The European Medicines Agency (EMA) has adopted a new guideline on manufacture of the finished dosage form of medicinal products for human use (“the new Guideline”).

Background

The new guideline replaces the 1996 “Note for Guidance on Manufacture of the Finished Dosage Form” (CPMP/QWP/486/95) to reflect the requirements laid down in the Directive 2001/83/EC of 6 November 2001 on the Community code relating to medicinal products for human use.

The EMA’s new Guideline underlines that the document does not introduce any new requirements concerning authorised medicinal products. The main objective of the new Guideline is to provide clarity concerning the type and level of information that should be included in the Common Technical Document (CTD) Module 3 of the marketing authorisation application dossier for a medicinal product in relation to the manufacturing process description.

The new Guideline aims to address the complexity of the current manufacturing practices in terms of supply chains and worldwide manufacture and it takes into account the content and the principles of the ICH Q8 guideline.

Manufacturing process description in the CTD Module 3

The new Guideline applies to the manufacture of the finished dosage form of chemical and herbal medicinal products for human use. The Guideline clarifies that the principles provided therein also apply to biological medicinal products and, where relevant, to the manufacture of the finished dosage form of radiopharmaceuticals and chemical investigational medicinal products.

In particular, with respect to the “Description of Manufacturing Process and Process Controls” section of the CTD Module 3, the new Guideline requires that manufacturers should provide a narrative description of the entire manufacturing process. Manufacturers should provide a flow chart describing each stage of the process including in-process controls and showing at each stage where materials enter the process. The description must be adequately based on development data.

Among other aspects, the new Guideline discusses the technical adaptations proposed in the manufacturing process. The EMA provides that technical adaptations are acceptable when the manufacturer provides evidence that all steps proposed will consistently produce any intermediate and finished product that comply with the in-process controls and the product specifications.

With respect to the “Controls of Critical Steps and Intermediates” section of the CTD Module 3, the new Guideline provides that all critical steps and intermediates identified during the manufacture of the finished product should be listed in this section including any in-process controls, applied test methods and acceptance criteria.

For complex control strategies, manufacturers must describe the frequency of in-process controls and provide information concerning how unexpected deviations from the approved manufacturing process would be detected and managed.

Page 12 of the Annex to the new Guideline provides an example of manufacturing process description that aims at clarifying the EMA’s expectations in terms of level of detail. The Annex provides an illustration of the information that could be provided, depending on the development approach followed.

The new Guideline will come into effect six months after the date of its publication, i.e. on 14 February 2018.