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21 CFR Part 11
Instrument Qualification, Operational Qualification, Performance Qualification Validation Documentation

     Current Good Manufacturing Practice (cGMP) requires that all aspects of producing and testing of biologic products be controlled so that the product can be reproducible manufactured according to desired specifications. Controlled manufacturing requires validation of equipment and processes. The Current Good Manufacturing Practices Regulations for Finished Pharmaceuticals described in 21 CFR Parts 210 and 211 describes what is required for validation. Specifically, Section 211.110 states that control procedures shall be established to monitor the output and validate the performance of those manufacturing processes that may be responsible for causing variability in the characteristics of in-process material and the drug product.

     The FDA defines validation as the establishment of documented evidence that provides a high degree of assurance that a  specific process will consistently produce a product meeting its pre-determined specifications and quality characteristics. Process validation is essential to quality assurance because quality can not be tested in a final product without complete destruction of the product in most cases. Therefore, all critical processes used to produce a final product must be adequately designed, implemented, and controlled. comprehensive validation mitigates alternative in-process testing and final product testing.

     Process validation involves the following:

  1. Identify all the processes that impact the safety and effectiveness of a final biological product to include environmental controls, manufacturing equipment, process control, critical utilities, and component specifications.Preparing validation protocols that identify key elements of a process and having them approved prior to the start of a study
  2. Executing sufficient numbers of replicate runs that will create test conditions to measure upper and lower processing limits, as well as appropriate challenge conditions.

     Equipment validation:

     All automatic, mechanical, and electronic equipment used in production, quality control testing, packaging, and storage of cGMP product must be validated. 21 CFR section 211.68 states the following:

     Automatic, ,mechanical, or electronic equipment or other types of equipment, including computers, or related systems that will perform a function satisfactorily, may be used in the manufacture, processing, packing, and holding of a drug product. If such equipment is used, it shall routinely be calibrated, inspected, or checked according to a written program designed to assure proper performance.

     An equipment validation protocol consists of the following: Design Specification, Installation Qualification (IQ) Operational Qualification (OQ), and Performance Qualification (PQ). Ideally, prospective validations shall be performed on all new pieces of equipment used in the production of a cGMP product. Retrospective validations shall be performed for equipment placed into use without comprehensive validations, and shall also include a modified Design Specification, IQ, OQ, PQ. The need for re-validation shall be assessed as necessary for all critical pieces of equipment. The re-validation protocol may not be as extensive as the prospective and retrospective validations. Re-validation requirements shall also be determined after equipment is moved or altered by a part replacement or any other type of service.

     The Quality System Regulation, 21 CFR Part 820(i), specifies the following for validation of automated processes:

     When computers or automated data processing systems are used as part of production or the quality system, the manufacturer shall validate computer software for its intended use according to an established protocol. All software changes shall be validated before approval and issuance. These validation activities and results shall be documented.

     MTX Lab Systems, Inc. performs custom, client and instrument specific validations for microplate instrumentation  in accordance to cGMP, CBER, and CDER guidelines. The validation protocols include the following:

  • Instrument conformance to requirements verification
  • Functional checkout of computer system interface
  • Performance testing (includes power failure assessment)
  • System suitability testing-Repeatability (Measure variability)Intermediate
  • Precision/Robustness
  • Performance Verification Testing (PQ)Verification of SOPs and pertinent programs
  • Summary Report
  • Client Comments Section
  • Approval Page