Personnel and Key Personnel
9. Personnel:
9.1 Principle. The establishment and maintenance of a satisfactory system of QA and the correct manufacture and control of pharmaceutical products and active ingredients rely upon people. For this reason there must be sufficient qualified personnel to carry out all the tasks for which the manufacturer is responsible. Individual responsibilities should be clearly defined and understood by the persons concerned and recorded as written descriptions.
General:
9.2 The manufacturer should have an adequate number of personnel with the necessary qualifications and practical experience. The responsibilities placed on any one individual should not be so extensive as to present any risk to quality.
9.3 Responsible staff should have its specific duties recorded in written descriptions and adequate authority to carry out its responsibilities. Its duties may be delegated to designated deputies with a satisfactory level of qualifications. There should be no gaps or unexplained overlaps in the responsibilities of personnel concerned with the application of GMP. The manufacturer should have an organization chart.
9.4 All personnel should be aware of the principles of GMP that affect them and receive initial and continuing training, including hygiene instruction, relevant to their needs. All personnel should be motivated to support the establishment and maintenance of high quality standards.
9.5 Steps should be taken to prevent unauthorized people from entering production, storage and QC areas. Personnel who do not work in these areas should not use them as a passageway.
Key Personnel:
9.6 Key personnel include the heads of production, the head(s) of quality unit(s) and the authorized person. The quality unit(s) typically comprise the quality assurance and quality control functions. In some cases, these could be combined in one department. The authorized person may also be responsible for one or more of these quality unit(s). Normally, key posts should be occupied by full-time personnel. The heads of production and quality unit(s) 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 production and quality unit(s) for 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;
(c) Microbiology;
(d) Pharmaceutical sciences and technology;
(e) Pharmacology and toxicology;
(f) Physiology;
(g) Other related sciences.
They should also have adequate practical experience in the manufacture and QA of pharmaceutical products. In order to gain such experience, a preparatory period may be required, during which they should perform 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 QC of pharmaceutical products.
9.8 The heads of the production and the quality unit(s) 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 QA;
(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 production generally has the following responsibilities:
(a) To ensure that products are produced and stored in accordance with 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(s) of the quality unit(s) generally have the following responsibilities:
(a) To approve or reject starting materials, packaging materials, and intermediate, bulk and finished products in relation to 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 QC 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 unit personnel is carried out and adapted according to need;
(i) Establishment, implementation and maintenance of the quality system;
(j) Supervision of the regular internal audits or self-inspections;
(k) Participation in external audit (vendor audit);
(l) Participation in validation programmes.
Other duties of QC 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 or supply.
9.12 Assessment of finished products should embrace all relevant factors, including the production conditions, the results of in-process testing, the manufacturing (including packaging) documentation, compliance with the specification for the finished product, and an examination of the finished pack.
9.13 No batch of product is to be released for sale or supply prior to certification by the authorized person(s). In certain countries, by law, the batch release is a task of the authorized person from production together with the authorized person from QC.
9.14 The authorized 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;
(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 QC 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 medicines 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 QC 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 QC;
(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).
9.15 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 QA by means of batch review.
WHO Good Manufacturing Practices For Pharmaceutical Products: Main Principles
(Annex 2, WHO Technical Report Series 986, 2014)
