Why ISPE put peptide and oligo facility design in one guide

Jim Love designs plants for two drug classes that look alike on a process flow diagram and were built by engineers drawing on different bodies of knowledge. Peptides, he says, came up through active pharmaceutical ingredient chemistry. Oligonucleotides came up through biotechnology.

Speaking in a recent MarketScale interview, Love, Oligonucleotide/Peptide Market Leader at CRB, described ISPE's new Baseline Guide as an attempt to put both modalities into one facility document for the first time. The guide carries a GMP survey of existing plants, a section on how sustainability and scale will change the processes, and a safety framework for the piping and equipment that connect everything. Each part, in his telling, answers a question an owner struggles to answer alone.

ISPE's own event pages show how long the document has been in motion. On its site, the society lists an October 2024 session titled ISPE Baseline Guide for Oligonucleotide Facility Design, presented by Love with Francis Ring, Assistant Director at Ionis Pharmaceuticals, and Paul Richards, Distinguished Engineer at Biogen. By October 2025 it was running a session on balancing current and future oligo manufacturing needs with Adam Michaud, whom its site lists as a chapter lead and contributor to the guide.

What changed in the last year is the pressure on the peptide side. In June 2026, Drug Discovery News reported that for GLP-1 drugs, the diabetes and weight-loss peptides that include semaglutide and tirzepatide, manufacturing and not discovery had become the limiting factor, with demand running ahead of supply for years. ISPE's pages call the document the Oligonucleotide Baseline Guide and give neither a volume number nor a release date.

Two modalities, two inheritances

A peptide is a short chain of amino acids, the same building blocks as a protein. An oligonucleotide is a short chain of nucleotides, the building blocks of DNA and RNA. Both are assembled by solid-phase synthesis, in which the chain is built one unit at a time on a solid resin, so the plants that make them come together in much the same way, Love says.

The difference is age. Peptides are the older modality and oligos the newer, and the industry was thinking about different things when each generation of capacity was built, Love says. Peptide plants inherited API thinking and oligo plants inherited biotech thinking, and ISPE's guide now carries both.

API, the active pharmaceutical ingredient, is the chemically made drug substance, and API plants are organized around chemical reactions and the solvents they consume. Biotechnology plants are organized around biological processes and the controls that follow from them. Love's point is that both traditions have something to say about a peptide or oligo facility, and a guide written from one side would leave half the design unexamined.

For an engineer scoping a new plant, that framing is the practical payoff. The question becomes which choices from each tradition the site should adopt, and the guide's survey is built to answer it.

A survey of the plants that already exist

GMP, good manufacturing practice, is the set of quality rules a drug plant must follow so every batch is made and documented the same way. The guide's first component is a GMP survey of facilities that already make oligos and peptides.

The survey does not prescribe a layout. It records the choices existing operators made and gives a reader a basis for making the same decisions in a different facility that uses these modalities, Love says. For a company moving a program from a contract manufacturer to its own site, that is the difference between copying a predecessor and understanding why the predecessor chose what it did.

Who answered matters as much as what was asked. Owner-operator companies are the ones that own a plant and run it, as distinct from the design firms and equipment suppliers that help build it. Love says those companies made up an unusually large share of the guide's contributors.

That composition, he argues, is what lets the industry stand behind the document as a standard. A reader can treat the survey's choices as decisions someone paid to live with, which is a different kind of evidence from a vendor's recommended practice.

Why peptide capacity got hard to add

The scale pressure Love describes has a specific origin on the peptide side. Most GLP-1 drugs are peptides produced by solid-phase synthesis, Drug Discovery News reported in June 2026, and semaglutide and tirzepatide each need 30 to 40 or more coupling cycles.

Each coupling cycle attaches one more amino acid to the chain anchored on the resin, so a longer peptide means more cycles and more of everything each cycle uses. Semaglutide is 31 amino acids long and tirzepatide 39, near the upper limit of what the method handles comfortably, according to Drug Discovery News. That is why the publication describes the process as solvent-intensive, costly and difficult to scale to the volumes now required.

The industry's response was capital. IntuitionLabs, in a report updated in October 2026, put Eli Lilly's commitment to new plants in Indiana, Wisconsin, Pennsylvania and Alabama at more than $15 billion, and Novo Nordisk's planned North Carolina facility at $4.1 billion, opening around 2029. The same report, citing a late-2025 KFF poll, said 12% of U.S. adults reported currently taking a GLP-1 drug.

Love says the modalities will change a lot because of scale and sustainability. Set beside IntuitionLabs' figures, that is a plant program measured in billions of dollars whose design conventions are being written while the buildings go up.

Supply has since caught up, at least on paper. In its April 1, 2026 update, FDA stated that neither tirzepatide nor semaglutide appeared on the U.S. drug shortage list, according to IntuitionLabs. The same report notes that shortages of skilled staff can delay plant ramps, which is a facility problem that more square footage does not solve.

Piping is where scale stops being intuitive

The guide's third component is a safety framework for what Love calls the connective equipment: the piping, transfers and utilities that join the process units into a plant.

The hazard, in his telling, is that a design that works at one size does not scale by proportion. A pilot facility and a commercial one may run the same chemistry, but the volumes of solvent moving between vessels and out to waste or recovery grow with the batch, and the lines that carry them have to be sized, routed and protected before the building is drawn. IntuitionLabs' October 2026 report describes solvent and resin waste pushing manufacturers toward recovery systems, which adds another set of lines to the same framework.

ISPE's own material gives a sense of who shaped the guide. On its site, the society lists Adam Michaud, Senior Director of Engineering at Nitto Denko Avecia, as a chapter lead and contributor to the guide, and notes that he led engineering for Avecia's M5 expansion in Milford, Massachusetts, a finalist for the 2025 ISPE Facility of the Year Award. ISPE's page does not say which chapter he led.

For the operator, the ask is simple. Bring the connective design into the earliest scoping conversation, when the site still has room to route it, and use the guide's framework as the checklist for that meeting.

Sustainability will rewrite the process before the next plant is finished

Love's second takeaway is a forecast. Sustainability and scale will change how peptides and oligos are made, and the guide tries to say where the technology is heading and how that will land on facilities.

The process science is already moving. In February 2025, a study in Ultrasonics Sonochemistry, available through the National Institutes of Health's PubMed Central archive, described an ultrasound-assisted solid-phase peptide synthesis method aimed at producing less waste with more efficiency. On its own site, ISPE lists a January 2025 session by Yufei Wei, Senior Advisor-Engineering at Eli Lilly and Company, on solvent and reagent in-situ reuse in solid-phase oligonucleotide synthesis.

Contract manufacturers are moving too. IntuitionLabs reports that major peptide contract development and manufacturing organizations, the companies that make drug substance for others, are investing in greener, scalable synthesis platforms with continuous processes to improve yields and reduce waste. The same report cites industry projections of roughly 13% annual growth in the GLP-1 peptide CDMO market through 2034.

Facility guidance alone has not relieved the bottleneck, and the chemistry may move out from under it. Drug Discovery News reported in June 2026 that oral small molecules such as orforglipron change the economics of the class, because conventional chemical synthesis is cheaper and more scalable than peptide manufacturing.

Love's answer is that the guide was written for that kind of movement. A document that only described today's facilities would age with them, and one that reads the direction of the process gives an owner a basis to design for the plant it will need later.

What a voluntary guide can and cannot do with regulators

ISPE's Baseline Guides are a series of facility design documents, and Love says they have always worked the same way. A voluntary consensus on facility design, Love says, is what makes the regulator's job easier. Align the industry on what a facility should look like, and inspectors meet the same logic site after site.

Where that consensus has limits, the regulator's own documents show it. FDA's Center for Drug Evaluation and Research issued guidance on clinical pharmacology considerations for oligonucleotide therapeutics, under docket FDA-2022-D-0235 opened in 2022, that recommends four evaluations during development: the potential for QTc interval prolongation, an immunogenicity risk assessment, the effect of hepatic and renal impairment, and the potential for drug-drug interactions. QTc is a measure of the heart's electrical recovery between beats, and immunogenicity is a drug's tendency to provoke an immune response.

In a separate draft under docket FDA-2024-D-4624, FDA said oligonucleotide-based therapeutics present nonclinical safety challenges that differ in many regards from those for small-molecule drugs or therapeutic proteins. That sorting, neither a small molecule nor a protein, is the regulator's version of Love's point: oligos sit between the API and biotech traditions, and the rules reflect it.

Neither FDA page mentions ISPE or a Baseline Guide, and ISPE's event pages describe no formal step by which a guide becomes a regulatory requirement. The guide's weight, as Love describes it, comes from the industry standing behind it, so that the facility choices an inspector sees are ones the field has already agreed on. For a quality or engineering lead, that means reading the guide as the design consensus an auditor will compare against, while FDA's oligonucleotide guidances remain the documents that govern what the product must demonstrate.

U.S. Pharmacopeia is convening in the same space. USP has scheduled a Peptides and Oligonucleotides Workshop for March 3 and 4, 2027, at its headquarters in Rockville, Maryland, with abstract topics that include chemo-enzymatic oligonucleotide synthesis, green and sustainable peptide manufacturing, CDMO partnerships and starting material sourcing. Abstracts are due October 30, 2026, with acceptance notices in December 2026.

The signal Love points to is whether the next generation of oligo and peptide plants is designed with connective equipment, sustainability and scale thought through ahead of time, with the guide as the common reference. The USP workshop in March 2027 is the next public reading of how fast the manufacturing science behind the two modalities is converging.