Process validation protocols

Process Validation (PV) verifies the performance of the overall product manufacturing process. PV is performed on the entire product manufacturing process, which includes all support, processes, preparation of media, components, buffers, formulation, filtration, filling, and packaging. 

All equipment, processes, and quality assurance test procedures must be validated (or verified if using a compendial method) prior to the start of Process Validation. 

Process Validation is performed in accordance with a preapproved written protocol. The specific PV attributes and process parameters to be verified during the performance of the protocol will be developed from the finished product specifications, research and development data, the manufacturing process capability, cGMP requirements, and other specific documentation. These, along with the acceptance criteria, will be approved as part of the protocol approval process. 

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Let us examine what a protocol should accomplish. During an inspection of a given product or process, FDA will more times than not conduct a review of the process validation protocol. As mentioned earlier, the process entails everything used to manufacture the transdermal—procedures, personnel, methods, documents, and so on. Given the fact that the protocol will likely fall under FDA scrutiny at some point and that other documents used to complete the validation may as well, it should be easy to understand that the process validation protocol should be used to reference as many of these other supporting documents as possible. 

Qualification Verification. Again, the process validation protocol should reference all items that support the validation the procedures, personnel, methods, and equipment. This section therefore lists and summarizes the various installation, operational, and performance/process qualifications completed for the equipment used in the process validation. These qualifications should list each by equipment name and number and qualification and type. A typical verification section is illustrated below. 

A development report should be written prior to the process validation protocol by the research and development group and will serve as the basis for items to be included in the validation protocol. Parameters such as process limits, formulation compatibility with process equipment, time limitations of production, and any problems encountered and their resolution, should be addressed. Aerosol... 

The process validation protocol of a new aerosol product should be written by a qualified manufacturing or validation specialist familiar with aerosols. Others experienced in oral dosage forms such as suspensions or solutions would also be helpful. These technical specialists may be within the research, validation, or technical support departments, since this work will be done prior to approval of a new product. Approval of the protocol should be given by quality assurance, quality control, production management, and research. 

The scope section describes what the process validation protocol covers, the number of batches, and what it does not cover. In this part, usually packaging validation or mouthpiece testing is included or excluded. Any worst-case tests may be briefly described. Stability commitments and stability protocols should be mentioned. 

Raw materials, solvents, catalysts, gases, processing aids, processing water, steam, packaging materials and bioburden Process validation protocol Sampling and testing strategy... 

Eventually the point will be reached at which the development of a product is complete the formulation is finalized, the equipment has been selected, the analytical methods are validated, the development transfer report has been issued, and the Preapproval Inspection (PAI) is anticipated. Now is the time to consider validation of both the manufacturing and cleaning processes. Although some process validation may have also been completed or a process validation protocol may have been prepared and approved, it is likely that very little has been finished that would enable us to state that the cleaning process is fully validated. 

It clearly expects to see a process validation protocol included in the submission. Validation data should be generated for all products. It is accepted, however, that the amount of data presented in the application dossier will to a certain extent depend on the nature and complexity of the drug substance, drug product, and manufacturing process. 

List of all applicable reports supporting manufacturing process development (e.g., process validation protocols and reports, cleaning validation, protocols and reports, and batch production records). 

We can recognize three distinct but interdependent, effective standards 1) USP-NF standards, 2) current good manufacturing practices, and 3) in-house quality assurance or process validation protocols. The three programs are different but have the same objective drug product quality. The official standards are developed to be meaningful in this multiple context. In recent years, a similar array has occurred in most developed nations, and this is rightfully seen as a measure of success. 

Stability report establishing expiry dating and Process validation protocol for formal three-batch validation of production-size batches. 

During preapproval inspection, the FDA accepts a process-validation protocol based on the company s commitment to complete successfully three production-size validation batches prior to product launch. In some situations a prevalidation (process demonstration qualification) production-size batch is completed before the entire formal three-batch program is carried out. 

A process validation protocol should be complied for each manufacturer if the manufacturing procedure is not identical (including the equipment) and should specify tests, test parameters, product specifications and production equipment. At least the first two production batches of each manufacturer must be validated and follow-up stability data submitted as they become available. Each step of the manufacturing process must be controlled to maximise the probability that the finished product consistently meets all quality and design specifications. The procedure for coating the tablets, the ingredients, equipment and controls should be included. 

The principles of planning, organizing and performing process validation are similar to those for qualification. It should be done in accordance with process validation protocols, data should be collected and reviewed against predetermined acceptance criteria, and reflected in process validation reports. 

IQ Installation Qualification protocol OQ Operational Qualification protocol PQ Performance Qualification protocol PV Process Validation protocol PM Preventive Maintenance procedure... 

Enhanced turn-over package Installation qualification protocols Operational qualification protocols Change control initiation Cycle development Performance qualification protocol Process validation protocols Validation final reports Validation package Certificate for use in manufacturing Required protocols and procedures for dry production Required protocols and procedures for liquid and semisolid products... 

When qualification is complete, process validation (PV) can begin. In some cases, PV may be conducted concurrently with IQ, for example, where an item of equipment is dedicated to one process producing one product Process validation is organised and administered in the same way as qualification, by the writing and issuing of process validation protocols and the accumulation and review of data against agreed acceptance criteria... 

The process validation protocol is a preapproved written plan stating how the validation will be conducted and identifying acceptance criteria as well as sampling and assay requirements [33] and other testing details [3]. It is a prospective experimental plan that when executed produces documented evidence that the system has been validated [25]. The protocol defines the system to be validated, identifies operating variables and probable control parameters, and indicates the number of... 

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