Regulatory
CMC

Leaders in Chemistry, Manufacturing & Controls

Why CMC Matters

The Molecule Gets the Attention. The CMC Package Gets You Approved.

More programs stall on chemistry, manufacturing, and controls than on efficacy. A specification set too tight to pass validation, a process change with no comparability data behind it, a Module 3 that contradicts the batch records: none of these are clinical problems, and all of them can hold a filing. CMC is also uniquely unforgiving of timing. What is right for a first-in-human IND is wrong for a commercial NDA, and evidence you failed to collect in Phase 1 cannot be recovered at registration. We build CMC programs that are phase-appropriate at every stage and defensible at the end, so the manufacturing story is an asset in your submission rather than the reason it waits.

Process change before a pivotal batch? Comparability is easier to plan than to reconstruct.

Talk to an Expert
The CMC Lifecycle

One Continuous Story, From First IND to Commercial Supply.

CMC is not a set of independent tasks; it is a single narrative that has to stay coherent as your product moves from grams to metric tons. We follow that arc through six stages, each building the evidence the next one depends on. Jump to any phase, or read it as the timeline it is.

Stage 1CMC Strategy & the Development Plan

The phase-appropriate roadmap: what evidence each milestone requires, and what to build now versus defer without creating a gap later.
Stage 2Drug Substance & Drug Product

Process and formulation development framed by QbD: critical quality attributes, critical process parameters, and the design space to defend them.
Stage 3Analytical Methods & Specifications

Validated methods, justified specifications, and a stability program that supports the shelf life you actually need to claim.
Stage 4Control Strategy & Process Validation

The control strategy that ties CQAs to controls, plus process validation and comparability that survive a pre-approval inspection.
Stage 5Module 3 Authoring & Submission

Module 3 and the 2.3 Quality Overall Summary authored to tell one consistent story across IND, IMPD, NDA, BLA, and MAA.
Stage 6Post-Approval Lifecycle

Post-approval change management under ICH Q12: variations, comparability, and an established-conditions strategy that keeps supply moving.
Stage 1CMC Strategy & the Development Plan

Decide Now What You Can Defer, Before Deferring Becomes a Gap.

The hardest CMC judgment is not what to do; it is what not to do yet. Over-invest early and you burn cash characterizing a process you will change anyway. Under-invest and you reach registration with a hole no amount of money can backfill. We set the phase-appropriate plan against your regulatory milestones: the evidence each submission genuinely requires, the studies that must start early because their data takes years to mature, and the decisions that can safely wait. It is the roadmap every later stage is measured against.

What We Set

  • Phase-appropriate CMC development plans mapped to program milestones
  • Target product profile translated into quality target product profile (QTPP)
  • Gap assessments against ICH, FDA, and EMA expectations by phase
  • CMC risk register with mitigation owners and timing
  • CMC content and timing for Type B, pre-IND, and scientific advice meetings
  • Make-versus-defer decisions on characterization and validation
  • Budget and CDMO capacity planning against the filing calendar
Stage 2Drug Substance & Drug Product

Understand the Product Well Enough to Argue for It.

Regulators no longer accept a process that works; they expect one you understand. Quality by Design reframes development as a search for the relationship between what you do and what you get: which attributes actually matter to the patient, which parameters move them, and how wide the operating window can be before quality is at risk. We run substance and product development that produces this understanding, so your specifications and control strategy rest on characterization rather than on a handful of lucky batches.

What We Develop

  • Critical quality attribute (CQA) identification and risk assessment
  • Critical process parameter (CPP) studies and design-space definition
  • Formulation and drug-product development, including specialized dosage forms
  • Drug substance route and process development, scale-up, and tech transfer
  • Excipient compatibility and container-closure system selection
  • Quality by Design (QbD) study design and reporting
  • Drug Master File (DMF) strategy and authoring
Stage 3Analytical Methods & Specifications

Every Number in Your Dossier Is Only as Good as the Method Behind It.

Analytical methods are the instruments through which a regulator sees your product, and a specification is a promise you make about every future batch. Set an acceptance criterion too tightly and routine variation becomes an out-of-specification investigation; set it loosely and you cannot justify it against the clinical experience. We develop and validate the methods, justify each specification against real batch and stability data, and design the stability program so the shelf life you claim is the shelf life you can prove.

What We Build

  • Analytical method development, validation, and transfer per ICH Q2
  • Specification setting and justification per ICH Q6A/Q6B
  • Stability program design and shelf-life determination per ICH Q1
  • Impurity, degradation, and extractables/leachables strategy (ICH Q3)
  • Reference standard qualification and management
  • Out-of-specification and out-of-trend investigation support
  • Analytical comparability protocols for process changes

Module 3 due at the same time as everything else? Get CMC authors who have filed it before.

Request a Review
Stage 4Control Strategy & Process Validation

Prove the Process Does What You Say, Every Time.

By registration, the question shifts from can you make it to can you make it reliably, at scale, forever. The control strategy is the answer written down: how each critical attribute is controlled, by which test, at which step, with what justification. Process validation demonstrates it holds across the ranges you claim, and when the process has changed since your clinical batches, comparability proves the product did not. This is the evidence a pre-approval inspection exists to test, and the most common reason a CMC package fails one.

What We Establish

  • Integrated control strategy linking CQAs to in-process and release controls
  • Process validation lifecycle per FDA guidance and ICH Q8–Q11
  • Comparability protocols and studies for process and site changes (ICH Q5E)
  • Design space and real-time release testing strategy
  • Pre-approval inspection (PAI) readiness for drug substance and product
  • CDMO oversight, quality agreements, and person-in-plant support
  • Contamination control and sterility assurance strategy where applicable
Stage 5Module 3 Authoring & Submission

Years of Work, Read as One Document. It Has to Agree With Itself.

The reviewer never sees your labs. They see Module 3, and they read it looking for the seams: a specification in 3.2.S that the stability data in 3.2.P will not support, a Quality Overall Summary that oversells what the body of the dossier proves, a batch analysis that contradicts the process description. We author the module and the 2.3 summary as a single coherent argument, reconcile every number against its source, and prepare the responses to the CMC questions that arrive after filing.

What We Author

  • Module 3 (3.2.S and 3.2.P) for IND, IMPD, NDA, BLA, and MAA
  • Module 2.3 Quality Overall Summary
  • Cross-module consistency and source-data reconciliation
  • eCTD lifecycle planning and submission-ready formatting
  • US and ex-US dossier strategy, including regional variants
  • CMC responses to Information Requests, RFIs, and Complete Response Letters
  • CMC content for agency meetings and briefing packages
Stage 6Post-Approval Lifecycle

Approval Is the Midpoint. The Product Still Has to Change.

A commercial product is never static: sites move, suppliers change, processes improve, and every change has to reach dozens of markets on their own regulatory clocks without ever interrupting supply. ICH Q12 gives you tools to manage this deliberately, through established conditions and post-approval change management protocols that pre-agree the reporting category before you need it. We build the lifecycle strategy that turns each change from a supply risk into a routine variation, filed on time, in the right category, in every market.

What We Manage

  • Post-approval change management strategy under ICH Q12
  • Established conditions and PACMP design
  • Variation classification and global filing strategy (FDA, EMA, and beyond)
  • Post-approval comparability for site, scale, and process changes
  • Annual reports, PAS, CBE-30, and Type IA/IB/II variation authoring
  • Supply continuity and change-control regulatory assessment
  • Legacy product CMC remediation and dossier modernization
Where CMC Gets Harder

Two Places the Standard Path Bends.

The lifecycle above holds for most programs. Two situations rewrite it: advanced modalities whose CMC is the hardest part of the whole program, and a manufacturing crisis that arrives without waiting for the roadmap.

Biologics, Cell & Gene Therapy

For Advanced Modalities, the Process Is the Product.

For a small molecule, the structure is defined and the process serves it. For a biologic, a cell therapy, or a gene therapy, the process largely defines the product, and a change you cannot fully characterize can be a change to the drug itself. Comparability carries far more weight, potency assays are often the critical unsolved problem, and agencies expect a control strategy matched to that complexity. We bring modality-specific CMC experience to the programs where manufacturing, not the clinic, is the gating risk.

Included Capabilities

  • Biologics CMC strategy and comparability (ICH Q5A–Q5E)
  • Cell and gene therapy CMC, potency assay, and characterization strategy
  • Viral safety, vector, and cell-bank qualification
  • Analytical strategy for complex and heterogeneous products
  • CMC for accelerated and expedited programs where data matures late
  • Manufacturing scale-out and site strategy for living products
CMC Crisis & Remediation

When a Batch Fails or a Finding Lands, the Roadmap Waits.

A confirmed out-of-specification result on a pivotal batch, a CMC-driven Complete Response Letter, a comparability failure after a process change, a 483 that threatens supply: these do not arrive on schedule, and they are rarely just technical. We run CMC remediation under pressure, diagnosing the real root cause, separating the science problem from the documentation problem, and building the response that protects both the filing and the supply chain.

Included Capabilities

  • CMC-driven Complete Response Letter analysis and response strategy
  • Out-of-specification and comparability failure investigation support
  • Root-cause triage: process, method, or documentation
  • Pre-approval and for-cause inspection response (483, EIR)
  • Supply-continuity risk assessment and mitigation filing
  • Independent CMC due diligence for licensing and acquisition
Who You're Working With

Scientists Who Have Owned the Process, Not Just Reviewed the Paper.

CMC judgment comes from having run the development, sat in the plant, and answered the agency's questions. Our teams combine former CMC reviewers with industry scientists who have taken products from first IND to commercial validation, so the advice reflects both how it is assessed and how it is actually made.

Former Agency CMC Reviewers

Consultants who have reviewed Module 3 for the FDA and EMA. They know which questions the quality assessor asks first, and what turns a routine review into a deficiency.

Industry Development Scientists

Process chemists, analytical leads, and manufacturing heads who have owned CQAs, run validation campaigns, and stood in front of a pre-approval inspection.

Phase-Appropriate Judgment

The rarest CMC skill is knowing what is enough for the stage you are in. Our teams calibrate the work to the milestone instead of gold-plating every phase.

Modality Breadth

Small molecules, peptides, biologics, cell and gene therapies, and combination products, across drug substance, drug product, and the analytical work that ties them together.

Work With Us

Wherever You Are on the Lifecycle, Start Here.

Tell us where the product stands: first IND, mid-phase process change, registration filing, or a post-approval problem that will not wait. We'll match you with a senior CMC lead who has been through that stage and respond within one business day. All inquiries are strictly confidential.

Schedule a Call Send a Detailed Inquiry
Insights & News

Thought Leadership on CMC.

Our team's perspectives on phase-appropriate development, comparability, and the CMC decisions that decide a filing: coming soon. In the meantime, reach out directly with a question you'd like to see addressed.

Coming Soon

What "Phase-Appropriate" Actually Means

The evidence each milestone requires, and the studies you cannot start late.

Coming Soon

Comparability Before You Change the Process

Why the protocol you write beforehand is worth ten you write after.

Coming Soon

ICH Q12 in Practice: Established Conditions

Using post-approval change tools to protect commercial supply.