Two important guidelines from the European Commission were recently published. These include Good Distribution Practices of Active Substances used in Medicinal Products and Formalized Risk Assessment for Ascertaining the Appropriate Good Manufacturing Practice for Excipients for Medicinal Products for Human Use. Both may be found in the Official Journal of the European Union, Information and Notices, dated March 21, 2015. They represent finalization of the versions published for comment in February 2013 and those draft versions maybe found HERE and HERE respectively. A copy of the Official Journal of the European Union that I have highlighted to identify the additions not present in the draft version may be found HERE. Overall, there is greater specificity in the requirements in the finalized versions than existed in the drafts. Distributors and manufacturers would be well served to evaluate whether any changes in process or procedures need to be made to comply in advance of the implementation date. Selected significant additions present in the final version that were not in the draft include:
GDPs for Active Substances:
2.2. The quality system should be adequately resourced with competent personnel, and suitable and sufficient premises, equipment and facilities. It should ensure that:
(i) active substances are procured, imported, held, supplied or exported in a way that is compliant with the requirements of GDP for active substances;
(ii) management responsibilities are clearly specified;
(iii) active substances are delivered to the right recipients within a satisfactory time period;
(iv) records are made contemporaneously;
(v) deviations from established procedures are documented and investigated;
4.2 Documentation should be sufficiently comprehensive with respect to the scope of the distributor’s activities and in a language understood by personnel. It should be written in clear, unambiguous language and be free from errors.
4.3 Any alteration made in the documentation should be signed and dated; the alteration should permit the reading of the original documentation. Where appropriate, the reason for the alteration should be recorded.
6.10. Electronic Warehouse Management Systems should be validated.
6.12 Where storage or transportation of active substances is contracted out the distributor should ensure that the contract acceptor knows and follows the appropriate storage and transport conditions. There must be a written contract between the contract giver and the contract acceptor, which clearly establishes the duties of each party. The contract acceptor should not sub-contract any of the work entrusted to him under the contract without the contract giver’s written authorization.
Risk Assessment for Ascertaining the Appropriate Good Manufacturing Practice for Excipients
2.3 For each excipient….Areas for consideration should include, but not be limited to:
(vii) Environmental control and storage / transportation conditions including cold chain management if appropriate.
(viii) Supply chain complexity
(ix) Stability of excipient
(x) Packaging integrity evidence
2.4. Additionally, with respect to the use and function of each excipient, the manufacturing authorisation holder should consider:
(i) the pharmaceutical form and use of the medicinal product containing the excipient;
(ii) the function of the excipient in the formulation, e.g. lubricant in a tablet product or preservative material in a liquid formulation, etc.;
(iii) the proportion of the excipient in the medicinal product composition;
(iv) daily patient intake of the excipient;
(v) any known quality defects/fraudulent adulterations, both globally and at a local company level related to the excipient;
(vi) whether the excipient is a composite;
(vii) known or potential impact on the critical quality attributes of the medicinal product;
(viii) other factors as identified or known to be relevant to assuring patient safety.
Again, for the identification of all additions made to the final guidelines, please click HERE.