Elemental Analysis in a GMP Quality Control Laboratory
Results Snapshot
A GMP quality control laboratory engaged Terraforme Biosciences to implement a complete ICP MS capability, from user requirements through qualification and validated method execution. The goal was a rugged, flexible elemental testing program that could support cosmetics, pharmaceuticals, dietary supplements, NHPs, and consumer goods.
- Implemented a full GMP equipment lifecycle for a new ICP MS and closed vessel microwave digestion platform (URS through change control release)
- Enabled routine compliance testing for the classic “big four” heavy metals (cadmium, arsenic, lead, mercury) plus antimony, which Health Canada explicitly identifies as a heavy metal of concern for cosmetics and personal care products in Canada.
- Delivered an expanded multi element panel to support both contaminant testing and elemental active ingredient assays (for example magnesium or iron based products)
- Developed and validated a digestion and ICP MS method designed for diverse matrices, from simple lotions and APIs to challenging herbal materials
- Established a flexible workflow that supported an abridged heavy metals run, an extended panel, or both, reducing prep time and standards usage when a limited scope was sufficient
Client Context
Terraforme Biosciences supported the client through two connected workstreams: GMP implementation of the equipment platform, and development plus validation of the analytical method.
GMP Implementation and Qualification
- Authored a User Requirement Specification (URS) and supported vendor selection against intended use, GMP expectations, serviceability, and long term operating cost
- Supported installation planning and execution with the instrument vendor and site stakeholders
- Developed equipment use, maintenance, and operational SOPs for ICP MS and microwave digestion
- Built a calibration and verification plan for microwave digestion sensors and critical controls
- Executed qualification documentation through controlled change control release, including URS traceability and objective evidence packages for both the ICP MS and the digestion platform
Method development and validation
- Selected fit for purpose analytical standards and defined a practical standards strategy using commercially available materials
- Optimized microwave digestion conditions across expected matrices, including challenging herbal materials (including siliceous matrices)
- Optimized ICP MS parameters, internal standards strategy, and sample prep additives to address known behaviors such as mercury memory effects
- Developed reagent and standard stability positions to support routine execution and scheduling
- Authored validation protocols aligned to compendial and guideline expectations for elemental impurities testing (USP procedures, ICH Q3D risk based framework, and Ph Eur expectations where applicable)
- Executed validation studies, authored validation reports, and delivered final SOPs plus training materials for controlled deployment
The challenge
This project combined several categories of complexity that often collide in GMP labs:
A Wide Matrix Envelope
The method needed to perform reliably across very different products. Simple matrices (some lotions and APIs) can be straightforward, but botanicals and complex natural matrices can be digestion limited and interference prone.
Volatile and Difficult Analytes
Some elements are prone to volatility or memory effects (especially mercury). That pushes sample preparation toward closed vessel microwave digestion and requires deliberate method controls and additives to ensure carryover and stability risks are addressed in a practical way.
Multi Sector Compliance Expectations
The method needed to support cosmetic and personal care heavy metal impurity expectations in Canada, while also aligning to pharmaceutical elemental impurity frameworks used globally (ICH Q3D and compendial procedures).
What We Did
Terraforme Biosciences provided end-to-end support to move the lab from a “clean slate” to a fully operational, validated testing suite:
Equipment Selection & Qualification:
- Authored the User Requirement Specification (URS) and managed vendor selection.
- Coordinated the installation of both the ICP-MS and a closed-vessel microwave digestion system.
- Established calibration plans for microwave sensors and equipment maintenance SOPs.
Method Development and Optimization
- Developed specialized digestion programs to ensure complete recovery of volatile elements.
- Implemented additives to mitigate mercury memory effects in the sample introduction system.
- Selected internal standards and commercial multi-element standards to maximize accuracy across 31 different targets.
Validation and Compliance
- Built a URS Traceability Matrix to ensure every requirement was tested during qualification.
- Drafted and executed validation protocols harmonized to USP, ICH, and Ph. Eur. standards.
- Authored final validation reports and generated the Master SOP and training modules.
The Approach
Our strategy focused on three core pillars:
Full Lifecycle Integration
We didn’t just “install a machine.” We integrated the equipment into the client’s Quality Management System (QMS) through robust change control and traceable documentation.
Method Ruggedness by Design
We focused heavily on the digestion phase, ensuring that even tough herbal materials were fully mineralized, which is the foundation of reliable ICP-MS data.
Tiered Testing Efficiency
We designed a flexible “abridged vs. extended” configuration. This allows the lab to batch multiple sample types together, reducing standard usage and prep time while still offering customers tailored testing options.
Deliverables
1) GMP Qualification Package
URS, Traceability Matrix, and final Change Control documentation. Equipment SOPs: Detailed procedures for usage, maintenance, and microwave sensor calibration.
2) Validated Analytical Method
A robust procedure covering 31 elements in various matrices.
3) Validation Documentation
Harmonized protocols (USP/ICH/Ph. Eur.) and comprehensive execution reports.
4) Training Package
Content to align lab analysts on new ICP-MS workflows and sample prep techniques.
Final List of Elements
| Aluminium (Al) | Antimony (Sb) | Arsenic (As) | Barium (Ba) | Beryllium (Be) |
| Boron (B) | Cadmium (Cd) | Calcium (Ca) | Chromium (Cr) | Cobalt (Co) |
| Copper (Cu) | Iron (Fe) | Lead (Pb) | Lithium (Li) | Magnesium (Mg) |
| Manganese (Mn) | Mercury (Hg) | Molybdenum (Mb) | Nickel (Ni) | Potassium (K) |
| Selenium (Se) | Silicon (Si) | Silver (Ag) | Sodium (Na) | Strontium (Sr) |
| Thallium (Tl) | Tin (Sn) | Titanium (Ti) | Vanadium (V) | Zinc (Zn) |
Lessons Learned
Elements have their own personalities! Lead will appear if glassware is used in sample prep workflow, mercury likes to stick to plastic, and many elements will change their ionization potentials in the presence of different matrix components.
An autosampler enclosure is a good investment. Even in a clean facility, dust contains many common elements such as calcium, magnesium, sodium and so forth which can land in the open sample or calibration tubes.
Closed-Vessel is Mandatory: For diverse product lines, closed-vessel microwave digestion is the only way to ensure the recovery of volatile elements like Mercury and Selenium across all matrices.
Matrix Matters: “One-size-fits-all” digestion often fails on siliceous or high-fat samples. Developing a “worst-case” digestion protocol ensures method ruggedness for future, unknown sample types.
Flexibility Drives ROI: By allowing abridged and extended runs to be batched together, a lab can significantly reduce the overhead of expensive multi-element standards and cleaning cycles.
Ready To Grow?
If you are planning a new method implementation, or need a GMP qualification and validation package that will stand up to audits, Terraforme Biosciences can help you define “good,” execute efficiently, and embed the program into your QMS.
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