Good Manufacturing Practice, or GMP, is a set of regulations issued by the US Food and Drug Administration under the Federal Food, Drug and Cosmetic Act.
They require processors, manufacturers and packagers of medical devices, drugs and foods to take proactive steps towards ensuring the safety, effectiveness and purity of their products. These regulations ensure quality approach and practices to reduce (or remove) errors and contamination, in order to protect consumers.
GMP Inspections – Types and Objectives
To keep inspections relevant, GMP processes are categorized according to several types, each with different objectives:
- Pre-Approval Inspection (PAI)
The primary objective is to confirm readiness for commercially manufacturing a product, and investigations include:
• Manufacturing/GMP trends
• Material handling methods and processes
• Procedures being followed
• The feasibility of the process to deliver products of acceptable quality
• Manufacturer’s conformance to application
• Quality or integrity of data being collected (e.g. assessment or calibrations of measurement instruments).
A PAI might result in a ‘withhold’ recommendation based on inadequate lab controls or QA (quality assurance) functions, insufficient controls for process, data and production, etc.
A complete inspection of all the GMP guidelines, conducted in cases like:
• The first time that manufacturers establish themselves
• Existing manufacturers apply for the renewal of their licenses
• Establishments which have a history of GMP non-compliance
• When it has been 3-5 years since the last inspection
• Changes are made, e.g.:
• New products are manufactured or new product lines set up
• Modifications made to manufacturing methods
• Key personnel replaced
• New equipment or premises used
The objectives are to determine compliance with GMP requirements and provide feedback/evidence necessary for action, so establishments can improve compliance.
Routine inspections also gather data to support approval decisions for applications, and to aid the FDA determine if current GMP requirements, guidance and regulatory policies are adequate to safeguard consumers.
As the name suggests, these only focus on a limited number of requirements under GMP (selected as indicators of compliance).
• Unlike routine inspections, the objective of this inspection is not to thoroughly check each aspect of the processes, but to indicate the establishment’s (and processes’) attitude towards GMP conformance.
• Another difference is that concise inspections are designed to identify if there have been any significant changes to the process, typically when there is a history of consistent GMP compliance.
Non-compliance should trigger a thorough inspection to check for other deficits and the extent of effects.
When inspection reveals the shortcomings in processes, corrective action may be prescribed:
• Reassessment or re-inspection could take place anywhere from 6 weeks to 6 months after initial inspection (based on the nature of defects and corrective work required).
• It could take place with or without prior warning, and the results of corrective action monitored.
• It takes specific GMP requirements into account which have either been inadequately implemented or not observed at all.
Performed in order to conduct spot checks focusing on a single product, group of related products, or specific operations:
• Depending on the reason, inspections could take place with or without prior warning. Sometimes, they may be used to advise about specific regulatory requirements.
• In case of product complaints, inspection would typically be performed without advance warning, to investigate possible quality defects.
• In case of product recalls or adverse reactions to a drug, inspection would focus on the specific product or process that may have caused it.
• Inspection could also be conducted in case of an export certificate or marketing authorization application, or simply to gather specific data about operations.
Quality Systems Review
This inspection will typically describe the QA system and manual.
• Similar to reviews carried out when manufacturers apply for international standards accreditation (ISO 9000), its objective is to review quality systems and determine their effectiveness.
• The manual is a document that lists the manufacturer’s QA approach, quality management structure and policy, standards to be observed, and correctly defined operational processes, as well as QA activities like policy implementation, QC (quality control), record keeping, etc.
Deficiencies Detected By GMP Inspections
• Analytical and process validation
• Equipment validation services
• Test/measuring equipment calibration and qualification
• Complaints and product recall
• Computerized systems validation, documentation and control
• Potential contamination
• Documentation for manufacturing elements/procedures
• Quality system documentation
• Monitoring and control of production operations
• Product testing (intermediate, bulk and finished)
Calibration has a huge impact on the ability to be compliant by ensuring measurement accuracy and reliability, so set up a regular service schedule. Consult a calibration service provider familiar with GMP requirements, before your next inspection rolls around!