USP〈1665〉 CHARACTERIZATION OF PLASTIC COMPONENTS AND SYSTEMS USED TO MANUFACTURE PHARMACEUTICAL DRUG PRODUCTS AND BIOPHARMACEUTICAL DRUG SUBSTANCES AND PRODUCTS

1. INTRODUCTION

2. SCOPE

3. GENERAL PRINCIPLES

3.1 Discussion

3.2 Material Characterization

3.3 Component Characterization

4. ASSESSMENT PROCESS

4.1 Initial Assessment

4.2 Risk Assessment of Components

4.3 Establishing the Level of Component Chemical Characterization

5. TESTING OF PLASTIC COMPONENTS AND SYSTEMS

5.1 Standard Extraction Protocol

5.2 Testing the Extracts and Generating the Extractables Profile

5.3 Evaluation of the Extractables Profile Established by Implementing the Standard Extraction Protocol

6. QUALIFICATION OF MANUFACTURING COMPONENTS AND SYSTEMS

6.1 General

6.2 Chemical Qualification

6.3 Alternate Approaches for Qualification

GLOSSARY

APPENDIX

An Example of a Risk Evaluation Matrix

1. INTRODUCTION

A manufacturing process is the sum of those steps required to convert starting raw materials into a manufactured pharmaceutical or biopharmaceutical product. Manufacturing processes are performed utilizing manufacturing systems which are the sum of the components that together comprise the equipment that converts starting raw materials into biopharmaceutical drug substances (DSs) or pharmaceutical or biopharmaceutical drug products (DPs).

Manufacturing systems can be partially or completely constructed from plastic materials. Plastics used in manufacturing systems possess a range of molecular weights and contain plastic additives such as antioxidants, stabilizers, lubricants, plasticizers, and colorants. Several factors dictate the types of plastics that are used in manufacturing components, the types and amounts of additives that are used in plastic materials and the processes used to convert the plastic materials into components or systems.

The process stream, production intermediates, DS, or the DP itself could directly contact, and potentially interact with, one or more plastic components of the manufacturing system at some point during the manufacturing process. During contact, substances could leach from a manufacturing component and become incorporated into the process stream. If these substances persist in the process stream through subsequent process operations, they could accumulate in either a DS or DP as process equipment-related leachables (PERLs). If they are present in the DP, PERLs have the potential to alter critical quality attributes of the DP, such as safety.

Plastic Components and Systems Used to Manufacture Pharmaceutical Drug Products and Biopharmaceutical Drug Substances and Products 〈665〉 addresses these interactions by providing a risk-based means for chemically characterizing and qualifying plastic components used to manufacture biopharmaceutical drug substances and pharmaceutical and biopharmaceutical drug products. Chapter 〈1665〉 communicates the key concepts behind and provides additional information and guidance regarding the applicability and the application of 〈665〉.

2. SCOPE

In general, components of pharmaceutical and biopharmaceutical manufacturing systems can be grouped based on the function or operation that the component performs, including:

Fluid transfer and transport (e.g., tubing and connectors)

Mixing, reacting, and fermenting (e.g., tank liners, mixer bags, bioreactors, impellers, tubing, and container ports)

Storage (e.g., containers [and associated ports and/or tubing] for raw materials, production reagents, and process intermediates)

Processing (e.g., filters and chromatography columns)

Filling devices (e.g., filling needles)

Small components (e.g., o-rings, gaskets, check valves, septa, diaphragms, polymer pump surfaces, and sensors)

Source from USP and Please refer to USP for details:https://online.uspnf.com/uspnf/document/2_GUID-B2665FAF-027F-46AA-8093-2292E0666F03_10201_en-US?

plastic pharmaceutical packaging

Polymer Vial 2ml 5ml 10ml for cell and gene therapies