| Title: Metal Detection | |||||
| Guidance Number: 95 | |||||
| Prepared by: | Date: | Supersedes: | |||
| Checked by: | Date: | Date Issued: | |||
| Approved by: | Date: | Review Date: | |||
Introduction
This document provides guidance in the installation, use and maintenance of metal detectors in Pharmaceutical and Animal Health solid oral dosage form drug products and medical devices that by design do not contain metal components.
1. Definitions– the following terms apply specifically to metal detection as used in this guidance. Rotonoid – double acting electrical solenoid valve that is electrically controlled in two directions (e.g., open and closed) with no spring return.
2. Site quality team’s decision on whether routine metal detection operations are required for products at their Site should be based on, and not limited to, the following factors:
- Product history of metal contamination incidents (e.g., equipment failures, equipment metal-to-metal contact causing contamination, raw materials with metal contaminants);
- Assessment of manufacturing and/or packaging processes involved in terms of possible metal contamination
- Effectiveness of the metal prevention systems and processes used at the site; and
- Commitments to Regulatory Authorities.
3. Action Levels for the total number of units (e.g., tablets, capsules, bottles) isolated by the metal detector should be developed by the quality team based on and not limited to:
- Historical data on the number of units contaminated with metal according to product and/or manufacturing or packaging process step;
- Investigation reports [e.g., Deviation Reports] including any documented product recovery from contaminated units; an
Applicable quantitative results indicating that preventive measures have reduced metal contamination in manufacturing and/or packaging process steps. Such preventive measures include and are not limited to:
- Installation of rare earth magnets at raw material charging stations;
- Raw material process improvements by the vendor that reduced contamination; and
- Manufacturing or packaging equipment set-up improvements that reduced contamination resulting from equipment wear.
4. Examples of locations of Metal Detectors for routine use include:
- In the manufacturing process, installation of the metal detector immediately after the tablet press or encapsulation machine;
- If a deduster is used in the tabletting or encapsulation process, installation of the metal detector immediately after the deduster; and
- In the packaging process, installation of a metal detector immediately after the bottle filling process. Rationale for placement of the metal detectors should be documented.
5. The Metal Detector should be positioned such that the detector does not interfere with the process and the detector is not in contact with adjacent manufacturing or packaging equipment. Any chutes or conveyors passing through detectors should be aligned to not interfere with reject gate operation.
6. Purchase of a New Metal Detector should include and is not limited to:
- Must be robust;
- Have noise filters and seals;
- Have reject gate rotonoids;
- Are cleanable;
- Have required sensitivity levels;
- Have internal seals to reduce radio frequency interference;
- Have static grounding measures;
- Have necessary alarms, either audible or light post or both; and
- Means to verify and acknowledge the fact that rejects went into reject bin.
7. Metal Detectors Sensitivity Settings should be set during equipment installation and setup such that:
- Good product (i.e., product that may contain metal but less than the detection level) is not rejected; and
- The cylinder carriers that are used to challenge the metal detector are detected and rejected.
If either of these tests fails, the metal detector should be re-adjusted and the adjustment documented.
8. All Metal Detectors used in Manufacturing Operations (including, but not limited to, encapsulation and tabletting) should be qualified and subsequently set-up and operated such that the detectors will, 100 percent of the time, detect and isolate spherical 0.5mm ferrous, spherical 0.5mm non-ferrous, and spherical 0.8mm stainless steel metal embedded in discs or cylinder carriers that are used to challenge the system.
9. All Metal Detectors used in Packaging Operations should be qualified and subsequently set-up and operated such that the detectors will, 100 percent of the time, detect and isolate spherical 1.0mm ferrous, spherical 1.0mm non-ferrous, and spherical 1.5mm stainless steel metal embedded in discs or cylinder carriers that are used to challenge the system.
10. Critical Process Parameters and Critical Process Parameter Ranges should be identified and documented as part of the metal detector qualification, and should include, and are not limited to:
- Reject gate reaction time, if reject gates are present;
- Length of time reject gate stays open;
- Throughput process speed; and
- Sensitivity settings.
- Metal detector is installed according to specifications;
- Utilities (e.g., electrical, air supply) are identified and the direction of flow indicated when necessary; and
- Routine preventive maintenance measures are established.
12. Metal Detector OQ should include, and is not limited to:
- Alarm tests;
- Test for radio frequency interference;
- Challenge metal detectors used in manufacturing operations with discs/cylinders containing spherical 0.5mm ferrous, 0.5mm non-ferrous, and 0.8mm stainless steel metal;
- Challenge metal detectors used in packaging operations with discs/cylinders containing spherical 1.0mm ferrous, 1.0mm non-ferrous, and 1.5mm stainless steel metal;
- The above challenge tests should be performed with the manufacturing or packaging process performing at its maximum validated throughput rate;
- Sensitivity settings for each product or group of products with the same product signal noise are established;
- Reject gate reaction and delay time for each product or group of products with the same product signal noise is established; and
- Length of time that reject gate stays open is established.
13. The Metal Detector Sensitivity Settings should be verified and documented by a qualified operator during the set-up operation.
14. Metal Detection Equipment Set-Up and Operating Parameters for each product or process combination should include, and are not limited to:
- Clean and dust-free environment during set-up;
- Correct sensitivity settings for each product or product group;
- The reject gate reaction and delay time, when a reject gate is used;
- Length of time reject gate stays open;
- Throughput speed; and
- Correct chute and chute alignment for aperture size.
15. In-Line Metal Detector Challenges should be conducted with the process equipment running. Each challenge should consist of three passes of the challenge disc/cylinder through the aperture. Such in-process challenge tests should be performed and documented, at a minimum, as follows:
- Lot/batch start-up;
- After re-starting equipment (e.g., after breaks, shift changes, or downtime exceeding two hours); and
- At the end of a batch/lot.
16. For Metal Detectors Equipped with Audible and/or Visual Alarms, operators in the vicinity of the equipment should be signaled when metal has been detected and diverted or isolated.
An in-process control (IPC) limit for the number of units diverted or isolated by the metal detector during processing should be established for each process or product. Any excursions from the in-process control limit should be evaluated during processing. Note: This in-process control limit during processing is separate and distinct from the end of processing action limit.
17. Product Units (e.g., Tablets, Capsules, Packaged Units) that are isolated by the metal detector reject mechanism should not be returned to the acceptable units of the lot unless an investigation reveals an assignable cause associated with the metal detector. Such product units should be placed in Quarantine-HOLD status pending the completion of the investigation. Product units that are found acceptable on re-inspection may be returned to the acceptable units of the lot being processed, with the approval of the site quality team.
Re-inspection should be performed following a written and approved protocol or Site Standard Operating Procedure (SOP). Product units that are isolated by the metal detector during re-inspection should be rejected and not returned to the acceptable units.
Such rejected product units should be collected in a dedicated container that is properly labeled as to its contents (e.g., “Metal Detector-Rejects”).
18. An Investigation should be conducted and documented if the quantity of units isolated by the metal detector exceeds the action level. The lot should not proceed to another processing step until the site quality team reviews the investigation report and determines the status of the lot.
19. Accountability of Units with Metal Contaminants should be summarized in the investigation report when a process deviation causes metal contamination of a lot. Rejected units may be dissolved in a solvent and evaluated to determine metal type and source, if feasible, as part of the investigation.
20. Accidental Introduction of Metal during a process step should result in the process immediately being stopped and an investigation conducted. The operation should not continue until the Site Quality Authority has reviewed the investigation and approves continuing the process.