chemical Tag

The European Medicines Agency (EMA) provides answers to frequently asked questions on Good Manufacturing Practice (GMP) and Good Distribution Practice (GDP) on its website. These have been discussed and agreed by the GMP/GDP Inspectors Working Group.

The guide, in the form of a question and answer (Q&A), provides further interpretation of the GMP and GDP guidelines published by the European Commission.

On January 28, 2022, Directive 2001/82/EC – EU Code for Veterinary Medicinal Products was repealed, as a result, the legal requirements for veterinary medicinal products have been updated and will be regulated according to Regulation (EU) 2019/6 of the European Parliament and of the Council on veterinary medicinal products. This regulation includes provisions on authorisation, post-authorisation measures, manufacture, import, export, supply and use of veterinary medicinal products, as well as restrictions and sanctions. Accordingly, the questions and answers have been supplemented and updated.

The new chapter deals with requirements for active substances that are used as starting materials for the manufacture of veterinary medicinal products.

The following are some questions that have been answered:


  1. Do active substances used as starting materials in veterinary medicinal products have to comply with Good Manufacturing Practices (“GMP”) for active substances for human medicinal products?
  2. Are there new obligations for active substances used as starting materials in veterinary medicinal products under the Veterinary Medicines Regulation?
  3. Is a GMP certificate mandatory for manufacturing sites?
  4. Can inspections conducted by third country competent authorities be considered when deciding whether a Union inspection should be triggered?


The complete list of questions and answers is available on the EMA website.

On 28 January 2022, the Veterinary Medicinal Products Regulation (Regulation (EU) 2019/6), updating the existing rules on the authorization and use of veterinary medicinal products in the European Union, entered into force.

Regulation (EU) 2019/6 repealed Directive 2001/82/EC; bringing new measures to increase the availability and safety of veterinary medicines, it should also strengthen EU action against antimicrobial resistance. In addition, it amended the provisions of Regulation (EU) 726/2004 on the authorization and supervision of veterinary medicinal products, which currently governs the centralized marketing authorization procedure for both human and veterinary medicinal products.

In accordance with Regulation (EU) 2019/6, the European Commission added two standalone GDP regulations, all documents can be found in Eudralex Volume 4:

The documents were developed analogously to the GDP guidelines for for medicinal products for human use and related active substances.

In the Pharmacopeial Forum, PF 48(1), a proposal for a new general chapter <1504> Quality Attributes of Starting Materials for the Chemical Synthesis of Therapeutic Peptides was published. The draft of the new chapter is available on PF Online.

Structure of the New Chapter

The new chapter is divided into the following sections:

  • Scope
  • Introduction
  • Supplier qualification and evaluation of synthetic route
  • Amino acid derivatives (AAD)-related impurities originating from amino acids
  • AAD-related impurities originating from the AAD manufacturing process
  • Non-AAD impurities
  • Conclusion and recommendations for AAD specifications


According to the Expert Panel, the purpose of the new chapter is to provide an overview of the minimum quality attributes required for Starting Materials used in the production of synthetic therapeutic peptides. Consideration in the new chapter focuses on the most commonly used protected amino acid derivatives (AAD). However, the general concepts and guidance described can be applied to all peptide starting materials.

As these starting materials (amino acids, protected amino acid derivatives, and fragments ) have the potential to directly impact the quality of the drug substance, special attention must be paid to the quality attributes.

The synthetic route for the amino acid derivative could potentially lead to several impurities, which depending on the classification could be related to a different degree of criticality.

According to the new chapter, the most common quality attributes to be used for protected amino acid derivative starting materials are:

  • Appearance
  • Identification
  • Related impurities
  • Other impurities (not related)
  • Assay by titration
  • Other components