21 CFR Part 820 and 210 mandates that where the accuracy of instruments and or instrument sensors is judged as critical to the final efficacy, quality and or safety of a regulated product or could prove injurious to the integrity of any associated predicated data or data records; the individual instrument must be considered as a, “Critical Instrument”. Critical instruments must be entered into a planned calibration program and subjected to routine calibration against master instruments traceable to national standards, at a periodicity that has a written justification. They must be placarded with a “Calibrated Label”. This SOP lists, details and defines each of the 11 essential elements of cGMP compliant calibration and calibration management. It includes sample document formats, calibration labels layouts and details the importance of the post calibration report. The SOP concludes with a fully detailed; ready to use, Calibration Manager Auditor document. This is your complete calibration SOP to purchase and use.

Quantity

In the Validation Risk Assessment, Document I felt that the work was only half done. It was very well laid out and very intuitive to follow. But while I was able to determine the Risk Category and Validation extent I felt that it did not deal with any of the Business process or system risks. Is that a separate document?

From everything I had read till now it seemed that once you determine if you need to validate you then need to determine your risk with using the system and the system risks. Some articles even talk about initiating the Risk process prior to buying the system and starting to identify the risks with the current process or old system being updated. Thanks ------------------------------------------------------------------------------------------------------------

Validation Online Reply:

The FDA (along with EC and WHO) realized a long time ago that the scope of any validation task must be allowed to be adjusted to avoid over burdening companies with repetitive and or unnecessary tasks. However this adjusted validation scope must be reviewed to verify that all applicable aspects of the task will be adequately validated. This review must be justified and documented.

We are all aware that risk assessment’s come in many formats; for instance, we have on our site a fully approvable FMEA which we use ourselves for all aspects of concept development and design development; however the Validation Risk Assessment (VRA) is a very different document and was specifically designed to assess and define the appropriate scope of any validation task. As such; it is a very important document which is mandated by the FDA and regularly reviewed by them.
Is the scope of your validation adequate? Is probable the most important question in validation and the VRA must give assurance that it is.

The pit- fall(s) of using multiple event Risk Assessments (such as FMEA’s) is simply that there are not (in validation) multiple variations or answers available. At the validation stage the system / process / equipment / program has already been bought / built / written / installed and commissioned. All aspects of design / functionality / safety / operability will have been fully debated and integrated at the URS stage and reviewed and approved at the DQ stage.

Hope this explains the use and importance of the VRA.
Regards
Alex

Customer Response:

Thank You for your response, I do understand and see the value of the Validation Risk Assessment, it was money well spent and I also agree with your comments about doing risk Assessments after the product is in the door and we in validation are only told after the fact. “By the way we need you to validate this next week” is a usual user response.

The FMEA is it a protocol and Spreadsheet or just a spreadsheet? Is there instructions on how to use it like the VRA? Is it possible to get a preview? I will need more information in order to receive authorization to purchase it.

 According to a recent study conducted by the U.K. based Medicines and Healthcare Products Regulatory Agency (MHRA), a staggering 43% of critical and major product deficiencies are related to ineffective temperature control and monitoring during storage and transportation.

Similarly the World Health Organization (WHO) recently maintained that 25% of all vaccine products arrive at their final destination in a degraded state. Given the high cost of conducting global clinical trials and the even higher cost of failure, regulatory agencies and pharmaceutical companies alike now demand that every party involved in the pharmaceutical supply chain - transportation and logistics providers included − conform to GxP guidelines and immediately activate procedures to attain Cold Chain Validation compliance.

1. WHO’s “Good distribution practices for pharmaceutical products” and “Guide to good storage practices for pharmaceuticals”

2. FDA’s “cGMP / 21 CFR 211”

3. U.S. Pharmacopeia (USP) <1079> “Good Storage and Shipping Practices”

4. Canada’s “Guidelines for Temperature Control of Drug Products during Storage and Transportation”

5. Ireland’s “Guide to control and monitoring of storage and transportation temperature conditions for medicinal products and active substances”

6. EU’s “Guidelines on Good Distribution Practice of Medicinal Products for Human Use” (94/C 63/03)

It is anticipated that these finding will move all things to do with - product quality in transit - to the top of visiting regulators inspection lists. The obvious priority being the thermal validation of transit containers - be they demountable or integral to a motor vehicle.

Validation of these containers and or vehicles is not difficult and can be tackled (using our fully detailed documents) by most technicians and or laboratory assistants.