the first sentence of the ICH Q7 document is read but the second missed.

What do you have to do the “qualify” it? I recommend a simple qualification plan – rather like a validation protocol – with a testing plan to check the key parameters of the assay such as accuracy, precision, specificity and ruggedness, including interferences. That sounds like a validation and it is: but an abbreviated one touching only on the parameters of issues that make your product unique or challenging.

Posted in Commercial Manufacturing, Compendial Methods, GMP, Warning Letter| Tags: Services|9 Comments

As Calcott Consulting spreads its wings and extends its reach into the Pharmaceutical and Biotech industry, it is time to start a blog. This is the first (and hopefully not the last post).The topic for today is VENDOR QUALIFICATION.

I routinely review FDA warning letters every month or so to see how the industry is faring and to get new information for all my classes and training sessions and the one that caught my eye was this topic. I think we are all aware of the Baxter – Heparin incident and how a lack of oversight brought disaster to the company and also its Chinese vendor of heparin. It did also cause quite stir in the industry and with the public at large.

Is this an isolated incident or is part of deeper issue in the industry? I think the latter.

I see in my audits lcak of clarity in these programs to qualify and manage vendors of services and materials whether it be a testing lab, a provider of services eg. maintenance or raw materials. Too often when I ask the question “show me your vendor managemnt or qualification program”, I am presented with an audit of the company. Similarly, when I scan and read the group discussions in LinkedIn, I am amazed by some of the questions that indicate a lack of understanding of the first principles of what needs to be done. And this is by people who are in the field in senior positions.

So what are they doing wrong. I have included some links below to go directly to the warning letters but companies who fail clearly demonstrate at least a few of the following:

1. Delegation of all responsibility and accountability to the service provider. It does not matter who does the work, you are still responsible for the outcome.
2. No objective demonstration that the vendor can provide what they say they can do.
3. No tracking of performance to assure the vendor continues to provide the service at an acceptable level.
4. Accepting sub standard materials and services

This is to name but 4. Read through the attached links to see the details.

Warning Letters to Allure Labs, Scientific Protein Labs, and Toxin Technology Labs

Posted in Vendor Qualification, Warning Letter| Tags: Services|Leave a comment