This article is the first in a series that talks about the Annex 15 of the EU Guidelines for Good Manufacturing Practice for Medicinal Products for Human and Veterinary Use.
Annex 15 describes the principles of qualification and validation which are applicable to the facilities, equipment, utilities and processes used for the manufacture of medicinal products.
This Annex describes the principles of qualification and validation which are applicable to the facilities, equipment, utilities and processes used for the manufacture of medicinal products and may also be used as supplementary optional guidance for active substances without introduction of additional requirements to EudraLex, Volume 4, Part II. It is a GMP requirement that manufacturers control the critical aspects of their particular operations through qualification and validation over the life cycle of the product and process. Any planned changes to the facilities, equipment, utilities and processes, which may affect the quality of the product, should be formally documented and the impact on the validated status or control strategy assessed. Computerised systems used for the manufacture of medicinal products should also be validated according to the requirements of Annex 11. The relevant concepts and guidance presented in ICH Q8, Q9, Q10 and Q11 should also be taken into account.
A quality risk management approach should be applied throughout the lifecycle of a medicinal product. As part of a quality risk management system, decisions on the scope and extent of qualification and validation should be based on a justified and documented risk assessment of the facilities, equipment, utilities and processes. Retrospective validation is no longer considered an acceptable approach. Data supporting qualification and/or validation studies which were obtained from sources outside of the manufacturers own programmes may be used provided that this approach has been justified and that there is adequate assurance that controls were in place throughout the acquisition of such data.
1.1. All qualification and validation activities should be planned and take the life cycle of facilities, equipment, utilities, process and product into consideration.
1.2. Qualification and validation activities should only be performed by suitably trained personnel who follow approved procedures.
1.3. Qualification/validation personnel should report as defined in the pharmaceutical quality system although this may not necessarily be to a quality management or a quality assurance function. However, there should be appropriate quality oversight over the whole validation life cycle.
1.4. The key elements of the site qualification and validation programme should be clearly defined and documented in a validation master plan (VMP) or equivalent document.
1.5. The VMP or equivalent document should define the qualification/validation system and include or reference information on at least the following:
i. Qualification and Validation policy;
ii. The organisational structure including roles and responsibilities for qualification and validation activities;
iii. Summary of the facilities, equipment, systems, processes on site and the qualification and validation status;
iv. Change control and deviation management for qualification and validation;
v. Guidance on developing acceptance criteria;
vi. References to existing documents;
vii. The qualification and validation strategy, including requalification, where applicable.
1.6. For large and complex projects, planning takes on added importance and separate validation plans may enhance clarity
1.7. A quality risk management approach should be used for qualification and validation activities. In light of increased knowledge and understanding from any changes during the project phase or during commercial production, the risk assessments should be repeated, as required. The way in which risk assessments are used to support qualification and validation activities should be clearly documented.
1.8. Appropriate checks should be incorporated into qualification and validation work to ensure the integrity of all data obtained.
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