The proposed dietary supplement cGMPs are modelled after the food cGMPs where the emphasis is not on the purity of the product alone but also on their safety and microbial contamination. These rules are aimed at preventing adulteration and introduction, transmission, or spread of communicable diseases due to microbial pathogens.
The three points that distinguish the dietary supplement cGMPs from the drugs cGMPs are:
- Drugs are tested for related impurities and any impurity more than 0.1% is identified and its safety tested. However, for dietary supplements the "non-actives" can be upto 90% or above can be present. For example, a herbal extract may contain only 10% actives. The rest need not be profiled.
- The second difference is the emphasis on elimination of microbial contamination in dietary supplements. This is to prevent a healthy person who is consuming the dietary supplement from getting sick due to pathogens.
- The third point is that the dietary supplement must have GRAS status, (Generally Recognized As Safe), whereas drugs can be new molecules.
Dietary supplements can be considered as falling somewhere along the continuum between conventional foods on the one hand and drugs on the other. In addition they must meet the pre-set standards for purity and integrity on a consistent basis, just like drugs.
USFDA, taking a lead has proposed a set of rules for organizations which do manufacturing, packaging, holding of herbal products to ensure that the product will meet the specs and will not be adulterated or misbranded. Herbs in use prior to January 1958 anywhere in the world will get GRAS status. For others, data must be generated to show their safety or scientific published literature for their safety should be evidenced to convince the FDA. Having a GRAS status is an essential requirement to qualify as a dietary supplement (DS).
FDA has not proposed specific requirements for disintegration, dissolution, bioavailability, and expiration dating for dietary supplements and dietary ingredients, which are a must for drugs. For botanicals unlike drugs, expiration date is not mandatory but "desirable".
Proposed Regulations - Areas Covered:
- Personnel
- Physical plants
- Equipment and utensils
- Production and process controls
- Holding and distributing
- Consumer complaints related to Good Manufacturing Practices and
- Records and record keeping
Basic objectives of the proposed rules on cGMPs:
- Include ingredient identity testing for predetermined specifications and analytical method validation.
- Ensure that the dietary supplements are produced in a sanitary facility using a master batch procedure.
- Require that manufacturers have documented evidence that their manufacturing process is under control on a consistent basis (pro-cess validation)
- Require manufacturers to test their products for heavy metals, pesticides, solvent residues, and for toxic contaminants such as aflatoxins, lectins, ochrotoxins etc.
- Expiration dating based on stability data is desirable
- Companies report adverse reactions based on consumer complaints
Highlight of the Proposed Rules:
Manufacturers will be responsible that their products are safe and effective. The labels must be truthful and not misleading.
- Personnel requirements: Person must have the required education and training. Those with open wounds or infections will not be allowed inside the plant. Hygienic facilities like clean toilets and practices like washing hands with anti-microbial soap and sanitizing with hot air blowers or disposable towels become a must. Training must be conducted and records of training session kept.
- Physical plant requirements are intended to help prevent cross contamination. Design and construction of the plant that is properly ventilated, layout is unilateral, floors and walls are smooth for easier cleaning and cleanable drainages. The contact surfaces of the reactors and other vessels must be smooth and seamless
- Equipment should be of appropriate design, construction and workmanship for their intended use.
- Calibration of all measu-ring and weighing devices and documented cleaning procedures
- Packaging materials should not contaminate the product
- Production and Process Control: Process must be validated to give consistence results. Proper in-process
GMP for dietary supplements controls; label controls; written manufacturing and batch records are a must. The specifications must have pre-set standards, validated method of analysis and strict adherence to specifications are needed for incoming raw materials as well.
Holding and Distributing:
During holding, protection of products by controlled temperate, humidity and exposure to light conditions; packaging and labeling against contamination and deterioration; label control and documentation for disposal of unused labels, separate dispensing rooms are a must.
Consumer Complaints:
Written records, review and processing of complaints which involve a possible failure of the product to meet any of its specifications including complaints of adverse reactions is an essential part of cGMP rules. Each complaint investigation must be documented and relevant files maintained.
For the purpose of these regulations, a consumer complaint about a product quality may or may not include concerns about a possible hazard to health. However, if consumer complaint does include an adverse event (illness or injury related to safety of a particular dietary ingredient), it will be independent of whether the product is produced under cGMPs.
Record Keeping:
This would indicate as to how long a firm must keep certain records to show that the cGMP requirements were complied with (3 years beyond the date of manufacture).
When a deviation occurs, it must be documented to prove that required quality control measures and practices were performed as often as necessary to ensure pre-set controls
Identity of Botanicals:
Grown plant cannot be identified with certainty from species to species in powdered form. Therefore, chemicals, markers or actives' content in the plant material must be given in the specification (Certificate of botanical identity would be an adequate record in the form of a voucher specimen of the plant that would be held for a specified period of time).
- (Dr R K Bammi (Director) & Dr S Natarajan (R&D Advisor) Sami Labs Ltd, Bangalore)