European Directorate for the Quality of Medicines & HealthCare (EDQM) has issued the draft guidelines on substances for pharmaceutical use. Comments on the draft guidelines which are now being circulated to the industry globally including India have to be submitted before September 30, 2012.

According to the draft document, the general monograph does not apply to herbal drugs for plant medications, extracts or mother tinctures for homoeopathic preparations. Now the European regulatory authority calls for separate general monographs.

When a substance for pharmaceutical use is indicated in an individual monograph the requirements of viral safety apply. This is because the substances for pharmaceutical use are the starting materials for subsequent formulation to prepare medicinal products. Depending on the formulation, certain substances may be used either as active substances or as excipients. Solid substances may be compacted, coated, granulated, powdered to a certain fineness or processed. A monograph is applicable to a substance processed with excipients only where such processing is mentioned in the definition section of the monograph.

Substance special pharma grade intended for human and veterinary use which is of appropriate quality for the manufacture of all dosage forms can be used. Under the Polymorphism, the individual monographs do not usually specify crystalline or amorphous forms, unless bioavailability is affected. All forms of a substance for pharmaceutical use must comply with the requirements of the monograph, stated the guideline.

Further, EDQM insisted that substances for pharmaceutical use must be manufactured by procedures that are designed to ensure a consistent quality and comply with the requirements of the individual monograph or approved specification. It must be undertaken under conditions of good manufacturing practices.

The drug regulatory authority went on to state that whether or not it is specifically stated in the individual monograph, if the substance is a  recombinant protein or obtained as a direct gene product based on genetic modification, it should also comply with the requirements of the general monograph.

Products of recombinant DNA technology obtained from animals susceptible to transmissible spongiform encephalopathies other than by experimental challenge, should also comply with the requirements of the general monograph.

Under the products of fermentation, if solvents are used during production, they should be of suitable quality. In addition, their toxicity and their residual level must be taken into consideration and if water is used during production, should also be of the desired quality.

The provisions of chapter 5.20 of the guidance focuses on the residues of metal catalysts and metal reagents used in the production of substances for pharmaceutical use. If substances are produced or processed to yield a certain form or grade, EDQM insists that it should comply with the requirements of the monograph. Certain functionality-related tests may be suggested to  control properties which will help to ascertain the microbiological quality, sterility and bacterial endotoxins.

With reference to the labelling, EDQM has also insisted that it is subject to national regulation and international agreements. The statements under the heading labelling need to be comprehensive to demonstrate compliance or non-compliance with the monograph.

The industry has positively reacted to the EDQM guidance and stated that such stringent measures are needed to manufacture the drugs in the wake of a proliferation of counterfeits in the market and non adherence to quality practices.