Calculation of MACO

GOOD VALIDATION PRACTICE (cGVP) CLEANING VALIDATION
21

Dear Validation Engineer,

mg/swab is the actual result found from selected area, which further extrapolate to entire product contact area of equipment, later on it will be calcaulated through diffrent approaches i.e 10ppm approach and/or 0.1% approach. and then you can convert into ppm or 1/1000000.

Thanks

22

hi,

i have some problem during MACO calculation, during MACO calculation for worst case product, our MACO is lower than LOD or LOQ value. In that case which limit we select for our worst case product.[attach]245[/attach]
as per attached file.

Regards

ANIL SAXENA

MACO.doc (52.5 KB)

23

Dear all

Pls suggest the reference publication to get the TDD values.

Thanks

Prasad

24

Dear Mr.Reddy

Please note to calculate the MACO, first you should know the both products TDD (Therepetic daily dose) then you can calculate the MACO as per the equation given in the APIC cleaning validation guide. Then you can get the MACO in mg.

If you donā€™t have the TDD of the products , you can calculate the MACO as per general limit criteria. O.1% general limit for intermediates and 0.01% criteria for finished products. You can multiply the subsequent product batch size in mg and devided by 100 to get the MACO in mg.

If you have TDD of the products, then also you can calculate the MACO as per general limit criteria and compare the both carryover and you can consider which ever is lower value [Worst case].

You can calculate the MACO in ppm, you should know the surface areas of the equipment train of the facility. Please note only common equipments surface areas shall be considered for calculation.

For calculation part you can refer APIC guideline.

Thanks

Prasad

25

Dear

For formulation (Tablets & Capsule) facility which guideline is acceptable for calculation of MACO.

Thanks

Anil

26

Dear all

We are having a multi product facility and one of the product TDD not known, So we are calculated the MACO value as per LD50, But carry over of the product attained below LOD value of cleaning method. So the cleaning method is not capable to detect the carryover limit. So how we calculate the carryover, we shall go with general limit calculation?

In the APIC guideline general limit chapter explains as follows:

ā€œIf the calculation methods based on therapeutic doses or toxicological data result in unacceptably high or irrelevant carryover figures, or toxicological data for intermediates are not known, the approach of a general limit may be suitableā€.

As per general limit calculation we got the carry over value above detection limit, Shall we consider the clause and calculate as per general limit? Or any alternations availble to conclude the problem. pls suggest.

Thanks

VJV Prasad

27

Dear Experts,

could you provide me how to set a acceptance criteria for rinse samples with examples please.

Thanking you

Pulla Reddy

28

[quote=Pulla Reddy]Dear Experts,

could you provide me how to set a acceptance criteria for rinse samples with examples please.

Thanking you

Pulla Reddy[/quote]

Dear Mr.Reddy,

First you shall calculate the MACO of existing product to subsequent product as per TDD and General limit methods. Consider the lowest MACO value from the both methods. The considered MACO value shall be divided by total rinse volume of the equipment train and then you will get the total equipment train MACO limit for rinse.

Eg: MACO value as per TDD: 850 ppm
MACO value as per General limit: 758 ppm

  Consider the General limit MACO value (758 PPM) for further calculation

  MACO value for total equipment train =   MACO value/Total equipment train rinse volume
   i.e.     758/75 = 10.1 ppm

MACO value for individual equipment = MACO of total equipment train X individual equipment surface area/ Total equipment train surface area

Hope you clarified

Regards

29

ā€œDetermining Cleaning Validation Acceptance limits for Pharmaceutical Manufacturing Operationsā€ by Fourman Gary L. and Michael V. Mullen, Pharmaceutical Technology

please provide the soft copy of this artical.

30

For the MACO Calculation u can use 10 ppm and TDD (Daily dose) criteria, in which the lowest MACO shall be used to established the Limit during cleaning validation.
Suppose your minimum batch size is 25 Kg. therefore as per the 10 ppm criteria your MACO will be

MACO (mg) = 0.00001 x MBS (mg.) where MBS is Minimum batch size in the set of Equipment
MACO (mg) = 0.00001 x 25000000 = 250 mg. is the MACO as per the 10 ppm criteria.

According to the Therapeutic Daily Dose criteria

MACO (mg.) = TDD(Previous) x MBS (mg) / SF x TDD next

Among the above two method the lowest MACO can be consider to established the limit.One more thing is that your limit shall be analytically achivable .

Thanks & Regards

Ashvin Acharya

31

Dear Sir,
Can you tell me how to set the rinse volume? Do we need set the different acceptence criteria for each and every equipment or can we set the one general limit for entire rinse sample? As per our practise we usually establish a single value for all the equipments in train. For example when we calculate the MACO value for each and every equipment then we are selecting stringent limit. Is it acceptable?

32

Dear Reddy,

Common rinse volume and limits for all equipments not at all acceptable, you can refer APIC guideline for calculation rinse volumes and limits for each equipment in the train.

[quote=Pulla Reddy]Dear Sir,
Can you tell me how to set the rinse volume? Do we need set the different acceptence criteria for each and every equipment or can we set the one general limit for entire rinse sample? As per our practise we usually establish a single value for all the equipments in train. For example when we calculate the MACO value for each and every equipment then we are selecting stringent limit. Is it acceptable?[/quote]

33

Dear Team,

plz share excel sheet for calculation of MACO for swab and rinse for liquid and OSD. bansalvishu1978@gmail.com.

Plz share if anything is specific to cosmetics

regards
vishal

34

Please share the link

35

Hi,

Please give me example how to calculate MaCO base on 10 ppm criteria of different product manufacturers in same manufacturing vessel for rinse Method.

Ghulam Mohiuddin
ghulammohiudin63@gmail.com

36

How to calculate MACO for different products manufactured in same vessel by rinse method? Please sir tell me with example?

Thank you.

37

Dear Ghulam,

It is very simple. First check the batch size of product in Kg. e.g. if the batch size is 100 kg than

1 ppm will be = 1mg in 1 kg (1000000 mg).

for 10 ppm =10 mg in 1 kg

now multiply 10 mg with your batch size i.e. 10X100 kg = 1000 mg. so 1000 mg is your 10 ppm criteria for 100 kg batch size.