Methylnaltrexone bromide 3.2.P.

5 Control of Drug Product

3.2.P.5.2 Analytical Procedures

TABLE OF CONTENTS

1.0 SCOPE......................................................................................................................2

2.0 SPECIAL PRECAUTIONS......................................................................................2

3.0 INSTRUMENT SETUP...........................................................................................2

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Method L28228-147: Strength, Degradation, Content Uniformity and Identification
ofMOA-728 (Methylnaltrexone Bromide) in Parenteral Formulations by High-
Performance Liquid Chromatography (HPLC)

1.0 SCOPE

This HPLC method is used to determine the strength, degradation, content uniformity and
identification of MOA-728 in parenteral formulations. The method-reporting limit for
impurities is 0.05%.

2.0 SPECIAL PRECAUTIONS

Use low actinic glassware.

3.0 INSTRUMENT SETUP

Methylnaltrexone bromide 3.2.P.3 Manufacture
3.2.P.3.3 Description of Manufacturing
Process and Process Controls

1.1 DESCRIPTION OF MANUFACTURING PROCESS AND PROCESS CONTROLS

1.2 Manufacturing Process Flow Diagram

The flow diagram for the manufacture of Methylnaltrexone Bromide Injection, 20 mg/mL is
provided in Figure 1-1.

Figure 1-1: Flow Chart for the Manufacturing/Packaging Process of Methylnaltrexone

Bromide Injection, 20 mg/mL

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Methylnaltrexone bromide 3.2.P.3 Manufacture
3.2.P.3.3 Description of Manufacturing
Process and Process Controls

Sterile Filtration and Holding

11. Purge the sterile hold tank with nitrogen (optional) prior to the sterile filtration of the bulk
solution.
12. Filter the bulk solution in the portable compounding tank through one 0.22 m bubble point
tested hydrophilic filter, (an optional, redundant 0.22 m bubble point tested hydrophilic
filter may be used, and would be connected in series,) into the sterile holding tank. The
sterilization process is complete upon this final filtration.
13. A post-filtration bubble point test is done.

Filling
14. Aseptically fill the sterile bulk solution into previously sterilized and depyrogenated 3 mL
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Methylnaltrexone bromide 3.2.P.3 Manufacture
3.2.P.3.3 Description of Manufacturing
Process and Process Controls
Type I USP flint glass vials at a target net weight gain of 0.81 g ( 0.1 g).
15. Apply filtered nitrogen (optional) to the headspace of each filled vial until the sterilized
stoppers are inserted immediately after filling.

Capping
16. Apply aluminum overseals with flip-top caps to the filled vials.
17. Store the vials at room temperature. Inspect the vials.

1.3 Reprocessing Operations

There are no reprocessing operations for the manufacture of Methylnaltrexone Bromide
Injection, 20 mg/mL.

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Methylnaltrexone bromide 3.2.P.3 Manufacture
3.2.P.3.5 Process Validation and/or Evaluation

Table 1-1: Area Classifications and Gowning

a. = Current Gowning Level Descriptions:

b. = No additional gowning required.
c. = Company issued uniforms/lab coats, hair covers, beard covers, and captive shoes or shoe covers.
d. = Scrub suit, coverall, additional hair cover, additional beard cover, additional shoe covers, gloves, and goggles.
e. = Scrub suit, hair covers, beard covers, shoe covers, and sterile gown (includes: sterile coverall, hood, booties, gloves,
mask with shield or mask and goggles)
f. = Company issued uniforms/lab coats, hair covers, beard covers, shoe covers, additional hair covers and shoe covers,
tyvek suit, gloves, tyvek sleeves.

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