Sunday, December 13, 2020

Product Reconciliation In Pharmaceutical Industries

 Product Reconciliation In Pharmaceutical Industries

Product reconciliation is a process which is used to calculate and monitor the line loss or yield of a product which is under manufacturing.

Calculation of yield or line loss is monitored during every stage of manufacturing to ensure that yield or line loss is within the recommended range. All pharmaceutical industries have an SOP which defines the final yield of a pharmaceutical product after packaging.

What is the yield?

Yield is usually measured in percentage and it is the ratio of product quantity before manufacturing and product quantity after manufacturing or ratio of the theoretical  quantity of the product to the practical quantity of the product and its formula is as follow,

            Yield =Quantity of product after manufacturing÷Quantity of the product before manufacturing×100


or 


 Yield =Actual Quantity ÷ Theoretical Quantity ×100


Example

In the pharmaceutical industry, a batch of tablets was manufactured having 50 kg standard batch size after dispensing and 49.0 kg after coating.

Calculate the yield of the product.

By using above formula add values in it as follow

            yield=50÷49.0×100=98.0%

So yield of the product is 98.0%.

What is line loss?

Line Loss is the measure of material loss during each manufacturing stage. Line loss may occur starting from dispensing stage to the end of finish product dispatch.

Line loss is measured by the following formula,


Line loss = Quantity of product before manufacturing - Quantity of product after manufacturing


Example

In the pharmaceutical industry, a batch of tablets was manufactured having 60 kg standard batch size after dispensing and 59.5 kg after coating.

Calculate the line loss of product.

By using above formula add values in it as

            Line Loss=60-59.5=0.500 kg

Line loss of the product is 0.500 kg.

Reasons for Line loss

Line loss may occur due to the following reasons and in following stages.

Dispensing

  • During dispensing some powder materials may swipe with return air due to the dusty environment.

  • Some materials may adhere to the scopes during dispensing.

  • Some materials may  adhere to the polythene bags.

  • By any leakage or spillage.

Dispensing is a common procedure before starting of all dosage forms but manufacturing stages vary depending upon the type of dosage form here we will take the example of tablet dosage form to discuss yield and line loss.

Granulation

During granulation, line loss may occur due to the following main reasons


  • Some materials may adhere to the polythene bags when they are removed from polythene bags.

  • Material loss During sieving due to the dusty environment.

  • During mixing and kneading some material sticks to the walls and blades of the mixer.

  • Fine powder loss through dryer filters during the drying process.

During granulation, yield or line loss is calculated after drying and final blending stage.

Example

 A tabler batch was dispensed having total standard weight as 75 kg. It was manufactured by a wet granulation method and dried in FBD. After drying, the product weight is 74.0 kg. Tablet weight is 750 mg and the number of tablets is 100,000 tablets.Calculate the yield and line loss of product.

First,we will calculate the yield of the product by the following formula,


  Yield =Quantity of product after drying÷Quantity of the product before manufacturing×100

Add values in above formula


                  Yield=74÷75×100

                          =98.66%


Now calculate the line loss by the following formula


Line loss = Quantity of product before Drying - Quantity of product after After drying

After adding values

              Line loss= 75-74= 1 kg

After blending yield and line loss is calculated in the same way as mentioned above.

Example

The product discussed in the above example was sieved through an oscillating granulator and mixed in the blender. After blending its final weight is 73.7 kg. Calculate yield and line loss of the product.

First we will calculate yield of the product


         %Yield=73.7÷75×100

                     =98.26%

Line loss is 

            Line loss = 75-73.7=1.3 kg

Results

After drying yield is 98.66 and line loss is 1.0 kg.After final blending, the product yield and line loss is calculated for all granulation stages starting from sieving to the final blending,so total yield and line loss after complete  granulation is 98.26% and 1.3 kg respectively.

Compression

During compression line loss may occur due to the following main reasons,


  • Product loss During loading of product in hoppers.

  • Due to the dusty environment.

  • Product loss during inprocess parameters checking.

  • At the end of the compression stage, some powders or granules are left in the feeder or die and are not able to be compressed due to very low quantity.

  • Some powders or granules may be left in tablet deduster.

Example

The above mentioned granulated product 73.7 kg was delivered to the compression area and after compression, the batch weight is 73 kg.Calculate yield and line loss of product at compression stage.

Use following formula


   Yield =Quantity of product after Compression÷Quantity of the product before compression×100


              Yield=73÷73.7×100

                          =99.05%


Line loss is calculated as


              Line loss = 73.7-73.0=0.7 kg


Results.

During compression stage yield is 99.05% and line loss is 0.7 kg.

If we want to calculate total yield and line loss of two stages mean granulation stage and compression stage then it is calculated as follow,


 Yield =Quantity of product after Compression÷Quantity of the product before granulation×100


                 Yield=73.0÷75×100

                          =97.33%


Line loss is calculated as


Line loss = Quantity of product before granulation - Quantity of product after After compression


Add values in above formula


                     75-73=2.0 kg


So line loss of two stages is 2.0 kg and yield is 97.33%.

Coating

In tablet coating, extra weight is deposited on each tablet by spraying solution or suspension of the polymer so the weight  of the product is increased.

Line loss in the coating may occur due to the following reason

  • Wastage of coating material through the exhaust.

  • Higher inlet temperature and low spray rate results in material loss.


Example

The coatingting material used to coat the above mentioned tablets batch is 2 kg. The batch size was 100,000 and we delivered 73 kg for coating. Number of tablets for 73 kg is

       73×1000×1000÷750=97333 tabs.

Coating material for each tablet is 

                2×1000×1000= 20 mg 

so after coating, theoretically,each tablet weight should be

                         750+20= 770 mg 

But After coating, we achieve 764 mg per tablet, meaning 6 mg loss per tablet.

Yield calculation for 100,000 tablets

                 100,000×770= 77 kg

we have total weight of the batch after coating as follow

                            74.362 kg


        Yield =74.362÷77×100=96.574


        Line loss = 77-74.362=2.638 kg


Results

We can see that as the number of stages of a manufacturing process increase, the yield is decreased and line loss is increased.

From granulation to coating total yield is 96.574 and line loss is 2.638 kg.

Product reconciliation for Encapsulation.

Hard gelatin capsules are used to fill powders, granules or pellets. Some powders are available which are ready to fill and some are mixed in a blender before filling in hard gelatin shells.


Example

In the pharmaceutical industry, a batch of 1000,000 capsules was filled with filling weight 150  mg and empty hard  gelatin shell weight was 70 mg. After filling the total weight obtained is 219 kg.

 Calculate yield and line loss.

First we will calculate the yield as follow,


          Yield =Actual Quantity of Capsules÷Theoretical Quantity of Capsules ×100


Actual quantity is 219 kg.

For theoretical quantity first we will calculate the weight of 1000,000 capsules.  For this multiply the total number of capsules by filled weight.

How to calculate filled weight?

Filled weight is the combination of filling weight and weight of an empty hard gelatin shell.

So Filled weight is

Filling weight + weight of empty shell

                    150+70=220 mg

So the filled weight is 220 mg.

Now calculate weight of 1000,0000 capsules as follow,

           1000,000×220=22000,0000 mg

Convert milligrams into  kilograms as follow

         22000,0000÷1000÷1000=220 kg

So for yield use following formula


             Yield =Actual Quantity of Capsules÷Theoretical Quantity of Capsules ×100


After adding values 

 

              Yield=221÷222×100

                          =99.54%

Line loss is calculated as follow


Line loss =Theoretical or standard  Quantity of capsules - Actual Quantity of capsules 


                   222-221=1.0 kg

Results

After filling, the yield is 99.54% and line loss is 1.0 kg.


Conclusion

Product reconciliation is an important and critical process performed in the pharmaceutical industries.

During all manufacturing stages monitoring of yield or line loss gives us data to check the process efficiency and measures are taken to reduce the line loss and to increase the yield.


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2 comments:

  1. Informative. Can u please guide about reconciliation in API production process.

    ReplyDelete
  2. Basic concept is same for all processes

    ReplyDelete