Process Validation for medical devices

1. Process Validation for medical devices The word validation is so important that its misinterpretation can lead us to non-compliance. Its official regulatory word. Let us understand in layman’s language. We have process to produce piece of material with length of 50cm and specification says 50 plus and minus 1 cm. This means any piece above 51 cm and any piece below 49 cm will not be accepted. So, what is issue here measure all pieces and select the only one in range. Looks very easy but if you are producing 5000 pieces per hour and you are running machine for 12 hours continuously. Can you check all 60000 pieces? Process excellence came into practice and stated whether your process is capable to produce product with desired specification? Say for one time you will measure all 60000 pieces and you find them all between 49.5 to 50.5 CM. This is great so now you occasionally check at regular interval, and you still found within above range, one can prove that process is capable and stands validated. The Medical device field is not that simple, and specification of product is also complex. Sometime measurements itself is destructive. In such scenario, validation may seem difficult but that is also a good answer to this problem. What regulatory compliance needs as process validation? Definition: (US FDA Quality System) Process validation means establishing by objective evidence that process consistently produces product or result meeting its predetermined specification.

2. All highlighted words have deep meaning and must be interpreted in the same way regulatory desires. Guidance documents for doing such activities are available. (IMDRF Published in 2004) ISO 13485:2016 states that “The organisation shall validate any production processes and service provision where resultant output cannot be verified by subsequent monitoring or measurement. Similarly, US FDA also states similar requirement but in little detail. Copied from document as such (a) “Where the results of a process cannot be fully verified by subsequent inspection and test, the process shall be validated with a high degree of assurance and approved according to established procedures. The validation activities and results, including the date and signature of the individual(s) approving the validation and where appropriate the major equipment validated, shall be documented.” (b) Each manufacturer shall establish and maintain procedures for monitoring and control of process parameters for validated processes to ensure that the specified requirements continue to be met. Once again, the yellow highlighted words have deep meaning stressing the specific way to carryout activities. Let us look at some specific processes. 1, Sterilisation and sterile packing and sealing 2, Aseptic filling 3, Clean Room ambient conditions 4, Lyophilisation 5, Heat treating, soldering, welding, painting, and plating. 6, Plastic injection moulding. In this technical language these processes are called special processes.In most of cases testing is destructive. Risk is very high to patient and process needs lots of control. Like sterilisation in which one assures that all living organisms are killed in the process, and nothing should survive or else it can grow on storage. This is assured by treating the known heat resistant organism (Bacillus stereothermophillus) in specified known concentration (Usually one million organisms in one ampoule with D value around 2, means resistant to heat. The process is qualified if nothing survives from this organism. So, we prove indirectly that if these organism gets killed all organism gets killed. The scenario considered for this experiment is called worst case scenario. Guidance is available for all above mentioned processes. In many processes, the measurement is quite possible like measuring dimension, visual inspection of circuit boards or testing of wiring and its hardness, one must define variation possible in such processes. Once known, one must have adequate plan to control them. Now let us understand basic steps of process validation and documentation needed for such process. Process validation is like small project and smallest failure is treated as failure and not only process needs to be repeated but one need to document reason for failure and justification to avoid the same. So, consider following steps.

3. 1.Form team like project team with process expert and other required experts or trained personnelare part of the team. There are core team people who will do actual work but there are also supporting members like purchasing who will ensure that material procured are from approved vendors and would not do any variation in that aspect for any financial gain. 2.Create Plan usually called VMP (Validation Master Plan) where entire process is described s to what is going to be done, who is going to do this, when it will be done, how it will be done and the criteria for declaring them to be successful. Measurement methods. 3.VMP may have couple of processes and involving couple of equipment. As starting point the equipment suitability is established by qualifying it called DQ (design qualification). DQ also protocol is made before hand and some team members reviews it and approves it along with final approval from QA. This applies to all documents. 4.The equipment or many such equipment are installed in specific manner and its run is verified so no failure occurs which is called IQ (installation qualification). Run means blank run without product. 5.Next step is to run OQ (operational qualification) of each process separately and verifying by measurements of the output. Document and get them reviewed and approved. Each protocol is mini plan itself. Result document is called report. Each document is reviewed and approved. 6.All the processes are then combined to start the main process qualification called PQ (Performance qualification) The output is measured to verify whether our criteria defined earlier is met or not. 7.Make final report which will include all above documents, what process controls were used and the same will be continued in regular production and document the whatever limited measurement we may do and results of those will decide continuation of process performance in above predefined range. 8.We must do the repetitionof the process in limited manner called Re-Validation at specified interval usually not later than a year or less depending upon the risk and limitation of the process. This is to prove that continuity of the process is established. See above mentioned process definition. Similarly other supporting staff from engineering, R&D, QC, regulatory are involved with priority of their role during this project execution so success happens, and time is not lost. 9.Revalidation may be required to perform earlier if some change occurs in Raw material source or specification, equipment change or major maintenance in equipment or final product specification is tightened little more. These are just few examples of changes. They will undergo as per change control procedure, risk assessment, review and then team will decide what actions and what part of revalidation is necessary. Entire process will be repeated in whole or in part depending upon decision by team based on evaluation of change. Though guidance documents are available, Process experts are there, this documentation is always part of audit scrutiny by regulatory. Many observations in above processes were found and non- compliances were issued. In view of suchimplication, it is highly recommended that initial first-time support of consultant like IZiel is taken.