Grade B number of air changes

Dear friend,

I am a little in doubt about the next…

We have an new built plant which is planned to fill parenteral sterile vials. I was in inspection of the same and I have found too much mistakes there.
The first one (and serious…by my opinion) is the number of air changes inside of class B. This room will be used for filling of vials.
Machines are under laminar flow cabinets in ISO 5 class A and that is OK, but in background of the filling process (mentioned class B), I have measured only 20 to 25 AC/Hr:eek:
What I will do??? To say ‘’ this is not good’’ or try to do recovery test and wait for results??? What will happen if recovery test approach successfully?? Shall I give permission to continue media fill test???
What say the law in this case, how is your expiriences???

thanks in advance, kindly regards:)

Milan:(

Hi,

I am not having more experience in sterile plant since i am working in non-sterile plant.If possible i will try to collect details regarding ur query from my friends

Many thanks dear Sowmya, anyway… I am coming from non-sterile OSD plant, also…and I haven’t so much expiriences with sterile, same like u.
I have read a new one Annex 1 (Februar 08) EU GMP, and ISO 14644 ( 1 and 4. part) and still have not answer about AC/Hr.
In the case class B needs more than 25 AC/Hr, I must recommend to change HVAC units and it will be very bad info. i am still not sure what to do in this case:confused:

thx, rgds…

Milan:rolleyes:

ISPE Guide for Sterile Manufacturing Facilities (Volume 3, Published: January 1999), specifies a minimum of 20 air changes per hour is required in controlled areas. How many air changes depends on clean room design, cleaning schedule, personnel clothing and discipline, number of personnel inside room, etc.

Theoretically, if you are able to prove that with 20 air changes per hour, in both “at rest” and “in operation” conditions, you fulfill particulate and microbiology conditions, than can say that 20 changes is enough (in practice, this is not enough). More air changes give you more creditableness on system performance. If the air supply remains constant, the cleanroom is dirtier if there are more people in the cleanroom, more activity from people, cleanroom garments that are less effective in preventing dispersion of contamination, and more contamination coming from production machinery and processes.

In FDA Guidance for Industry; Sterile Drug Products Produced by Aseptic Processing — Current Good Manufacturing Practice, it is stated: “For Class 100,000 (ISO 8) supporting rooms, airflow sufficient to achieve at least 20 air changes per hour is typically acceptable. Significantly higher air change rates are normally needed for Class 10,000 and Class 100 areas.”

You can also find the equitation’s for calculating the required number of air changes, in function of all above mentioned parameters, and see, what the figures say.

My opinion, perform engineering study and measuring with available air changes. If the measurements’ shows that current air changes is not enough to maintain specified environmental conditions, You will need to make changes on Your system in order to improve it and increase the number of air changes.

Good luck LeKler :slight_smile:

Dear Del,:wink:

x1000 times thx for good and competent answer
Yes, my friend:) I have found the same points regarding air changes, it seems the meassuring will brings the final decision.
That’s my fear and night mare, as we there have installed chinesse:eek: equipment which requests more people-operaters than it is normal, also I am afraid, eqipment will make higher particulate contamination than other kind of the same equipment. Well, will see…
But, before of all…I need to change all terminal HEPA filters as they all are damaged and can not approach DOP test on 0,3u particulates. Should I say…all HEPAs are made in China, very bad filter media, bad support line…arrghhhljlj…bljak!!!
Simply said…God, help me!

thanks again friends, kindly regards,

cubica;)

Dear Cubica

As I have found in my company’s regulation, for class B the recommended air change rates should be between 30 and 40 per hour. ISPE guides only refers to controlled areas, but class B is more critical than class C or D, so you should try to attempt at least 30 changes per hour. If you don’t have an appropriate change rate, your recovery test will not work. And maybe you don’t need to change your HVAC unit, just increase speed. Talk to you engineering team.

Hope it helps

Marcos 38

Many thanks friend, I think I should do that. At present time I am in searching for good manufacturer of vial filling line, the next job willl be reconstruction of hole plant.

Thanks again, all of you are great,
kindly regards,

cubica

As the experince acquired, normally the no. of air change is around 30-50 times for class B area, besides, the personnel control system is critical important and can give strong supporting to minimize the possiblity of the failure.

Although I believe in China the complicated garments change system is not a must somehow, but undoubtly, it does contribute to the good maintenance of clean area.

wiston

As the experince acquired, normally the no. of air change is around 30-50 times for class B area, besides, the personnel control system is critical important and can give strong supporting to minimize the possiblity of the failure.

Although I believe in China the complicated garments change system is not a must somehow, but undoubtly, it does contribute to the good maintenance of clean area.

wiston

Dear Winston, thanks for answer,
regarding mentioned plant I didn’t tell that we already have instaled an chinese line inside. The same can not bring us good media fill test so we need to change all line, that is my second problem. LAFs, sterilizator, autoclave, washing, filling, capping, labelling…every mentioned system can NOT approach qualification, even IQ test…
On the first, we need to reconstruct the hole plant, at same time-buy a new one line for powder filling of vials (sterile, parenteral, aseptic).
I have reduced all manufactures to the next five…

  1. Bausch
  2. Bosch
  3. Romaco
  4. Ima
  5. Optima

Please, friends (which caming from sterile manufacturing), tell me what is your expiriences regarding mentioned manufacturers??? I will really appreciate any logic suggestions.

Thx in adv,

cubica:o

Bosch is one of the best manufacturer. Cost of Bosch equipment is very high.Second comes the MAR and Romaco which is also good one. Cost is lower than Bosch.

Warm Regards
Ravindra Upare

Dear:
I have to admit that there is a big gap between the chinese machinery and western ones, however, I doubt that all the machineries are failed to pass the validation in operation, because some FDA certificated pharmaceutical companies in China also use the local autoclave and local HVAC and clean rooms and Utility system.

But the filling, washing, capping is indeed from BOSH.

wiston
Wiston_chen@hotmail.com

Also, one more thing I’d like to remind you that there is hundreds of manufacturers of different level, therefore you’d better do a good homework and vendor assessment before purchasing.

I hope you will find something worthy your efforts in China.

Best Regards

Wiston

dear Wiston, many thanks…regarding sterile production machinery, there is no any doubt, only western machine can be obtained.
But, you are right about some chinesse products…for example, we have here excelent bin containers from China, other similar equipment, also. They are several times cheaper than western merchandise and looks verry good, also, I have tested them, operational 100%. Materials OK, valves OK, capacity test OK. I preasume that all other s.s. goods from China are also verry good and I can recommend to buy the same at any time.
As I know, many western company avoid to sell their machines to the China or arround, because exists possibillity to copying all lines and machines. Please, do not be angry on me, but I think that is China too far-away from good quality of the pharma machines productions at present time. maybe, one day…who will know…?

thanks, regards,

cubica:rolleyes:

Dear Cubica:

Without doubt that Chinese Pharma staff need to make more unremitting efforts!

Actually, I don’t work in machinery industry, but in the clean room and HVAC.
it is because I have to get a basic knowledge of most of the machinery probably invovled in the clean room in my work, that’s why …

by the way, what do you think the current situration of HVAC and clean room syste of China in pharmaceutical industry.

Regards
Wiston:)

Dear Wiston,

I can kindly recommend chinesse st.st. goods only as I told in previous post. Really, I have not experiences about HVAC and clean rooms, only within machines…unfortunatelly…not good. I have seen some HEPA chinesse but was bad, also.:o

o yes, clothing staffs are good and cheaper. Well, I am sure, better time comes for china production but we need wait.

kindly regards,

cubica:D

[quote=wiston]Dear:
I have to admit that there is a big gap between the chinese machinery and western ones, however, I doubt that all the machineries are failed to pass the validation in operation, because some FDA certificated pharmaceutical companies in China also use the local autoclave and local HVAC and clean rooms and Utility system.

But the filling, washing, capping is indeed from BOSH.

wiston
Wiston_chen@hotmail.com[/quote]

I fully agree with you. However the gap is now becoming narrow. I just returned from local pharmaceutical exhibition in Zhengzhou, in May 2008.
Comparing with the same exhibition for international buyers in Beijing and Shanghai, and also with Interpack/ Achema, China manufacturers are still left behind, especially in qualification scheme. However observing for more than 25 years, within 10 years time, the gap will be closer, though European machine is still ahead, in particular for papers works and other supporting procedural items.
Spend extra efforts before purchasing the critical equipment, visit the manufacturing site, their customers either in China and overseas, the most important one makes a cost benefit analysis.

regards,
Paulus Gunawan

As long as the Grade 'B" areas (Surrounding of UDF ) are meeting the Non viable airborne particle counts as per EU in “at rest” conditions, minimum of 20 Airchanges per hour can be acceptable in my openion

Gopala krishna

Dear friends,
Could you please provide me information about different classes of ISO. I am familiar with Class A, B, C and D and also with Class 100, 1000, 10000 and 100000. But I do not have idea about class 1, 2,3,4,5, 6 and 7 of ISO. Could you please provide me some information about these classes. Could you please compare the different classes with reference to class A, B, C and D or class 100, 1000, 10000 and 100000. You could also provide me the guideline saying about this.

Prawan Dahal

[quote=daprawan]Dear friends,
Could you please provide me information about different classes of ISO. I am familiar with Class A, B, C and D and also with Class 100, 1000, 10000 and 100000. But I do not have idea about class 1, 2,3,4,5, 6 and 7 of ISO. Could you please provide me some information about these classes. Could you please compare the different classes with reference to class A, B, C and D or class 100, 1000, 10000 and 100000. You could also provide me the guideline saying about this.

Prawan Dahal[/quote]

Dear Prawan,

Room type FDA 2004 FDA 1987 EU ISO
Critical area Class 100 Class 100 Grade A Class 5
Adjacent areas Class 10,000 Class 100,000 Grade B Class 7
Prep areas Class 100,000 Class 100,000 Grade C Class 8