In-process tests

Manufacturing Processes Flow charts for production steps, controls for contamination, removal of impurities, purification steps, in-process tests, and batch records... 

In-Process Testing Packaging and Labeling of Finished BPC Expiration Dating or Reevaluation Dating Laboratory Controls Stability Testing... 

The following in-process tests were performed during the media fill process ... 

Technical Report No. 25 Blend Uniformity Analysis Validation and In-Process Testing. J Pharm Sci Technol 1997 Supplement, 51(S3). 

Additionally, what is a company s commitment to technology and engineering support before and after start-up Who provides the training costs Who pays what Are the in-process testing equipment and necessary analytical equipment operational, qualified, and ready when needed Who will perform the validation requirements (equipment and process) These are some of the key questions and concerns that go beyond the hardware issues and technology that must be addressed prior to the project start-up. 

As an example of the additional requirements posed by bilayered tablets during scale-up, a summary of the typical in-process tests is shown in Table 10. 

The term in-process testing is synonymous with process control. From an engineering perspective tests at the end of a process do not provide any direct means to keep a process under control. It is well recognized that such tests simply accept or reject lots and depending on the operating characteristic curve of a test accepted lots are no better than the rejected ones (14). 

Furthermore, significant industry and FDA resources are spent debating issues related to acceptable variability, need for additional in-process testing and how specification acceptance limits should be established. Often these debates are focused on acceptance limits or the statistical aspects. In these debates a proportionate focus on the underlying manufacturing science is often missing. For example ... 

There should be a clear distinction between in-process controls and validation. In-process tests are performed during the manufacture of each batch using specifications and methods devised during the development phase. The aim is to monitor the process continuously and not exactly validate it. When a new manufacturing formula or method is adopted, steps should be taken to demonstrate its suitability for routine processing prior to the validation. The defined process using the materials and equipment specified should be shown to yield a product consistently of the required quahty. 

Blend uniformity analysis validation and in-process testing. Technical Report No. 25. J. Pharmaceu. Sci. Technol. 51(suppl) 53, 1997. 

As part of the design of the facility, we may determine the appropriateness of using dedicated areas, multifunctional areas, as well as coimnon areas. For large clinical and production batches, all unit operations are usually maintained in dedicated areas. This helps minimize the possibilities of cross-contamination as well as allow for many different products to be manufactured simultaneously. For the small-scale experimental batches, multifunctional areas may be used. For example, sizing and blending may be done in one room. Common areas may also be incorporated into the facility. Typical uses for these areas include work-in-process areas and in-process testing areas. 

In-process testing is especially critical, if the material being produced is to be used for human consumption. The types of in-process testing requirements will vary with the process. However, following is a brief description of the types of the in-process testing requirements of a solid-dose manufacturing process. 

During the design of the facility, provisions must be made for the areas for in-process testing to be carried out. Much of the testing may be done in common areas, i.e., tablet and capsule testing. However, some must be done in specialized areas, i.e., uniformity testing. 

Unit Operation In-Process Monitoring PAT Application In-Process Testing PAT Application... 

Not all of the in-process tests enumerated above are required to demonstrate that the process is in a state of control. Selections of test parameters should be made on the basis of the critical processing variables to be evaluated. 

In-process testing and acceptance criteria Finished product testing and acceptance criteria Test method references Formulation... 

Once this has been done, one can proceed to actual product testing utilizing these parameters and their specifications to validate that the process will produce acceptable product. The testing can be conducted on samples during the manufacture (in-process tests) or on the finished product (finished product tests). Each product may have its own idiosyncrasies requiring special tests, but generally the in-process and finished product tests that would be required for all solid dosage forms in process validation are as follows. 

Category 1 Medical devices that are controlled by in-process tests, with critical specifications designed for both individual products and a group, but not implemented in human and animals. 

The medical devices in category 4 of Table 1 are controlled in-process testing with critical specifications designed for individual products or a group of products and are implanted. The compatibility of product materials with tissue and cells, the stability of product in the implanted site, and the sterility of product should be key factors to assure the product safety. Intraocular lenses and pacemakers are included in this category. 

By phase II, stability assays should be validated and a good faith effort made to validate all in-process tests. Release assays should also be validated. Removal of product and process-related impurities should be demonstrated. Stability of cells during growth should be validated. 

A few other issues related to process validation are under discussion. One is resin lifetime. Some firms are proposing concurrent validation rather than generating prospective laboratory scale for the entire lifetime. The concurrent approach would probably require more in-process testing, but the data generated may be more reliable since they are obtained at manufacturing scale. Clearly, eliminating the small-scale studies at this time for steps in which viral clearance is claimed will be quite difficult if not impossible. 

Process flowcharts. A flow diagram should indicate the process steps and addition of raw materials. If possible, major equipment and special environmental conditions may be included in the flowchart. In-process tests may also be included. A second flowchart for activities, raw material suppliers, shipments, and testing would also assist in the overall picture of the aerosol manufacturing scheme, especially for multiple site or third-party activities. An example of a process flowchart for a fictitious suspension product (2160.4-kg batch size for 100,000 units) is shown in Figure 6. 

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