A Guide to GMP Regulations – Part 2: GMP Personnel and Documentation

25 January 2022

This is the second part in a 4-part blog series on A Guide to GMP Regulations. Part 1: What is GMP? Can be found here.

EudraLex Volume 4, and the CFR Title 21, provide strict guidelines of Good Manufacturing Practice (GMP) which they expect manufacturers to adhere to, to ensure that high levels are met consistently when producing and controlling medicinal products. There are strict standards set when it comes to the documentation of processes, and how different areas have different responsibilities during these processes.

Ensuring that medicinal products are manufactured correctly relies on the performance of personnel. It is therefore a GMP requirement that sufficient, qualified personnel carry out tasks associated with manufacture, quality control and release of these products.

Responsibilities

Individuals should have clearly defined roles within the facility, and these should be understood by these staff members, and recorded. Personnel should have the necessary qualifications and practical experience to ensure that they can carry out their specific roles. This allows each individual to perform the roles they have been set to a high standard, ensuring that quality is maintained throughout manufacture, quality control and release.

It is important to understand that no one individual should have responsibilities so extensive that this may pose a risk to the product of the quality – individuals should be able to manage their workload to ensure that the quality of their work can be maintained, and if that individual were to be replaced, their replacement is able to successfully take over all of those duties without putting the quality of the product at risk.

If an individual is unable to manage their workload to a high quality, there is no assurance that the quality of the processes will be maintained to a high standard consistently, and if an individual were to leave and there was no successful replacement of that individual, consistent quality may be put at risk.

It is now well understood that any person who has any illness or open lesion which may impact the safety or quality of the product should not enter any environment which would put them in contact with components, containers, in-process materials, or drug products.

The time of the exclusion should determine whether the individual requires requalification before resuming activities; for example, an individual with an illness which led to a week of exclusion would not likely require requalification, however a longer-term illness meaning the individual was excluded for a year would likely require requalification before manufacturing activities can be resumed.

Key roles in a GMP manufacturing unit

Some of the key roles within a GMP manufacturing unit include the QP (Qualified person), the Head of Production and the Head of Quality Control. QPs are responsible for the release of medicinal products manufactured within the European Union, and they must ensure that each batch has been manufactured in compliance with the relevant regulations. They are also responsible for ensuring that products manufactured in third countries have undergone sufficient analysis to ensure that the quality of the product meets the requirements relevant to the product.

The Head of Production is responsible for ensuring that products are produced and stored appropriately, and that the appropriate documentation is maintained to ensure quality of the product. They are also responsible for approving working procedures and records and ensuring that the Production department equipment and facilities are qualified, validated and maintained to the correct high standards. They should also ensure that all staff within the Production department are trained to the level required for their role, and that their training is maintained to a high standard. All of this is done to ensure that a high-quality product can be produced consistently.

The Head of Quality is responsible for the approval or rejection of all materials used within Production, from starting materials, packaging materials, intermediates, bulk, and finished products. They should ensure that the correct testing is performed on all materials, and that the correct records have been evaluated against the correct specifications.

The Head of Quality is also responsible for the approval of specifications, sampling instructions, test methods and other Quality Control procedures, approval and monitoring of contract analysis performed, and ensuring that the Quality department facilities are qualified, maintained and validated to the correct high standards. As with the Head of Production, the Head of Quality is also responsible for the training of the Quality Control staff members to the required high standards of the roles. All of this is done to ensure that a high-quality product can be approved and released consistently.

Quality Assurance

A Quality unit should be in place in all GMP manufacturing facilities. This unit has the responsibility for approval or rejection of any components or products throughout the manufacturing process. The Quality unit should review production records, ensuring that any errors which have occurred are fully investigated, and all procedures and specifications have been met before approval or rejection.

Personnel should be appropriately trained and qualified before entering any manufacturing area, and a program should be established by the Quality unit to regularly assess individuals to ensure that they meet the relevant criteria to enter these manufacturing environments.

Documentation

A key to maintaining quality assurance is the maintenance of good documentation practices. Before the release of any medicinal product or intermediate, all documentation should be reviewed to ensure that all steps of the processes have been documented, and that the principles of data integrity have been met.

To ensure that GMP requirements are followed, all procedures must be effectively documented. A good documentation system allows confidence that procedures are validated and controlled. It must also ensure that all activities (directly or indirectly impacting product quality) are recorded. This ensures that all requirements and specifications can be met reliably and repeatably, by ensuring that the correct processes have been carried out. If steps have not been documented, or incorrect data integrity has been used during the documentation, this could cast a doubt over the quality of the product.

Good documentation practices should be adhered to whether entries are handwritten or electronic. These good documentation practices are detailed by the ALCOA+ principles, ensuring that any records made are Attributable, Legible, Contemporaneous, Original, Accurate, Complete, Consistent and Enduring.

Manufacturing facilities often rely heavily on paper-based systems which pose significant data integrity risks, such as illegible or destroyed records, or possible back-dating of annotations. If these systems are used, multiple reviews of documentation must be performed to ensure that good documentation practices are being adhered to.

Additional requirements must also be in place for batch documentation, which must be kept for at least one year after expiry of the batch (or 5 years after certification of the batch, whichever is longest).

Recently, many documents have begun to be used electronically rather than paper based. One such system is SmartControl EM, which allows users to record all of the relevant information regarding their environmental monitoring directly into the software and allows analysis and reporting of this data in a compliant manner.

ALCOA+ principles still apply to any electronically produced documents. Appropriate controls should be put into place for electronic or hybrid documents, including ensuring that master documents are in place, records are controlled, and complete audit trails are still available for these documents. Using SmartControl EM allows users to comply with ALCOA+ principles throughout the document lifecycle, and allows compliant and safe storage of all data.

Learn more about how SmartControl EM can help your facility meet regulation, enhance data integrity and take better environmental monitoring decisions.