Good Manufacturing Practice (GMP’s) for Medical Devices...
The fundamental concepts of current Good Manufacturing Practice:
• Consistency – one can only have confidence in a process if it leads to the right result every time.
• Continual Improvement – what is acceptable today may not necessarily be accepted next year. Thus GMPs evolve over time: hence the word “current”.
Note: Good Manufacturing Practice is not related to health and safety of employees and not related to production efficiency, although there may be some knock on efficiency effects.
Good Manufacturing Practice in Medical Device Manufacturing:General Requirements:
• All handling of materials and products through:
… needs to be performed in accordance with written procedures and recorded.
• Operations on different products should not be carried out simultaneously or consecutively in the same room or area unless there is no risk of mix-up or cross-contamination.
• Any deviation from instructions or procedures should be avoided as far as possible. If deviations occur, they should be performed in accordance with an approved procedure, approved in writing by a designated person.
• There need to be checks on yields and reconciliation of quantities to ensure that there are no discrepancies outside acceptable limits.
• At all time during processing, all materials, all bulk containers, all major items of equipment, rooms and packaging lines being used should be labelled or otherwise clearly identified.
• Access to production premises should be restricted to authorized personnel.
• Non-medicinal products should not be produced in areas or with equipment destined for the production of medical products.
• In-process controls are usually performed within the production area. The performance of such in-process controls, should not have any negative effect on the quality of the product or another product.
Prevention of cross-contamination:• When dry materials and products are used in production, special precautions should be taken to prevent the generation and dissemination of dust. There needs to be appropriate air control e.g. supply and extraction of air of suitable quality.
• Contamination of a raw material or of a product by another material or product must be avoided. Accidental cross-contamination can arise from uncontrolled release of dust, gases, particles, vapors, sprays or organisms from materials and products in process, from residues on equipment, from intruding insects, from operators’ clothing, skin, etc.
• The risk of contamination from the most hazardous, highly sensitizing materials such as living organisms, hormones, cytotoxic substances, and others must be avoided by taking appropriate actions e.g. carrying out production in dedicated and self-contained areas, conducting campaign production followed by appropriate cleaning in accordance with a validated cleaning procedure, providing appropriately designed airlocks, pressure differentials and air supply and extraction systems.
• Minimizing the risk of contamination caused by recirculation or re-entry of untreated or insufficiently treated air.
• Wearing protective clothing, using cleaning and decontamination procedures of known effectiveness, using a closed system in production.
• A program of testing for residues and using cleanliness status labels on equipment may need to be instigated.
• Measures to prevent cross-contamination and their effectiveness should be checked periodically according to Standard Operating Procedures. Production areas require periodic environmental monitoring. Before any processing, operation work areas and equipment should be clean and free from any starting materials, products, product residues, labels or documents not required for the current operation.
• Any necessary in-process controls and environmental controls should be carried out and recorded. Always clearly indicate any failures of equipment or services (e.g. water, gas) to equipment, all defective equipment should be withdrawn from where they could be used. After use, production equipment should be cleaned without delay, stored under clean and dry conditions in a separate area (if necessary). Time limits for storage of equipment after cleaning and before use may need to be established. Containers for filling should be cleaned before filling.
• Any significant deviation from the expected yield needs to be recorded and investigated.
• Check pipelines and other pieces of equipment used for transportation of products. Pipes used for conveying distilled or deionized water need to be sanitized and stored according to written procedures (with defined action limits for microbiological contamination).
• Equipment and instruments should be serviced and calibrated at pre-specified intervals, must have records maintained, checked daily or prior to use and have clearly indicated the date of calibration and servicing, recalibration (label attached to instrument).
• Repair and maintenance operations must not represent any hazard to the quality of the products.
Good Manufacturing Practice for Medical Devices with a Biological element:
• Standard Operating Procedures for manufacturing operations need to be available and up to date.
• Raw materials need to have their source, origin, method of manufacture and quality controls defined and in place.
• Media and culture shall be added to fermenter and other vessels under carefully controlled conditions to avoid contamination
• Media should be sterilized in situ. In line sterilizing filters for routine addition of gases, media, acids, alkalis, deforming agents, etc. to ferment should be used where possible.
• Validation of sterilization must be effective as per all validations.
• Inactivation process: measures should be taken to avoid risk of cross-contamination between treated and untreated products.
• Equipment used for chromatography, should be dedicated to purification of one product, should be sterilized or sanitized between batches, need to define the life span of columns and the sterilization method.
• In-process controls play an especially important role in ensuring the consistent quality of any biological elements associated with medical device products because certain deficiencies may not be revealed by testing the finished product.
• Tests that are crucial for quality control but that cannot be carried out on the finished product shall be performed at an appropriate stage of production.
• Samples of intermediate and final products shall be retained in sufficient amount and under appropriate storage conditions to allow the repetition or confirmation of a batch control.
• Certain operations require the continuous monitoring of data during a production process e.g. monitoring and recording of physical parameters during fermentation.
- Validation. Classification. Regulation. Requirements. Current best practices.
- FDA cGMP’s. EU MDR’s / MDD’s.
- FDA Medical Device Regulation.
- FDA Medical Device Classification.
- EU Medical Device Regulation and Classification (per MDD’s).
- European Medical Device Regulations (MDR’s).
- Current Good Manufacturing Practices. QSR’s. General requirements of the QSR’s.
- Quality System requirements to maintain compliant Validations.
- Medical Device Process Validation. IQ. OQ. PQ’s.
- Medical Device Software Validation.
- Medical Device Design Validation.
- Electronic Signature, Electronic Records.
- Life Cycle Approach to Validation.
- Risk Identification. Documentation. DHR’s. DMR’s.
- Etc. Etc. …
- Information | Understanding | Best Practice >>>
FDA – Medical Devices; Current Good Manufacturing Practice (CGMP) Final Rule; Quality System Regulation
On 23 April 2020 the EU Council and the Parliament adopted Regulation 2020/561 amending Regulation (EU) 2017/745 on medical devices regarding application dates of certain of its provisions. This Regulation postpones the date of application for most Medical Devices Regulation provisions by one year – until 26 May 2021.
Regulation (EU) 2017/745 of the European Parliament and of the Council of 5 April 2017 on medical devices, amending Directive 2001/83/EC, Regulation (EC) No 178/2002 and Regulation (EC) No 1223/2009 and repealing Council Directives 90/385/EEC and 93/42/EEC
Regulation (EU) 2017/746 of the European Parliament and of the Council of 5 April 2017 on in vitro diagnostic medical devices and repealing Directive 98/79/EC and Commission Decision 2010/227/EU
Regulation 2020/561 of the European Parliament and of the Council of 23 April 2020 amending Regulation (EU) 2017/745 on medical devices as regards the dates of application of certain of its provisions