Validation Protocol

Validation Protocol

Validation Protocol

Advanced has implemented a quality management system that is registered to and meets the requirements of the FDA for Medical Devices as found in 21 CFR part 820 (cGMP) and the international standard ISO 13485:2003. These requirements include manufacturing process validation. Essentially, validation involves providing objective evidence that specific requirements can be consistently met. These validation and qualification (IQ/OQ/PQ) activities can apply to the molding process, the final device assembly process, as well as to the equipment being utilized for these processes. In some cases, a process failure mode and effects analysis (PFMEA) is performed. Validation protocols (plans) are developed with the customer since each customer application and associated risk is unique. 

Each industry tends to have its own nomenclature for manufacturing process qualification. In the Medical Device community, the most common phrasing is installation qualification/operational qualification/performance qualification (IQ/OQ/PQ). Although the automotive industry follows the production part approval process (PPAP), some medical companies refer to qualification process as PPAP. Many of the elements overlap and specific requirements vary by customer. IQ/OQ/PQ tends to be more thorough.

During the Installation Qualification (IQ), the objective is to make sure the tool is functional and a series of inspections, checklists, and studies are performed. This includes using the tools of Scientific Injection Molding (SIM), which culminates in the generation of a cosmetic process window. Parts from the center of this cosmetic window can be used for the initial evaluation of the measurement system via gage repeatability & reproducibility (Gage R&R) studies and the parts themselves can be evaluated dimensionally to get initial feedback on the steel sizing via a First Article Inspection Report (FAIR).

Once the IQ has been successfully completed, the next step is typically to perform a design of experiments (DOE). The purpose of the experiments is to understand the relationship between selected process factors (e.g. melt or mold temperature, hold pressure, etc.) and how the output of the process responds to changes in those factors. Through the DOE process, a response surface can be created to model the behavior of the process via regression analysis. We then use this response surface to find the worst case portion of a proposed process window to validate.

These worst case portions of the process are used in the Operational Qualification (OQ). The purpose of the OQ is to verify the process is statistically capable of producing parts that meet customer requirements even at the edge of the process. If the manufacturing process includes purchased components or sub-assembly operations, the OQ validation protocol may include using the extremes of these as well (e.g. the output of the stamping process OQ feeds into the molding process OQ). The results of these studies would be reviewed relative to Cpk and/or Ppk requirements (typically 95% lower confidence limit of 1.33). At this stage, documentation would be developed including a manufacturing work instruction, quality work instruction, in-process inspection plan, and master process sheet.

Once the OQ report is approved, the Performance Qualification (PQ) may commence. The purpose of the PQ is to verify that the process, under anticipated production conditions such as nominal process settings, is statistically capable of producing parts that meet customer requirements. The PQ includes expected sources of potential process variation, such as multiple setups, production over multiple shifts, using multiple sets of personnel and, when possible or deemed important, multiple lots of raw materials or inserts. Samples from the PQ are evaluated per the control plan and protocol, capability studies are performed, and a report is submitted for production approval.  Since the PQ is run under production conditions, the parts produced are usually considered to be saleable product if the validation is successful.

For assembly programs, a master validation plan is developed with the customer. Qualification activities can involve purchased components, assembly methods, testing methods, labeling, and sterile barrier packaging. Critical to assembly programs are the training of the assembly operators and the per lot documentation requirements including the device history record (DHR). 

Increasingly, equipment IQ and OQ activities are performed on molding and assembly equipment. Equipment IQ is intended to make sure the equipment is installed according to manufacturer recommendations. Equipment OQ is intended to make sure the equipment operates within predetermined limits. When tools are transferred, or when significant changes are made to a tool, purchased component, process, or equipment, re-qualification activities are performed.