A Guide to GMP Regulations – Part 1: What is GMP?
This is the first part in a 4-part blog series on A Guide to GMP Regulations.
The production of pharmaceuticals requires high levels of management, from the development, to the manufacture and control of medicinal products. Regulatory bodies within this industry, therefore, expect manufacturers to adhere to strict guidelines of Good Manufacturing Practice (GMP) to ensure that these high levels are met consistently.
Depending on where pharmaceutical products will be produced and marketed, regulations, or interpretations of regulations, may slightly vary. For example, goods sold within Europe must follow guidelines set out by the European Commission, whereas those sold in the USA must meet the regulations set out by the FDA. The European Commission have set out their GMP guidelines in EudraLex Volume 4, and the FDA have set out their guidelines within their Code of Federal Regulations (CFR) Title 21, which provides regulations for food and drugs within the United States.
So, what is GMP?
GMP is a set of systems in place to ensure that products can be produced consistently to a high standard and are controlled to the standards appropriate for their intended use. GMP is intended to regulate both the production, and quality control of products.
According to EudraLex Volume 4, there are 11 basic requirements of GMP:
i) Processes should be clearly defined and reviewed to show that the manufacture of products comply with their specifications
• Every step should be documented and follow clearly defined procedures
• These procedures should be reviewed regularly to ensure that they allow for consistent manufacture, and allow products to be manufactured to their specifications
ii) Critical steps of the manufacturing process should be validated
• This should ensure that the steps can be performed consistently, and produce the desired outcome
• Any significant changes to the process should also be validated to ensure these changes do not alter the desired outcome
iii) All necessary facilities for GMP are provided, ensuring that GMP requirements can be met. These facilities include:
• Qualified and trained personnel
o Ensuring tasks can be carried out correctly by competent staff members
• Adequate premises and space
o Not only should the correct facilities be in place to allow for the manufacture, but adequate space should be provided to ensure that processes can be carried out effectively
o Limited space can increase the risk to the product
• Suitable equipment and services
o Equipment and services should be validated and maintained to ensure that they are suitable for the processes being carried out
• Correct materials, containers, and labels
o Ensuring that the correct materials are available is essential to ensure that manufacture can be carried out to the correct standard
o Containers must be suitable for the processes being carried out
o Labels must be correct for starting materials, intermediates and for finished product to ensure it is clear what each material contains
• Approved procedures and instructions
o Ensuring that personnel are able to follow these procedures and instructions, which have been set out in the pharmaceutical quality system and approved
• Suitable storage and transport
o Ensuring that products can be stored and transported correctly is essential to maintain the quality of the product before distribution
iv) Instructions and procedures should be written in clear and unambiguous language
• This should ensure that they can be followed easily, ensuring personnel can consistently follow these instructions
• Instructions should be specifically applicable to facilities available
v) Procedures are carried out correctly, and operators are trained to do so
• If procedures are clear and personnel trained correctly, procedures can be carried out correctly and to a high standard
vi) Records should be made to demonstrate that all steps were taken
• This provides assurance that the correct procedures were followed, and that the quality and quantity of product met expectations during manufacture
• This is applicable for both procedures performed manually, and also for those performed using instruments which record results and statuses
vii) Any significant deviations are fully recorded and investigated
• Investigations should aim to identify why the impact of the deviation, why it occurred, and implement corrective or preventative actions to prevent the deviation from reoccurring
viii) Records of manufacture and distribution must be retained in a comprehensible and accessible form to ensure that the history of the batch can be traced if required
• This ensures that if any issues are discovered, there is full traceability of the manufacturing process and where products have been distributed to
ix) The distribution of products minimises any risk to their quality and takes account of Good Distribution Practice
• Ensuring that no additional risk is placed on the quality of the product during distribution
x) A system is available to recall any batch of product, from sale or supply, in case of defects or issues detected in manufacture after release
• If issues or defects are identified, there must be a way to ensure that any product which has been released can be recalled minimising risks
xi) Complaints about products are examined and any defects are investigated
• Measures should be taken to prevent reoccurrence if defective products are discovered
These principles apply to all stages of production and quality control, and as such, any personnel working within a GMP manufacturing facility involved in the manufacture, processing, packaging, or holding of products should be trained to fully understand these requirements and should receive ongoing training relevant to their roles within the facility.