GMP for nutritional supplements

Implementation of good manufacturing practices in the production of nutraceuticals has become imperative for maintaining a significant share in the global market, say R M Gupta, S Vishweshwar and Uttara Joshi

The importance of nutraceuticals have been well recognized by regulatory authorities all over the world. US FDA has issued guidelines on GMP for nutraceuticals. Implementation of good manufacturing practices (GMP) for the production of quality nutraceutical is a must for global market share.

Organization and personnel

Responsibilities of Quality Control unit: A quality control unit should be established that has the responsibility and authority to approve or reject all components, product containers, closures, in-process materials, packaging material, labelling, and finished nutritional products, and the authority to review production records to ensure that no errors have occurred or, for approving or rejecting products manufactured, processed, packed, or held under contract by another company.

The quality control unit should have the responsibility for approving or rejecting all procedures or specifications that impact on the identity, strength, quality, and purity of the nutritional product. All responsibilities and procedures applicable to the quality control unit should be in writing.

Personnel qualifications: Each person engaged in the manufacture of a nutritional product should have the proper education, training, and experience (or any combination thereof) needed to perform the assigned functions. Training should be in the particular operation(s) that the employee performs and should be based on current good manufacturing practices as they relate to the employee’s functions.

Each person responsible for supervising the manufacture of a nutritional product should have the proper education, training, and experience (or any combination thereof) to perform assigned functions in such a manner as to provide assurance that the product has the safety, identity, strength, quality, and purity that it is represented to possess. An adequate number of qualified personnel to perform and supervise the manufacture of each nutritional product should be provided.

Personnel responsibilities: Personnel engaged in the manufacture of a nutritional product should wear clean clothing appropriate for the duties they perform. Protective apparel, such as head and hand covering, should be worn, as necessary, to protect products from contamination. All personnel should practice good sanitation and health habits. All personnel should take any other necessary precaution to prevent contamination of products with microorganisms or foreign substances including, but not limited to, perspiration, hair, cosmetics, tobacco, chemicals, and medicants.

Buildings and facilities: Any building or buildings used in the manufacture of a nutritional product should be of suitable size, construction, and location to facilitate cleaning, maintenance, and proper operations.

These separate or defined areas are as follows:

• An area for the receipt, identification, storage, and withholding from use of components, product containers, closures, and labelling, pending the appropriate sampling, testing, or examination by the quality control unit before release for manufacturing or packaging.
• An area for the storage of released components, product containers, closures, and labelling.
• An area for storage of in-process materials.
• An area for manufacturing and processing operations.
• An area for packaging and labelling operations.
• An area for control and laboratory operations.

Any building used in the manufacture of a nutritional product shall be maintained in a good state of repair. Lighting: Adequate lighting should be provided in all areas and should not expose bulk or finished product to adulteration or contamination.

Ventilation, air filtration, air heating and cooling: Adequate ventilation should be provided, as well as equipment for adequate control over microorganisms, dust, humidity, and temperature when appropriate for the manufacture of a nutritional product.

Plumbing: Potable water should be supplied in a plumbing system free of defects that could contribute contamination to any nutritional product. Potable water should meet the standards prescribed in the Environmental Protection Agency’s Primary Drinking Water Regulations (40 CFR Part 141). Sewage and refuse: Sewage, trash, and other refuse in and from the building and immediate premises should be disposed of in a safe and sanitary manner.

Washing and toilet facilities: Adequate washing facilities should be provided, including hot and cold water, soap or detergent, air driers or single-service towels, and clean toilet facilities easily accessible to working areas.

Sanitation: Any building used in the manufacture of a nutritional product should be maintained in a clean and sanitary matter shall be held and disposed of in a timely and sanitary manner.

Equipment: Equipment used in the manufacture of a nutritional product should be of appropriate design, adequate size, and suitably located to facilitate operations for its intended use and for its cleaning and maintenance.

Construction: All equipment should be constructed so that surfaces that contact components, in-process materials, or finished products are not reactive, additive, or absorptive so as to alter the safety, identity, strength, quality, or purity of the product beyond the established requirements.

Equipment and utensils should be cleaned, maintained, and sanitized at appropriate intervals to prevent malfunctions or contamination that would alter the safety, identity, strength, quality, or purity of the product beyond the established requirements.

Written procedures for cleaning and maintaining equipment, including utensils, used in the manufacture of a product should be established and followed.

Components, product containers and closures

Written procedures describing in sufficient detail the receipt, identification, storage, handling, sampling, testing, and approval or rejection of components, product containers, and closures should be provided. Components, product containers, and closures at all times should be handled and stored in a manner to prevent contamination.

Receipt and storage of untested components, product containers, and closures Upon receipt and before acceptance, each container or grouping of containers of components, product containers, and closures should be examined visually for appropriate labelling as to contents, container damage, or broken seals, and for contamination. They are then stored under quarantine until they have been tested or examined, as appropriate, and released.

Testing and approval or rejection: Each lot of components, product containers, and closures should be sampled, tested, or examined, as appropriate, and released for use by the quality control unit Representative samples should be collected for testing or examination. The following procedures should be used to collect the samples: At least one test should be conducted to verify the identity of each component of a product if skip-lot testing is used.

Each component should be tested for conformity with all appropriate written specifications for purity, Representative samples should be collected for testing or examination. The number of containers sampled, and the amount of material taken from each container, should be based upon appropriate criteria such as statistical criteria for component variability, confidence levels, and degree of precision desired, the past quality history of the supplier, and the quantity needed for analysis and reserve where required.

Procedures used to collect the samples: The containers of components selected should be cleaned, where necessary, by appropriate means.

• The containers should be opened, sampled, and resealed in a manner designed to prevent contamination of their contents and contamination of other components, product containers, or closures.
• These containers should be identified so that the following information can be determined: name of the material sampled, the lot number, the container from which the sample was taken, the date on which the sample was taken, and the name of the person who collected the sample

Procedures to examine and test the samples:

• At least one test should be conducted to verify the identity of each component of a product if skip-lot testing is used.
• Each component should be tested for conformity with all appropriate written specifications for purity, strength, and quality. However, a report of analysis may be accepted from the supplier of a component, provided that at least one identity test is conducted on such component by the manufacturer. Containers and closures should be tested for conformance with all appropriate written procedures.
• However, a certificate of testing may be accepted from the supplier, provided that at least a visual identification is conducted on such containers/closures by the manufacturer.
• Each lot of a component, product container, or closure that is liable to contamination with filth, insect infestation, or other extraneous adulterant should be examined against established specifications for such contamination. Skip-lot examination should not apply in such cases. Each lot of a component, product container, or closure that is liable to microbiological contamination that is objectionable in view of its intended use should be subjected to microbiological tests before use.

Skip-lot examination should not apply in such cases. Any lot of component, product container, or closure that meets the appropriate written specifications of identity, strength, quality, and purity and related tests may be approved and released for use.

• Any lot of such material that does not meet such specifications should be rejected. Representative samples should be collected for testing or examination. The number of containers sampled, and the amount of material taken from each container, should be based upon appropriate criteria such as statistical criteria for component variability, confidence levels, and degree of precision desired, the past quality history of the supplier, and the quantity needed for analysis and reserve where required. The following procedures should be used to collect the samples: The containers of components selected should be cleaned, where necessary, by appropriate means.
• The containers should be opened, sampled, and resealed in a manner designed to prevent contamination of their contents and contamination of other components, product containers, or closures.
• These containers should be identified so that the following information can be determined: name of the material sampled, the lot number, the container from which the sample was taken, the date on which the sample was taken, and the name of the person who collected the sample. Use the following procedure to examine and test the samples:
• At least one test should be conducted to verify the identity of each component of a product if skip-lot testing is used. Each component should be tested for conformity with all appropriate written specifications for purity, strength, and quality. However, a report of analysis may be accepted from the supplier of a component, provided that at least one identity test is conducted on such component by the manufacturer. Containers and closures should be tested for conformance with all appropriate written procedures.
• However, a certificate of testing may be accepted from the supplier, provided that at least a visual identification is conducted on such containers/closures by the manufacturer.
• Each lot of a component, product container, or closure that is liable to contamination with filth, insect infestation, or other extraneous adulterant should be examined against established specifications for such contamination. Skip-lot examination should not apply in such cases. Each lot of a component, product container, or closure that is liable to microbiological contamination that is objectionable in view of its intended use should be subjected to microbiological tests before use.

Skip-lot examination should not apply in such cases. Any lot of component, product container, or closure that meets the appropriate written specifications of identity, strength, quality, and purity and related tests may be approved and released for use. Any lot of such material that does not meet such specifications should be rejected. Use of approved components, product containers, and closures components, product containers, and closures approved for use should be rotated so that the oldest approved stock is used first. Deviation from the requirement is permitted if such deviation is temporary and appropriate.

To be continued

The writers R M Gupta is with Perfect Consultants, S Vishweshwar is with M M Research Foundation and Uttara Joshi is lecturer, Modern College of Pharmacy, Pune part III is final