药明康德发布多肽制造五大趋势科普稿：口服给药推升API需求，但无订单/业绩等增量事实

WuXi AppTec outlines five peptide manufacturing trends for 2026 as oral dosing raises API demand and moves scale-up pressure into purification and supply.
San Diego, CA, Oct. 21, 2026 (GLOBE NEWSWIRE) --
Oral peptide dosing can require 10 to 100 times the dose, and therefore the active pharmaceutical ingredient (API), when oral bioavailability falls below 1%, according to a 2026 review in Frontiers in Drug Delivery.¹ The shift is shaping
peptide manufacturing trends in 2026
, moving scale-up pressure past synthesis and into route design, building-block supply, purification and drug product. In one published WuXi TIDES peptide program, the team raised overall route yield from less than 0.1% to 3%. It delivered Good Laboratory Practice (GLP) and Good Manufacturing Practice (GMP) API in 10 months.
1. Oral Peptide Dosing Can Multiply the API a Program Must Make
In practical terms, a peptide dosed at 1 mg per day by injection would need approximately 100 mg per day orally at 1% bioavailability. The same review in Frontiers in Drug Delivery notes that manufacturing costs for synthetic peptides scale approximately linearly with dose, so that increase carries into raw material needs, manufacturing capacity and quality control. It also describes oral semaglutide as a boundary case rather than proof that oral delivery suits most peptides.
Oral octreotide shows the multiplier in an approved product. According to the FDA label for Mycapssa, a single 20 mg oral dose of octreotide acetate produced systemic exposure similar to a 0.1 mg subcutaneous dose, a 200-fold difference in administered mass.² The comparison is specific to that product and study, but it shows how far oral delivery can raise the API a program has to make.
As a result, the API needed for an oral program cannot be estimated from the injectable dose. Eventual dose, patient population, route yield, purification recovery and drug product requirements have to be modeled together, early.
In a
published case study
, WuXi TIDES evaluated four synthesis routes and eight sets of conditions for a next-generation oral cyclic peptide, moving from a 50-g demonstration batch to a 1-kg demonstration batch and then a 6-kg GLP batch within six months. The case covers preclinical scale-up and does not establish clinical performance or commercial manufacturing readiness.
“Oral delivery changes how much API a peptide program has to make. A patient may absorb only a small share of each dose, yet every gram of API still has to be synthesized, purified and released to specification, so route efficiency and downstream capacity become early design choices,” said Yu Lu, Senior Vice President, WuXi TIDES, part of WuXi AppTec.
2. Fragment Routes Raised One Long-Peptide Yield From Under 0.1% to 3%
The coupling efficiency and overall yield drop sharply when peptides longer than 50 amino acids are built by conventional solid-phase synthesis. Hybrid and convergent routes get around that limit: shorter fragments are prepared separately, then joined.
Published work on the kilogram-scale GMP manufacture of tirzepatide shows the approach at volume.³ Researchers developed a hybrid solid- and liquid-phase route with continuous processing, real-time analytical monitoring and nanofiltration for intermediate purification.
In a
published WuXi TIDES program
, a complex peptide conjugate needed an 87-step synthesis. The team rebuilt the original route as fragments under 50 amino acids, linked by chemical ligation. Overall yield rose from less than 0.1% to 3%. Separate teams could make fragments in parallel, which shortened the timeline. WuXi TIDES runs solid-phase, liquid-phase and hybrid synthesis, using both linear and convergent routes, on its peptide API process development platform.
3. Building-Block Supply Is Moving Onto the Critical Path
Unnatural amino acids, linkers and other modified components can determine both route design and timeline. When a required building block has limited commercial supply, teams have three options: qualify a new source, make it internally or redesign the route.
In the same conjugate program, three unnatural amino acid starting materials were in limited supply. WuXi TIDES developed synthetic processes for them and produced more than 3 kg in-house to support GLP and GMP production. That took an external supply dependency off the program’s critical path.
4. Purification Capacity Has to Match Synthesis Output
A faster route moves the bottleneck downstream if chromatography, filtration, isolation and analytical throughput do not scale with it. Purification often trades purity against recovery, since narrower chromatographic fractions improve purity but leave usable product in neighboring fractions. Research on synthetic glucagon showed that continuous multicolumn chromatography with internal recycling of product-containing fractions could ease that trade-off.⁴
In the conjugate program, the original column material was unstable under basic buffer conditions. WuXi TIDES screened alternatives and worked with the supplier on a custom alkali-resistant blend. The new column reduced impurities by 80% and increased final overall yield by 20%. WuXi TIDES also includes continuous chromatography in its peptide purification toolbox.
5. Drug Product Belongs in the Scale-Up Plan
Oral peptide programs rely on formulation approaches built around a molecule’s absorption, including permeation enhancers and specialized dosage forms. The Frontiers in Drug Delivery review concludes that oral success depends on molecular pharmacology rather than formulation technology. API volume, solid-state requirements, the formulation process and finished-dose capacity therefore need to be planned together. Integrated contract research, development and manufacturing organization (CRDMO) models offer one way to coordinate that planning. WuXi TIDES provides peptide API and drug product development and manufacturing, including spray drying, under one global quality system, from preclinical through commercial stages.
As oral peptide programs advance, the API required per patient will keep shaping peptide manufacturing decisions, from route selection through the finished dose.
Sources:
¹ Niazi, Sarfaraz K. "Oral Delivery of Peptides and Proteins: Pharmacokinetic Boundaries, Negative Selection, and Route Triage."
Frontiers in Drug Delivery
, vol. 6, 2026, article 1776167,
https://doi.org/10.3389/fddev.2026.1776167
.
² Chiesi USA, Inc. "Mycapssa (Octreotide) Capsule, Delayed Release."
DailyMed
, National Library of Medicine, 24 July 2025, dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=58d80bc6-bdfb-4908-93e7-aace447c8d1a.
³ Frederick, Michael O., et al. "Kilogram-Scale GMP Manufacture of Tirzepatide Using a Hybrid SPPS/LPPS Approach with Continuous Manufacturing."
Organic Process Research & Development
, vol. 25, no. 7, July 2021, pp. 1628–36,
https://doi.org/10.1021/acs.oprd.1c00108
.
⁴ Luca, Chiara De et al. “From batch to continuous chromatographic purification of a therapeutic peptide through multicolumn countercurrent solvent gradient purification.” Journal of chromatography. A vol. 1625 (2020): 461304. doi:10.1016/j.chroma.2020.461304
Frequently Asked Questions
Question: What are the biggest peptide manufacturing trends in 2026?
Answer: Five trends are shaping peptide manufacturing in 2026:
Oral dosing that multiplies API demand
Fragment-based routes for long peptides
Building-block supply moving onto the critical path
Purification capacity that must match synthesis output
Drug product planned alongside API
At oral bioavailability below 1%, a program can need 10 to 100 times the dose. That pushes pressure through every step after synthesis.
Question: How much more API does an oral peptide need than an injectable?
Answer: At 1% oral bioavailability, a peptide dosed at 1 mg per day by injection would need approximately 100 mg per day orally, according to a 2026 review in Frontiers in Drug Delivery. The review puts typical oral bioavailability for systemic peptides below 1% and notes that synthetic peptide manufacturing costs scale approximately linearly with dose. The actual multiplier depends on the molecule, formulation and pharmacokinetics.
Question: Why are hybrid or fragment-based routes used for long peptides?
Answer: Coupling efficiency and overall yield drop sharply when peptides longer than 50 amino acids are built by conventional solid-phase synthesis. Fragment routes make shorter pieces separately and join them. In one published WuXi TIDES program, an 87-step peptide conjugate was rebuilt from fragments under 50 amino acids linked by chemical ligation. Overall yield rose from less than 0.1% to 3%, and parallel fragment work shortened the timeline.
Question: When should peptide building-block supply be addressed?
Answer: Building-block supply should be addressed during lead optimization, before candidate selection is complete and before a scarce component becomes a critical-path dependency. Unnatural amino acids and linkers can have limited availability at development scale. In one published program, WuXi TIDES developed processes for three limited-supply unnatural amino acids and produced more than 3 kg in-house to support GLP and GMP production.
Question: Why does purification become the bottleneck as peptide production scales?
Answer: Higher synthesis output moves the constraint downstream if chromatography, filtration and isolation capacity do not grow at the same rate. Column chemistry matters as much as column size. In one published WuXi TIDES program, a custom alkali-resistant stationary phase reduced impurities by 80% and increased final overall yield by 20%. That program delivered GLP and GMP API in 10 months.
About WuXi AppTec
WuXi AppTec is a trusted partner and contributor to the pharmaceutical and life sciences industries, providing R&D and manufacturing services that help advance healthcare innovation. With operations across Asia, Europe, and North America, we offer integrated, end-to-end services through our unique CRDMO (Contract Research, Development, and Manufacturing Organization) platform. We are privileged to work alongside partners across 30+ countries, supporting their efforts to bring breakthrough treatments to patients. Guided by our vision that every drug can be made, and every disease can be treated, we are committed to advancing breakthroughs for patients—one collaboration at a time. Learn more at
https://www.wuxiapptec.com
.