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STANDARD OPERATING PROCEDURE

ESTABLISHING % YIELD RANGE FOR TRIAL AND VALIDATION

Title

BATCHES

SOP No.

ARDXXX-00

Effective Date

1.0

Function

Research and
Development

Page No.

1 of 4

`OBJECTIVE
To lay down a procedure for establishing % yield for intermediate and Active
Pharmaceutical Ingredients (API) stages.

2.0

SCOPE
This procedure is applicable to all APIs and intermediates developed in IPD
(Integrated Product Development) of Dr.Reddys laboratories limited.

3.0

RESPONSIBILITY

3.1

R&D and PE are responsible for establishing the yield range for trial batches from
development batches & CPP batches data.

3.2

NPM and R&D and PE are responsible for establishing the yield ranges for Process
Validation (PV) and commercial batches.

4.0

DEFINITION(s)
Not applicable.

5.0

TO BE REVISED BEFORE

6.0

PROCEDURE

6.1

Formula for the calculation of % yield for intermediate or API.

6.2

Output Weight
Molecular weight of input
------------------- X ------------------------------------ X 100
Input Weight
Molecular weight of output
R&D and PE shall finalise the % yield from lab and pilot plant batches after
completion of Optimization, what-if and spiking study experiments.

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STANDARD OPERATING PROCEDURE


ESTABLISHING % YIELD RANGE FOR TRIAL AND VALIDATION

Title

BATCHES

SOP No.

ARDXXX-00

Effective Date

6.3

Function

Research and
Development

Page No.

2 of 4

Minimum three batches as per final process, purging experimental data with specified
impurities and scale dependent what-ifs shall be considered for fixing the yield
range. Why purging & what-if are required?

6.3

An example for the yield finalization is given in below table

S.No.
1.
2.
3.
4.

Experiment /
Batch No.
#001
#002
#003
#004

Input
(g/ Kg)
100.0 g
100.0 g
100.0 g
100.0 g

(%) Yield

Remarks

75.0
74.0
76.0
68.0

Final Process yield from lab


experiments

Purging experiment with input having


2-3% impurities (for intermediates)
5.
#005
100.0 g
67.0
Least yielding scale dependent (SD)
parameter what-if experiment shall be
considered (Ex: longer hours addition)
6.
#006
5.0 Kg
64.0
% yield from CPP batch executed with
final process.
(Fixing of lower range).
Lower range of % yield shall be considered from spiking data / SD what-if data/ CPP batch
executed with final process.
%Yield shall be proposed as : 64 76% (Average %Yield: 70)
6.4

%Yield range for trial batch shall be fixed based on the T&V batch size also
considering the handling losses (high contribution of handling loss in lower batch
sizes) as per below table.

S.No.

T&V Batch size

Allowed variation from lab %

% Yield Range

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STANDARD OPERATING PROCEDURE


ESTABLISHING % YIELD RANGE FOR TRIAL AND VALIDATION

Title

BATCHES

SOP No.

ARDXXX-00

Effective Date

1.
1-2 Kg
2.
2-5 Kg
3.
5-10 Kg
4.
>10 Kg
Note: Higher % Yield should be maximum 100.

Function

Research and
Development

Page No.

3 of 4

yield
25 %
70 25 %
20 %
70 20 %
15 %
70 15 %
10 %
70 10 %
What is the rationale for allowed variation & yield

range?
6.5

Actual yield obtained in trial batches shall be considered for establishing the yield
range for process validation batches.

6.6

Acceptable limit for % Yield for unit operations (Sieving, milling, micronisation,
blending etc.,) shall be established by NPM team based on previous products
historical data.

6.7

Based on actual yield obtained in process validation batches and 10-15 commercial
batches control limits, action and alert limits for % yield shall be established.

6.8

% Yield variations in validation and commercial batches which are beyond the
acceptance criteria shall be investigated in the below areas (but not limited to)

6.8.1

Charging less quantity of raw materials / intermediates etc.,

6.8.2

Losses during charging operations

6.8.3

Spillage during the work-up / layer separation operations

6.8.4

Hold up losses

6.8.5

Product loss in to the Filtered MLs during the filtration due to the solubility of
material in solvent/ Leakage of filtration bed.

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STANDARD OPERATING PROCEDURE


ESTABLISHING % YIELD RANGE FOR TRIAL AND VALIDATION

Title

BATCHES

SOP No.

ARDXXX-00

Effective Date

6.8.6

Function

Research and
Development

Page No.

4 of 4

Sublimation during the drying due to lower boiling point of product.


.

What is the rationale for allowed variation & yield range?

Validation
Allowed % yield
Batch size
variation from lab
1-2 Kg
25%
2-5 Kg
20%
5-10 Kg
15%
>10 Kg
10%
7.0
REFERENCE(s) :
SOP No(*)

% Yield
Range
70 25 %
70 20 %
70 15 %
70 10 %

Acceptance criteria for yield variations


in validation batches (%RSD)
NMT 20%
NMT 15%
NMT 10%

Title

ARD007

Process development flow

*Current Version
8.0

9.0

ABBREVIATION(s)
Abbreviation
AR&D
DQA
R&D
API
PE
ANNEXURE(s)

Full Description
Analytical Research and Development
Development Quality Assurance
Research and Development
Active pharmaceutical ingredient
Process Engineering

Not applicable.
10.0

FORMAT(s)
Details/Title of Format

Format No.*

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STANDARD OPERATING PROCEDURE


ESTABLISHING % YIELD RANGE FOR TRIAL AND VALIDATION

Title

BATCHES

SOP No.

ARDXXX-00

Effective Date

Function

Research and
Development

Page No.

5 of 4

NA

*Current Version

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