1.  Introduction

Objective of this article is to conduct a thorough review and understanding on the manually conduct visual inspection process for liquid Injectable products in liquid and lyophilized form and to explore the complications identified during the routine process. Along with that troubleshot to overcome from the challenges.  Evaluation quality of product during batch release and consider continuous process improvement opportunities.  Following topics are considered in the review,

• Process controls
• Regulatory expectation
• Current trend
• Identifying further scope of improvement
• Inspector training and evaluation process
• Defect Kit preparation and maintenance

The scope of this review is limited to the inspection process of liquid and lyophilized Injectables products filled in clear or amber colour glass container manufactured through aseptic process by considering conventional / Isolator technology and inspected through manual process.

2.  Background

Sterile injectable products are used extensively in health care. Patients, caregivers, manufacturers, and regulators have an inherent expectation for safe and effective injectable drug products. This expectation requires injectable pharmaceuticals to be produced to standards of quality, purity, and sterility that include being essentially free of extraneous matter such as particles. Despite guidance in producing product that is “essentially free” of particles, manufacturing such product is very challenging. A gap exists between the observation of small quantities of particles in injectable pharmaceutical products and patient documented safety concerns resulting from the inadvertent administration of particles to patients. Thus, a need exists to create a framework to describe and assess the potential risk.

3.  Overview of Manufacturing Process

Injectable manufacturing process is design such a way that it provides a high degree of assurance for patient case towards health care system. Manufacturing consisting complex process steps, outcome is not only claim the sterility of the product. To provide the product safety, purity and efficacy it is mandatory that product should to be free from any visual particulate defects.
Each product is manufactured in either liquid filled or lyophilized powder form, sterile filtered bulk product solution is filled and over sealed (in liquid vials) or half stopper for lyophilisation (in lyophilized powder vials), lyophilized vials are full stopper and over sealed. The complete manufacturing and packaging is performed using qualified manufacturing equipment and facility by trained technical staff. API, excipients and primary packaging materials are sourced from the approved vendor source. All incoming material lots are subject to a strict incoming material checks for compliance to the respective approved specifications as per written and approved procedures. Material is approved for manufacturing only after demonstration of conformance to all specifications. Only approved lots are released for manufacturing.
The bulk product solution manufacturing steps are critically controlled and maintained in accordance with approved manufacturing procedures throughout the manufacturing process and actual observations / conditions are appropriately documented in the approved manufacturing record.
The entire aseptic manufacturing process is divided into major seven parts:

• Compounding of API and Excipients
• Depyrogenation of vials and sterilization of equipment/ accessories, compounding/ filtration vessels, closures and over seals
• *Decontamination of the Filling line Isolators
• Sterilizing grade filtration at point of fill and aseptic filling process
• Vial receiving, filling, stopper and sealing
• Transfer of filled and half stopper vials for Lyophilizer loading and unloading
• Transfer of stopper vials post lyophilisation to vials sealing

*Step to be consider for Isolator Technology
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