T RESHMA, ASSISTANT PROFESSOR, DEPT.

OF PQA - RIPER

UNIT - II
II.I ORAGANIZATION AND PERSONNEL
Personnel
Definition:
It is defined as “the staff or employees who are working in the organization or company” is
known as personnel.
➢ The manufacturing, monitoring, quality control and quality assurance areas which depend
on the personnel.
➢ So, the personnel engaged in pharmaceutical industry shall have the minimum
qualification, practical experience and adequate training to handle the different tasks.
➢ Individual responsibilities of the personnel should be clearly defined and understood by the
process and recorded as written description and the responsibilities should not be more
extensive because it will lack the quality of product.
Responsibilities of Personnel:
➢ All the personnel should aware the principles of Good Manufacturing Process (GMP).
➢ Personnel should get the initial and continuing training.
➢ All the personnel should follow the hygiene instruction.
Organization
Definition:
It is defined as an “organization refers to a company or a group of companies involved in the
research, development, manufacturing, marketing, and distribution of pharmaceutical drugs or
medical products”.
➢ The organization should have “Organization Chart”, which includes:
1. Head of Production
2. Head of Quality Assurance
3. Head of Quality Control
➢ Responsibilities of Production Department:
• To ensure that products are produced and stored according to appropriate
documentation to obtain the required quality.
• To approve the instructions relating to production operations and to ensure their
strict implementation.
• To check the maintenance of department premises and equipment.
• To ensure that the production records are evaluated and signed by an authorized
person before they send to the Quality control department.
• To ensure that the appropriate validation is done.
• To ensure that the required initial and continuing training to the department
personnel.

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T RESHMA, ASSISTANT PROFESSOR, DEPT. OF PQA - RIPER

➢ Responsibilities of Quality Assurance Department:

• To develop, implement, manage, audit and maintain GMP quality system and also
GMP complaint document control system.
• To ensure the cGMP requirements and quality standards are recognized, understood
and maintained across the company.
• To provide the quality guidance to the product development, projects and programs
• To work across all specializations of companies to ensure that the company
maintains for inspection as per regulatory agencies.
• To ensure the development of departmental SOP’s.
➢ Responsibilities of Quality Control Department:
• To approve or reject the Raw materials, Finished Products, Packaging materials and
Bulk materials.
• To evaluate the batch records.
• To ensure that all necessary testing is carried out.
• To approve the specifications, sampling, instructions, test methods and any other
Quality control procedures.
• To approve and monitor any contract analyst.
• To check or inspect the department premises and equipment’s.
• To ensure that the appropriate validations are done.
• To ensure that the required initial and continuing training to the department
personnel.
➢ Joint Responsibilities of Production, Quality Assurance and Quality Control
Department:
• The authorization of written procedures and other documents, amendments.
• Monitoring and control of the manufacturing environment.
• Maintain the plant hygiene.
• The process validation.
• To provide the training to the personnel.
• To approve and monitoring of incoming materials from suppliers.
• To approve and monitoring of contract manufacturer.
• To design and monitor storage conditions for materials and products.
• To maintain the records.
• To inspect, investigate and collection of samples.
Training:
It is defined as “Training refers to the process of teaching and developing skills, knowledge,
and competencies in individuals or groups. It involves providing instruction, guidance, and
practice to improve performance and enhance capabilities in a particular area”.
➢ Training is divided into two types, which includes
1. Induction Training
2. Continuous Training

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T RESHMA, ASSISTANT PROFESSOR, DEPT. OF PQA - RIPER

Induction Training:
➢ Induction training is also called as Introduction training or Orientation training, refers to
the employees who are newly joined in the company
➢ It is designed to introduce them to the company, its policies, procedures, culture, and their
specific job role.
➢ The primary purpose of induction training is to help new employees become familiar with
their work environment, understand their responsibilities, and integrate smoothly into the
organization.
➢ This training is again sub-divided into two types,
• General Training:
In this, the employees get the training related to the GMP and importance of GMP
to the company.
• Specified Training:
In this, the employees get the training related to their department issues of
individual departments.
Continuous Training:
➢ Continuous training includes a written re-training program for all the employees to ensure
that their skills are continually up to date and that they are introduced to changes in practice.
➢ The effectiveness of the training should be checked.
➢ If any new project has been started the continuous training will be provided.
➢ If the staff are entering into special areas such as Sterile area, the area where highly active,
infectious, toxic and sensitive material are handles.
Hygiene or Personnel Hygiene:
➢ All the personnel who are working in the industry should maintain the high level
of hygiene and health conditions.
➢ The personnel hygiene measures include,
• Minimum or required number of persons should present in sterile room or clean
room.
• Personnel working in clean area should report any condition or issues which may
cause the contamination to the clean room.
• Should not wear watches and jewellery in sterile area.
• Should no use any cosmetic products.
• The hair, beard and moustache should be properly covered.
• The protective clothing and appropriate shoes should be used.
• The employees are instructed and encouraged to report their illness to the head of
the company.
• Proper haircut, nail and shave should be done.
• If anyone’s body is having sweating nature, the company has to take proper care to
avoid the contamination.
• Should not eat, drink and chew in industry.
• Operator/ Worker/ Staff/ Manager should avoid the direct contact with

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T RESHMA, ASSISTANT PROFESSOR, DEPT. OF PQA - RIPER

o Raw materials
o Bulk materials
o Primary packaging materials
• The company should provide the personal hygiene procedures.
Maintenance of Personal Records:
➢ Records are maintained to ensure that all products are manufacture as per guidelines.
➢ Records are maintained to ensure that the authorized person has all the information, which
is necessary to decide release of manufactured products into the market or for sale.
➢ Records should be approved, signed and dated by authorized person.
➢ No record should be changed or modified without informing authorized person.
➢ The changes made in the record should be checked, signed and dated by authorized person.
Along with changed record, the original record also retained.
➢ Records should be regularly reviewed and kept up to date.
➢ Record should be prepared after the process is completed.
➢ All the records should be stored in Electronic Data Processing System and eCTD (Electrical
Common Technical Document) format.
➢ The records are retained for at least one year after the expiry of finished product.
II.II PREMISES
Definition:
➢ Premises is defined as “the work place or all the buildings where the manufacturing &
analysis of the product will take place by complying GMP standards for the quality of the
product”.
BUILDINGS AND FACILITIES:
Design and Construction:
Design of Premises:
The layout should be designed in such a way that
• It Minimizes the risk of errors.
• Permit effective cleaning & maintenance.
• Avoid cross contamination.
• Should have adequate safety and security features for workers against accidents or
injury.
• Should have sufficient scope for modifications & adjustments whenever needed.

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T RESHMA, ASSISTANT PROFESSOR, DEPT. OF PQA - RIPER

Plant Layout:

Construction of Premises:
The construction premises include,
• Suitable materials should be used for construction of premise.
• Material used should withstand pressures, vibrations and other effects.
• It should ensure proper cleaning, materials used should also ensure sterility of area.
• There should be continual electric supply.
• Suitable lighting should be present in visual check area.
• Effective ventilation should be present.
• In areas where high amount of dust generation could occur like sampling, weighing,
mixing areas, special focus should be done.
Classification of areas:

➢ Ancillary areas
• Rest and Refreshment rooms.
• Toilets and Washrooms.
• Clothes storage areas.
• Changing rooms for employees.
• Rest and Refreshment Rooms should be separate from other areas.
• Facilities for Toilets should not communicate directly with production or storage
areas.
•Areas for change rooms and storage of clothes and for washing, and toilet purpose
should be easily accessible and appropriate for the number of users.
➢ Storage areas
• There should be different store for different category of materials.
• They should be clean, dry, sufficiently lit and maintained within acceptable temperature
limits.
• Special care should be taken in storage of following:
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T RESHMA, ASSISTANT PROFESSOR, DEPT. OF PQA - RIPER

o Highly active and radioactive materials.

o Narcotics.
o Substances having risks of abuse.
o Dangerous substances having potential to cause fire or explosion.
➢ Weighing areas
• There should be provision of dust control.
o Weighing balances should be present under LAF (laminar air flow).
o Weighing area can be a part of storage or production area.
➢ Production areas
• Self-contained facilities must be available for the production of particular
pharmaceutical products:
o Sensitizing materials (e.g., penicillin’s).
o Biological preparations (e.g., Live microorganisms).
o Antibiotics, Hormonal products, Cytotoxic substances, Some non-
pharmaceutical products.
• There should be separate area with adequate space for each process to be performed.
• There should be taken for the maintaining proper lighting, air control facility &
ventilation.
• Enough space should be available to keep the equipment’s to perform the process
properly.
• Area for the packaging should be properly designed to avoid mix up.
➢ Quality control areas
• Quality control laboratories should be separate from production areas.
• Separate areas should be available for microbial, biological and radio-isotope analysis
methods.
• Separate air-handling units (AHUs) and other provisions are needed for biological,
microbiological and radioisotope laboratories.
• There should be separate space for performing wet analysis (like titration) and
instrumental analysis (like UV spectrometry).
• There should be adequate & suitable storage space for following:
o Analysis samples
o Reference standards (if necessary, with cooling)
o Solvents & reagents
o Records
o Stability chambers
➢ Maintain drainage area for proper waste management.
MAINTENANCE OF BUILDINGS AND FACILITIES:
Definition:
It is defined as, any building used in manufacturing, processing, packaging, handling of drug
product shall be maintained in good state.
➢ Facility maintenance includes maintenance of following things:
• Leakage from ceiling or other surfaces.
• Leakages from pipe lines of waters, steam, gases etc.

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T RESHMA, ASSISTANT PROFESSOR, DEPT. OF PQA - RIPER

• Plumbing problems.
• Loose or broken tiles.
• Improper closing of doors, windows.
• Improper electrical wiring.
• Improper electrical fittings/ fixtures like roof leakage, building image etc.
Importance of Maintenance:
• It avoids the contamination.
• It will produce good quality of product.
• The systemic and smooth functioning of organization.
• It enhances the Safety.
• It minimizes the accidents in the organization.
SANITATION OF BUILDINGS AND FACILITIES:
Definition:
It is defined as, any building used in manufacturing, processing, packaging, handling of drug
product shall be maintained in clean and sanitary condition.
➢ In order to maintain sanitation and cleaning we have to consider following points.
• Create and maintain safe working environment.
• Remove dust and dirt which can affect product quality.
• Minimize the risk of cross-contamination occurring between products.
• Reduce the levels of microbial contamination.
Importance of Sanitation:
• Removal of dust, dirt and other waste material.
• Minimizes the risk of contamination between different product in same area.
• It controls the pest. So that, it does not affect the quality of materials.
• Reduce the growth of microorganisms in work area.
• GMP has given the guidelines for Sanitation as follows:
o Building shall be free of rodents, birds, insects and other any insects.
o Traces of organic waste shall be disposed in a timely and sanitary manner.
o There shall be written procedure for sanitation and assign responsibility, explain
sufficient detail for cleaning and methods, materials and equipment’s to be used
in sanitation.
o There shall be written procedures for the use of suitable rodenticides,
insecticides, fungicides etc.
ENVIRONMENTAL CONTROL OF BUILDINGS AND FACILITIES:
Definition:
It is defined as the degree to which individuals or groups can modify and adapt features of their
physical workplace to enhance the effectiveness of the work.

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T RESHMA, ASSISTANT PROFESSOR, DEPT. OF PQA - RIPER

➢ Air handling units for sterile product manufacturing shall be different from those of
other areas. Such as HVAC (Heating Ventilation and Air Conditioning) System, which
have the different components like,
• Local Heating System
• Local Ventilation System
• Local Air Conditioning System
• Local Cooling System
➢ Critical areas such as aseptic filling areas, sterilized components unloading areas.
➢ For products which are filled aseptically, the filling room shall meet Grade B condition
at rest.
➢ For products which are terminally sterilized, the filling room shall meet Grade C
conditions.
➢ Differential pressure between areas of different environmental shall be maintained.
➢ Temperature and humidity in the Aseptic areas shall not exceed 27◦C and 55% Relative
Humidity respectively.
➢ All the parameters listed above shall be verified and monitored at regular periodic
intervals.
➢ Recommended frequencies for Periodic monitoring shall be as follows:
o Particulate monitoring in Air : 6 monthly
o HEPA Filter integrity testing : Yearly
o Air Change Rates : 6 Monthly
o Air Pressure differential : Daily
o Temperature and Humidity : Daily
o Microbial monitoring : Daily
UTILITIES & MAINTENANCE OF STERILE AREA:
➢ All the utilities should be qualified and monitored on regular basis.
➢ Smooth and easily cleanable Floors, 'Walls and Ceilings.
➢ Temperature and humidity controls.
➢ Air supply with HEPA filters under positive pressure.
➢ Environmental conditions monitoring system.
➢ A system for Cleaning and disinfecting to produce aseptic/ sterile conditions.
• Floors, walls and ceilings of sterile areas should be subjected to intensive and
frequent cleaning and sanitation.
• Temperature and humidity in the sterile areas should be controlled and maintained
according to operations performed (68◦F temperature and 45% Relative Humidity
is suitable).
• The air in sterile areas should be provided by air supply fitted with HEPA filters
• Sterile areas should have positive differential pressure related to adjoining areas and
"Air pressure differentials should be monitored automatically.
• HEPA filters should be tested at regular intervals.
• Cleaning and disinfection of sterile areas, Facilities and equipment’s should be done
regularly and procedure used for cleaning and disinfection must be validated with
respect to both removal of previous product contamination and effective
disinfection, disinfectant should be changed periodically to minimize the possibility
of microbial.

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T RESHMA, ASSISTANT PROFESSOR, DEPT. OF PQA - RIPER

➢ Utility Service should include,

o The Utilities that could affect the Product quality are steam, gases, compressed
air, heating, ventilation and air conditioning. All this should be qualified,
monitored and proper action should be taken when the limits are exceeded.
o Adequate ventilation, air filtration and exhaust system should be provided and
it should be designed and constructed to minimize the risk of contamination and
cross-contamination.
o If air is re-circulated to the production area, appropriate measures should be
taken to control the risks associated.
o Permanently installed water pipes should be identified and monitored.
o Drains should have adequate size and provided with air break or a suitable
device to prevent the back flow.
MAINTENANCE OF STERILE AREA:
• Maintenance of Sterile area should include,
o The clean room should have the minimum personnel.
o All the personnel working in the organization should have regular training.
o Personnel hygiene should be maintained.
o Clean
CONTROL OF CONTAMINATION:
• Mainly contamination is done by two sources.
1. Facilities
2. People
• So, the above mentioned two sources are mainly controlled to prevent the contamination.
1. Control of Contamination by Facilities:
➢ In the areas/ Facilities where sterile products are manufactured air should be supplied under
positive differential pressure with HEPA filters designed to keep Microorganisms and other
particles at low level.
➢ In sterile areas all the surfaces of floors, walls, ceilings etc. should be hard and free from
cracks to avoid dust and microorganism accumulation and should permit easy cleaning.
➢ Access to sterile areas must be Controlled/ Restricted to people and entry and exit to sterile
areas should be only permitted through change areas.
2. Control of Contamination by People:
➢ All the personnel working in aseptic/sterile areas should emphasize on following points to
control the contamination.
➢ Keep Body, hair, face, hands and nails clean.
➢ Report illness, injury, respiratory and skin problems.
➢ Follow the written changing and wash-up procedures.
➢ Do not use cosmetic and wear jewellery and wrist watches.
➢ Do not take papers and documents in sterile area.
➢ Avoid eating, chewing, drinking and smoking in sterile areas.
➢ Avoid coughing and sneezing (If it is unavoidable, please leave the sterile area).
➢ Use gloves and disinfect them regularly.
➢ Follow the written changing and wash-up procedures.

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T RESHMA, ASSISTANT PROFESSOR, DEPT. OF PQA - RIPER

II.III EQUIPMENT’S AND RAW MATERIALS

EQUIPMENT:
Definition:
Equipment is defined as a physical entity which is used to carry out a general or specific
activity in the pharmaceutical plant.
E.g., Tablet Punching Machine, Hardness tester, Friabilator etc.
Selection of Equipment:
• Should check for the availability of spares and services.
• Equipment cleanability should be checked.
• The ease of cleaning accessibility to the parts of equipment should be checked.
• The ease of disassemble and reassemble of equipment parts should be checked.
• Environmental issues and Environmental control conditions should be checked.
• Availability of design and maintenance manuals should be checked.
• Cost should be checked.
Purchase Specifications of Equipment:
➢ Right Source
➢ Right Quality
➢ Right Quantity
➢ Right Price
➢ Right Time
➢ Right mode of transportation
Maintenance of Equipment:
• Equipment must be located, designed, constructed and maintained to meet the standards of
process to be carried out.
• The layout and design of the equipment must aim to minimize the risk of errors and permit
the effective cleaning and maintenance to avoid cross contamination, dust and dirt.
• Equipment should be properly installed to minimize the errors.
• Written procedures should be established for cleaning of equipment. The procedure
includes,

o Assign the responsibility for cleaning of equipment to the cleaning staff.

o Cleaning schedules should be designed.
o A complete description of cleaning methods and materials should be provided.
o Provide the instructions of disassemble and reassemble of equipment parts for
cleaning.
o Provide instructions for protection of cleaned equipment’s from contamination
before use.
o Inspection of equipment for cleanliness.

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T RESHMA, ASSISTANT PROFESSOR, DEPT. OF PQA - RIPER

Raw Materials:
Definition:
Raw Material is defined as the basic material from which a product is made.
E.g., API, Excipients such as coloring agent, flavoring agent, sweetening agent etc.
Raw material can be either active or inactive.
Selection of Raw Materials:
• Selection of vendors based on
o Past history of vendor
o Trend of material quality
o Commitment of quality and delivery due date
o Compliance of quality parameters
• Vendor qualification should be checked based on
o Evaluation of sample
o Perform the vendor audit
• Responses to the invited quotations should be checked.
• Records of the vendor and vendor certification should be checked.
• The price of raw material should be checked.
• Selection of raw material based on ABC analysis category.
o “A” indicates - high purity
o “B” indicates - medium purity
o “C” indicates - low purity
Purchase Specifications of Raw Materials:
➢ By inspection
➢ By sample
➢ By description of brand
➢ By grading or Analysis
Steps involved before Purchase:
• Purchase requisition.
• Selection of supplies.
• Inviting Quotation.
• Placing the order.
• Receiving the material.
• Checking of invoice or bill.
• Recording of bills in books.
• Releasing the payment to the supplier.
Maintenance of Raw Materials:
Area Specifications:
• Clean, Dry and Maintained within acceptable temperature.
• Designed and equipped reception area.
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T RESHMA, ASSISTANT PROFESSOR, DEPT. OF PQA - RIPER

• Ensuring of quarantine status.

• Separate sampling area.
• Segregation for storage of rejected, recalled or returned material.
• Safe and secure area for narcotics and highly active, dangerous and risky material.
• First in First out rule (FIFO) - First expiring First Out (FEFO).
Storage conditions:
• Room temperature should be 30° C and R. H. 60%
• A.C storage (25± 2 ° C & R.H. 45 – 55%) at Low temp. storage 2 – 8 ° C.
• Separate area for Sterile product storage in A.C.
• Light sensitive material should be stored in amber color container, hermitically sealed
container, Labeling of material in storage area.

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