GMP Organization and Personnel

Responsibilities of quality control unit
(a)    There shall be a quality control unit that shall have the responsibility and authority to approve or reject all components, drug product containers, closures, in-process materials, packaging materials, labeling, and drug products, and the authority to review production records to assure that no errors have occurred, or, if errors have occurred, that they have been fully investigated. The quality control unit shall be responsible for approving or rejecting drug products manufacture, processed, packed, or held under contract by another company.

(b)    Adequate laboratory facilities for the testing and approval (or rejection) of components, drug product containers, closures, packaging materials, in-process materials, and drug products shall be available to the quality control unit.

(c)    The quality control unit shall have the responsibility for approving or rejecting all procedures or specifications impacting on the identity, strength, quality, and purity of the drug product.

(d)    The responsibilities and procedures applicable to the quality control unit shall be in writing: such written procedures shall be followed.

        The CGMP’s focus all responsibility for quality onto the QC unit. There are no defined responsibilities for production management – unlike the European and World Health Organization (WHO) guidelines, which define both separate and joint responsibilities for these functions. This latter approach more clearly emphasizes that the consistent achievement of quality standards requires a team effort.

        Within the production operation all quality-impacting procedures and systems are to be approved by QC. Typically, these include such procedures as standard operating procedures (SOPs), process validation protocols, supplier certification protocols, complaint handling, process control procedures, and even design of buildings. Since some of these systems are “owned” by other functions, it is essential that QC have effective procedures to ensure that such systems are reviews in a timely manner and that changes cannot be introduced without approval. During 1985 and 1986 several companies had serious problems associated with changes in formulations and manufacturing processes, which then failed to comply with requirements of NDA and ANDA documentation. These discrepancies resulted in halting of distribution and recalls, with significant loss of revenue to the companies involved. Some of these situations occurred because economies and expedition overwhelmed inadequate approval systems.

        QC is also responsible for approving or rejecting labeling. This responsibility lies in two areas. First, new or modified labeling should be reviews to ensure that it complies with the ANA, NA, OTC monograph, or other official requirements that are applicable. This checking may be delegated to other functions, but QC must assure that the checkers are qualified to perform their function and that they have done so. Second, incoming labeling supplies are to be evaluated to assure they are correct. These responsibilities to no apply to promotional literature.

        The approval/rejection responsibility also applies to operation contracted out to other companies. This does not necessarily require any additional or duplicate testing. Provided the contractor has adequate procedures and is in full compliance with CGMPs, it should only be necessary to compare the test data with specification and with data from previous batches to identify trends.

        No guidance is provided about the actual organization of the QC department, and a wide range of viable alternatives are in effect. One of the simplest, but very effective, is the subdivision into quality control-all inspection and testing and quality assurance-all systems and procedures including batch review and audit. With the increased reliance on non-QC personnel for quality-related activities, such as in-process control ad customer complaint coordination, the role of the quality assurance (QA) unit has become critical. The regulations essentially expect the QC/QA function to provide an independent policy-type role, to monitor the entire production process from purchasing of materials to distribution and use of the product. The function should also be proactive by evaluating data on processes, materials, and suppliers and recommending changes that will improve efficiency and consistency. QC should be a resource that plays a positive role in improving profitability. More will be said about this in future chapters.

Some companies have taken the team approach a stage further by the introduction of self-managed work teams. The various functions or disciplines are incorporated into the team, which can be responsible for all its operational requirements. This can include, in extreme cases, hiring of new team members, discipline, allocation of wage increases or bonuses, work scheduling, product testing, and release/rejection decisions. In these instances there still needs to be an independent QC evaluation for final release/rejection to satisfy the regulations.

PERSONNEL QUALIFICATIONS
(a)    Each person engaged in the manufacture, processing, packing, or holding of a drug product shall have education, training, and experience, or any combination thereof, to enable that person to perform the assigned functions. Training shall be in the particular operations that the employee performs and in current good manufacturing practice (including the current good manufacturing practice regulations in this chapter and written procedures required by these regulations) as they relate to the employee's functions. Training in current good manufacturing practice shall be conducted by qualified individuals on a continuing basis and with sufficient frequency to assure that employees remain familiar with CGMP requirements applicable to them.

(b)    Each person responsible for supervising the manufacture, processing, packing, or holding of drug product shall have the education, training, and experience, or any combination thereof to perform assigned functions in such a manner as to provide assurance that the drug product has the safety, identity, strength, quality, and purity that it purports or is represented to possess.

(c)    There shall be an adequate number of qualified personnel to perform and supervise the manufacture, processing, packing, or holding of each drug product.

    The development and training of employees, at all levels, should be seen as a continuous process (figure ) in which performance appraisal plays a key role.

      The GMP regulations do not attempt to define the education, knowledge, skills, or experience required for the different types of job within a pharmaceutical company. This is significantly different from the European and WHO guidelines, which do specify the knowledge and experience requirements for those individuals designated as responsible for production and quality. The consistent achievement of quality standards requires understanding of, and compliance with, established procedures. Consequently, initial screening should select only those individuals who have such basic skills as reading, writing, and numeracy. An employee who cannot understand written instructions will find it difficult to follow procedures, an inability to write coherently will inhibit the recording of a typical situations, while a lack of numeracy could make it impossible to perform certain in-process testing such as statistical process controls. For certain positions color vision may also be important, and some 10% of the population have some degree of color vision problem.

    Education and training records must be maintained and kept current : FDA inspectors may ask for confirmation of adequate training.
    The responsibility for training of employees should reside with departmental management. However, the QC department should monitor or audit to ensure that the appropriate training has been given. This could include review of training module content and also of training records. Additionally, QC staff themselves are likely to be involved in providing some of the training.
    Training, although essential, is more effective in a supportive environment. If management, by example, demonstrate that compliance with procedures is important and encourage participation in improvements, then training will be put into practice. The acknowledgement of ahievement by public recognition or remuneration, often termed positive reinforcement, has a significant impact. The demonstration by example is further illustrated in a later section.


PERSONNEL RESPONSIBILITIES:

(a)    Personnel engaged in the manufacture, processing, packing, or holding of a drug product shall wear clean clothing appropriate for the duties they perform. Protective apparel, such as head, face, hand, and arm coverings, shall be worn as necessary to protect drug products from contamination.

(b)    Personnel shall practice good sanitation and health habits.

(c)    Only personnel authorized by supervisory personnel shall enter those areas of the buildings and facilities designated as limited-access 
         areas.

(d)    Any person shown at any time (either by medical examination or by supervisory observation) to have an apparent illness or open lesions that may adversely affect the safety or quality of drug products shall be excluded from direct contact with components, drug product containers, closures, in-process materials, and drug products until the condition is corrected or determined by competent medical personnel not to jeopardize the safety or quality of drug products. All personnel shall be instructed to report to supervisory personnel any health conditions that may have an adverse effect on drug products.
   
The wearing of uniforms for manufacturing and control operations is not mandated. Only that clothing shall be cleaned and appropriate for the duties being performed. In defining what clothing is appropriate it is necessary to consider the end purpose. For example, it would be inappropriate to require hair covering to protect the product from the inadvertent ingress of hair and then to allow employees to wear clothing that incompletely covered the hair, did not cover beards or moustaches, or left the arms uncovered. Yet such situations do exist.
   
The use of plant uniforms is generally a more satisfactory way of maintaining adequate standards of dress and the following guidelines may be applied :

1.    A sufficient amount of clean uniforms is provided so that changes can be made at an adequate denied frequency or whenever they 
       became soiled.
2.    Washing and sanitation procedures should be checked to confirm their effectiveness.
3.    Employees in special clean areas should wear only lint-free garments to prevent scheduling.
4.    Garments should be designed and use material that maximizes personal comfort.
5.    The range of clothing available would normally include:
    a.    Hats or hair cover
    b.    Beard and moustache covers
c.    Coveralls – preferably with no pockets, or pockets suitably designed to prevent articles falling out
    d.    Disposable gloves
    e.    Foot covers or shoes
    f.    Masks
    g.    Safety glasses or goggles
    h.    Appropriate clean-room for sterile areas
6.    Employees should be shown how and when to wear the appropriate clothing.   
7.    Work clothing should not be worn outside of the appropriate plant area, and changing rooms should be available.
    Separating an ill worker or one with open lesions from the product by use of gloves, masks, or special clothing is not recommended. The discomfort involved in their use tempts the worker to discard them when not being observed. The requirement of this section to report adverse health conditions will not be effective unless a set of specific conditions to be reported is provided. Again, be guided by current legal advice as to the substance and receipt of such information.
    The primary objective of this section of the regulations is to protect eh product from potential contamination from personnel – particulate matter including hair, fibers, and outside "dirt" cross-contamination carried on clothing from other processes, microorganisms shed from skin and from the mouth and nose. However, an employer also has a responsibility to protect the employee from unacceptable exposure to the materials being handled, many of which have physiological properties. Where potential exposure is to very potent materials, testing of blood or urine samples may be warranted. Wherever possible, barrier or containment facilities or equipment should be used to protect personnel from extremely hazardous materials. The use of masks or breathing equipment should only be used as the sole precaution in rare circumstances of for less hazardous materials.