21 CFR Part 606 Regulations

CGMP Guidelines for Blood Establishments

The U.S. Food and Drug Administration (FDA) CGMPs establish a system for ensuring that medical products are produced consistently and according to applicable quality standards based on their intended use and as required by product specifications. These guidelines are in place to prevent the occurrence of adverse events by ensuring product safety, potency and efficacy.

As they pertain to blood and blood components specifically, the CGMPs in 21 CFR Part 606 aim to minimize the transmission of bloodborne diseases. Adhering to CGMP requirements throughout the entire blood production process – spanning from donor to recipient – is essential to consistent blood product quality and safety. Examples of blood collection and production activities governed by CGMPs include: applying the appropriate donor selection criteria; preventing errors during testing; and supporting traceability with adequate documentation of each step in the process.

Key Requirements of 21 CFR Part 606

21 CFR 606.20 – Personnel:

The personnel responsible for collection, processing, compatibility testing, storage or distribution of blood and blood components shall be adequate in number, educational background, training and experience, including professional training as necessary to assure competent performance and to ensure that the final product has the safety, purity, potency, identity and effectiveness it purports or is represented to possess.

21 CFR 606.100(b) – Standard operating procedures:

Written standard operating procedures (SOPs) must be maintained and shall include all steps to be followed in the collection, processing, compatibility testing, storage, and distribution of blood and blood components for transfusion, and further manufacturing purposes. Such procedures must be available to the personnel for use in the areas where the procedures are performed.

21 CFR 606.140 – Laboratory controls:

Laboratory control procedures shall include adequate provisions for monitoring the reliability, accuracy, precision and performance of laboratory test procedures and instruments.

21 CFR 606.170 – Adverse reaction file:

Records shall be maintained of any complaints of adverse reactions that result from blood collection or transfusion. A thorough investigation of each reported adverse reaction shall be made. A written report of the investigation shall be prepared and maintained as part of the record for that lot or unit of final product by the collecting or transfusing facility.

21 CFR 606.171 – Reporting of product deviations by licensed manufacturers, unlicensed registered blood establishments, and transfusion services:

21 CFR Part 606 does not use the term corrective and preventive action (CAPA), but section 606.171 states that all biological product deviations should be investigated in accordance with the applicable provisions of 21 CFR Parts 211 and 820, both of which require the establishment of CAPA procedures.

Compliance Program for Blood and Blood Components Guidance Manual-7342.001, Attachment B – Product quality review:

A review of records must be conducted at least annually to evaluate the quality standards of each product and to determine if there is a need for changes in product specifications or manufacturing or control SOPs (21 CFR Part 211.180(e)). SOPs for this review must be in writing.

CGMP Requirements

CGMPs apply to all regulated manufacturers of medical products intended for human consumption or use. By establishing minimum requirements for the methods, facilities and controls used in manufacturing, processing and packaging, CGMPs intend to ensure the safety and quality of pharmaceuticals, medical devices, biologicals and other regulated products. The FDA conducts routine inspections of blood establishments to ensure compliance with 21 CFR Part 606 CGMP requirements for blood and blood components. Depending on their intended use, these products can be classified as either drugs, devices or combination products, so additional regulations may apply.

MasterControl Features

In the following ways, MasterControl’s configurable, easy-to-use and integrated suite of solutions addresses the CGMP requirements in 21 CFR Part 606:

• MasterControl Training™ automates the assignment and monitoring of training tasks and grading of online exams. In keeping with 21 CFR Part 606 requirements, the solution supports sequencing of training courses, which automatically launches the subsequent training course after a prerequisite is completed. It also provides a group signoff feature for verifying training of large groups of employees.
• MasterControl Documents™ automates routing, escalation, approval and delivery of SOPs, policies and other documentation. It provides a centralized, web-based repository that's both secure and accessible to all authorized users. MasterControl provides automatic revision control to ensure that only the current version of an SOP is available. When a user makes a change in the InfoCard (the MasterControl tool that contains basic information about every record), the user must enter a reason for the change. The system tracks these changes and makes them available through reports which helps in maintaining 21 CFR Part 606 compliance.
• MasterControl Audit™ automates, streamlines and effectively manages the audit process, which is recognized as one of the best ways to monitor and document the reliability and accuracy of laboratory test procedures. The solution provides advanced tracking capabilities, from scheduling and planning to execution and completion, and basic audit information and audit findings are captured and tracked with best practice forms that are in compliance with 21 CFR Part 606 requirements. All recurring audit-related activities can be scheduled automatically, and the available analytics and reporting functionality provide management with increased visibility.
• MasterControl Customer Complaints™ streamlines the 21 CFR Part 606 complaint handling process and reduces the lifecycle from submission to resolution. A simple three-step process is facilitated in a pre-configured, multi-page form that starts with processing the complaint, then moving to internal investigation, and culminating with issue resolution. The solution includes the FDA's MedWatch 3500A form for mandatory reporting of adverse events, ensuring that the required data is collected immediately while allowing a seamless handover to an adverse events specialist.
• MasterControl CAPA™ integrates the corrective and preventive action process with other quality processes. The solution supports an “8D” best practice process that guides the quality team through every step of CAPA, helping to sustain 21 CFR Part 606 compliance. A CAPA form can be launched directly from another form (e.g., a nonconformance report), and relevant data is entered automatically in the CAPA form which reduces the need for data entry and eliminates related data entry errors. With customizable reporting capabilities, managers can easily monitor the entire quality management lifecycle.
• MasterControl Change Control™ streamlines the entire change control procedure for faster turnaround. It offers a best practice form that incorporates priority level and prompts risk assessment and classification of a change as low, medium or high, easing the 21 CFR Part 606 regulatory filing process for high-risk changes. Customizable reports provide real-time status of change control tasks and the entire quality system.

MasterControl and CFR Compliance

MasterControl quality and regulatory software offers blood companies the robust and compliant functionality they need to comply with 21 CFR Part 606 and additional regulations set forth by the FDA and other global regulatory bodies. Across all regulated industries, MasterControl is the software of choice for thousands of companies wishing to achieve more consistent and reliable CFR compliance with greater efficiency, allowing them to bring their life-changing products to market sooner.

Trusted Software Provider of the FDA

MasterControl and its partner company, i4DM, have been the QMS providers for the FDA’s Office of Regulatory Affairs (ORA) since 2009. The FDA recently expanded its implementation of MasterControl’s Quality Excellence™ solutions to improve the quality and audit management processes of the Division of Pharmaceutical Analysis in the Center for Drug Evaluation and Research (CDER).

For more information on how MasterControl software and services can help your company improve efficiency while achieving FDA compliance, contact a MasterControl representative.