- QA is a concept that covers all matters which influence the quality of the medicinal product and ensures that it is suitable for intended use
- Ensures that the patients are not at risk due to inadequate safety, efficacy, quality
- Applied continously throughout the development process and to commercial manufacturing process
- Quality by design
Quality Assurance in Drug Development:
- GLP - Good Laboratory Practice (Labs and Animal Tests)
- GCP - Good Clincial Practice ( Human Clinical trials)
- GMP - Good Manufacturing Practice (Production)
- GPvP - Good Pharmacovigilance Practice (After launch)
GLP and GCP
1. GCP - Good Clincial Practice (Human Clinical trials) - GCP is an international ethical and scientific quality standard for designing, conducting and recording and reporting trials that involve participation of human subjects. Compliance ensures clinical trail data is credible and rights, safety and wellbeing of subjects are protected.
2. GLP - Good Laboratory Practice (Labs and Animal testing) - GLP embodies a set of prinicples that provide a framework within which laboratory studies are planned, performed, monitored, recorded, reported and archived. Ensures that data submitted to regulatory authorities is a true reflection of results obtained and can be relied upon when making risk assessments.
GMP - Good Manufacturing Practice - The part of quality assurance which ensures products are consistently manufactured to a quality appropriate to their intended use -
- Right product and strength
- Free from contamination
- Corrent container and label
Why do we need GMP? (other manufacturing industries don't have GMP)
- Pharmaceuticals are potent substances which can improve or maintain life, given to people who are ill. Impossible to judge the quality of pharmaceuticals visually.
- There is no unified system of GMP
- In the EU the legislation relating to GMP for human medicinal products is contained in Directive 2003/94/EEC, enforced by the MHRA. Guidance on the legislation is found in "The Orange Guide" Rules and Guidance for Pharmaceutical Manufacturers and distributors (2002)
GMP - personnel, premises and equipment
- Head of Production, Head of Quality Control -Work independantly of each other
- Qualified Person (EU only) legal and personal liability to ensure that the principles and guidelines of GMP have been followed
- Training required for all personnel, personal hygine standards must be maintained
Premises - controlled so product quality isn't effected
- Minimise the risk of cross contamination
- Maintenance procedures and pest control procedures must be in place
- Controlled enviroment and controlled access to enviroment
- Design of production areas should facillitate cleaning
Equipment - manufacturing equipment should be designed, located and maintained to suit its intended purpose, equipment should be designed so that it can be easily cleaned
GMP - documentation
Documentation (paper and electronic) provides enhanced process control and allows batch history to be traced, records should be madde at the time the action is taken and should be maintained for a year after the end off product shelf-life.
Documentation used in GMP:
- Standard operating procedures SOPs
- Batch records - provide a detailed history of a product batch
- Labelling (Materials, products, equipment, rooms)
- Log books for equipment and rooms
- Test methods - written procedures for testing
- Specifications - physical, chemical or microbiological criteria that the product must meet
- Problem investigations - initiated following an unusual/unwanted occurance
GMP - QC and Complaints
QC - Quality Control:
- Analysis of raw materials and finished product. Test data must fall within definied specification limits.
- Only a limited number of samples tested, only parameters known to be critical to the product are tested.
Complaints and Product Recall:
- Written procedures should be available detailing the action to be taken in the event of complant
- Complaint records should be reviewed regularly to identify trends and reccuring problems
- Complaits relating to serious quality problems should be notified to the relevant regulatory authorities
- It should be possible to initate recall procedures swiftly
- Relevant regulatory authorities must be informed of any product recall
The Future Pharmaceutical Quality System
Quality by Design - GbD:
- A "systematic approach to development that begins with predefined objectives and emphasises product and process understanding and process control, based on sound sciencce and quality risk management"
- Higher level of assurance of product quality; more efficient and cost effective processes; simplification of regulatory changes to commercial product
- IMPORTANT - our patients deserve safe, efficacious and innovative medicines that make a positive difference to their lives.
Quality Risk Management
- A "systematic process for the assessment, control, communication and review of risks to the quality of the drug product" applies to development, manufacturing and distribution.
- Guidance includes principles and examples of tools for quality risk management. Evaulation of risk to quality should be based on scientific knowledge and link to the protection of the patient.