1. Pharmaceutical Quality System:
1.1 Principle. The manufacturer must assume responsibility for the quality of the pharmaceutical products to ensure that they are fit for their intended use, comply with the requirements of the marketing authorization and do not place patients at risk due to inadequate safety, quality or efficacy. The attainment of this quality objective is the responsibility of senior management and requires the participation and commitment of staff in many different departments and at all levels within the company, the company’s suppliers and the distributors. To achieve this quality objective reliably there must be a comprehensively designed and correctly implemented Pharmaceutical Quality System (PQS) incorporating GMP and QRM.
1.2 Senior management has the ultimate responsibility to ensure an effective PQS is in place, is adequately resourced, and that roles, responsibilities, and authorities are defined, communicated and implemented throughout the organization. Senior management’s leadership and active participation in the PQS is essential. This leadership should ensure the support and commitment of staff at all levels and sites within the organization to the PQS.
1.3 Quality management is a wide-ranging concept covering all matters that individually or collectively influence the quality of a product. It is the totality of the arrangements made with the object of ensuring that pharmaceutical products are of the quality required for their intended use. Quality management, therefore, incorporates GMP and other factors, including those outside the scope of this guide, such as product design and development.
1.4 GMP applies to the life-cycle stages from the manufacture of investigational medicinal products, technology transfer, and commercial manufacturing, through to product discontinuation. The PQS can extend to the pharmaceutical development life-cycle stage and should facilitate innovation and continual improvement and strengthen the link between pharmaceutical development and manufacturing activities. All parts of the PQS should be adequately resourced and maintained, including being provided with sufficient competent personnel, suitable premises, equipment and facilities.
1.5 The PQS appropriate to the manufacture of pharmaceutical products should ensure that:
a) Product realization is achieved by designing, qualifying, planning, implementing, maintaining and continuously improving a system that allows the consistent delivery of products with appropriate quality attributes;
b) Product and process knowledge is managed throughout all life cycle stages;
c) Pharmaceutical products are designed and developed in a way that takes account of the requirements of GMP and other associated codes such as those of good laboratory practice (GLP) and good clinical practice (GCP);
d) Production and control operations are clearly specified in a written form and GMP requirements are adopted;
e) Managerial responsibilities are clearly specified in job descriptions;
f) Arrangements are made for the manufacture, supply and use of the correct starting and packaging materials, the selection and monitoring of suppliers and for verifying that each delivery is the correct material from the approved supply chain;
g) All necessary controls on starting materials, intermediate products, and bulk products and other in-process controls, calibrations and validations are carried out;
h) The finished product is correctly processed and checked, according to the defined procedures;
i) Pharmaceutical products are not sold or supplied before the authorized persons (see also sections 9.11 and 9.12) have certified that each production batch has been produced and controlled in accordance with the requirements of the marketing authorization and any other regulations relevant to the production, control and release of pharmaceutical products;
j) Processes are in place to assure the management of outsourced activities;
k) Satisfactory arrangements exist to ensure, as far as possible, that the pharmaceutical products are stored, distributed and subsequently handled so that quality is maintained throughout their shelf-life;
l) There is a procedure for self-inspection and/or quality audit that regularly appraises the effectiveness and applicability of the PQS;
m) Product and processes are monitored and the results taken into account in batch release, in the investigation of deviations and, with a view to taking preventive action to avoid potential deviations occurring in the future;
n) Arrangements are in place for the prospective evaluation and approval of planned changes and their approval prior to implementation taking into account regulatory notification and approval where required. After implementation of any change, an evaluation is undertaken to confirm that the quality objectives were achieved and that there was no unintended adverse impact on product quality;
o) Regular reviews of the quality of pharmaceutical products are conducted with the objective of verifying the consistency of the process and identifying where there is a need for improvement;
p) A state of control is established and maintained by developing and using effective monitoring and control systems for process performance and product quality;
q) Continual improvement is facilitated through the implementation of quality improvements appropriate to the current level of process and product knowledge;
r) There is a system for QRM;
s) Deviations, suspected product defects and other problems are reported, investigated and recorded. An appropriate level of root cause analysis is applied during such investigations. The most likely root cause(s) should be identified and appropriate corrective actions and/or preventive actions (CAPAs) should be identified and taken. The effectiveness of CAPAs should be monitored.
1.6 There should be periodic management reviews, with the involvement of senior management, of the operation of the PQS to identify opportunities for continual improvement of products, processes and the system itself. Unless otherwise justified, such reviews should be conducted at least annually.
1.7 The PQS should be defined and documented. A quality manual or equivalent documentation should be established and should contain a description of the quality management system including management responsibilities.
WHO Good Manufacturing Practices For Pharmaceutical Products: Main Principles
(Annex 2, WHO Technical Report Series 986, 2014)
