Glossary

A cell bank is a repository or collection of cells that are derived from a single cell source, such as a cell line or primary cell culture. These cells are carefully maintained and preserved under controlled conditions, allowing researchers and manufacturers to have a renewable and consistent source of cells for various applications, including scientific research, drug development, biotechnology, and production of therapeutic products.

Extractables:

Extractables are chemical compounds that are extracted from a container, closure system or other packaging material, manufacturing materials, or medical devices when the materials are exposed to various extraction solutions or solvents under exaggerated laboratory conditions of time and temperature. Extractables may include additives, process impurities, polymeric components and degradation products from the materials manufacturing process. Understanding the extractables provides insight into potential leachables, and allows for an assessment of potential risks to the product or patient.

Leachables:

Leachables, on the other hand, are the chemical compounds that migrate from the container closure system, packaging material, or medical device into the drug product over time under normal storage conditions or during the product's intended use. Unlike extractables, which are identified during controlled studies, leachables are detected in the actual drug product, and their presence could be a concern if they exceed acceptable safety levels. Leachables are monitored during stability studies and throughout the drug product's shelf life to ensure that they do not pose any adverse effects on the drug's stability, safety, or efficacy. Evaluating and controlling leachables is critical in regulatory submissions and maintaining the product's compliance with safety standards.

Fill and finish, also known as aseptic fill and finish, is a critical step in the pharmaceutical manufacturing process. It refers to the final stages of producing sterile drugs or biologics, where the drug substance (active pharmaceutical ingredient) is formulated and sterile filtered into its final container (such as vials) and prepared for distribution or use.

USP 381 is a general chapter in the United States Pharmacopeia that describes the standards and tests for elastomeric closures for injections. Elastomeric closures are rubber-like materials that are used to seal various containers, syringes, cartridges, etc. that contain injectable drugs products, drug substances, or biological products. The chapter covers the following aspects of the closures: 

Physio-chemical properties: These include the identity, purity, and compatibility of the closures to be used for their intended use. The physiochemical tests outlined in USP 381 are intended to measure the level of impurities and contaminants that may reside within a closure to ensure they are within acceptable levels according to the USP requirements.  The tests provide assurance into the integrity of the closure and are used to determine if impurities have the ability to leach out of the rubber material negatively impacting the drug product or substance within the closure system. 

Functional properties: These include the integrity and performance of the closures. The tests check the quality, reliability, functionality, and performance of the closure when pierced with a hypodermic needle. The functional properties evaluated for rubber closures include but are not limited to testing, the force needed to piece the closure, the ability of the closure to seal-self after closure (used in multidose applications), and how well the integrity of the closure is maintained when subjected to multiple punctures. 

Biological properties: These include the biocompatibility and safety of the closures. The tests evaluate the potential of the closures to cause adverse effects on living tissues or systems, such as irritation, inflammation, or toxicity. The tests also examine the immunological response of the closures, such as antigenicity or pyrogenicity.

The chapter aims to ensure that the closures are safe, effective, and compatible with the products they are intended to protect. 

What is USP 467?

USP 467 is a section of the US Pharmacopeia that establishes the limits of residual solvents in pharmaceutical and dietary supplement products. The purpose is to safeguard patients.

Residual solvents are organic compounds. They are used or produced during the production of drugs, excipients, or dietary components.

What does USP Chapter 467 cover?

USP 467 classifies residual solvents into three classes based on their risk assessment: Class 1 (solvents to be avoided), Class 2 (solvents to be limited), and Class 3 (solvents with low toxic potential). USP 467 also provides analytical procedures for the identification, control, and quantification of residual solvents, as well as options for describing their limits.

What is its importance for biopharma industry?

USP 467 is important for the biopharma industry because it helps to ensure the quality and safety of pharmaceutical and dietary supplement products by minimizing the exposure of patients to potentially harmful residual solvents. Residual solvents can affect the stability, efficacy, and purity of the products, as well as the performance of the analytical methods. To meet regulations, prevent recalls, and maintain reputation, the biopharma industry should adhere to USP 467 guidelines and methods.

USP 467 assists the biopharma industry in selecting appropriate solvents for their products. It also aids in enhancing solvent recovery and recycling. This, in turn, encourages innovation and the development of new products. USP 467 is a key resource for ensuring the quality and safety of pharmaceutical and dietary supplement products for the benefit of the patient and the biopharma industry.

Sources: https://www.uspnf.com/sites/default/files/usp_pdf/EN/USPNF/revisions/gc-467-residual-solvents-ira-20190927.pdf

The USP 661, titled " Plastic Packaging System and their Materials of Construction" is part of the USP-NF (United States Pharmacopeia–National Formulary), which sets standards for the quality, purity, strength, and consistency of drugs and their ingredients.

Chapter 661 specifically focuses on plastic articles (materials, components, and systems) used in the construction of containers for pharmaceutical products. This includes considerations for the choice of materials to ensure they are suitable for the intended use and do not adversely affect the quality or safety of the pharmaceutical product. The chapter provides guidelines and specifications for various types of plastics.

What does USP Chapter 661 cover?

It provides standards and guidelines for plastic materials used in the construction of containers for pharmaceutical products. The primary focus is on ensuring that these materials are suitable for their intended use and do not adversely impact the quality, safety, or efficacy of the pharmaceutical product.
The chapter addresses various types of plastics, including:

• Polyethylene (High-Density Polyethylene and Low-Density Polyethylene)
• Polypropylene
• Polyethylene Terephthalate
• Polyethylene Terephthalate G

The scope of testing within the chapter evaluates the following properties of plastic:

• Identification
• Physiochemical
• Biological

What is its importance for biopharma industry?

USP Chapter 661 has a significant importance in the biopharmaceutical industry as it sets standards for plastic articles, ensuring they meet stringent quality criteria.

This is pivotal for safeguarding the integrity of biopharmaceutical products, preventing interactions that could compromise their safety or efficacy.

The chapter's focus on stability and compatibility addresses the sensitivity of biopharmaceuticals to storage conditions, while standardized materials contribute to consistency and reproducibility in manufacturing. By mitigating risks associated with container-related issues, such as leachables or extractables, the industry upholds product quality.

Furthermore, global recognition of USP standards promotes international collaboration and trade by establishing a common ground for quality and safety expectations in the biopharmaceutical sector.

Sources: https://www.uspnf.com/sites/default/files/usp_pdf/EN/USPNF/revisions/661_rb_notice.pdf

USP 1072 is a chapter within the United States Pharmacopeia (USP) that addresses standards and guidelines related to disinfectants and antiseptics. It aims to ensure that disinfectants and antiseptics used in various applications, including biopharmaceutical production, meet appropriate standards for efficacy and safety.

Why is USP 1072 Important for Biopharma Product Testing?

Regulatory Compliance

Biopharmaceutical companies must comply with regulatory standards to ensure the safety and efficacy of their products. Adherence to USP 1072 is important for biopharma product testing as it demonstrates compliance with recognized standards for disinfectants and antiseptics, which may be required by regulatory authorities like the FDA.

Contamination Control

Biopharmaceutical production processes require strict control over contamination to maintain product quality and integrity. Proper use of disinfectants and antiseptics, in accordance with USP 1072 guidelines, helps control microbial contamination in manufacturing facilities, equipment, and materials, reducing the risk of product contamination.

Product Quality Assurance

The use of effective disinfectants and antiseptics is essential for maintaining the quality and purity of biopharmaceutical products. Testing conducted in accordance with USP 1072 ensures that these products meet specified standards for efficacy, ensuring that they can effectively eliminate or control microbial contaminants that may compromise product quality.

USP 1072 Covers

Disinfectants and antiseptics

The chapter addresses the selection of appropriate chemical disinfectants and their bactericidal, fungicidal, and sporicidal efficacy. It also discusses the application of disinfectants in sterile pharmaceutical manufacturing areas, along with regulatory and safety considerations. Additionally, it mentions antiseptics, which are used to decontaminate human skin and exposed tissues, and chemical sterilants for decontaminating surfaces in manufacturing areas and sterility testing.

USP 1224 is a chapter within the United States Pharmacopeia (USP) that addresses the transfer of analytical procedures between laboratories or sites. This chapter provides guidelines and recommendations for ensuring that analytical methods are accurately and reliably transferred without loss of integrity or precision. It covers the necessary steps and considerations for transferring analytical procedures effectively, maintaining consistency and reliability in analytical testing across different locations.

Why is USP 1224 Important for Biopharma Product Testing?

Consistency in Testing

Biopharmaceutical companies often conduct analytical testing at multiple sites or laboratories. USP 1224 ensures that analytical procedures can be transferred between these sites without compromising the accuracy or reliability of the testing. This helps maintain consistency in testing results, ensuring that products meet quality and regulatory requirements regardless of where they are tested.

Quality Control

Accurate and reliable analytical testing is essential for ensuring the quality and safety of biopharmaceutical products. USP 1224 provides guidance on how to transfer analytical procedures while maintaining the quality and integrity of the testing process. By following the recommendations in this chapter, biopharma companies can effectively control the quality of their analytical testing procedures.

Regulatory Compliance

Regulatory authorities, such as the U.S. Food and Drug Administration (FDA), expect biopharmaceutical companies to adhere to standardized procedures for analytical testing. USP 1224 provides a recognized framework for transferring analytical methods, which can help companies demonstrate compliance with regulatory requirements and guidelines.

USP 1224 Covers several aspects of biopharma product testing

Method Transfer Protocol

USP 1224 outlines the key components of a method transfer protocol, including the responsibilities of sending and receiving laboratories, acceptance criteria, and documentation requirements. This protocol serves as a roadmap for transferring analytical procedures between laboratories.

Types of Transfers

The chapter discusses approaches for transferring analytical procedures to a receiving laboratory. This may involve comparing results obtained from the sending and receiving laboratories, co-validation of the analytical procedure by the sending and receiving laboratories, or partial validation or revalidation of the analytical procedure by the receiving laboratory to ensure that the transferred method performs consistently across different settings. Validation activities may include specificity testing, accuracy assessment, precision studies, and other validation parameters.