2. vWHAT ARE NUTRACEUTICALS ?
The term “Nutraceutical” combines two words –
“nutrients” (a nourishing food components) and
pharmaceutical (a medicinal drug ).
Stephen Defelice , define “nutraceutical” as a food
or part of food that provide medical or health benefits
including the prevention and treatment of disease
3. ØThere are some basic manufacturing regulations or guidelines that
are available to the nutraceutical industry for producing quality
products.
ØHowever, in most cases it could be noted that these regulations are
not adequate in providing guidance for the manufacturing facilities,
testing, etc.
ØNutraceutical industries are equally responsible for ensuring the
safety of their consumable products. For example, the combination of
nutraceutical and prescription drugs can be crucial or often may lead
to adverse reactions if not controlled properly.
GOOD MANUFACTURING PRACTICES
FOR NUTRACEUTICALS
4. GMP for nutraceuticals includes
1. Premises
• Personnel and material flow
• Walls and ceiling
• Heating, ventilation, and air conditioning system
• Utilities
• Water system
• Pest control
2. Equipment
• Preventative maintenance
• Equipment ID
• Log books
• Qualification of major equipment
• Calibration program of instruments
• Cleaning
5. GMP for nutraceuticals includes
3. Personnel
• Qualification
• Job responsibilities
• Training
• Health and hygiene
• Organization chart with reporting structure
4. Quality assurance
5. Sanitation program
6. Operations
7. Specifications
8. Stability
9. Samples
10. Record
11. Recalls
6. 1. PREMISES
Ø The building and other facilities for the manufacturing of nutraceuticals
in the form of powders, tablets, capsules, and liquids should have the
following minimum requirements to produce quality products meeting
customer requirements and other regulations
Ø Maintenance activities of plant and buildings should be planned,
conducted, and documented in a manner that prevents contamination
risks.
Ø Facilities designed for handling laboratory animals must be isolated
from the manufacturing areas and comply with the relevant regulations
in force.
7. 1. PREMISES
Personnel and material flow
• Manufacturing and testing facilities should be
designed to allow unidirectional flow of the
materials and products throughout the
manufacturing, packaging, storage, and testing
process.
• This is required to ensure against the potential
mix-ups and cross-contamination of the materials.
• To comply with these requirements, the firm needs
to design the proper physical segregation of
material and products in every stage of
manufacturing and storage.
• For example, adequate design of air- locks for
material and personnel entry would separate GMP
areas and non-GMP areas and would prevent
direct access from manufacturing and packaging
areas to the outside environment.
Walls and ceiling
• The doors, walls, ceilings, and floors should not
contain any holes or gaps.
• Wooden doors and walls should not be used and
material that sheds particles should be avoided.
• epoxy flooring should be used to permit effective
cleaning.
• Production areas where dust is generated must
have collection systems and procedures for
disposal of collected dust.
8. 1. PREMISES
Heating, ventilation, and air
conditioning system
• Adequate ventilation should be provided in
manufacturing and packing areas where there is
potential exposure of product to environment and
people.
• no regulatory requirements to use terminal HEPA
filters in air-handling units.
• it is recommended to use either HEPA filters or an
industry standard adequate filtration system that is
equivalent in multiproduct facilities to avoid cross-
contamination during recirculation of air within the
manufacturing rooms.
• In absence of proper air filtration units , it required
risk assessment documentation to support designed
HVAC.
• Lighting which used in ware houses and production
area is made of explosion proof quality
Utilities
• Compressed air and any type of inert gases used in
production should be of adequate quality and a
procedure should be in place to evaluate the quality
of such air/gas at a specified frequency.
• Any liquids and gases used in production must be
clearly identified as to their content.
9. 1. PREMISES
water system
• Required for liquid preparations.
• Recommended to use purified or distilled water
complying with USP standards.
• The firm is advised to qualify the water system
for its intended purpose.
Pest control
• The nutraceutical industry is proven to indulge in
manufacturing of certain chemicals that could
potentially attract insects from the surrounding
environment.
• The firm is advised to have adequate measures in
place to prevent infestation of pests, rodents, and
insects into the production and operation
affiliated areas.
• Documentation required:
üMinimum GMP documentation required
includes floor plans indicating material,
personnel flow, and room pressure differential
üCleaning and sanitation records
üPest control records
üTemperature and humidity records
10. 2. EQUIPMENT
Ø The equipment used for production, packaging, and storage of a product should be designed to meet the required
quality characteristics and should be located in areas that permit the installation, operation, cleaning,
maintenance, and qualification activities.
Ø The material considered for the design and construction of equipment and accessories that are in direct contact
with components and in-process or finished products should not be reactive and additive or have any untoward
impact on the product quality.
Ø Any substance required for the operation of equipment, such as lubricants, coolants, oils, etc., should
• not be in contact with the components of the formula, primary packaging of the product, or the product
itself.
• acquired on the basis of an approved specification.
Ø Equipment that is unsuitable for its intended use should either be removed or clearly labeled for quarantine status.
Ø It is recommended that the computer systems installed on computers to control the manufacturing process are
validated.
11. 2. EQUIPMENT
Preventative
maintenance
• There should be preventive maintenance procedures for critical
equipment used in operations.
• A written preventive maintenance program at an established
frequency should be in place for critical equipment.
Equipment ID
• All equipment used in production should have a unique
identification numbering system.
Log books
• Equipment usage logs should be maintained for critical process
operations and should include product identification, date of
operation, cleaning, and personnel involved with such activity.
12. • The equipment should be qualified for the process and product to be
manufactured.
• There should be a standard written procedure describing the qualification
process of major equipment.
Qualification Of
Major Equipment
• Any automatic, mechanical, and/or instrument used in the
monitoring and control of critical process parameters should be
calibrated and inspected according to a written program. And it
should be documented and controlled.
• an established calibration frequency, calibration method,
approved limits for accuracy and precision, and identification of
the equipment or instrument.
• In the event that the calibration of equipment and instruments
are performed by an external service provider, it should comply
with the provisions laid down by internal company policies.
Calibration
Program Of
Instruments
• Equipment and utensils should be cleaned and maintained in accordance with an
established procedure and program.
• This should contain a description of cleaning methods, level of cleanliness
required, and frequency of such cleaning activities. Records should be maintained.
Cleaning
13. 3. PERSONNEL
Ø The duties and responsibilities of personnel should be in writing and
signed by each employee
• The personnel responsible for the manufacture and control
(testing) of products, including temporary staff, should be
qualified for the function assigned to them.
• The qualification criteria should be based on experience,
education, and training for the role.
QUALIFICATION
• There should be a written procedure in place describing the
job accountability of the aligned job functions.
• A periodic review and evaluation of job performance should
in place for all levels in production-related jobs
JOB
RESPONSIBILITIES
14. • There should be a written program for training and
continuous training of personnel in the functions assigned
to them.
Training
• There should be a written program in place describing the
health and hygiene requirements to be followed by
personnel responsible for manufacturing and testing
activities.
Health and hygiene
• There should be a detailed and updated organizational chart
that clearly identifies the units responsible for production
and quality of the highest order and they should report to
each other.
Organization chart with
reporting structure
15. 4. QUALITY ASSURANCE
Ø There should be a written document describing the system of quality management
according to established policies and quality objectives.
Ø A quality unit should be responsible for approval of product specifications and
standard operating procedures.
Ø There should be a system and written procedures in place to ensure that all
deviations or non-conformances to specifications, procedures, and methods of
analysis are investigated, evaluated, and documented. Analytical results confirmed to
be out of specification could be considered as deviations or non-conformances.
Ø There should be a written procedure for handling product complaints.
Ø There should be a written procedure outlining the process of batch record review and
release/rejection of raw materials and finished products.
16. 4. QUALITY ASSURANCE
Ø It is recommended to have a written procedure that includes identification, documentation, review, and
approval of changes related to manufacturing pro- cesses and methods of analysis.
Ø The quality unit is advised to have a system in place for selection, evaluation, and qualification of suppliers and
vendors. There should be a system to ensure that all suppliers are assessed before being approved and included
in the list of suppliers of raw materials and packaging materials utilized for manufacturing of finished products.
• Documentation required:
o Deviation logs
o Change control logs
o List of SOP (SOP index)
o Master signature list
o Trend reports
o Risk assessments
o Documentation control (batch records, investigations, analytical reports,
o methods, specifications SOPs, etc.)
17. 5. SANITATION PROGRAM
Ø The manufacturing establishment should have written procedures designed to ensure its safe
and sanitary operation and maintenance.
Ø The cleaning procedures should include the cleaning and sanitizing requirements for the
establishment and for all equipment and utensils in it.
Ø A list of all cleaning and sanitizing agents used in the cleaning process should exist, including
their concentrations and uses.
Ø The cleaning intervals for manufacturing areas as well as for equipment should be
established.
18. 6. OPERATIONS
Ø There should be established procedures outlining the clear identification and
separation by physical or control system during manufacturing operations of
multiple products in the same facility.
Ø adequate measures in the manufacturing area to prevent cross-contamination.
Ø Operations should be carried out according to the production process and should be
registered in controlled documents for each batch or lot of the product.
Ø Packaging operations should be performed with the materials specified in the
corresponding packaging order and as per the instructions laid down in a specific
packaging procedure.
19. 7. SPECIFICATIONS
Ø Develop and implement written specifications for all raw and finished
products.
Ø Ensure specifications are maintained and every change is approved by
the quality assurance person prior to use. Set up and follow written
procedures that describe the tests to be conducted to ensure the identity
and purity of finished products. If required, potency must be tested as per
predefined, approved specifications.
Ø Procedure should be in place to ensure each lot of raw and finished
products are in compliance with specifications prior to release
20. 8. STABILITY
Ø Stability studies should be carried out in at least three pilot batches of the same product that
have been manufactured by applying the same manufacturing method that simulates the
process that will be used in the manufacture of commercial pro- duction lots.
Ø Stability studies should be carried out in the same container-closure system or a representative
system to the one proposed for its final storage and distribution.
Ø The conditions of the stability study and its duration should be adequate to cover the storage,
distribution, and usage of the product. The frequency of analysis of stability samples should
be established for the product under study.
21. 9. SAMPLES
Ø There should be a written program in place describing the sampling
practices followed for incoming materials and intermediate, in-
process, and finished products.
Ø The sampling plan should comply with an international standard,
e.g., military standard and ANSI standard.
Ø Based on a specified acceptable level the firm is advised to approve
or reject a production lot.
22. Ø Data should be recorded by the person who performed the activity and once the activity is
completed.
Ø Data recorded should be clear, legible, and ineradicable.
Ø Any correction should be made in such a manner that the original data is not blacked out.
Ø The corrected data should be signed and dated by the person making the correction.
Ø For electronic records, a system should be in place for tracking and for audit traceability to
identify at least the changes made, date of change, and individual who made the changes.
Ø There should be a standard written procedure for the retention period of documents at the
firm.
Ø This includes production records, testing records, distribution records, and all other records
that are deemed to be critical for the control of quality of the product.
10. RECORDS
23. 11. RECALL
ØThere should be written procedures that define controls to
ensure the effective recall of a product, including notification
to regulatory authorities, if applicable.
ØThe procedure should include the following items:
o Personnel responsible for initiating and coordinating recall
activities
o Outlining the steps for implementing a recall
o Distribution records should be maintained for lot
traceability
o Notification to regulatory agencies, if applicable
24. REFERENCE
Nutraceutical and functional food regulation in the United
States and all around the world, second edition , Edited by
Debasis Bagchi,
page no. 64 to 74.
file:///Users/admin/Downloads/RegulationBook2ndEd2014.
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