Diagnostics & IVD Enzymes (ISO 13485 / IVDR)

Design → ISO 13485 → Market. We manufacture and kit IVD-grade enzymes and master mixes—PCR, RT-qPCR, CRISPR Cas12/Cas13—under ISO 13485 with full design transfer, lot release, and stability evidence that stands up in audits and technical file reviews.

Executive overview

Diagnostics lives on precision and repeatability. It is not enough for a polymerase to be fast; it must be fast every time, through the full expiry, across shipping lanes, and in the hands of thousands of users. That means methodical ISO 13485 design transfer, a Device Master Record that actually governs what is made, Device History Records that prove what happened, and IVDR documentation that ties performance claims to data. It also means manufacturing suites that are DNase/RNase-free, rigorous anti-carryover controls, and lyophilisation that produces cakes which reconstitute identically whether the kit is opened week one or month twenty-four.

Mika Biologics is a microbial-first CDMO with a dedicated diagnostics/IVD line. We produce polymerases, reverse transcriptases, ligases, nicking enzymes, RNase inhibitors, and CRISPR reagents at scale, in bulk liquid and lyophilised formats, and we fill, pouch, label, and kit under ISO 13485 with IVDR technical file support. OEM/white-label is standard; your brand, your market authorisation, our manufacturing and quality system.

What we deliver

Enzymes and mixes
• DNA polymerases (standard, hot-start, high-fidelity, fast cycling)
• RTs (thermostable, one-step RT-qPCR compatible)
• Ligases (T4 and thermostable), nickases, endonucleases where applicable
• RNase inhibitors (recombinant, DTT-tolerant options)
• CRISPR reagents: Cas12/Cas13 proteins, reaction buffers; optional gRNA handling under controlled chain-of-custody

Formats and presentations
• Bulk liquids in validated cold-chain containers
• Lyophilised beads/pellets and cakes (tubes, PCR strips, 96-well plates)
• Kitting: buffers, dNTPs, MgCl₂, reference controls, UNG/dUTP carry-over prevention packs, positive/negative controls
• Pouching & desiccation: high-barrier foils with verified MVTR, desiccant canisters/sachets, oxygen scavengers where indicated
• Labels & IFUs: UDI-ready art files, language packs, IFU version control

Quality and regulatory
• ISO 13485 QMS, ISO 14971 risk management, IEC 62366 usability inputs, clean environmental monitoring plans
• Design Transfer → DMR → DHR with full traceability and change control
• IVDR technical file inputs (GSPR mapping, analytical performance, stability/shelf-life, PMS/PMPF plans); US market support aligning to QSR/21 CFR 820 as needed

Stability and claims
• Real-time and accelerated stability (temperature/humidity matrices)
• Shipping lane simulations (thermal cycling, agitation) and in-use robustness (multiple freeze–thaw, bench time)
• Expiry assignment, re-labelling policy, lot bridging and carryover of evidence for line extensions

Design transfer to ISO 13485

We start with your Design Inputs (performance requirements, user needs, operating ranges, interfaces) and convert them into controlled documents:

• Design Outputs: bill of materials (BOM), specifications (enzymes, buffers, packaging), assembly and fill instructions, QC panels, IFU drafts
• Verification: each output tested against the input; performance envelopes (LOD/LOQ, linearity, tolerance to inhibitors such as hemoglobin/heparin/EDTA, salt/pH windows)
• Design Review: cross-functional sign-off with action logs
• Transfer to DMR: material codes, approved suppliers, equipment and calibration requirements, environmental controls, validated processes (lyo cycles, fill volumes, seal parameters)
• DHR generation: batch records that capture what actually occurred, including deviations, rework, and release decision rationale

We keep Risk Management (ISO 14971) live throughout: FMEA that actually drives controls (e.g., UNG/dUTP inclusion to mitigate amplicon carry-over; UV/chemical decontamination SOPs; segregated pre- and post-amplification areas; single-use anti-aerosol consumables).

Manufacturing architecture

Upstream enzyme production
Microbial expression (E. coli, Pichia) with DoE-defined conditions to maximise soluble, active enzyme and eliminate adventitious nucleases. Purification stacks (affinity/ion-exchange/HIC) are chosen for activity retention and low endotoxin; final polish removes trace host DNA/RNA and proteases.

Formulation and master-mix design
• Buffer chemistries optimised for speed, fidelity, and inhibition tolerance; Mg²⁺ windows validated
• Hot-start systems (antibody, aptamer, chemical) with activation kinetics characterised across thermal profiles
• RT-qPCR one-step compatibility: RT activity preserved through early cycles without inhibiting polymerase function
• CRISPR assay buffers tuned for Cas collateral cleavage kinetics and reporter stability
• Anti-carryover: dUTP + UNG options validated for impact on sensitivity

Lyophilisation
• Thermal mapping (Tg′/Tc), controlled nucleation when needed, primary/secondary drying tuned to activity retention
• Cake mechanics, residual moisture and water activity set to support ambient or 2–8 °C storage claims
• Reconstitution profiles (time to clarity, homogeneity) and mixing resilience (vortex/time)

Filling, sealing, and kitting
• Fill volumes verified with weight and vision systems; CV targets typically ≤1.5% for bulk liquids and ≤2.0% equivalent for beads
• Heat-seal parameters and burst/leak tests for pouches; seal integrity verification integrated into in-process checks
• Plate/tube formats with position maps; plate sealing validated for evaporation and edge effects
• Kitting cells with barcode-driven pick/pack and reconciliation; palletising with shock/tilt indicators if needed

Contamination control
• Segregated pre-amp suites with positive pressure relative to surrounding corridors; UV and chemical decon routines; dU-only policies for certain lines
• Environmental monitoring for DNase/RNase and amplicon contamination: swab/assay routines with action limits and CAPA triggers
• Dedicated smallware and single-use plastics; aerosol-resistant tips; gowning matrices that prevent cross-flow

Lot release testing

Enzymes (polymerase/RT/ligase/inhibitor)
• Identity: LC-MS intact mass or peptide mapping (phase-appropriate)
• Activity: Units/mg and Units/mL at operating temps; for high-fidelity enzymes, error rate and processivity characterisation
• Inhibitor tolerance: hemoglobin/heparin/EDTA; salt/pH ranges
• Residuals: host DNA (qPCR), host protein (ELISA), endotoxin (route-appropriate; for IVD bench use we still control)
• DNase/RNase absence: nuclease assays with spiked controls
• Stability: accelerated timepoints or real-time interim supporting expiry

Master mix / kit components
• Functional: LOD across a panel; amplification efficiency (slope), R² ≥ threshold, Cq repeatability across runs and instruments
• Specificity: NTCs, cross-reactivity panel
• Robustness: thermal cycling variation, pipetting variation tolerance
• Reconstitution: time, final volume accuracy, homogeneity
• Packaging: seal integrity (burst/leak), MVTR verification by gravimetric or instrumented methods, desiccant efficacy

CRISPR reagents
• Cas purity and activity: cleavage assays (on-target collateral kinetics for Cas12/13)
• Buffer compatibility with reporters; fluorescence background and S/N
• Shelf-life: fluorescence drift under accelerated and real-time storage; plate reader compatibility

Sample COA excerpts

High-fidelity DNA Polymerase, 5 U/µL
Identity: LC-MS intact mass matches theoretical
Activity: ≥ 5 U/µL (Spec ≥ 5 U/µL)
Fidelity (error rate): ≤ 1 × 10⁻⁶ per bp
Processivity: ≥ 50 nt per binding event
Inhibitor tolerance: Pass (EDTA ≤ 0.5 mM; heparin ≤ 2 U/mL)
Residual DNA: < 10 pg/µg protein
DNase: Not detected
Endotoxin: ≤ Spec
Appearance/pH: Clear, pH 8.3 ± 0.1
Stability: Accelerated Month 1 within acceptance

Lyophilised One-Step RT-qPCR Master Mix (8-tube strip)
Reconstitution time: ≤ 60 s to clarity
Cq repeatability: SD ≤ 0.25 at 32 cycles (n=24)
Amplification efficiency: 90–110%
LOD (copies/reaction): ≤ Spec for target panel
Moisture (per tube): 1.2% w/w (Spec ≤ 2.0%)
Seal integrity: Pass burst/leak tests
Desiccant residual capacity: Pass
Storage: 2–8 °C; ambient tolerance 72 h (in-use)

Stability and claim support

We execute real-time studies to the intended shelf-life (e.g., 24 months at 2–8 °C or ambient for certain lyo lines) with accelerated arms to inform interim use. Protocols define temperatures, humidity (if relevant), interval testing (Cq drift, LOD stability, activity retention), and acceptance criteria. Shipping simulations (freeze–thaw cycles, thermal excursions, agitation) support label claims for transit. Under IVDR, expiry claims for CE-marked products must rest on real-time data; accelerated is supportive. We provide the data trail and updates for technical file maintenance.

IVDR technical file and regulatory support

We prepare technical file content aligned to the General Safety and Performance Requirements (GSPRs), including:
• Device description, intended purpose, and variants
• Design and manufacturing information (DMR, flow diagrams, critical materials, supplier controls)
• Analytical performance (precision, accuracy, limit of detection, linearity, specificity, robustness) and, if applicable, clinical performance strategy for assays supplied as part of a system
• Stability plans and data, shelf-life justification, in-use protocols
• Risk management file (ISO 14971), including contamination and misuse scenarios
• PMS/PMPF plans tailored to OEM/white-label realities
• Labelling and IFU compliance, UDI records, and EUDAMED inputs (where applicable)

For the US, we support QSR-aligned documentation and performance summaries that dovetail with your regulatory pathway.

Method transfer SLAs

We transfer your assays and acceptance criteria into our QMS without friction.
• Document intake: SOPs, system suitability, reference materials, historical data
• Bridging: side-by-side experiments on sponsor vs Mika platforms with pre-defined success metrics
• Qualification/validation: phase-appropriate verification, followed by partial/full validation as required
• Ownership and maintenance: change control, periodic review, reagent lifecycle and alternative qualification where supply risk exists.

Packaging and logistics

We validate high-barrier pouches (foil laminates with qualified MVTR), desiccant loads, and oxygen scavengers when enzymes are oxygen-sensitive. Labels are UDI-ready and IFUs are version-controlled. Outer cartons undergo drop/stack vibration tests. Cold-chain and ambient shipping profiles are qualified, with data loggers for performance studies. Storage and transport conditions are reflected exactly in the IFU and technical file.

Onboarding in 30 days

Day 10: Design Input capture; risk register skeleton; draft QC panel and acceptance table
Day 20: DMR outline; lyo/fill feasibility protocols; pouch/packaging proposal; draft stability protocol
Day 30: Transfer plan; first engineering lots schedule; technical file index; QA/RA meeting to align dossier roadmap

Inter-page guidance

For upstream expression and polishing of enzyme precursors, see Synthetic Biology Tools & Enzyme Engineering. For formulation science and aseptic behaviours, see Formulation & Aseptic Fill-Finish (Grade A Isolators). For analytics (SEC-MALS, LC-MS, endotoxin rFC/LAL, method transfer), see Analytical & QC for Microbial Biologics. For lifecycle validation and dashboards, see Process Characterization, PPQ & CPV for Microbial Platforms.

Diagnostics & IVD Enzymes FAQ

Do you support both bulk reagents and finished kits?
Yes. We manufacture bulk enzymes and buffers, and we also fill, pouch, label, and kit finished products under ISO 13485 with DHRs suitable for IVDR technical files.

Can you achieve ambient-stable lyophilised PCR mixes?
Frequently yes. We design excipient systems and lyophilisation cycles to meet ambient shelf-life targets, then prove them by real-time and accelerated stability with LOD/Cq performance criteria.

How do you prevent amplicon carry-over contamination?
dUTP/UNG workflows, segregated pre- and post-amp suites, UV/chemical decontamination, environmental swabs with action limits, and dU-only policies where appropriate.

Can you white-label and protect our IP?
Yes. OEM/white-label is standard, with confidentiality and restricted access to proprietary sequences, assay compositions, and controls.

Do you provide IFU and label development?
Yes. We generate UDI-ready labels and IFUs, manage translations, control versions, and ensure alignment with IVDR and local labelling rules.

What stability evidence is needed for IVDR?
Real-time shelf-life data supporting the labelled expiry, with accelerated as supporting evidence, plus in-use stability, shipping simulations, and robustness. We build the plan and produce the datasets.

Can you handle CRISPR diagnostics?
Yes. We produce Cas12/Cas13 proteins and buffers, qualify reporter behaviour, and assemble kits; gRNA handling can be included under strict chain-of-custody.

How tight are your fill tolerances?
Typical CV targets are ≤1.5% for liquids and ≤2.0% equivalent for lyo beads/cakes, with 100% in-process weight checks for critical formats.

Can you take over a running product and rebase under ISO 13485/IVDR?
Yes. We perform gap analysis, rebuild the DMR, re-establish validation evidence, and generate a technical file index to stabilise and scale the product.

Do you support US and EU in parallel?
Yes. Our documentation can be tailored to QSR and IVDR simultaneously, sharing a single evidence spine.