(2003; 148 pages)
9.6 Key personnel include the head of production, the head of quality control and the authorized person. Normally, key posts should be occupied by full-time personnel. The heads of production and quality control should be independent of each other. In large organizations, it may be necessary to delegate some of the functions; however, the responsibility cannot be delegated.
9.7 Key personnel responsible for supervising the manufacture and quality control of pharmaceutical products should possess the qualifications of a scientific education and practical experience required by national legislation. Their education should include the study of an appropriate combination of:
(a) chemistry (analytical or organic) or biochemistry;
(b) chemical engineering;
(d) pharmaceutical sciences and technology;
(e) pharmacology and toxicology;
(g) other related sciences.
They should also have adequate practical experience in the manufacture and quality assurance of pharmaceutical products. In order to gain such experience, a preparatory period may be required, during which they should exercise their duties under professional guidance. The scientific education and practical experience of experts should be such as to enable them to exercise independent professional judgement, based on the application of scientific principles and understanding to the practical problems encountered in the manufacture and quality control of pharmaceutical products.
9.8 The heads of the production and quality control generally have some shared, or jointly exercised, responsibilities relating to quality. These may include, depending on national regulations:
(a) authorization of written procedures and other documents, including amendments;
(b) monitoring and control of the manufacturing environment;
(c) plant hygiene;
(d) process validation and calibration of analytical apparatus;
(e) training, including the application and principles of quality assurance;
(f) approval and monitoring of suppliers of materials;
(g) approval and monitoring of contract manufacturers;
(h) designation and monitoring of storage conditions for materials and products;
(i) performance and evaluation of in-process controls;
(j) retention of records;
(k) monitoring of compliance with GMP requirements;
(l) inspection, investigation and taking of samples in order to monitor factors that may affect product quality.
9.9 The head of the production generally has the following responsibilities:
(a) to ensure that products are produced and stored according to the appropriate documentation in order to obtain the required quality;
(b) to approve the instructions relating to production operations, including the in-process controls, and to ensure their strict implementation;
(c) to ensure that the production records are evaluated and signed by a designated person;
(d) to check the maintenance of the department, premises, and equipment;
(e) to ensure that the appropriate process validations and calibrations of control equipment are performed and recorded and the reports made available;
(f) to ensure that the required initial and continuing training of production personnel is carried out and adapted according to need.
9.10 The head of the quality control generally has the following responsibilities:
(a) to approve or reject starting materials, packaging materials, and intermediate, bulk and finished products in relation with their specifications;
(b) to evaluate batch records;
(c) to ensure that all necessary testing is carried out;
(d) to approve sampling instructions, specifications, test methods and other quality control procedures;
(e) to approve and monitor analyses carried out under contract;
(f) to check the maintenance of the department, premises and equipment;
(g) to ensure that the appropriate validations, including those of analytical procedures, and calibrations of control equipment are carried out;
(h) to ensure that the required initial and continuing training of quality control personnel is carried out and adapted according to need.
Other duties of the quality control are summarized in sections 17.3 and 17.4.
9.11 The authorized person is responsible for compliance with technical or regulatory requirements related to the quality of finished products and the approval of the release of the finished product for sale.
9.12 The authorized person will also be involved in other activities, including the following:
(a) implementation (and, when needed, establishment) of the quality system;
(b) participation in the development of the company’s quality manual;
(c) supervision of the regular internal audits or self-inspections;
(d) oversight of the quality control department;
(e) participation in external audit (vendor audit);
(f) participation in validation programmes.
9.13 The function of the approval of the release of a finished batch or a product can be delegated to a designated person with appropriate qualifications and experience who will release the product in accordance with an approved procedure. This is normally done by quality assurance by means of batch review.
9.14 The person responsible for approving a batch for release should always ensure that the following requirements have been met:
(a) the marketing authorization and the manufacturing authorization requirements for the product have been met for the batch concerned;
(b) the principles and guidelines of GMP, as laid down in the guidelines published by WHO, have been followed;
(c) the principal manufacturing and testing processes have been validated, if different;
(d) all the necessary checks and tests have been performed and account taken of the production conditions and manufacturing records;
(e) any planned changes or deviations in manufacturing or quality control have been notified in accordance with a well defined reporting system before any product is released. Such changes may need notification to, and approval by, the drug regulatory authority;
(f) any additional sampling, inspection, tests and checks have been carried out or initiated, as appropriate, to cover planned changes and deviations;
(g) all necessary production and quality control documentation has been completed and endorsed by supervisors trained in appropriate disciplines;
(h) appropriate audits, self-inspections and spot-checks are carried out by experienced and trained staff;
(i) approval has been given by the head of quality control;
(j) all relevant factors have been considered, including any not specifically associated with the output batch directly under review (e.g. subdivision of output batches from a common input, factors associated with continuous production runs).