Visa, senior professional GxP regulations Paul Daniel often meet with questions about the validation.Most problems for GxP regulations others are common problems in the industry, we can use beforeThe articleIn the published material easy to answer.But sometimes, we will encounter new problems.

In this article, Paul answered a he had never met the problem.In order to ensure reasonable answer, he contacted a have decades of experience in life science validation validation of the expert.Sometimes two heads are better than one, especially when special problems.

In view of this, we invite you to attend"Validation: craigslist"Network seminar.Axis Consulting, Josh Keenan will preside over the seminar with Paul, they will try to answer questions about the GxP compliance verification together.For details and register...

M. wrote:

Hello, Paul:

I've been watching you on a network conference, I have a related to the seasonal change on the influence of the temperature control of space problem.In our company, we according to time and temperature sensitive type is suitable for drug storage temperature dynamic distributionThe WHO modeling guidelines, to the warehouse in the summer and winter temperature dynamic distribution validation studies.Through the temperature distribution of dynamic validation activity, we found that under the condition of use in the summer of 22.2 ° C temperature set point, under the condition of winter use 22.8 ° C temperature set point can be ideal to control room temperature.We usually by an authenticated temperature set point to control our temperature sensitive storage places, so I want to know you to set up two set points (one for winter conditions, one for summer conditions) of suitability for any ideas.If so, whether we should shoulder months (April and October) in both in the form of programmed to switch between the set point.If you can provide any insight, I would be most grateful.

thank you
M

Paul wrote:

Thank you for your contact with me!I think I can answer, but I also want to have with me to editISPE controlled temperature test chamber good practice guideCheck the new version of a colleague.Hope the two of us to participate can provide more comprehensive solutions to your problems.

As far as I am concerned, in an ideal world, we will always need only a single set point for the whole year.Obviously, as you can find, reality is more complex.I want to know whether you can confirm the set point of the 72 ° F for winter temperature is too low?Or 73 ° F the set point for the summer temperature is too high?I guess you should still pulling in this respect, otherwise we will not proceed with the communication.You can find 72.5 ° F a compromise?I mean, 1 degree Fahrenheit is half a degree Celsius.This really is a very small difference, may be less than the instrument error of control sensor.

Do you have for hvac experts view can adjust the hvac system, so that you can use a single set point to operate?You might have done so, I just want to confirm the...

I don't have met warehouse according to the season change the set point in the process of operation, but this does not mean that it's not feasible.I have seen a company use incubator in this way.Not the set point of seasonal changes, but the set point based on product specifications frequently change.In order to support the change of the set point, they in each set point of each device on the dynamic distribution of validation.When need to calibration temperature probe, they expressed their doubts to the visa.As you might expect, only is beyond the scope of conventional wide can meet the needs of them so many set point.

But for your warehouse, in my opinion, to switch to the seasonal programmatic way set point is feasible method.My intuition told me that need to be all this change in relation to the other has scheduled events, such as PM or calibration.Maybe you can use it as a part of change control, to ensure that the correct track.

I all this change on the basis of procedural intuition is the result of my experience in warehouse distribution of dynamic verification.Seasonally change the set point is a kind of unusual phenomena, and unusual phenomena tend to cause reviewers' questions.In order to answer questions during the audit, the ideal preparation is formulate relevant procedure.

Let us with ISPE good practice guide editing colleague D check it.

D wrote:

Paul and m., hello:

Thank you for let me participate in the discussion.First of all, Paul and I agree, usually in a warehouse there is no need to change the set point, and he put forward several advantages.According to my experience, I do not have to change the test chamber for winter or summer application Settings.But for the sake of full disclosure, I just a few management in and outside storage GMP products used for the test chamber, so there is no need to adjust.

The following is I will consider several factors:

• test acceptance standard is what?According to the USP, temperature for 15 ° to 30 ° C, C, or if it is to ensure that the drug stability, temperature deviation can be plus or minus 2 ° C.The reason why I put forward this problem is: according to the test acceptance criteria, the set point will change once out of specification, not make them or do you just notice the trend looks different and wanted to compensate, in order to improve the temperature alarm limit of allowed?

• probe located in where?If they are too close to the wall or ceiling, may lead to different readings.Move on wall thermal fault location, if the sensor too close to, may affect reading.

As mentioned earlier, one degree of temperature deviation is very small.If we consider the uncertainty of measurement of the sensor used, can always read still 1 ° C temperature?

This is an interesting question, so I make a phone call to one of my own and run a test chamber manufacturing company of friends, put forward the problem to him.He said he has not met the problem.He made test chamber in accordance with GMP and other regulatory requirements, and his thoughts as much as I do;This result may be caused by many factors.

1. The sensor is placed
2. Air supply source
3. The air velocity
4. Load test box

Having said that, if you must according to season change the set point, Paul and I have the same concerns: from the point of view of the audit, any unusual activity in GxP related applications will cause problems.My advice is as follows:

A. determine when and what Settings to use to study the dynamic distribution of temperature.Audit industry, some people believe, if you change the set point or any other Settings, you must to carry on the dynamic distribution of the test chamber to test and verify.It can depend on to allow for much change.Someone said, will the set point changes once there won't be much different.It will depend on how much test acceptance limit span.

I work for a large pharmaceutical companies for nearly 30 years, is to develop the stability, reference standards and laboratory equipment mainly review the contacts.If I have to change the conditions of the test chamber, before I will change on the dynamic distribution of verification, so that I can make a "cover" from the condition to end the whole process of testing the condition, and then change the set point or any other adjustments.Later, I will for it verifies the dynamic distribution.If the test fails for the first time, I need to submit the deviation to show that samples are safe.If the second test to fail...In fact is not likely to fail, because before starting the test, you can according to need to make any operation test chamber.I will even gather data in the test chamber.

B. if you want to switch back and forth between the set point and not verified dynamic distribution, every time you can in the current temperature to carry on the dynamic distribution of the test chamber, rerunning the dynamic distribution and seasonal change until after the verification.To this, my question is, how do you know how cold or hot, it will become and how will this affect test the temperature in the oven?

C. continuous dynamic distributed authentication: I haven't tried before, but if you continuous verifies the dynamic distribution and make all sensor alarm, I think you can prove that all Settings are reasonable, because you always know whether they are within the scope of the restrictions.Visa will host aContinuous dynamic distribution verification network seminar, Paul will illustrate webinars on its working principle.

Based on my experience, the personnel focused mainly on whether or not you according to the experiment box manufacturer's recommended box, as well as products and sample is stored under the required temperature.Ensure that the calibration and record all the sensors.

Thank you again for Paul let me participate in discussions - this is a difficult problem!

Shun ShangQi!
D.

M. replied:

My friends, thank you very much for your detailed reply.More specifically, we are in a large warehouse to confirm level temperature distribution of dynamic verification, in order to realize the among 20 to 25 ° C, not use controlled storage test chamber.

According to USP standards, we do allow deviation, but on the whole, in a week of the summer and winter dynamic distribution of validation study, we keep all sensors (each data point) between 20 to 25 ° C.We allow to explain the deviation (such as open caisson) or other short deviation less than one hour.

Our problem is that we in some storage space layout of several sensors always dropped to below 20 ° C during the winter, or rose to more than 25 ° C in the summer.In the past, our facilities group moved only seasonally, thermostat, in order to keep the temperature a little cooler in the summer when, make temperature more warm during the winter (in), so as to avoid beyond the range of fluctuation of hot/cold spots.

We have the old warehouse and air treatment equipment.As you suggested, we have been asked them to lock the set point, and regard it as qualified, verifies the dynamic distribution does not need to three years.When they change the set point, I have been called for a new dynamic distribution of validation studies.

In order to comply withUSP < 659 > packaging and storage requirements, we try to avoid in any data points "magic" 25 ° C, and we need average kinetic temperature calculation, which has no definite descriptions or acceptance criteria.

After the discussion with you both, I will continue to strive for the use of a single set point and improve the airflow or insulating layer to alleviate the seasonal fluctuations.

Thank you again!
M.