NOVAMED PHARMACEUTICAL

QUALITY CONTROL DEPARTMENT

Standard Operating Procedure
TITLE PAGE NO. :
1 of 5
In-Process Testing of Infusions
Mfg License No : 000590
DOC. CODE. NO INPROCESS PROCEDURE REFERENCE :
QC/IPC/007/N-145 INH

0PREPARED BY : DATE : CHECKED BY : DATE: APPROVED BY : DATE:

Senior Q.C. Officer Asst.Q.C.Manager Q.C. Manager

CONTENTS

1) PURPOSE
2) SCOPE
3) DESCRIPTION
4) APPEARANCE
5) EXTRACTABLE VOLUME VARIATION
6) PARTICULATE MATTER

REVISION NO: ISSUE DATE: EFFECTIVE DATE: NEXT REVIEW DATE:

00 03-Aug-2016 04-Aug-2016 03-Aug-2018
 NOVAMED PHARMACEUTICAL
QUALITY CONTROL DEPARTMENT
Standard Operating Procedure
TITLE PAGE NO. :
2 of 5
In-Process Testing of Infusions
Mfg License No : 000590
DOC. CODE. NO INPROCESS PROCEDURE REFERENCE :
QC/IPC/007/N-145 INH

1) PURPOSE
To provide detailed procedure for the Inprocess product analysis of Infusions.
2) SCOPE
This SOP gives detailed outline for the Inprocess product analysis of Infusions & will cover testing activities on
physical, chemical & instrumental basis.
3) DESCRIPTION

3.1) MACHINERY & EQUIPMENTS

3.1.1 Clarity chamber

3.1.2 Beakers
3.1.3 Graduated Cylinder

3.2 Tests / Parameters

Sr. # Physical Test Specification

1. Description A clear, colourless or light yellowish colour clear liquid free

from foreign particle filled in a clear glass Bottle sealed with
32mm bromobutyl rubber stopper and with a blue colour flip off
seal.
2. Extractable volume variation 100.0—102.0ml, 200.0-205.0mL, 300-305.0mL
3. Particulate matter The solution is clear and free from foreign particles.

4.0 DESCRIPTION/APPEARANCE

Take sample in a clean dry test tube and note the color of the so lution, it should be clear, colorless or
slightly yellowish colour clear solution free from foreign particle.

REVISION NO: ISSUE DATE: EFFECTIVE DATE: NEXT REVIEW DATE:

00 03-Aug-2016 04-Aug-2016 03-Aug-2018
 NOVAMED PHARMACEUTICAL
QUALITY CONTROL DEPARTMENT
Standard Operating Procedure
TITLE PAGE NO. :
3 of 5
In-Process Testing of Infusions
Mfg License No : 000590
DOC. CODE. NO INPROCESS PROCEDURE REFERENCE :
QC/IPC/007/N-145 INH

5.0 EXTRACTABLE VOLUME VARIATION TEST

Select 1 container and discharge the contents of the infusion bottle into a standardized dry cylinder (graduated to
contain rather than to deliver the designated volume) of such size that the volume to be measured occupies at least
40% of the cylinder’s rated volume. The measured volume should not less than the nominal volume.

Recommended Excess Volume

Labeled Size For mobile liquids For Viscous Liquids
0.5ml 0.10ml 0.12ml
1.0ml 0.10ml 0.15ml
2.0ml 0.15ml 0.25ml
5.0ml 0.30ml 0.50ml
10.0ml 0.50ml 0.70ml
20.0ml 0.60ml 0.90ml
30.0ml 0.80ml 1.20ml
50.0ml or more 2% 3%

6.0 PARTICULATE MATTER

A-Visible Particles

Gently swirl or invert each individual container, making sure that no air bubbles are introduced and observe for
about 5 seconds in front of the white panel. Repeat the procedure in front of the black panel.

Record the presence of any particles. Repeat the procedure for a further 19 containers. The preparation fails the test
if one or more particles are found in more than one container.

Apparatus for visible particles

REVISION NO: ISSUE DATE: EFFECTIVE DATE: NEXT REVIEW DATE:

00 03-Aug-2016 04-Aug-2016 03-Aug-2018
 NOVAMED PHARMACEUTICAL
QUALITY CONTROL DEPARTMENT
Standard Operating Procedure
TITLE PAGE NO. :
4 of 5
In-Process Testing of Infusions
Mfg License No : 000590
DOC. CODE. NO INPROCESS PROCEDURE REFERENCE :
QC/IPC/007/N-145 INH

B-Subvisible particles
Prepare the test specimens in the following sequence. Outside of the laminar enclosure, remove outer closures,
sealing bands, and any loose or shedding paper labels. Rinse the exteriors of the containers with filtered distilled or
deionized water. Protect the containers from environmental contamination until analyzed. Withdraw the contents of
the containers under test in a manner least likely to generate particles that could enter the sample. Contents of
containers with removable stoppers may be withdrawn directly by removing the closures. Sampling devices having
a needle to penetrate the unit closure may also be employed.
The number of test specimens must be adequate to provide a statistically sound assessment of whether a batch or
other large group of units represented by the test specimens meets or exceeds the limits. If the volume in the
container is less than 25 mL, test a solution pool of 10 or more units. Single small-volume injection units may be
tested if the individual unit volume is 25 mL or more. For large-volume injections, individual units are tested. For
large-volume injections or for small-volume injections where the individual unit volume is 25 mL or more, fewer
than 10 units may be tested, based on the definition of an appropriate sampling plan.
Sample preparation

REVISION NO: ISSUE DATE: EFFECTIVE DATE: NEXT REVIEW DATE:

00 03-Aug-2016 04-Aug-2016 03-Aug-2018
 NOVAMED PHARMACEUTICAL
QUALITY CONTROL DEPARTMENT
Standard Operating Procedure
TITLE PAGE NO. :
5 of 5
In-Process Testing of Infusions
Mfg License No : 000590
DOC. CODE. NO INPROCESS PROCEDURE REFERENCE :
QC/IPC/007/N-145 INH

Volume in Container Less than 25 mL— Prepare the containers as directed under Test Preparation. Mix and
suspend the particulate matter in each unit by inverting the unit 20 times. In a cleaned container, open and combine
the contents of 10 or more units to obtain a volume of not less than 20 mL. Degas the pooled solution by sonicating
for about 30 seconds or by allowing the solution to stand undisturbed until it is free from air bubbles. Gently stir
the contents of the container by hand-swirling or by mechanical means, taking care not to introduce air bubbles or
contamination. Withdraw a minimum of three aliquots, each not less than 5-mL in volume, into the light
obscuration counter sensor. Discard the data from the first portion.
Calculations
Pooled Samples (Small-Volume Injections) — Average the counts from the two or more aliquot portions analyzed.
Calculate the number of particles in each container by the formula:
PVT / VAn,
in which P is the average particle count obtained from the portions analyzed; VT is the volume of pooled sample, in
mL; VA is the volume, in mL, of each portion analyzed; and n is the number of containers pooled.
Individual Samples (Small-Volume Injections)— Average the counts obtained for the 5-mL or greater aliquot
portions from each separate unit analyzed, and calculate the number of particles in each container by the formula:
PV / VA,
in which P is the average particle count obtained from the portions analyzed; V is the volume, in mL, of the tested
unit; and VA is the volume, in mL, of each portion analyzed.
Interpretation
The injection meets the requirements of the test if the calculated number of particles present in each discrete unit
tested or in each pooled sample tested does not exceed the appropriate value listed in Table 1.

Table 1. Light Obscuration Test Particle Count

10 µm 25 µm
Small-Volume Injections 6000 per 60 per
container container
Large-Volume Injections 25 3 per mL

REVISION NO: ISSUE DATE: EFFECTIVE DATE: NEXT REVIEW DATE:

00 03-Aug-2016 04-Aug-2016 03-Aug-2018