What is Calibration, Verification, and Validation in pharmaceuticals?

Calibration, Verification, and Validation

These Calibration, Verification, and Validation three words are widely used in the pharmaceutical industry. Some may get confused with interchangeable meanings or lack of understanding. Here we try to describe these three words.

A. Calibration:

In Analytical Department, Formulation Department or Quality Assurance Department Calibration has the same meaning. Calibration is the process of assurance of Instrument\Equipments are performing the same assurance that it was performing from the date of instrument installation.

Normally Calibration is the Same as performance Qualification (PQ) of Instrument\Equipments.

Reason for the same is that be an assurance of working ability of Instrument\Equipments are same till date.

Industries have a different frequency for the same instrument as per their requirement. For Example, calibration of HPLC, calibration frequency is Six Monthly to Yearly basis. Quality Control (QC) where HPLC work is more, they preferred to minimize the risk by lowering the frequency by 3 Months.

B. Verification

About Verification it is basically used in Quality Control and ADL (Analytical Development Lab.). As verification comes in two types.

1. Compendial Method Verification (i.e., USP, EP, IP, JP Monograph)

2. Developed Method Verification at contract manufacturing organization CMO or Manufacturing Plant (Part of Technology Transfer)

What is Analytical Method Verification?

According to the definition in USP general chapter <1226>, “Verification of Compendial Procedures,” method verification is an assessment concentrating on how the analytical test procedure is appropriate for its intended use under actual experimental conditions, such as specific drug substance/product, environment, personnel, equipment, and reagent.

When a compendial method or a previously validated method is used with new or different products, equipment, or laboratories for the first time to obtain appropriate results, analytical method verification is usually required.

For example, a client has requested a contract analysis of Product XYZ from a contract manufacturing organization (CMO) laboratory. An official test Method A from the client will be accomplished on Product XYZ. Now, what does this mean?

In this case:

Method A was validated in the client’s laboratory and used for analysis on Product XYZ.
As Method A was used in the original laboratory for analysis on Product XYZ, method verification is required before Product XYZ is analyzed with Method A in the contract manufacturing organization laboratory.
Finally, before applying Method A on Product A for the first time, the laboratory must complete method verification.

C. Validation

Validation is the process of establishing written evidence that a specific process will consistently create a product that meets its pre-determined specifications and quality qualities. This is referred to as validation.

Validation is a more complex word in different departments.

For Example:

In Production

A. Process Validation: Required to validate the whole process of production before its implementation with regulatory permission.

B. Sterilization Process Validation

C. Cleaning Validation

In Quality Control/ADL

A. Analytical Method Validation

B. Cleaning Validation

In Quality Assurance or GLP Department

A. Computer System Validation (CSV)

What is the Difference Between Analytical Method Verification and Analytical Method Validation?

Analytical Method Validation (AMV) assesses an established technique’s performance by examining several analytical properties and determining whether the method is appropriate for its intended use.

Analytical Method Verification: Rather than repeating the validation process, method verification employs the appropriate analytical performance characteristics as defined in the method validation to produce accurate data for specific types of sample, environment, or equipment.

A CMO might receive an order from a licensee or a patent owner who has produced a new medicinal product, for example. The client will next permit the CMO to create a scale-up batch production process as well as analytical test methods to meet regulatory compliance standards.

A method validation is necessary if the client has not established a proper analytical method for the regulatory requirement. The laboratory will need to establish an in-house method based on regulatory requirements like United States Pharmacopeia (USP) and perform method validation to ensure the analytical method can meet the intended application.

Method Validation is required if the customer/Client has not produced a proper analytical method for the regulatory need. The laboratory will need to develop an in-house method based on regulatory requirements such as the United States Pharmacopeia (USP) and execute method validation to guarantee that the analytical method can meet the application’s requirements.

Registered Compendial or Monograph available, the user may use this method and there is no need for validation but as an assurance agency required Method Verification of the method on this product. This may assure the proper analysis of products on-site and Laboratory.

To summarise, method validation is typically performed to an “in-house method” developed by a laboratory, whereas method verification is typically applied to a “compendia method or previously validated method” when it is used for the first time in a specific laboratory.