Validations

GOOD VALIDATION PRACTICE (cGVP)
1

Dears,
Please specify the difference between prospective and concurrent validations in API
Regards
svr
Quality assurance

2

Prospective validation should be conducted prior to the commercial distribution of an API produced by a new or substantially modified process. This validation approach should involve obtaining and evaluating documented processing and analytical control information for multiple batches manufactured, sampled, and tested according to a preestablished validation plan.

When prospectively validating a process, data from laboratory- and/or pilot-scale batches should identify critical quality attributes and specifications, critical steps, control ranges, and in-process tests. Scale-up batches could be used to generate data to confirm or refine earlier work, and production-scale batches should provide data showing consistency of the process.

The number of process runs should depend on the complexity of the process or the magnitude of the process change being considered. Although three consecutive, successful production lots should be used as a guide, there could be situations where additional process runs are warranted to prove consistency of the process (e.g., complex API processes or API processes with prolonged completion times). If a validation lot fails for reasons unrelated to process performance (e.g., power failure or equipment breakdown), that lot should be removed from the validation study and an additional validation run conducted.

[COLOR=“darkred”]FDA considers concurrent validation to be a subset of prospective validation. The Agency recognizes that in a limited number of cases it may be impossible to complete validation of an API process in a timely manner when data from replicate production runs are unavailable because:

  1. Only a limited number of API batches intended for clinical or orphan drug products have been produced;

  2. API batches are produced infrequently (e.g., limited market demand, complex multi-step API processes with long completion times); or

  3. APIs batches are produced by a modified process (e.g., a validated process goes outside the proven acceptable range of a critical operating parameter and the batch is subjected to intensive analytical tests).

In such cases, firms should do all of the following:

  1. Document the reasons for not completing process validation before shipment of the API;

  2. Perform all of the elements of prospective validation, as discussed in Section XIII.C., exclusive of replicate production run testing, before releasing any batch for distribution;

  3. Conduct intensive in-process monitoring and testing, along with intensive testing of each API batch, to show that each production run resulted in an API meeting its predetermined quality characteristics and specifications (such data should also be assessed under the validation protocol to determine consistency of the process);.

  4. Provide for the Quality Control unit to evaluate batch production records, in-process controls, and analytical data from each process run to determine whether each batch should be released.

The level of intensive in-process and final API testing should be greater than levels for validated routine production runs, and should only be reduced to routine levels after the process has been determined to be validated. In addition, data from production runs that are evaluated as part of the validation studies should encompass the operating ranges that are approved for use during routine process control.

The Agency cautions that this validation approach should be applied with discretion so as not to:

  1. Unduly delay completion of, or avoid performing, meaningful validation; or

  2. Distribute API batches manufactured before completion of validation for a prolonged period of time.

This approach should not be viewed as a viable alternative where the number and frequency of API production runs permit timely completion of validation prior to API distribution. If analysis of data shows that the process used to manufacture the distributed batches was not, in fact, validated, no additional batches should be distributed until corrections have been implemented and the process has been determined to be validated.[/color] --ABOVE ARE FROM FDA

Concurrent validation is a particular form of prospective validation, in which the batch or batches produced are released, based on more extensive testing, before the entire validation study is complete.–ICH Q7A Guidance