QM: 7.5.2 Validation of processes for production and service provision

Introduction

This clause is highly relevant and important in Pharmaceutical and Bio-pharmaceutical manufacturing. Not only in sterile formulations & medical devices where final product shall meet higher quality standards but also in other dosage forms where variations within the lot are inevitable due to certain intrinsic factors. Each and every unit cannot be tested and final testing is based upon sampling design adopted. Whatever the sampling plan is it does not represent the entire lot. Therefore in such case ISO standard emphasizes on the validation of the process to attain a confidence on final product produced using these validated processes in addition to sample testing.

Guidance documents are published by different regulatory agencies which underline the regulatory expectations for process validation in pharmaceutical and biopharmaceutical industry. One such document, Guidelines on General Principles of Process Validation, was published by FDA in 1987. Since then there have been lot of technical advances in the field and the document was revised and published in 2011. The current guidance document emphasizes on scientific approach to process validation and aligns process validation activities with a product lifecycle concept and with existing FDA guidance, including the FDA/International Conference on Harmonization (ICH) guidences for industry, Q8(R2) Pharmaceutical Development, Q9 Quality Risk Management, and Q10 Pharmaceutical Quality System.

The processes which require validations are (but not limited to): sterilization, disinfection, aseptic processing, sterile packaging, inactivation studies, studies for impurity removal (especially virus removal in biopharmaceuticals), lyophelization, mixing and homogenization, water and steam generation and distribution, washing and cleaning etc.

Records of such processes include validation protocol and reports, equipment maintenance records, calibration records, personal qualification, training records, testing records etc.

ISO 9001:2008 standards emphasizes that, ‘The organization shall validate any processes for production and service provision where the resulting output cannot be verified by subsequent monitoring or measurement and, as a consequence, deficiencies become apparent only after the product is in use or the service has been delivered. Validation shall demonstrate the ability of these processes to achieve planned results.’

7.5.2

Validation of Processes for Production & Service Provision

7.5.2 Validation of processes for production and service provision

The processes where the resulting output cannot be verified by subsequent monitoring or measurement and as a consequence deficiencies become apparent only after the product is in use of the service has been delivered are identified and defined in the DMF/Regulatory Dossier.

It is the responsibility of the process owner and Quality Assurance department for identifying, defining criteria, validating and documenting such processes. They are also responsible for review, qualification and approval of the processes, approval of equipment, qualification of personnel and the use of methods and procedures. Where applicable other departments may assist in establishing validation specifications and testing of samples.

Control of significant operations and parameters of processes are validated by applicable methods, such as qualified equipment, work instruction, process procedure and documented change management process.

The process owner and Quality Assurance are responsible for selecting and implementing appropriate process validation. Arrangements are made as applicable for these processes:

         Defined criteria for review and approval of these processes is in place,

Equipments used for such processes are qualified and approved; personnel involved in such processes are trained and qualified,

Specific methods and procedures used in such processes are documented and made available at the site of activity,

Appropriate records as per the QMS requirements are generated during performance of these processes; these records are reviewed before release of the product and archived as per the QMS requirement,

Revalidation of the processes is performed at defined intervals to identify and rectify any deviation from state of control. The revalidation is also performed when there is any change in the process (pertaining to man, material, method and machine) which affects the state of control.