TITLE

DEPTT/
SECTION
TECHNICAL
SERVICE &
MAINTENANCE

PRODUCT FORMULATION
DEVELOPMENT
RELATED ISO 9001 CLAUSE
4.4

PREPARED BY

REVIEW & OPERATIONAL

APPROVAL BY

DOCUMENT #.
RP-SP/F-12

ISSUE #.
01

ISSUE DATE
11-10-2012

PAGE #.
1 of 3

ADMINISTRATIVE APPROVAL BY

1.0 PURPOSE
1.1 To device a system, establish a procedure, assign responsibilities and provide instructions for
1.1.1 Pre formulation development. (Design Input)
1.1.2 Formulation Development. (Design Input)
1.1.3 Process Development. (Design Input)
1.1.4 Verification of formulation. (Design Verification)
1.1.5 Validation of formulation. (Design Validation)
2.0 SCOPE
2.1 The procedure covers for all the non-sterile product dosage forms i.e. oral solids (tablets, capsules), syrups, manufactured by
Ray Pharmaceutical at its plant or arranges contract-manufacturing services.
2.2 The procedure covers all products marketed by Ray Pharmaceutical except those which are imported and marketed as it is or
marketed after packing at Ray Pharmaceutical.
2.3 This procedure does not cover those products, which are merely extension in the product family i.e. same product but in
different strengths and marketed in the same packaging configuration.
3.0 ABBREVIATIONS
3.1 CEO
=
3.2 MM
=
3.3 ME
=
3.4 QAM
=
3.5 PM
=
3.6 NSM
=

Chief Executive Officer

Marketing Manager
Maintenance Engineer
Quality Assurance Manager
Production Manager
National Sales Manager

4.0 DEFINITIONS
4.1 New drug / product MEANS ANY PRODUCT WHOSE FORMULATION WITH RESPECT TO MATERIALS, PROCESS, TEST
METHODS AND EQUIPMENTS INCLUDING PACKAGING IS DEVELOPED BY RAY PHARMACEUTICAL WHETHER
ENTIRELY OR IN COLLABORATION.

5.0 PROCEDURE
5.0 PREFORMULATION DEVELOPMENT
5.1.1 The Pre formulation activity consists of identifying the physical and chemical characteristics of active ingredient so that
its compatibility with the excipients can be identified.

5.1.2

Based on the product design input ME / QAM documents the tentative product composition, materials including
packing materials specifications whether controlled by Ray Pharmaceutical or regulatory specified, analytical methods
and stability methods development.
5.2 FORMULATION DEVELOPMENT
5.2.1 The ME based on documented tentative product composition runs the trial batch and documents the following
a) The batch size.
b) Quantity of materials charged.
c) Actual process parameters.
5.2.2 QAM arranges the testing of trial batch. Testing is performed through proposed pharmacopeia method or through
method developed by Ray Pharmaceutical.
5.2.3 QAM compares the test results against the product specifications.
5.2.4 If the test results does not comply with the specifications, the QAM in co-ordination with ME / PM discusses the
parameters which are non-complying and explore the parameters e.g. process parameters, process sequence and
effect of change in material % etc by which product parameters can be achieved.
5.2.5 Based on the technical exploration, another trial batch is run and tested.
5.2.6 This process will continue till the required product parameters are achieved.
5.2.7 When the product parameters are achieved, it is packed in proposed primary packaging component and placed on
stability studies at 30oC and 40oC at different humidity conditions for a period of six months (accelerated stability
studies) ---- Design Verification.
5.2.8 In case if the first trial batches achieve the product parameters no further trial batch is prepared and the product is
placed on stability.
NOTE
In case, where the formulation is derived from the Dossier or any other source where there is no need to establish the
pre-formulation in terms of excipients identification and their physical and chemical compatibility analysis, then the
stage of pre-formulation development will be skipped and the Manufacturing Instruction for the trial batch will be
developed.
5.3 PROCESS DEVELOPMENT
5.3.1 Before going for trial batch preparation ME / PM prepare the following.
a) Process flow diagram.
b) Prepare influence matrix.
c) Establish experimental manufacturing instruction.

5.3.2 PROCESS FLOW DIAGRAM

5.3.2.1 Process flow diagram contains the following
a) Identification of process.
b) Equipments used.
c) Materials used.
5.3.3 PREPARE INFLUENCE MATRIX
5.3.3.1 Based on the process flow identifies the each process controllable variables which can be influence the in-process
critical process parameters and critical quality attributes (product characteristics) and the tentative range of each
process parameter.
5.3.4 ESTABLISH EXPERIMENTAL MANUFACTURING INSTRUCTION
5.3.4.1 ME / PM prepares the experimental manufacturing instruction and identifies the following :
5.3.4.2 Based on the process flow identifies the each process controllable variables which can be influence the in-process
critical process parameters and critical quality attributes (product characteristics) and the tentative range of each
process parameter.
5.3.5 ESTABLISH EXPERIMENTAL MANUFACTURING INSTRUCTION
5.3.5.1 ME / PM prepares the experimental manufacturing instruction and identifies the following
a)
b)
c)
d)
e)

The logical sequence of process and charging of materials.

Process monitoring and controlling parameters and their range.
In-process test points.
Precautions related to handling of materials.
Applicable environmental controls.

6.0 RELATED DOCUMENTS

6.1 Pre formulation Development.
6.2 Process Flow.
6.3 Influence matrix.