(2002; 166 pages)
Quality of starting materials for drugs and vaccines
Dr Jose Pena, Chile
Starting material is defined as any active or inactive substance or compound, used in the manufacture of medicines, that is modified or disappears during the production process. The quality, safety and efficacy of pharmaceutical products are closely related to the quality of the starting materials. The consequences of using starting materials of inadequate quality can be serious, and this has led WHO to draft recommendations for all parties involved.
Guidelines that are generally accepted by national authorities have been drawn up for the quality control of starting materials for herbal medicinal products, vaccines, and pharmaceutical or biological products prepared by DNA recombinant technology. The uniformity of production depends on the quality of the starting material and therefore the physical, chemical and microbiological properties of such materials should be defined and well documented. The specification of the active substances and of the excipients should be re-evaluated periodically. Wherever possible, pharmacopoeial rules should be followed.
One of the challenges faced by many developing countries in the short term is to have therapeutic equivalence. In order to achieve this, we need to work on the basis of pharmaceutical equivalence, bioequivalence and GMP. A proposal, to be considered for adoption in February 2003 by the WHO Expert Committee on Pharmaceutical Specifications for a Certification Scheme for Starting Materials Circulating in International Trade, includes two possible schemes. The first one is a Model Certificate for the Production of the Pharmaceutical Raw Materials, to be issued by the national regulatory authority. If there is no such body, WHO proposes a Model Certificate for the Production of Pharmaceutical Starting Materials, to be issued by the producer. A Certificate for Pharmaceutical Starting Material can be requested within the framework of the Scheme by the exporter, the importer or the regulatory authority of the importing country.
The Certificate is intended to be a confidential document issued by the competent authority in the exporting country. If there are any doubts concerning the status or validity of the certificate, the competent authority in the importing country might require a copy to be sent directly from the certifying authority. If there is no specific approval, each certificate will be drawn up in the language of the certifying authority and it will be the applicant’s responsibility to provide any translations required. Since the issuing of these certificates means a heavier workload for the certifying authorities, this should probably be funded by the applicant; the certificate will be valid until a given date. However, the certificate would no longer be valid if the manufacturing process changes, or if the manufacturer does not comply with GMP. The certifying authority will be responsible for ensuring the authenticity of the data certified.
In parallel with implementation of the guideline on Good Trade and Distribution Practices, each certificate should identify the importing country so as to prevent misuse of the system and counterfeiting. Moreover, it can avoid the issuing of unnecessary complementary certificates by independent authorities. The certifying authority could have a comprehensive register of the countries to which starting materials have been exported.