Innovation in generics: Increased efficiency through peptide API synthesis expertise

With the healthcare landscape continually evolving, the generic medicines industry guarantees widespread access to affordable medications for millions of patients worldwide. Generics play a pivotal role in meeting the diverse needs of today, ensuring the consistent availability of medications. However, amidst the competitive and logistical hurdles the pharmaceutical industry faces, generics manufacturers must continually assess and fortify their resilience and adaptability strategies, in order to remain at the forefront of healthcare innovation in a changing global market.

In pharmaceutical manufacturing, API (Active Pharmaceutical Ingredients) production expertise is vital to achieve process efficiency and affordability. Industry leaders in generic drugs will incorporate technological and methodological synergies in the production of different APIs, with a collective responsibility to improve production processes to support the goals of the generic drug industry.

Among the different families of APIs, peptides represent a growing class, with challenges revolving around accessibility and affordability. One example of generic peptides that offer potential for improvement in the manufacturing process are Gonadotropin-releasing hormone (GnRH) analogues – Goserelin, Leuprorelin, and Triptorelin. Improving manufacturing not only improves affordability, but also brings about reliable and replicable quality, a resilient supply chain, and accelerated product innovation.

Peptide API synthesis – a uniquely challenging process

The production process of peptide APIs is not without obstacles. Peptides are a short chain of monomers called amino-acids and linked together in a certain order called a sequence, which is responsible for their biological properties. The nature of this class of molecules makes them complex and requires specialist expertise to synthesise them efficiently.

Peptide APIs are manufactured via a series of chemical reactions assembling a chain from monomeric components. The most common synthesis routes consist of either solid-phase peptide synthesis (SPPS) or liquid-phase peptide synthesis (such as GnRH analogues).

In SPPS, the peptide chain is built one amino acid at a time on a solid support, with each amino acid added one after another until the desired sequence is achieved. Meanwhile, liquid-phase peptide synthesis (LPPS) involves the coupling of amino acids in solution, resulting in greater flexibility in sequence. With SPPS being a purely linear approach, LPPS offers more convergence in the synthesis in comparison.

Such synthesis methods are effective in producing a variety of peptides, however, the process must be optimised in order to keep up with increasing customer demand and authorities’ requirements. Thus, it is vital to increase process efficiency and quality when multiple peptides are synthesised at the same time and on a similarly-scaled production floor – as adding more reactor capacity might not be possible. With this in mind, peptides sharing a constant segment of amino acids, such as the GnRH analogues, offer potential efficiency improvements using synergies in the manufacturing of various peptide APIs.

What is converging LPPS? Achieving efficiency through commonalities

Liquid-phase peptide synthesis (LPPS) is a particularly important synthesis method in the manufacturing of GnRH analogues, hosting numerous benefits.

Each of the GnRH analogue sequences have a “constant segment”, where they share the same amino acids. This common segment between different APIs confers numerous advantages when optimising manufacturing efficiency. The

general synthesis of these GnRH analogues is done through LPPS, which facilitates a convergent approach. The constant segments are synthesised individually and then used in all subsequent steps.

The customer then benefits from these synergies, through process efficiency, consistency in production quality, a more secure supply chain, accelerated development of new processes, and a faster time to market.

Converging LPPS provides significant advantages for synthesis of multiple peptides

1. Process efficiency

Through the convergent approach, greater efficiency is achieved by utilising common steps to produce multiple analogues, thus streamlining processes. These improvements, encompassing raw materials, labour, and overall production costs - which can have an impact on the price of the finished drug product for patients - are realised by customers through more attractive prices. This widens access to these life-saving medications, making them more available to a broader patient population.

2. Consistent quality

This approach also results in consistent quality in the manufacturing process. The “constant segment” shared among different analogues results in a more uniform production process, ensuring more product meets stringent quality checks. This in turn reduces production time, ensuring on-time supply of medications to patients.

3. More resilient supply chain

Through synthesis of multiple analogues via a common process, manufacturers reduce risk of shortages or disruptions in the supply chain. This is particularly important in making sure patients who depend on regular supply have reliable access to their medication, which is made possible by the continuous and consistent flow of APIs produced.

4. Faster development of new products

The convergent synthesis approach is able to accelerate the development of new GnRH analogues or new processes – in turn providing patients in need of urgent care with the medication they require more promptly and efficiently. Experienced manufacturers can navigate the complexities of convergent synthesis with assurance, resulting in a faster time to market.

Unlocking improved API development

When synthesising GnRH analogues, specialist production knowledge and experience is key in promoting efficiency and realising a multitude of benefits. From process efficiencies and reliable quality at scale to a flexible supply chain, the convergent approach through LPPS is a huge step forward in the improvement of pharmaceutical manufacturing.

As demand for generics medications grows, the ensured supply of APIs becomes increasingly important – along with ensuring such demand is responded to with affordable and accessible prices.