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November 29, 2021

The quality unit is an independent department, fulfilling quality assurance (QA), sterility assurance (SA) and compliance responsibilities. Quality control (QC), while it often functions as an independent department, is closely linked to the work of the quality unit. The QC team will evaluate the performance and adherence of materials throughout the manufacturing process; it also evaluates the facility, equipment and laboratory processes that govern operations. The quality unit and QC team work together to ensure the proper functioning of the Quality Management System (QMS).  

Quality Assurance Team  

The QA team (“Quality”) provides and maintains quality systems to assure compliance with phase-appropriate Good Manufacturing Practices (GMP) requirements. Quality carries out key processes such as document control and GMP training. Validation is outsourced and owned by Operations, with Quality oversight. 

Quality organizes incoming materials and oversees the supplier qualification program. Quality also performs line clearances, reviews batch records, and supplies client products with a Manufacturer’s release through the issuance of a Certificate of Conformance, along with a statement declaring that the batch has been reviewed and found to be manufactured in compliance with applicable CCRM procedures. 

Quality issues and controls key documents, including the Certificate of Analysis (COA), Certificate of Conformity (COC), and Transmissible Spongiform Encephalopathy (TSE) statements. TSE statements include Bovine Spongiform Encephalopathy (BSE) also known as mad-cow-disease, the scrapie disease in sheep, as well as the human form: the variant-Creutzfeldt-Jakob-Disease (vCJD). 

Sterility Assurance Team 

The SA team is responsible for Quality oversight of aseptic processing, environmental monitoring and microbial control programs. SA is also responsible for reviewing policies and procedures, environmental monitoring sample plans, clean room qualifications, environmental monitoring excursions, deviations and sterility failures.   

Compliance Team 

Compliance is responsible for overseeing the QMS and monitoring quality performance indicators as well as continuously monitoring and ensuring the overall compliance of GMP activities. Compliance is involved in the management of client audits, external audits (such as vendor audits), and internal audits. 

Quality Control Team  

QC may be carried out on-site, or outsourced, depending on the facility. Regardless, every GMP facility will have a team that is dedicated to overseeing this function. The QC team will be responsible for overseeing/performing raw material and final product testing. When custom, product-specific testing is required, the QC team will provide guidance to the client on how to incorporate that requirement into the manufacturing process.  

Functions of the Quality Unit 

Below we outline the many functions that the quality unit oversees in a GMP facility:  

1. Manufacturing Control 

Standard Operating Procedures (SOPs) and/or batch records are in place to govern all aspects of manufacturing to GMP standards, including testing, holding, packaging/labelling (if appropriate), and qualification. One of the many ways manufacturing must comply with GMP guidelines is by ensuring operators are trained and capable of performing their functions. Training oversight is performed by the Operations Manager, with Compliance performing audits, record reviews and enforcing compliance requirements.   

2. Materials Management 

SOPs specify the procedures for incoming material receiving, inspection, and release. Materials are released by Quality based on a COA comparison to internal specifications and inspection. Additional testing, if required, is available upon request. 

Once incoming material is cleared to enter the GMP facility, entry into the GMP production area happens via pass-throughs, and an SOP on disinfection is in place to ensure the new material does not introduce contaminants. 

3. GMP Document and Records Control 

Access to GMP documents, including archived/obsolete documents, is controlled by Quality. Controlled documents include policy documents, validation protocols and reports, specifications, batch records, laboratory notebooks, logbooks, investigation reports, training records, test methods and data, forms, SOPs and work instructions. 

Raw data are retained as originals or true copies, in compliance with 21CFR211. Quality maintains a signature log as a record of who is accessing documents.  

4. Training Management – Technical and GMP 

Quality is responsible for providing the GMP training program and maintaining training records. Department heads are responsible for performing technical training, including needs assessment, training and completing training records. QA and Compliance audit the records to verify that documented evidence of training meets current GMP requirements and company SOPs. Where necessary, hands-on demonstration of proficiency is required before an operator or analyst is considered trained. For example, operators are qualified on aseptic technique by a hands-on demonstration of proficiency. 

5. Change Control  

The process for introducing change controls is specified by SOPs. Each change to a GMP system is overseen and approved by Quality and appropriate technical experts. Changes to GMP items on-site are evaluated for their impact on products, validated systems and the facility.    

Where appropriate, computerized systems are managed with change history and/or change control in place.  Validated systems and systems with electronic signatures are designed to comply with 21CFR 11 and applicable rules.  

6. Incidents 

GMP incidents are overseen by Quality and are tracked through a central quality incident process. Depending on the category, each incident is triaged to the appropriate quality workflow. Categories include non-conforming material, Out-of-Specification (OOS) results, deviations, Corrective Action Preventative Action (CAPA), and product complaints. Quality reviews and approves all incidents for compliance with procedures and applicable regulations, tracks and trends them to closure, and collects metrics on efficacy of CAPA actions. These quality processes are robust and fully traceable.   

The Quality Agreement specifies how notification, consultation, review and client acknowledgment are handled for critical and major incidents.   

Periodically, Quality reports to management on compliance risk. As needed, Quality may convene a Materials Review Board, change control committee or other cross-functional teams that work jointly to assure that exceptions are investigated and remedied, and that resources are provided as appropriate.  

7.  Supplier Qualification 

SOPs should outline supplier qualification that is phase-appropriate. Management and qualification of incoming material suppliers are based on a risk assessment of both the incoming material and the supplier’s performance.  This model, as well as the current approval status of suppliers, is managed by the supplier module of the QMS. In this system, results from survey audits, on-site audits, or shipment complaints are tracked and utilized to define current risk and any need for mitigation actions. Led by Compliance, audits are performed on critical suppliers where the risk assessment indicates these are needed to fully assess and/or mitigate risk.   

Suppliers and incoming materials may be specified by the client or by the facility. When specified by the client, supplier qualification is the client’s responsibility unless otherwise specified in the Quality Agreement.   

8. Inspection and Audit Management 

Quality (Compliance) is responsible for the internal (self-audit) program, which oversees all GMP functions. In the event of a regulatory inspection or client audit, Quality (Compliance) hosts the inspection/audit. An SOP on inspections is in the master plan. 

9. Environmental Monitoring  

Routine environmental monitoring is performed by the SA team, while Operations perform dynamic monitoring under SA oversight during production. 

The quality unit ensures that a GMP facility functions within the parameters set out in regulations and guidance by closely integrating the QA, SA and Compliance teams. Ultimately, quality management is focused on ensuring the safety and reliability of products that are destined for use in humans.  

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