Choosing a CDMO: A Practical Guide for Emerging Biotech Companies.

Capability claims are cheap; relevant experience is not. Start by matching the modality and the specific technology, then narrow by stage and scale.

For biologics made in human or animal cell lines, viral safety is a defining capability. ICH Q5A(R2), in effect in the EU since June 2024, combines cell line and raw material testing, process viral clearance and product testing, adds next-generation sequencing as a virus detection method, and allows prior knowledge, including a manufacturer’s platform experience, to inform viral clearance evaluation ^[1]. Ask whether the CDMO has platform viral clearance data relevant to your process.

The ArgusBio directory currently documents biologics CDMOs, filterable by modality, expression platform and drug substance or drug product.

GMP expectations grow with the program, and the step from Phase 1 to Phase 2 supply matters more than many founders expect.

• Phase 1 (United States). Most Phase 1 investigational drugs are exempt from 21 CFR Part 211, though still subject to statutory CGMP, and FDA’s 2008 guidance describes the controls expected ^{[3] [2]}.
• Phase 2 and beyond. That exemption ends once the investigational drug is made available for Phase 2 or Phase 3 trials, and FDA’s Phase 1 guidance does not apply to material manufactured for those trials ^{[3] [2]}. A CDMO adequate for first-in-human supply needs to show it can support Part 211 compliance for later studies.
• Active ingredients for clinical trials. ICH Q7, which covers drug substance (including recombinant proteins) but excludes vaccines, whole cells and gene therapy active substances, expects controls consistent with the stage of development and recognizes that process validation is normally inappropriate where a single batch is made or the process is still changing, relying instead on controls, calibration and, where appropriate, equipment qualification ^[4].
• EU clinical supply. GMP for investigational medicinal products in the EU, including Phase 1 material (there is no equivalent of the US Phase 1 exemption), is set by Commission Delegated Regulation (EU) 2017/1569 and its detailed guideline, alongside EudraLex Volume 4, and requires a manufacturing or import authorisation and Qualified Person certification; advanced therapy investigational products follow Part IV rather than the detailed guideline ^[6]; sterile products are subject to the revised Annex 1, fully applicable since August 2024, and biological substances to Annex 2 ^[5].
• Commercial readiness. FDA’s process validation guidance describes three stages, process design, process qualification and continued process verification, and excludes clinical trial material from its definition of the commercial manufacturing process ^[7]. Commercial process validation capability matters when you choose a partner you hope to keep through launch. Clinical supply is not exempt from validation altogether: for sterile products, sterilization and aseptic processing (including media fills) must be validated or demonstrated from the first clinical batch, and for biologics, viral clearance must be demonstrated ^{[2] [6]}.

Many CDMOs are strong in one and partner for the other. Biologics drug substance manufacturers frequently rely on separate companies for fill-finish, which is not a problem if you know it and the interfaces are managed.

Q7 expects contract manufacturers not to pass work to subcontractors without the contract giver’s evaluation and approval ^[4]. Ask for every site and partner that will touch your product.

• Scale and equipment. Ask for the bioreactor or reactor scales available for your next two campaigns, not just the largest on site.
• Single-use versus stainless steel. Single-use systems can shorten changeover and suit multi-product clinical sites; stainless steel may suit large commercial volumes. Ask about supply continuity for single-use components.
• Capacity and slot timing. Ask when the next slots are, how far ahead they are booked, what reservation fees apply, and what happens to your slot if an earlier campaign overruns.
• Supply continuity. ICH Q9(R1) added the role of quality risk management in addressing product availability risks and supply chain control ^[8]. Ask how the CDMO assesses single points of failure in raw materials and equipment.

You cannot outsource responsibility. Under 21 CFR 211.22, your quality control unit remains responsible for approving or rejecting drug products manufactured, processed, packed or held under contract by another company ^[3]. ICH Q10 expects the company to assess a contract acceptor’s suitability and competence before outsourcing, define responsibilities in writing, and monitor performance ^[9].

FDA’s quality agreement guidance expects the agreement to define which party performs each CGMP activity, to be drafted by both quality units, and to be separate from, or severable from, commercial terms. Typical content includes scope, change control, deviation and investigation handling, and the agreement’s own life cycle ^[10].

Data integrity is part of quality, not a separate topic. FDA’s data integrity guidance sets out expectations on audit trail review, access controls and original records that translate directly into audit questions for a manufacturer’s laboratories ^[12].

Most emerging biotechs will transfer a process at least once: from an academic or discovery lab, between CDMOs, or to a larger site for later phases. ICH Q10 treats technology transfer as a product lifecycle stage and expects knowledge transfer when product ownership changes ^[9]. For biologics, a process change across sites or scales may require demonstrating comparability under ICH Q5E ^[13].

Release and stability testing often set the true timeline. Ask which methods are run in-house, which are subcontracted, and how long release takes after the batch is made.

• Method development, qualification and validation responsibilities across phases
• Reference standard strategy and who maintains it
• Stability program design and storage capacity. 21 CFR 211.166 requires a written stability program, and ICH Q1A(R2) describes registration stability expectations such as data on at least three primary batches; for biotechnological products, ICH Q5C applies ^{[3] [14]}
• A consolidated ICH Q1 stability guideline is in draft and, when final, will supersede Q1A–F and Q5C; check how the CDMO is preparing ^[15]
• Development knowledge to support the pharmaceutical development section of your filing, described in ICH Q8(R2) ^[16]

• Cold-chain shipping of drug substance and drug product, including temperature excursion handling
• Clinical packaging, labeling and distribution: in-house, partner, or your separate clinical supply vendor
• Qualified Person release for EU trials and import testing requirements ^[5]
• Storage of retained samples and records
• Contingency if the site faces an inspection finding or capacity loss

CDMO budgets change for predictable reasons. Agree the mechanics in advance.

Start from the biologics CDMO directory to see which organizations publicly document your modality and stage, compare them side by side, then use these questions to qualify the shortlist.