Im being continually fustrate by my companies lack of interpretation of the ISPE baseline guide.
We have an existing HVAC system that in a couple of months will support a new Blister Line. There are no specific requirements for the HVAC system apart from the norm which are not product critical, 21oC +/-2, 40-60Rh, Air Changes, Class 100,00. Ive been trying to get the powers that be to buy in to my new concept. We do not need to Qualify the system as it is indirect. The requirements indicated in the URS will all be tested during a commissioning document i will write. Filters will be checked after installation for DOP testing and put onto a PM schedule. Magnahelics are above the doors to ensure the correct pressures are being met so continuous monitoring will be performed. Particulate testing will be performed for 5 days as will Temp and Hum. They canât see the woods for the trees and its frustrating.
I actually think we need to get the ISPE baseline guide updated. One of the questions it asks is âdoes the system preserve product statusâ. Well if its a nitrogen system blanketing a product in a reactor then yes as if the N2 system failed then the product would be affected. But if its a HVAC system that does not effect the product if it failed, then should we be validating it in the first place. I know im right but its a new concept that people are struggling to come to terms with.
Does anyone think that my argument should stand up!?!
Hi Murray,
Welcome to our forum, could you please expand on the quote below. Are you going to test all of your URS requirements in the commissioning document? Just trying to understand a little moreâŚ
âThe requirements indicated in the URS will all be tested during a commissioning document i will write.â
Hello Mr keeffe,
As part of the commissioning document we will be testing what the URS should term (functional requirements) of the system. This is not indicated so you have to make a best guess based on your experience. If i can get the QA buy in to the approach then the critical requirements will be tested within the commissioning doc. Its really frustrating that they expect full qualification for a legacy system thats is not critical to the product and we are performing all the due diligence to ensure we can control our system.
Cheers,
Murray
Here is the analogy,
If you think about a compressed air system which opens and closes valves on a reactor system. This would be termed as an indirect system as it is not functionally critical to the product. It could be that its opening an actuating valve for chilled water or nitrogen.
So if we think of the Blister line which is the direct system the HVAC system is only supporting that system to ensure the pressure is maintained within the room which is verified by the Magnahelics. The filters themselves ensure the particulates are reduced.
In that respect the HVAC system is indirectly supporting the Blister line.
Your thoughts?
Yes, I agree thanks for the explanation.
In terms of HVAC validation (I would call it more commissioning to be honest), itâs usually the external vendor that would perform this commissioning process ie for air pressure, particulate count etc. I personally wouldnât go down the road of a validation lifecycle for this type of system. Is this the kind of response you were looking for?
Why go to all this hassle when commissioning will more than suffice.
Just my 2 centsâŚ
[quote=Murray MacInnes]Here is the analogy,
So if we think of the Blister line which is the direct system the HVAC system is only supporting that system to ensure the pressure is maintained within the room which is verified by the Magnahelics. The filters themselves ensure the particulates are reduced.
In that respect the HVAC system is indirectly supporting the Blister line.
Your thoughts?[/quote]
SorryâŚI would have to disagree with you, unless Iâve misunderstood you.
In my experience you would have to validate the HVAC system (retrospectively or prospectively) as it DOES directly affect the product, due to the fact that the HVAC system âcreates the environment/conditionsâ within which the product is manufactured and/or blister packed. All main pharma and biotech companies are validating their HVAC systems for this reason, as it impacts on GMP âfacility requirementsâ. There is also cross product cross contamination risks/issues here (GMP)!
Would you really say the same about a Class 100 (aseptic) area?? The fact itâs a Class 100,000 area makes little difference in my experience, an external auditor with facilities experience will expect your GMP facility HVAC to be validated.
However I would suggest a different approach; use your existing commissioning documents as reference documents for the IQ/OQ protocol tests, hence reducing the repeat work. But also include smoke testing of air flows and room pressure checks to ensure there is no product cross contamination risk between manufacturing/packaging suitesâŚcross contamination of products is a big risk in the eyes of an inspector!
Also, if you have a Building Management System hanging on the end of it e.g. a TREND BMS, then that would also have to be validated (CSV) including the âhead endâ and any EMS/FMS monitoring system and outstations that support the batch record information for QP sign-off.
Just my opinion though.
Good point David, didnât take that into consideration, you learn something newâŚ
David,
Have you every validated a Breathing Air system and if you have why?
Regards,
Murray
[quote=Murray MacInnes]David,
Have you every validated a Breathing Air system and if you have why?
Regards,
Murray[/quote]
Sorry, Iâve never validated a breathing air system.
Dave,
As the breathing air system does not affect the product even although you are introducing air into the area, you still need to qualify the air. We do this by verifing that the filter installed is to 0.01 miron to prevent any microbial growth with the air and reduce the particulate counts.
As the Temp/Hum is not critical to the are the same logic applies for the filters on the HVAC system.
Movement of people and various other parameter affect your environmental conditions and all you can do is reduce the risk.
I can understand where you were coming from but why do you think we need to qualify HVAC systems that are not temp/hum critical to the product?
Regards,
Murray
[quote=Murray MacInnes]Dave,
I can understand where you were coming from but why do you think we need to qualify HVAC systems that are not temp/hum critical to the product?
Regards,
Murray[/quote]
Depends on the product! Companies Iâve worked with run more than one product(s), some critical, some not critical, so they validate for the worse case scenario. Also, if the HVAC system services/supplies more than one area i.e. multiple products in multiple rooms etc, like a pharma development facility for example, then cross contamination has to be considered in the GMP design of the facility and its HVAC systemâŚitâs NOT just about temp and humidity criteriaâŚits about the entire design in meeting GMP facility expectations.
For example: âinlet and extract ductingâ; you cannot [should not] have un-isolated vertical ducting drops between GMP manufacturing suites serviced by the same HVAC system! As it increases the risk of cross contamination between suites should a HEPA filter failure occur. Most new GMP facility designs for HVAC systems would not engage in designs that had vertical drop HVAC ducts between suites. They should be at a 90 deg. angle to the main duct before entering the room to minimise the risk of cross product contamination (verified at IQ) in the event of a HEPA filter (if applicable) puncture/breakdown.
Again, this is just my opinion and what I have experienced over the years. This may not be appropriate for your particular company / product criticality / number of products / number of packaging and manufacturing suites etc etc. Maybe you could suggest a Risk Based Assessment to resolve the issue. But remember, cross product contamination has, in the past, been one of the main reasons of product recalls and/or patient injury/deaths, depending on the toxicity of the products weâre talking about.
Murray
Let me explain the fact that HVAC system does not affect the product indirectly. HVAC for your blister line is for creating a pressure inside the room and for creating the desired particulate. If due to some fact the HVAC design is not proper and that your desired room pressure and particulate are not achieved, dose your blister line still works as intended and gives a packing complying to its requirement which its intended to do? Certainly not. that is the reason HVAC should be validated going thru the complete validation cycle URS/DQ/IQ/OQ and PQ.
regards
Shaamu
dear daveh
i am with u on this issue.
HVAC systems must be validated before operation.
all regulatory bodies r asking now for HVAC validation documents,more specifically AHU WISE.
PRASAD
Q.A.
AVENTIS PHARMA ANKLESHWAR.
prasadaparajit@rediffmail.com
[quote=DaveH]SorryâŚI would have to disagree with you, unless Iâve misunderstood you.
In my experience you would have to validate the HVAC system (retrospectively or prospectively) as it DOES directly affect the product, due to the fact that the HVAC system âcreates the environment/conditionsâ within which the product is manufactured and/or blister packed. All main pharma and biotech companies are validating their HVAC systems for this reason, as it impacts on GMP âfacility requirementsâ. There is also cross product cross contamination risks/issues here (GMP)!
Would you really say the same about a Class 100 (aseptic) area?? The fact itâs a Class 100,000 area makes little difference in my experience, an external auditor with facilities experience will expect your GMP facility HVAC to be validated.
However I would suggest a different approach; use your existing commissioning documents as reference documents for the IQ/OQ protocol tests, hence reducing the repeat work. But also include smoke testing of air flows and room pressure checks to ensure there is no product cross contamination risk between manufacturing/packaging suitesâŚcross contamination of products is a big risk in the eyes of an inspector!
Also, if you have a Building Management System hanging on the end of it e.g. a TREND BMS, then that would also have to be validated (CSV) including the âhead endâ and any EMS/FMS monitoring system and outstations that support the batch record information for QP sign-off.
Just my opinion though.[/quote]
[quote=pvalidation]dear daveh
i am with u on this issue.
HVAC systems must be validated before operation.
all regulatory bodies r asking now for HVAC validation documents,more specifically AHU WISE.
PRASAD
Q.A.
AVENTIS PHARMA ANKLESHWAR.
prasadaparajit@rediffmail.com[/quote]
Qualification of Air balancing and uniformity must be initiated and its also verified priodically.
Hi Murray
Iâm with DaveH on this one, you have to have validated utilities in your pharma factory e.g. compair, PW, HAVC etc. Also your facility (e.g. the room in which your blister machine will be installed), has to be qualified. The main purposes are as DaveH said: The environment in which the operation takes place has to be suitable and under control and then thereâs is the cross-contamination issues. I have been working for multinationational companies for most of my time, and for a very long time for the same company that Prasad works for. I have faced FDA, WHO, local regulatory and corporate GMP audits from clients. You will be dead in the water without those qualifications/validations.
Regards
Michael
dear All
InterestingâŚ
in my experiance i came to know that the below points during HVAC Qualification.
- if you claim the classification of the room you should qualify entire parameter of HVAC
if you claim it is class 100000 at rest you should check the parameter sequentially at prospective stage
1.air velocity
2.air changes
3.installed filter leak lest
4.again air velocity
5.air changes calculation
6.air flow
7.differentiable pressure
8.Temperature
9.Humidity
8.air born particle counts
9.viable counts
10 recovery test
11 sound level
12.lighting level
13.vibration level
Purpose: though you have claiming the classification as class 100000 , in terms of airbone partcle counts you need to perform all thease tests.
HVAC may have direct impact on the product in some casess.some casess you need to maintain the humidity for the product and to avaid the cross contamination you need to qualify.
and one reason to perform all the tests , if you will not achieve particle counts with in the limits thease test results can be use full for further investigation.
Satya
Qualify Assurance
[quote=Murray MacInnes]
I actually think we need to get the ISPE baseline guide updated. One of the questions it asks is âdoes the system preserve product statusâ. [/quote]
Dear Mr. Murray MacInnes, I like the way you look the guidelines. You are search of logic before implementing them. I have seen many industries where guidelines are implemented blindly and have invested huge amount just to implement the guidelines eventhough that is not required for their case.
Yes, I agree with you. HVAC System is not responsible for preservation of product. HVAC System should not affect the stability of the product. I have seen nowhere that HVAC system preserve the product, it should be only of the quality that does not have any adverse affect on product quality, in term of particle, in term of temperature, RH etc.
You should not validate the HVAC System to prove that it preserve your product, but you should validate the HVAC system to prove that your HVAC system does not affect the quality of your product. Moreover, the air change per hour is needed to prove that dust generated are being flushed periodically.
Regarding validating breathing system, you should understand the breathing system. It involves process of inhaling your air inside the lungs and exhaling the air from the lungs. The source of air that we intake inside the area is the air that comes from HVAC system. the breathing air of healthy man do not have pathogenic organisms, if he is healthy and we do not have any system to enter inside the production area with lungs disease and the health condition is also periodically checked and that cover chest X-ray also. Moreover, the provision of clean room masks inside your clean room also filter the contaminant you generate during the breathing. The volume of air generated from HVAC system is usually more and with high velocity than breathing air and also the possibility of contaminants from HVAC system is very high than breathing air, so, it is not critical to validate your breathing system than validating your HVAC system. Moreover, if you validate your HVAC system during operation also, i.e. with peoples breathing then it is really worthless to validate your breathing system.
However, validating the breathing system will be good if you do not validate your HVAC system during operation phase.
Mr. Satya Lighting level is not part of HVAC Qualification?
Mr. Satya, Light level is not a part of HVAC Qualification.
[quote=pava_satya]dear All
InterestingâŚ
in my experiance i came to know that the below points during HVAC Qualification.
- if you claim the classification of the room you should qualify entire parameter of HVAC
if you claim it is class 100000 at rest you should check the parameter sequentially at prospective stage
1.air velocity
2.air changes
3.installed filter leak lest
4.again air velocity
5.air changes calculation
6.air flow
7.differentiable pressure
8.Temperature
9.Humidity
8.air born particle counts
9.viable counts
10 recovery test
11 sound level
12.lighting level
13.vibration level
Purpose: though you have claiming the classification as class 100000 , in terms of airbone partcle counts you need to perform all thease tests.
HVAC may have direct impact on the product in some casess.some casess you need to maintain the humidity for the product and to avaid the cross contamination you need to qualify.
and one reason to perform all the tests , if you will not achieve particle counts with in the limits thease test results can be use full for further investigation.
Satya
Qualify Assurance[/quote]
[quote=Murray MacInnes]Im being continually fustrate by my companies lack of interpretation of the ISPE baseline guide.
We have an existing HVAC system that in a couple of months will support a new Blister Line. There are no specific requirements for the HVAC system apart from the norm which are not product critical, 21oC +/-2, 40-60Rh, Air Changes, Class 100,00. Ive been trying to get the powers that be to buy in to my new concept. We do not need to Qualify the system as it is indirect. The requirements indicated in the URS will all be tested during a commissioning document i will write. Filters will be checked after installation for DOP testing and put onto a PM schedule. Magnahelics are above the doors to ensure the correct pressures are being met so continuous monitoring will be performed. Particulate testing will be performed for 5 days as will Temp and Hum. They canât see the woods for the trees and its frustrating.
I actually think we need to get the ISPE baseline guide updated. One of the questions it asks is âdoes the system preserve product statusâ. Well if its a nitrogen system blanketing a product in a reactor then yes as if the N2 system failed then the product would be affected. But if its a HVAC system that does not effect the product if it failed, then should we be validating it in the first place. I know im right but its a new concept that people are struggling to come to terms with.
Does anyone think that my argument should stand up!?![/quote]
You say that there is no need to qualify the HVAC because it is Indirect Impact, but donât you then perform Component Level Impact Assessment (CLIA). How would you classify the fan unit, VFD, pre-filters, instruments, integrity of the ductwork? Do you also include the HEPA filter as part of the system or a separate âroom systemâ?
If any component comes out critical the system should be upgraded to Direct Impact and the critical components should be identified in the IQ (IV) and come under change control.