Concurrent validation

Concurrent validation Validation undertaken while routine manufacture of product is also taking place... 

Kazdin, A. E., Rodgers, A., Colbus, D. (1986). The Hopelessness Scale for Children Psychometric characteristics and concurrent validity. Journal of Consulting and Clinical Psychology, 54, 241—255. 

Preproduction and concurrent validation three working days a week (e.g., Monday, Wednesday, Friday)... 

Preproduction and concurrent validation each tap point, once a week Ongoing validation each tap point, once a month... 

Concurrent validation at the start and in the middle of each working day Ongoing validation at the start of each working day... 

Concurrent validation is conducted under a protocol during the course of normal production. The first three production-scale batches must be monitored as comprehensively as possible. The evaluation of the results is used in establishing the acceptance criteria and specifications of subsequent in-process control and final product testing. Some form of concurrent validation, using statistical process control techniques (quality control charting), may be used throughout the product manufacturing life cycle. 

The categories listed above require qualification and validation documentation. It is advisable that process automation and companion computer-integrated manufacturing operations not be initiated until sufficient prospective and concurrent validation studies have been completed. 

Concurrent validation for resin lifetime Combined clearance studies... 

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. 

Concurrent validation, in which documented evidence is generated during the actual operation of the process, is sometimes adopted in clinical supply situations in which only limited material is available for the trials. 

The next concern raised by the question is the determination of whether prospective or concurrent validation is appropriate. This decision should be based on the nature of the PV activity. For a new facility, there is only one possible decision namely, prospective validation. When certain process changes are made, however, it may be appropriate to choose the concurrent validation approach. 

It should be evident that concurrent validation is especially useful as a QA tool. This approach to validation is useful to QA because it enables QA to set its own objectives as criteria for PV. For example, QA seeks to have every process validated. Most pharmaceutical products contain one or two active ingredients. Process validation is very straightforward for them however, a whole new situation exists for a multivitamin/multimineral product. Innovative techniques are thus needed to achieve adequate validation. 

Another case for concurrent validation is that effort that requires statistical (and possibly trend) analysis. It is appropriate to digress and explain what is meant by trend analysis. This activity really consists of product auditing, which is described in more detail elsewhere [32], Product auditing is a QA (management) technique in which each batch s analytical data provide a running score-board of product performance. The quality standards would be measured periodically (monthly, quarterly, or semiannually), which would depend entirely on the number of batches made per time interval. At least six batches would be made in the same manner per chosen time interval. The data would be measured, and then it would be determined (through charting the data) if the data fell between predetermined specification limits. Each new period s data would be... 

When the concept of concurrent validation is embraced by an organization, it is important for everyone to support QA s use of it as a QA tool. The quality standards of each discipline are normally stressed because of the normal commercial pressures, but it is essential that overall QA not be relaxed. The validation format in general and concurrent validation in particular will allow the flexibility needed for the situation, yet, it also provides the vehicle for a disciplined approach to ensure that no unacceptable product will be released. 

In the early 1980s some regulators treated consideration of retrospective or concurrent validation as almost sacrilegious, asserting that everything must be done prospectively. The issue became controversial. Fortunately, speakers on both sides of the controversy listened to each other, and by the twenty-first century, agreement on the subject had been achieved. 

All new computer systems must be prospectively validated before going into production. For existing computer systems, concurrent validation may be considered where limited documentation on the appropriate technology exists, and where an acceptable level of confidence can be established by reviewing and documenting the operating history. 

Concurrent Validation In some cases, a drug product or medical device may be manufactured individually or on a one-time basis. The concept of prospective or retrospective validation as it relates to those situations may have limited applicability. The data obtained during the manufacturing and assembly process may be used in conjunction with product testing, to demonstrate that the instant ran yielded a finished product meeting all of its specifications and quality characteristics (FDA). 

For most products, a properly structured PQ protocol will require rigorous acceptance criteria, whether employed concurrently or prospectively. A protocol with vague requirements will provide very little information about a process or system. The application of targeted sampling approach methods in conjunction with 3 x or higher sample sizes will result in the strongest support to process reliability. Concurrent validation can be used... 

Properly structured concurrent validation is nothing more than prospective validation in slow motion. The use of rigorous criteria and a worst-case sampling approach can assure the suitability of the process and acceptability of the product. The fact that it should be performed three times is more a product of regulatory safeguards and FDA guidance than a scientific necessity. 

No run-at-risk strategies would be allowed, such as concurrently validating the PK assay while collecting the samples to be assayed. 

Once the lyophilizer is unloaded, the removing of stoppered vials is compatible with good manufacturing practice and can therefore be implemented in the frame of a concurrent validation. 

The validation of lyophilization cycles is a complicated issue because the process parameters and the characteristics of the product are closely interrelated. The process affects the final product, but the characteristics of the product undergoing lyophilization impact the dependent operating parameters, the freeze-drying pattern, and dictate the basic requirements for a successful process. This interdependence limits the opportunities of using placebo formulations and most of the validation runs must be performed with active product. The high cost and limited availability of some materials, as well as the need to validate the process under conditions that are representative of routine production, justify that part of the validation is performed in a concurrent fashion. The concurrent validation should then be completed by a retrospective review of the data accumulated for commercial batches, so as to track the reproducibility, the reliability, and the trends of the process over a longer period of time. 

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