near miss guidelines

Concurrent Validation

Description: Concurrent Validation is one the approach of Process Validation where batches are released for marketing prior to approval of batches of complete validation package based on data of individual batch.

Concurrent Validation

  • In concurrent validation, batches are released for marketing prior to approval of batches of complete validation package based on data of individual batch.
  • It is acceptable when there is :
  • Low demand of product.
  • Low shelf life of product Or
  • Life threatening shortage of product
  • It can be also conducted when
  • Data from replicate runs are unavailable because only limited no. of batches produced.
  • API batches produced infrequently Or
  • API Produced by a validated process that has been modified
  • Itis used to establish documented evidence that a facility and process will perform, as they are intended, based on information generated during actual use of the process.
  • In exceptional circumstances (for example, in a case of immediate and urgent public health need) validation may need to be conducted in parallel with routine production. The VMP (Validation Master Plan) needs to define how product is managed throughout the process.
  • Typically, the product batches are quarantined until they can be demonstrated (QC analysis) to meet specifications.

Decision For Concurrent Validation

  • The decision to perform concurrent validation should not be made in a vacuum.
  • All stakeholders including management, Quality Assurance and the government regulatory agencies should all agree that concurrent validation is an acceptable approach for the system under consideration.
  • As always the principal requirement is patient, safety is not compromised.
  • The rationale to conduct concurrent validation should be documented along with the agreement to do so by all the stakeholders. This can be part of the Validation Plan or documented as a deviation.

Concurrent Validation Process

  • The concurrent validation process is identical to that of prospective validation. The process starts with the development of a Validation Plan, followed by the DQ, Risk Assessment (RA), IQ, OQ and PQ phases after which process, computer, analytical and cleaning validations are performed, ending with a final report.
  • Again, routine preventative maintenance, requalification and periodic review are performed.

Concurrent Release of PPQ (Process Performance Qualification) Batches

  • FDA expects that concurrent release will be used rarely.
  • In most cases, the PPQ study needs to be completed successfully and a high degree of assurance in the process achieved before commercial distribution of a product.
  •  In special situations, the PPQ protocol can be designed to release a PPQ batch for distribution before complete execution of the protocol steps and activities,
  • i.e., concurrent release.
  • Concurrent release might be appropriate for processes used infrequently for various reasons, such as to manufacture drugs for which there is limited demand (e.g., orphan drugs, minor use and minor species veterinary drugs) or which have short half lives (e.g., radiopharmaceuticals, including positron emission tomography drugs).
  • Concurrent release might also be appropriate for drugs that are medically necessary and are being manufactured in coordination with the Agency to alleviate a short supply.
  • Conclusions about a commercial manufacturing process can only be made after the PPQ protocol is fully executed and the data are fully evaluated.
  • If Stage 2 qualification is not successful (i.e., does not demonstrate that the process as designed is capable of reproducible performance at commercial scale), then additional design studies and qualification may be necessary.  
  • The new product and process understanding obtained from the unsuccessful qualification study(ies) can have negative implications if any lot was already distributed.
  • Full execution of Stages 1 and 2 of process validation is intended to preclude or minimize that outcome.
  • Circumstances and rationale for concurrent release should be fully described in the PPQ protocol.
  • Even when process performance assessment based on the PPQ protocol is still outstanding, any lot released concurrently must comply with all cGMPs, regulatory approval requirements, and PPQ protocol lot release criteria.
  • Lot release under a PPQ protocol is based upon meeting confidence levels appropriate for each quality attribute of the drug.
  • When warranted and used, concurrent release should be accompanied by a system for careful oversight of the distributed batch to facilitate rapid customer feedback.
  • For example, customer complaints and defect reports should be rapidly assessed to determine root cause and whether the process should be improved or changed.
  • Concurrently released lots must also be assessed in light of any negative PPQ study finding or conclusions and appropriate corrective action must be taken.
  • We recommend that each batch in a concurrent release program shall be evaluated for inclusion in the stability program.
  • It is important that stability test data be promptly evaluated to ensure rapid detection and correction of any problems.

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