Explore the key FDA regulations (21 CFR Part 211) for controlling components, drug product containers, and closures in pharmaceutical manufacturing. Learn about the challenges and solutions to ensure compliance and maintain product quality.
One of the most significant aspects of the pharmaceutical industry is drug safety, efficacy and quality. To meet these goals, FDA has developed fully written and comprehensive regulations on how the finished pharmaceutical products need to be produced. A key element of these regulations is the control of components and drug product containers, as described in Title 21, Part 211, Subpart E of the FDA regulatory guidelines. Although these criteria are critical to ensure the quality of product, a key challenge for pharmaceutical manufacturers is adoption of Quality by Design principles around regulation 21 CFR part 211,Subpart E which focuses on the control of components and drug product containers.
21 CFR Sec. 211.86
Use of components, drug product containers, and closures
Components, drug product containers, and closures approved for use shall be used on a first in, first out basis (first stock to expire is used first). Deviation from this requirement is permissible if such deviation is temporary and justifiable.
Use Rotation and approval of components:
The FDA requires that pharmaceutical companies use only approved components, drug product container, and closures with the oldest approved stock being utilized first. Even so, challenges can arise in managing approved components and their rotation. It is essential that companies also implement some form of inventory controls to account for the stock and help their staff make certain they are always using older items first so as not to let anything expire or go bad. It needs the documentation, procedures to be cleared among them with smooth working in which all departments are involved.
21 CFR Sec. 211.87
Retesting of approved components, drug product containers, and closures: Components, drug product containers, and closures shall be retested or re-examined as appropriate for identity, strength quality and purity by the quality control unit in accordance with § 211.84 as necessary, for e.g., if they have been stored for extended periods of time or exposed to air, heat or other conditions that may adversely affect the component, drug product container, or closure.
Temporary deviations (and retesting) permitted:
The FDA requires that the oldest available approved stock be used but may permit temporary deviations if appropriate. Nevertheless, determining the suitability and legitimacy of such deviations prove to be difficult. Manufacturers must maintain strong processes and records of justifications for these exceptions, ensuring that product quality and safety are not jeopardized. Furthermore, testing protocols, scheduling and resources associated with the retesting of components, drug product containers, and closures after storage or exposure to adverse conditions are complex.
21 CFR Sec. 211.89
Rejected materials, drug product containers and closures: Rejected materials, drug product containers and closures shall be identified and controlled under a quarantine system that prevents their use in manufacturing or processing operations for which they are unsuitable.
Rejected Component Management and Quarantine System:
Regulations require quarantine system for all rejected components / drug product containers and closures to prevent their usage in manufacturing or processing operations. Challanges of segregation, tracking and disposal of rejected items creates these operational hindrances to provide an efficient quarantine system. This requirement means that manufacturers must have solid procedures to identify and isolate the components which fail so that they are not used by accident, as well as methods for going through with their disposal. This requires interdepartmental arrangements communicating how quarantine of materials works.
Conclusion
The FDA make some rules about control of building blocks and containers for drug product, all associated with the quality, safeness, effectiveness of drugs. Nonetheless, several challenges exist for pharmaceutical manufacturers to reach compliance. Addressing these challenges, from managing approved components and their rotation to implementing appropriate retesting procedures, maintaining suitable storage conditions, and handling rejected components requires a combination of robust systems and processes as well as qualified personnel. With a strong will to battle these challenges, manufacturers can maintain their compliance with FDA regulations and play their part to the manufacturing of safe and good quality pharmaceutical goods for worldwide patients. Compliance with these regulations is essential for ensuring consumer confidence in the pharmaceutical sector and protecting public health.
Get in touch today or visit our website to find out how BioBoston Consulting can assist you with your regulatory activities.
