Support process validation

Now that all of the activities that support process validation are in place or have been performed, will the work and effort be appreciated by auditing bodies What measures can be taken to assure that they are There is one other aspect of transdermal validation that will increase the potential for the effort to be appreciated. This element is the protocol. What exactly is a protocol Who should approve this document ... 

Validation of Support Processes Test Functions and Acceptance Criteria... 

This procedure provides the information required to support the sterility assurance of the drug product (product name), USP, manufactured by ABC Pharmaceutical Industries. It references the FDA Guidance titled Guidance for Industry for the Submission of Documentation for Sterilization Process Validation in Applications for Human and Veterinary Dmg Products prepared by the Sterility Technical Committee of the Chemistry Manufacturing Controls Coordinating Committee of the Center for Dmg Evaluation and Research (CDER) and the Center for Veterinary Medicine (CVM) in November of 1994. 

Regulatory policies and procedures tailored to recognize the level of scientific knowledge supporting product applications, process validation, and process capability. 

This section describes sampling and testing the powder mix of demonstration and process validation batches used to support implementing the stratified sampling method described in this guidance. 

A VMP should be divided into chapters covering different subjects. First, an introduction should state the manufacture s validation policy, general description of the scope of those validation activities covered by the VMP, and their objectives, derivation, location, and schedule. Then, it must declare all validation activities and their organizational structure in terms of personnel responsibility for the VMP, validation protocols, validation work, report and document preparation projects, approval of the same validation protocols, reports in all stages of validation processes, and the training needs in support of validation. Other requirements of the VMP are cross references to other documents and to specific characteristics of the processes that are critical for yielding a quality product. Next, all validation activities comprised in the VMP should be summarized and compiled in a matrix format. Such a matrix should provide an overview and contain all items covered by the VMP that... 

As with other products, the amount of data needed to support the manufacturing process will vary from product to product. Development (data) should have identified critical phases of the operation, including the predetermined specifications that should be monitored during process validation. 

Process validation Inspection of the establishment to determine compliance with cGMP requirements and adherence to application requirements is a Field responsibility. CDER may request data to support validation of sterile processing operations for example, environmental monitoring, equipment validation, sterile fill validation, and associated sterile operations. 

In prospective process validation, an experimental plan called the validation protocol is executed (following completion of the qualification trials) before the process is put into commercial use. Most validation efforts require some degree of prospective experimentation to generate validation support data. This particular type of process validation is normally carried out in connection with the introduction of new drug products and their manufacturing processes. The formalized process validation program should never be undertaken unless and until the following operations and procedures have been completed satisfactorily ... 

The developmental documentation to support the validation of the process may contain the following ... 

Schenerman, M. A., Hope, J. N., Kletke, C. et al. Comparability testing of a humanized monoclonal antibody (Synagis0) to support cell line stability, process validation, and scale-up for manufacturing. Biologicals 27 203-215 (1999). 

Figure 9 Order and responsibilities for process activities supporting transdermal process validation.

Table 11 Sampling of Runs Required to Support Transdermal Process Validation... 

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. 

For example, most companies would rather reference their supporting documents than have FDA ask whether or not a particular document exists. Further, this practice will assure that the company has actually taken sufficient time and prepared the document referenced. There are those companies that prefer to voluntarily attach the documents rather than just reference them. This may not be in the best interest of CGMP manufacturers for two clear reasons. First, attaching every development report, every batch record, every analytical method, every support protocol/report and so forth will make a process validation document—a hefty document to begin with—too big to read. Second, volunteering any information is considered very dangerous, as it is very rare for a company to have no dirty laundry. Why hang it out for FDA or any audience to see ... 

Therefore, the recommendation is that the process validation document be used as a guide document, referencing support documents as appropriate, as illustrated in Figure 16. 

Figure 16 Schematic detailing how process validation document references other support documents. 

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. 

Provided that all transdermal process validations have been successfully completed, the focus shifts to the preapproval inspection (PAI). A target date for the PAI is typically known months in advance of the actual FDA visit. It is a good idea to finalize as many of the supporting protocols as possible during this time. If a company is fortunate enough to actually execute protocols and complete the summaries before the PAI, it is recommended that representative copies of the... 

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 regulatory authorities require the pharmaceutical manufacturer to maintain guidelines and procedures for all activities that could impact the quality, safety, identity, and purity of a pharmaceutical product. This includes procedures for implementing and supporting the validation life cycle and for process operation. 

Design, development, and system build is normally a period of intense activity, in which a supplier will be involved in life-cycle activities and will need to provide a set of auditable design and development documentation to support the validation program. For this, the entire design and development process should be carried out to written and approved procedures, and all design, development, testing, and verification activities should be documented and approved in order to provide a level of computer system documentation that can be used to support the pharmaceutical manufacturer s life-cycle qualification activities. 

On issue of a satisfactory and approved PQ summary report, it is demonstrated that the computer system supports the computerized operation, and conditional on satisfactory process validation is available for use in the GMP operating environment. 

Process validation verifies that the process will consistently produce the desired product each time it is run. It must be remembered that PV for the development process may not contain as much supporting data as is collected for the process when the product s NDA is being reviewed. The development group must still view the validation effort in a way that adds value to its work, however. The steps are as follows ... 

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