Hi All,

After viewing the lecture for this week, I have thought about the IQ, OQ, and PQ for the Syringe Filling Process – filling syringes with an injectible bone void filler.

IQ - meets specs including the amount of bone void filler added to each syringe; the amount of bone void filler fills the syringe; maximum and minimum filling points, use-by dates, and pressures at which syringe is filled; has specific SOP for filling the syringe; scheduled measurements of filling taken to ensure calibration

OQ - ensuring that each syringe is filled within the min/max range with bone void filler; finds the min/max pressures that syringe is filled up with and set as control limits

PQ - running the syringe filling process multiple times, with multiple vendors and show that variability is the same throughout

-Andrew Nashed

Hi Andrew,

I like the examples you provided for IQ, OQ, PQ for prefilled syringes, but I think that the IQ for a Syringe filling line may be a little different. For example the Installation qualification may include the following:
- Manual and Technical documentation availability
- filler electrical requirements meets the available plug specifications
- Calibration and Preventative Mentainance schedule available.
- Alarms, interlocks, safety and ergonomics requirements are met and operational
- Operator interface/ Emergency stopping mechanism present and operational

Fady Khalla

I agree with Fady. The IQ for all four would be along the lines of requirements and environment upon which the equipment will be installed. Such as the electrical outputs (120v 60hz or 3phase 240v 60hz), level bench where the machine will sit as to allow proper filling, negative pressurize room environment to prevent active medicine to contaminate outside cooridor, temperature range of the room.

For the antibiotic releasing hip stem manufacturing line which creates an artificial hip with an antibiotic coating on the surface, I believe the IQ involved in this manufacturing line would be written procedures on how to use the equipment to manufacture the artificial hip. As well as contain calibration/maintenance schedules to make sure the equipment is up to code and that there are no issues of malfunction. The OQ would be finding the control limit on the application of the antibiotic coating on the surface of the artificial hip. Lastly, the PQ would be producing a great number of hips with the same amount of antibiotic coating to show no variability.

Hi Viraj,

I agree with your approach but I believe you can to the following points:

IQ - In addition to the manuals, you should call out maintenance and calibration schedules as well as procedural protocols for the entire process.

OQ- I believe the OQ should determine your maximum operational window for two things, the application of the antibiotic and the actual manufacturing hipstem as well.

PQ - No variability is inherently impossible. We can run a PQ with and acceptable risk assessed variability.

Otherwise this is a very good summary. Well done!

Syringe Filling Process
IQ- Filling machine has working parts, SOP’s, WI’s, calibration schedule, maintenance schedule, meets OSHA standards, has qualified personnel trained on it
OQ- Syringes are filled with bone void filler to the same level and amount within a range each time (either checked by weight, or if density varies, by volume); Filling range/time must be established for optimal parameters; syringes are free of debris outside of product and do not leak product
PQ- Syringes are identical in filling volume, product, and are within spec for weight, visibility, packaging, and other specs; all raw materials from various venders have been tested on machine and at a production scale successfully

Vascular Graft Weaving Line
IQ- Weaving machine has working parts, SOP’s, WI’s, calibration schedule, maintenance schedule, meets OSHA standards, has qualified personnel trained on it
OQ- Weaving time and machine parameters are established for optimal performance; Weaves at these parameters should be durable enough to meet specification and standards
PQ- Weaves are identical in size, density and appearance and are within spec for weight, visibility, packaging, and other specs; all raw materials from various venders have been tested on machine and at a production scale successfully

Antibiotic releasing hip stem manufacturing line
IQ- Hip molding machine has working parts, SOP’s, WI’s, calibration schedule, maintenance schedule, meets OSHA standards, has qualified personnel trained on it; Antibiotic coating machine has working parts, SOP’s, WI’s, calibration schedule, maintenance schedule, meets OSHA standards, has qualified personnel trained on it
OQ- Hip molding machine has optimal parameters established as well as a range for the temperature, pressure, molding time, molding size, filling amount, curing time, and cooling time.
Antibiotic coating machine has optimal parameters established with a range for temperature, coating amount, coating time, density and temperature of antibiotic, and is reproducible.
PQ- Hips are identical in size, durability, structure, and even coating. The hips are checked for appearance, weight, sterility, defects, deviations, and packaging against the spec. Raw materials are tested from primary, secondary, and any tertiary vendors to ensure that production scale runs successfully.
Wound Healing Growth Factor and delivery device manufacturing line
IQ- Growth factor mixing and filling machine and bottle filling machine has working parts, SOP’s, WI’s, calibration schedule, maintenance schedule, meets OSHA standards, has qualified personnel trained on it.
OQ- Growth factor mixing machine has optimal parameters and ranges established including: amounts of each raw material, mixing time, temperature, speed, and cooling time.
Growth factor filling machine has optimal parameters and ranges established including: environmental sterility, filling amount, settling time since creation/mixing, and filling time.
Bottle machine has optimal parameters and ranges established including: air blowing station (to clean out bottle before filling), capping speed, pressure, and torsion.
PQ- Filled bottles are identical in size, volume, color, appearance and weight. The bottles are checked for appearance, weight, sterility, defects, deviations, and packaging against the spec. Raw materials are tested from primary, secondary, and any tertiary vendors to ensure that production scale runs successfully.

Hi Andrew, I have to agree with Fady Khalla on your IQ but never the less I think most of people have gave a lot of input on the syringe filling process for IQ, OQ, and PQ. so im just going to say that the IQ test plan for the syringe would contains detailed information on how the test are going to be performed on this respective device. Than the IQ report would be done after completion of the IQ which the results would be summarized, evaluated and compiled in an IQ report. All deviations, as well as measures taken to eliminate these, are documented. After the deviations have been eliminated, these must be tested again, documented and evaluated in a new IQ report.

Hey guys we have talk about IQ, OP and PQ about Syringe Filling Process – filling syringes with an injectable bone void filler and Vascular Graft Weaving Line – weaving the polyethylene fabric tubes that make up a vascular graft. Now I have a question about the CGMP (current good manufacturing practice) in manufacturing this two devices. We know that CGMP is a Regulations enforced by the US Food and Drug Administration (FDA) that provide for systems to assure proper design, monitoring, and control of manufacturing processes and facilities. What are you input about the CGMP for this two devices that you have come across on your job? I haven’t had no experience and hopefully someone has. All your input would be appreciated

For the Vascular Graft Weaving Line – weaving the polyethylene fabric tubes that make up a vascular graft... I believe that the IQ, OQ and PQ will be as following:

IQ- The machine weaving the polyethylene fabric has been installed under proper electrical configuration according to its installation SOP. The environmental area and conditions in which the machine has been installed is suitable for optimal performance. Safety features are under OSHA compliance. Equipment testing is being performed like calibration and ensuring that motors turn in the right direction.

OQ- The process control limits of the machine has been established to be capable of producing the optimal polyethylene weaving. Proper operational training has been conducted. Software V&V has been performed for intended use.

PQ- The machine has demonstrated a repeatable and long term stable process for producing an acceptable weaving by simulating the actual manufacturing conditions with all necessary raw material.

HI gh56,

I think that under the FDA the QSR embraces the same "umbrella'' approach to the CGMP regulation that was the underpinning of the original CGMP regulation. Because the regulation must apply to so many different types of devices, the regulation does not prescribe in detail how a manufacturer must produce a specific device. Rather, the regulation provides the framework that all manufacturers must follow by requiring that manufacturers develop and follow procedures and fill in the details that are appropriate to a given device according to the current state-of-the-art manufacturing for that specific device.
Manufacturers should use good judgment when developing their quality system and apply those sections of the QS regulation that are applicable to their specific products and operations, 21 CFR 820.5 of the QS regulation. Operating within this flexibility, it is the responsibility of each manufacturer to establish requirements for each type or family of devices that will result in devices that are safe and effective, and to establish methods and procedures to design, produce, distribute, etc. devices that meet the quality system requirements. The responsibility for meeting these requirements and for having objective evidence of meeting these requirements may not be delegated even though the actual work may be delegated.

I would agree with many that have commented in regards to the syringe filling process, vascular weaving line, antibiotic releasing hip stem manufacturing line, and wound healing growth factor and delivery device manufacturing line.

Syringe Filling Process:

IQ: Since the medical device is mechanically operated. the IQ would test the device if the outputs of the device meets the specs. An SOP or Work Instructions would need to be filled out to test the device for limitations, tolerances and calibrations. Another aspect is if the device needs to be maintenanced and how often does it need to be.
OP: Would test if the process of this device's action is reproducible, and can perform to spec and providing controlled limitations and how it performs in these limitations. In this case, the syringe is filled with a bone filler substance to a certain level at each time with a specific amount needed depending on the application. The rate of which the filling takes place will be tested if it meets the specs along with the consistency of the output ensuring there isn't any complications or incosistencies such as not being uniform.
PQ: Would show that the process can be done again and again the same way, ensuring that the variability is within the intended spec, we would call this consistency. A batch of syringes would be extracted and tested each with the same parameters such as volume, content color, extrusion rate, filling rate etc are the same for each. The performance of these would be tested to ensure that statistically it meets the acceptable range.

Vascular Graft Weaving Line:
IQ: The weaving process using polyethylene fabric tubes would be tested with an SOP or Work Instructions would need to be filled out to test the device for limitations, tolerances and calibrations. Another aspect is if the device needs to be maintenanced and how often does it need to be.
OQ: The rate of weaving time and device parameters will be tested to ensure which are the optimal parameters that the device must be set too, in addition the quality of the output of the product will be tested for durability, tensile strength and flexibility.
PQ: The processes of the output will be tested such as the size and consistency of quality of the output product will be tested to ensure that with each batch it fits within production acceptable range.

Antibiotic Releasing Hip stem Manufacturing Line:
IQ: The process of creating a hip-stem outline of the patient would require an SOP or Work Instructions would need to be filled out to test the device for limitations, tolerances and calibrations. Another aspect is if the device needs to be maintenanced and how often does it need to be.
OQ: The device would be tested for optimal parameters such as temperature, release rate of antibiotic, biocompatibility, and application rate will be tested to ensure it meets to specs.
PQ: The process of which the liquid growth factor that sits on the bottle will be tested to ensure that no complications are found or large variability. This would also include the production of these batches to ensure that they are not within acceptable ranges of acceptance.

Since the previous devices’ IQ, OQ, and PQs have been explained in great detail, what would the IQ, OQ and PQ look like for other devices? For example a femoral implant?

IQ- Femoral molding equipment meets the specs, working parts, can be installed, operated and maintained, has a maintenance schedule. Includes limitations and tolerances that are known to operator. SOPs or Work Instructions, calibration schedule, meets OSHA standards and training for personnel.
OQ-Femoral molding machine has optimal parameters including temperature, pressure, molding size, curing time, and cooling time. The process is reproducible, upper and lower limits of the process are found and control limits for the process are set.
PQ-Femoral implants are reproducible and are identical in size, structure, durability. The implants are checked for variations including; defects, weight, appearance, packaging against the spec. Raw materials are tested from primary, secondary, and tertiary vendors to ensure that production scale runs successfully.