Validation Introductory Concepts Evan Pasenello 2/19/04
What is Validation? “documented program providing a high degree of assurance that specific processes, or equipment, will consistently produce product meeting predetermined specifications and quality attributes” Proposed as 21 CFR 210.3b  FDA Guideline on Process Validation, 1987
Documented Program • Paper Work is in order • Why steps were taken • What actions were done • Compilation of results • Summary of findings
Assurance • Proven through testing • Equipment works as specified • Facility Specifications • Vendor Specifications • Repeatability • Consistency
Why Validation? • To protect the customer • Satisfy regulatory requirements “Compliance” • Safety of facility personnel • Qualify equipment
FDA • The Food and Drug Administration • FDA Website • The FDA regulates • Cosmetics • Food • Medical Devices • Drug Products • Non compliance = 483’s
THE FEDERAL FOOD, DRUG, AND COSMETIC (FDC) ACT1938 is passed by Congress, containing new provisions: • Extending control to cosmetics and therapeutic devices. • Requiring new drugs to be shown safe before marketing-starting a new system of drug regulation. • Eliminating the Sherley Amendment requirement to prove intent to defraud in drug misbranding cases. • Providing that safe tolerances be set for unavoidable poisonous substances. • Authorizing standards of identity, quality, and fill-of-container for foods. • Authorizing factory inspections. • Adding the remedy of court injunctions to the previous penalties of seizures and prosecutions. • http://www.fda.gov/opacom/backgrounders/miles.html
Code of Federal Regulations • 21 CFR - Food and Drugs • Companies abide by these guidelines • Provide guidance and rules for operations • cGMP • 21CFR part 11
The Six Validations • Analytical Method Validation • Computer Systems Validation • Utilities Validation (off line equipment) • Cleaning Validation • Process Validation (on line equipment) • Training Validation
HVAC Equipment How Does Validation Work? All aspects of a facility must be properly validated LAB Facility
When to validate? • Prospectively • New facilities • New, uninstalled equipment • Retrospectively • Established facilities • Relocated equipment Every system must be validated before any product is generated for human use.
The General Process • Design Qualification (DQ) • Installation Qualification (IQ) • Operation Qualification (OQ) • Performance Qualification (PQ) • Protocols • Standard Operating Procedures (SOPs)
Design Qualification • Does the design provide the necessary functions? • Are all the design features specified incorporated in the delivered equipment? • User Specifications
Installation Qualification • Is it there? • Have all the design features been installed as specified? • Does the installation match the drawing?
Operation Qualification • Does it work? • Does the equipment operate as needed to produce quality product? • Can you reliably control and measure all critical parameters?
Performance Qualification • Does the product work according to the business functions? • Does the product work in conjunction with other systems? • Test against procedures and acceptance criteria.
SOPs • SOPs are very important in industry • Provide documentation • Repeatability • Training • Accountability
Changes!! • Changes are allowed but must be documented • Change Control (Procedures) • Addendums (Protocols)
Equipment Facility Environment Manufacturing Steps Calibration Controls Process Controls Computer Systems Sanitizations Training Batch Records Change Controls Preventative Maintenance Validation Program
Validation Example Refrigerator
Installation Qualification • Compare with drawings and user manuals • check for correct circuitry, voltage, parts • check physical installation against manufacturer’s recommendations
Operational Qualification • Chamber Studies • Temperature range is correct • Temperature controls work • RTD Probe is calibrated and accurate
Performance Qualification • Chamber Studies • Loaded chamber for testing use