USP〈1504〉 QUALITY ATTRIBUTES OF STARTING MATERIALS FOR THE CHEMICAL SYNTHESIS OF THERAPEUTIC PEPTIDES

SCOPE

This general chapter is intended to provide guidance on the minimum quality attributes for starting materials used in the manufacture of synthetic therapeutic peptides. Because it is not possible to cover the wide variety of available starting materials that may be used, including amino acids, protected amino acid derivatives, and peptide fragments, the discussion in this chapter will be limited to the most commonly used protected amino acid derivatives (AAD), i.e., 9-fluorenylmethyloxycarbonyl (Fmoc) amino acid derivatives. However, it is intended that the general concepts and guidance provided for this class of starting materials should be applied to all peptide starting materials, where applicable. This chapter is to be used in conjunction with Quality Attributes of Synthetic Peptide Drug Substances 〈1503〉.

INTRODUCTION

The increased interest in peptides as drug candidates during the past few decades can be attributed to a number of factors, including advances in proteomics and high-throughput screening techniques, which have accelerated the development of new potential therapeutic candidates. Furthermore, the development of efficient synthetic chemical strategies, combined with robust purification processes and more powerful and discriminating analytical methodologies, have facilitated the manufacture of peptides with high-quality standards. The evolution of these synthetic strategies started with the manufacture of relatively short peptides but today, the manufacture of longer peptides, which traditionally have been manufactured by biological processes, is feasible using synthetic chemical techniques.

Because synthetic peptides are not classified as small molecules or biological products [final rule on the Definition of the Term “Biological Product” (85 FR 10057, February 21, 2020)], they are excluded from many guidance documents. 〈1503〉 provides an overview of the current status regarding the quality attributes of synthetic peptides used as drug substances.

In the manufacture of any active pharmaceutical ingredient (API; this term is used interchangeably with “drug substance”), the term “raw material” is used independently for describing starting materials (SMs), solvents, and reagents. From a quality point of view, the “most critical” raw materials are those that are incorporated as significant structural fragments into the structure of the API. From a regulatory perspective, these critical raw materials are known as SMs because their introduction into the manufacturing process establishes the point at which the production of the API begins.

Source from USP and Please refer to USP for details:https://online.uspnf.com/uspnf/document/2_GUID-06A07B0B-3865-40B6-A4C9-D77B5DAD0B3B_10101_en-US?

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