GxP is a shorthand umbrella term for regulated “Good Practice” standards in life sciences. The “x” is a variable that changes with the activity. For example, GMP applies to manufacturing, GLP concerns nonclinical laboratory studies, GCP covers clinical research, and so on. In the United States, core FDA GxP requirements for finished pharmaceuticals appear in 21 CFR Parts 210 and 211.

In the realm of pharmaceutical manufacturing, the day-to-day focus is usually GMP, so for our purposes, we’ll come from that angle. One neat and tidy way to organize requirements is by the “5 Ps of GMP”: People, Processes, Procedures, Premises, and Products.

While this framework is not a defined regulatory structure — the FDA does not officially organize its GMP regulations around any “5 Ps” — it’s a longstanding teaching/organizational model that traces back well into the archives of GMP literature. So, let’s group major manufacturing compliance responsibilities within those five areas and dive in.

THE 5 PS OF GXP REQUIREMENTS IN PHARMA MANUFACTURING

1. PEOPLE SHOULD BE QUALIFIED

Pharmaceutical quality is a product concept, but it springs from personnel who understand the work assigned to them.

In drug manufacturing, many FDA GxP requirements are expressed through the FDA’s CGMP regulations, which establish minimum requirements for how drugs are manufactured. 21 CFR Part 211 requires people involved in manufacturing to have appropriate education, training or experience for their assigned work. CGMP training must relate to the employee’s responsibilities and continue often enough to keep that knowledge current. Manufacturers are required to maintain enough qualified personnel to carry out and oversee production properly.

2. PROCESSES NEED DEFINED CONTROLS

A regulated process should produce consistent results under defined conditions. Manufacturers need to understand which variables affect the product and how those variables will be controlled.

The World Health Organization’s GMP guidance describes GMP as a system for ensuring products are consistently produced and controlled according to quality standards. WHO emphasizes that final-product testing alone cannot eliminate every manufacturing risk.

In other words, for GxP compliance requirements, the process must be both precise and repeatable.

3. PROCEDURES MUST MAKE WORK REPEATABLE

Standard operating procedures, or SOPs, are compliance cornerstones. Essentially, they are records of an approved process in the form of instructions employees can follow. Your SOPs establish how work should be performed and provide a reference point when something changes. Take equipment cleaning for example. Part 211 requires written procedures covering responsibility for cleaning and maintenance.

Defined procedures also help you to keep an ongoing manufacturing record. After all, if an inspection raises a question about a production event, the manufacturer needs documentation that shows which procedure applied and how the work was performed. There’s your SOP, on hand with the answer.

For compliance purposes, keep change control in mind. A revised process can’t be an informal adjustment on the floor. It needs an approved and documented path into production.

4. PREMISES AND EQUIPMENT HAVE TO BE WELL MAINTAINED

Facilities and equipment naturally affect product quality. They’re what you’re working with. So, Good Manufacturing Practices must somewhere address their design and control as part of pharmaceutical manufacturing.

The current 21 CFR Part 211 regulations also place specific controls on automated equipment. Automated systems must be routinely calibrated, inspected or checked under a written program, with records maintained. Computerized systems require controls over who can change regulated records, along with appropriate data verification and backup protections.

Your job is to provide systems (and their maintenance) for the proper design and monitoring of manufacturing processes and facilities. Only with reliable premises and equipment can approved processes remain under control.

Working with automated production cells? GxP validation requirements are part of system specification. Controls architecture, inspection functions, and data handling should also reflect those requirements.

5. PRODUCTS STILL SET THE STANDARD

This final “P” brings our framework back to its overall purpose: the pharmaceutical product has to meet its approved quality requirements.

WHO states that GMP spans production from incoming materials through completion of the finished product. Therefore, a final check is not enough to establish compliance. The quality system has to govern everything that happens throughout manufacturing of the product.

GxP requirements ultimately concern control over how a regulated product is produced. When automation enters the process, the equipment needs to operate within the same approved manufacturing framework.