Unit- 2 Organization and Personnel Pharmaceutical Quality Assurance

 

Introduction:-

In a complex field of manufacturing, it is important to have a sound quality system in place to make sure that products manufactured have the desired quality, safety and efficacy. At the same time, it is vital to recognize that even the best quality system is only as good as the people who make it work. Personnel are backbone of the manufacturing unit, and there must be sufficient number of adequately qualified and trained staff to ensure one achieves the desired quality products. No person should be burden with responsibilities that it presents a quality risk.

Organization:-

Sufficient number of personnel must be present to perform as well as supervise the manufacture, processing, packing and holding of every drug product. In a pharmaceutical industry different jobs are performed by different persons and hence it becomes more important that each employee has a clarity and understanding of the job description.

A Job Description (JD) is an organized and factual statement of the responsibilities of a specific job, in brief, it should tell the work, tasks, duties and responsibility of a job.

Ideally JD may include-

i) Organizational positions and operating relationships clearly mentioning job description and reporting.

ii) Individual assignments.

iii) Job summary in detail.

iv) Working conditions and hazards related to the job

v) Jobs/ duties, roles, responsibilities and accountability.

 

Key Personnel:-

It is defined as those positions in the organization, which have a direct impact on the working of the organization and quality of the products produced.

Some key personnel and their responsibilities are as follows:-

A.    Head of Production  department

1.     Approval of instructions relating to production operations including in process controls and their implementation

2.     Checking the maintenance of the department, premises and equipment

3.     Ensuring process validation, calibration of control equipments and maintenance of their records

4.     Ensuring the initial and continuing training of production personnel relevant to their needs

5.     Ensuring production and storage of products according to appropriate documentation

6.     Ensuring evaluation of the production records by an authorized person before they made available to quality control department.

 Head of Quality Unit(s) or Quality Control department

1. Approval or rejection of staring materials, packaging materials, intermediates, bulk and finished products.
2.  Evaluating batch record
3.  Ensuring that all necessary testing are carried out
4.    Approval of sampling instructions, specifications, test methods and other quality control procedures.
5. Approval and monitoring of analyses carried out under contract, if any
6.  Checking the maintenance, of the department, premises and equipment
7.  Ensuring initial and continuing training of quality control personnel relevant to their needs
8.  Ensuring validation of quality control procedures and calibration of control equipments and maintenance of their records.
9.  Ensuring initial and continuing training to quality control personnel
10.  Establishment, implementation and maintenance of quality system.
11.  Supervision of the regular internal audits or self inspection
12. Participation in external audit (vendor audit)
13.  Participation in validation programmes.

A.    Joint Responsibilities of Head of Production and Head of Quality unit(s)

1. Authorization of written procedures and other documents and their review

2.     Plant hygiene

3.     Monitoring and control of environment of production areas

4.     Process validation and calibration of quality control equipments

5.     Training of personnel in GMPs and QA principles

6.     Monitoring of compliance according to GMPs

7.     Approval and monitoring of suppliers of materials and products

8.     Retention of records for periods specified by national legislation

9.     Approval and monitoring of contract manufacturers, if any

10.  Performance and evaluation of in process control

11.  Inspection, investigation and sampling to monitor factors that may affect product qualiy

12. Monitoring of compliance with GMP requirements

A.    Authorized Person- The authorized person is responsible for compliance with technical or regulatory requirements and approves release of finished products for sale.

Before release of the product, the authorized person must ensure that following requirements have been met:

1.     Manufacturing authorization requirements for the product have been met in respect of batch to be released

2.     Principles and guidelines as outlined in GMP text have been followed

3.     If there has been changes in principle manufacturing and testing processes, they have been validated

4.     All required checks and tests have been performed and account has been taken of the production conditions and manufacturing records.

5.     Whether any plan deviation has been reported according to the established procedure, if these changes required notification to the regulatory authority, whether the same has been done

6.     Whether any additional sampling, test or checks have been carried out to ensure that there is no effect on quality of the finished product because of planned deviation

7.     Whether all the necessary records relating to production and quality control have been completed and have been duly endorsed by supervisors

8.     Whether appropriate audit, self inspection and spot checks are carried out by experienced and trained staff

9.     Whether approval; has been given by the head of quality control

Qualifications:-

Key personnel should have at least the qualification as prescribed under national legislation. Key personnel responsible for supervision of manufacture and quality control should have qualifications which will provide an appropriate combination of studies of the following-chemistry, biochemistry, chemical engineering, microbiology, pharmaceutical sciences and technology, pharmacology and toxicology, physiology.

They should have adequate practical experience in manufacture or quality control of drugs as the case maybe. In India, manufacturing of the drugs will be carried out under active direction and personal supervision of a person who has at least the following qualification and experience:-

-a graduate in pharmacy having at least 18 months experience in manufacture of drugs or

- a graduate in science having at least 3 years of experience in manufacture of drugs

- a graduate in medicine having at least 3 years of experience in manufacture of drugs

- a graduate in chemical engineering having at least 3 years of experience in manufacture of drugs

- a person holding any foreign qualification the quality and content of training of which are comparable with those, mentioned above.

Similarly, the head of quality control unit is required to possess, a degree of in medicine or science or pharmacy or pharmaceutical chemistry. Period of experience has not been mentioned under legislation and it has been left to the discretion of regulatory authority.

All persons engaged in the manufacturing, processing packaging, analyzing drug products must have necessary education, training and experience or an acceptable combination of these to ensure that they are capable of carrying out the assigned work.

Training:-

A person is called Trained Person when he has appropriate knowledge, skill, and attitude towards work.

Knowledge- it refers to the theoretical background expected in a person regarding the job to be performed and also the knowledge about the principles of all aspects of GMP, which may affect in area of work.

Skill- it refers to the practical experience he has and his ability to use his theoretical knowledge to perform the particular task given.

Attitude- Attitude is a behavioral trait of a person who is performing a task

Training makes personnel proficient in their duties. Therefore there should be initial and continuing training of personnel connected with production and quality control of drugs. Personnel working in special areas like sterile products area, areas where highly toxic, infectious or sensitizing materials are handled should be given specific training.

Training program should include at least the following topics

-        Principles of GMPs

-        Principles of GLP

-        Duties and responsibilities of different personnel,

-        Cleanliness, general hygiene, personal cleanliness and health

-        Characteristics of pharmaceuticals, their handling and dangers if any

-        First aid

-        Fire fighting and other safety measures

Training module for supervisors may also include topics like behavioral; sciences and management. Effectiveness of the training should be assessed periodically. Records of training to different personnel should be kept.

 

Hygiene:-

A sick person can contaminate the product and can also spread infection if he is suffering from infectious disease. Health of personnel therefore, is an important aspect. Medical examination of the personnel should be carried out periodically. First medical examination should be carried out at the time of recruitment. This applies even the temporary employees. When a person report for work after illness involving communicable disease, a competent medical officer should assess his health before he commences his work. Supervisors should be vigilant and should look out for person having sign of sickness. Person having sign of sickness should be transferred to low risk areas or should be sent home and should be advised medical examination. Personnel conducting visual examination should undergo periodic eye examination including color blindness.

For sanitation of workers, the management of pharmaceutical unit should provide:

-        Washing and toilet facilities- it should be clean, adequate for number of person using them and should have water, sinks, soap/liquid detergents, hand driers or towels.

-        Clean protective clothing, procedure and facilities for maintenance – protective clothing include garments and apparel, which include face coverings, hand coverings, shoe coverings,

Protective clothing should be appropriate for the intended purpose, for example, head covering should cover hair completely. They should not have pockets above waist level. Protective clothing for sterile area should not shed particles, should be avoid be pockets, tucks or belts, should be close fitting at neck, wrist and ankles. Readymade garments for sterile area are also available.

Change room with locker facility should be provided for each sex. Indian GMPs prescribe 8 sq.mt of 90 sq ft for change room. Change room should be adjacent to the washing area and before entry to the production areas. Person should change from street clothing to protective clothing before entering production areas. Garme3nts should be clean and should be changed 2-3 times a week for non-sterile operations. Protective clothing meant for sterile areas should be sterilized before use and should be changed with sterilized clothing each time a person enters into sterile area. Soiled clothing should stored in the closed container until it laundered. Clothing used by personnel working in the sensitizing drugs (e.g. Ampicilline) should be stored and laundered separately. Supervisor should discuss with workers working under him the topics mentioned there under:

 

-        Atmospheric conditions which promote or suppress growth of microorganisms.

-        Method which are used to control contamination, for example, maintenance of positive pressure in clean areas, UV lamps, heating, chemical disinfection, etc.

-        To produce product free from contamination is the responsibility of the manufacturer.

-        Supervisors should also give guidelines to workers on personal hygiene such as:-

i)                They should have bath daily and should change to fresh cloths before coming to work

ii)               They should clean hands regularly and invariably after visiting toilet using soap.

iii)             They should keep their hair clean and well controlled

iv)             They should trim their nails regularly.

v)               Direct contact should be avoided between operators hand and starting materials, intermediates, bulk products and primary packaging materials.

vi)             Smoking, eating, drinking, chewing should not be permitted in production and other areas where the quality of the product may be adversely affected.

Personal Records

Following records should be maintained for the personnel:-

1.     Job description for personnel

2.     Pre-post employment medical check ups

3.     Records for qualification, all education certificates, address proof, experience letter from previous company.

4.     Leave details, PF details, tax records, salary statements, promotion letters if any

5.     SOP of personal Hygiene

6.     SOP of dress code

7.     Sop on management policy on smoking drinking, eating and chewing

8.     Training manual

9.     SOP on training

10.  Records of consultant.