Sterilization TDF QC Check

Product family / worst-case rationale present and covers all variants

Common NB finding · see B1, B2 · Evidence: Product family assessment + variant matrix

Validation done on the current device and packaging revision, or change assessment provided

Common NB finding · see B3, I4 · Evidence: Revision comparison / change assessment

EO residuals tested at the correct contact category and at more than one time point

Common NB finding · see D9, D10, L1 · Evidence: Residuals report + dissipation curve

Pyrogenicity covers material-mediated pyrogens, not endotoxin only

Common NB finding · see G5–G7 · Evidence: Rabbit test or BEP rationale

Real-time aging study running alongside accelerated aging, with plan to confirm

Common NB finding · see H7, H8 · Evidence: Real-time protocol + interim results

Current standard editions used, or gap assessment for superseded editions

Common NB finding · see A8, M5 · Evidence: Standards list / gap assessment

Sterilizer's ISO 13485 certificate valid and quality agreement in place

Common NB finding · see I5, I6 · Evidence: Certificate copy + signed agreement

Latest requalification / dose audit provided

Common NB finding · see E8, I3 · Evidence: Latest requalification or dose audit report

Label shelf life does not exceed validated shelf life

Common NB finding · see H12, J5 · Evidence: Label vs shelf-life report

Sterilization section exists as a clearly indexed part of the TD, not scattered across V&V

Annex II §6.2(e) · Evidence: TD index pointing to sterilization, packaging, environment and shelf-life reports

TD describes the method used, including validation reports for packaging, sterilization and maintenance of sterility

Annex II §6.2(e) · Evidence: Method summary + validation report numbers

Validation report addresses bioburden, pyrogen and (if applicable) sterilant residues

Annex II §6.2(e) · Evidence: Each of the three explicitly covered or justified NA

Description of environmental conditions for relevant manufacturing steps is included

Annex II §6.2(e), Annex I §11.7 · Evidence: Cleanroom class, monitoring summary

GSPR checklist rows 11.4, 11.5, 11.6, 11.7 and 23.3 marked applicable, with standard and document reference per row

Annex I §11, §23 · Evidence: GSPR checklist with traceable references

GSPR 11.4: packaging maintains device characteristics and sterility during transport and storage

Annex I §11.4 · Evidence: Packaging validation + transport simulation

GSPR 11.5/11.6: designed, manufactured, packaged and sterilized by validated methods; sterility maintained until opening

Annex I §11.5, §11.6 · Evidence: Validation + shelf-life reports

List of applied standards with full edition (year + amendments); harmonised status checked; deviations from harmonised editions justified

Art. 8, Annex II §4 · Evidence: Standards list / gap assessment

Document numbers, revisions and dates in TD match the attached reports

QC consistency · Evidence: Cross-check table

Reports are signed/approved and in English (or a language accepted by the NB)

NB requirement · Evidence: Approved copies

All models/sizes/variants in scope of the certificate are covered by the sterilization validation

Annex II §1.1 · Evidence: Variant-to-validation matrix

Product family / grouping rationale documented; worst-case (master) product identified with justification (size, mass, density, lumens, mated surfaces, bioburden)

ISO 11135 / ISO 11137-1 product definition; AAMI TIR35 for radiation families · Evidence: Product family assessment

Product adoption into an existing validated cycle/dose assessed (new or changed devices)

ISO 11135 Annex E; ISO 11137-1 · Evidence: Adoption / equivalence report

Rationale for choice of sterilization method; material compatibility demonstrated

ISO 14937 §5; ISO 11137-1 §8.1 · Evidence: Compatibility / max-dose or max-exposure functional testing

Required SAL stated (10⁻⁶ for 'STERILE' claim); any other SAL justified by risk

EN 556-1 · Evidence: Stated SAL + demonstration in validation

Device performance and safety verified after sterilization (incl. worst-case: max dose / double cycle / re-sterilization if allowed)

Annex I §1, §11.6 · Evidence: Functional test reports post-sterilization

Re-sterilization by manufacturer (rework) allowed? Number of cycles validated and reflected in procedures

ISO 11135 / ISO 11137 · Evidence: Re-sterilization validation or prohibition in QMS

Cleanroom / controlled-environment classification for assembly and primary packaging stated and justified

ISO 14644-1; Annex I §11.7 · Evidence: Classification certificate, area layout

Environmental monitoring programme: particulates, viable air/surface, alert/action limits, frequency, trending

ISO 14644-2; EN 17141 · Evidence: EM procedure + recent trend summary

Personnel gowning, hygiene and training controls in place

ISO 13485 §6.4.2 · Evidence: Procedure reference

Process water / compressed air / cleaning agents controlled where they contact product

ISO 13485 §6.4; ISO 19227 (implant cleanliness) · Evidence: Specs + monitoring

Cleaning validation for devices with machining, oils, residues (esp. implants)

ISO 19227; ASTM F2459 · Evidence: Cleaning validation report

Supplier-sterilized or supplier-cleaned components controlled

ISO 13485 §7.4 · Evidence: Supplier agreements, incoming specs

Validation protocol approved before execution; acceptance criteria predefined

ISO 11135 §9 · Evidence: Signed protocol

Installation and operational qualification (IQ/OQ) of sterilizer and aeration equipment

ISO 11135 §9.2–9.3 · Evidence: IQ/OQ reports, calibration records

Approach stated (overkill half-cycle, BI/bioburden, or bioburden-based) and justified

ISO 11135 Annex A/B · Evidence: Validation rationale

Microbiological PQ: typically 3 half-cycles (or fractional cycles) + full cycle; BI/PCD placement at worst-case locations

ISO 11135 §9.5 · Evidence: MPQ report with BI map

PCD shown to be equal or more resistant than product (internal vs external PCD comparison)

ISO 11135 §9.5; ISO 11138-2 · Evidence: PCD resistance study

Physical PQ: temperature/humidity distribution, EO concentration, pressure profiles, load configuration and density defined

ISO 11135 §9.4 · Evidence: PPQ data, load patterns

BI certificates: B. atrophaeus, population, D-value, lot traceable

ISO 11138-1/-2 · Evidence: BI CoA

Sterility tests of product exposed to fractional/half cycles performed with method validation (bacteriostasis/fungistasis)

ISO 11737-2 · Evidence: Test reports + suitability

EO and ECH residuals tested on worst-case product, at correct exposure category (limited / prolonged / permanent contact)

ISO 10993-7 · Evidence: Residuals report vs TCL/TL limits

For implants (permanent contact): average daily dose and cumulative limits met; aeration time validated

ISO 10993-7 §4.3 · Evidence: Dissipation curve + release aeration time

Residual limits also assessed for neonates / special populations if in intended use

ISO 10993-7 · Evidence: Justification in report

Process specification (cycle parameters with tolerances) issued and matches validated cycle

ISO 11135 §9.6 · Evidence: Process spec document

Parametric release (if claimed) justified and validated

ISO 11135 §10.2 · Evidence: Parametric release validation

Maximum acceptable dose established; product and packaging functional after max dose (incl. aged samples)

ISO 11137-1 §8.1 · Evidence: Max-dose study

Sterilization dose established by recognised method: Method 1, Method 2, VDmax²⁵ / VDmax¹⁵ (ISO 11137-2) or VDmax^SD (ISO/TS 13004), or 25 kGy substantiation

ISO 11137-2; ISO/TS 13004 · Evidence: Dose setting report

Bioburden on 3 batches (10 samples/batch typical) with validated recovery efficiency used in dose setting

ISO 11737-1; ISO 11137-2 · Evidence: Bioburden + recovery report

Verification dose experiment: SIP justified, positives within acceptance

ISO 11137-2 · Evidence: VD experiment results

Dose mapping (OQ/PQ) for the defined loading pattern; Dmin/Dmax locations and ratio to routine monitoring position

ISO 11137-1 §9; ISO 11137-3 · Evidence: Dose mapping report

Dosimetry system calibrated, traceable to national standard; uncertainty considered

ISO 11137-3; ISO/ASTM 51261 · Evidence: Calibration certificate

Change of irradiator / source / e-beam ↔ gamma transfer assessed (re-mapping)

ISO 11137-1 §12.5 · Evidence: Transfer / re-mapping report

Quarterly (or justified frequency) dose audits defined; latest audit results and any augmentation

ISO 11137-1 §12.1; ISO 11137-2 · Evidence: Recent dose audit reports

Moist heat: cycle (temp/time/pressure), air removal, load, heat penetration and distribution studies; BI challenge (G. stearothermophilus)

ISO 17665 · Evidence: IQ/OQ/PQ reports

VH₂O₂: lumen/material claims, load limits, residual H₂O₂ addressed

ISO 22441; ISO 14937 · Evidence: Validation + residuals

Dry heat, LTSF or novel method: validated under ISO 14937 or method-specific standard; sterilant characterisation and residuals

ISO 20857; ISO 25424; ISO 14937 · Evidence: Validation report

Aseptic processing (if terminal sterilization not possible) justified and media fills performed

ISO 13408 series · Evidence: Justification + media fill reports

Devices supplied non-sterile and sterilized by user: at least one validated method in IFU (cleaning, disinfection, drying, sterilization parameters)

Annex I §23.4(n); EN ISO 17664-1 · Evidence: Reprocessing validation report

Reusable devices: number of reprocessing cycles validated and any limit stated in IFU

Annex I §23.4(n); ISO 17664-1 · Evidence: Lifetime / cycle study

Non-sterile devices needing user sterilization: packaging minimises contamination risk

Annex I §11.8 · Evidence: Packaging spec

Bioburden method validated: recovery efficiency (repetitive or spiked), correction factor applied

EN ISO 11737-1 · Evidence: Method validation report

Routine bioburden monitoring frequency, alert/action limits and trend data

ISO 11737-1 · Evidence: Trend summary (≥ last 12 months)

Bioburden characterised (aerobes, fungi; spore-formers where relevant to method)

ISO 11737-1 · Evidence: Characterisation data

Sterility test method suitability (bacteriostasis/fungistasis) done for each product family

EN ISO 11737-2 · Evidence: B/F test report

Bacterial endotoxin test (LAL/rFC) validated: inhibition/enhancement, extraction method

Ph. Eur. 2.6.14; USP <85>; ANSI/AAMI ST72 · Evidence: BET validation report

Endotoxin limit justified: commonly 20 EU/device; 2.15 EU/device for CSF/intrathecal contact

USP <161>; AAMI ST72 · Evidence: Limit rationale + results

Material-mediated pyrogenicity addressed (rabbit test or justification)

ISO 10993-11 · Evidence: Test report or BEP rationale

Endotoxin routine testing frequency defined (batch or justified sampling plan)

ANSI/AAMI ST72 · Evidence: Sampling plan

Test labs accredited (ISO/IEC 17025) or qualified under supplier controls

ISO 13485 §7.4 · Evidence: Accreditation scope

Sterile barrier system (SBS) and protective packaging fully described: materials, configuration, suppliers

EN ISO 11607-1 · Evidence: Packaging spec + drawings

SBS material compatible with sterilization method (porosity for EO/steam; radiation stability)

ISO 11607-1 §5 · Evidence: Material qualification

Microbial barrier properties of porous materials demonstrated

ISO 11607-1 §5.2; ASTM F1608 / F2638 · Evidence: Supplier data or test

Sealing process validated (IQ/OQ/PQ): temp, pressure, dwell; seal strength and integrity at process limits

EN ISO 11607-2 · Evidence: Seal validation report

Package integrity tests: seal strength (ASTM F88), dye penetration (F1929) or bubble (F2096), visual (F1886)

ISO 11607-1 Annex B · Evidence: Test reports

Transport / distribution simulation on worst-case configuration after sterilization

ASTM D4169 / ISTA · Evidence: Distribution test report

Accelerated aging: Q10, temperature, humidity justified; AAF calculation correct

ASTM F1980 · Evidence: Aging protocol + calculation

Real-time aging study initiated in parallel; status and plan to confirm the claimed shelf life

ASTM F1980; ISO 11607-1 §8 · Evidence: Real-time protocol + interim results

Device (not only packaging) stability over shelf life verified: material degradation, functional performance

Annex I §1, §6 · Evidence: Device stability report

Aged samples were sterilized at worst-case (max dose / multiple cycles) before aging

ISO 11607-1 · Evidence: Sample history in protocol

Aseptic presentation / usability of opening evaluated

ISO 11607-1 §7; IEC 62366-1 · Evidence: Usability evaluation

Shelf life claim on label = shelf life validated (no extrapolation beyond data)

Annex I §23.3(h) · Evidence: Label vs report match

Routine monitoring and product release criteria defined (BI/PCD results, parameters, dosimeter readings, residuals)

ISO 11135 §10; ISO 11137-1 §10 · Evidence: Release procedure

Sample batch record / certificate of processing provided

ISO 11135; ISO 11137-1 · Evidence: Example CoP

Requalification / revalidation frequency defined (e.g., EO annual review; radiation dose audits) and latest requalification attached

ISO 11135 §12; ISO 11137-1 §12 · Evidence: Latest requalification report

Change control triggers for re-validation: product, packaging, load, equipment, site, supplier

ISO 13485 §7.5.6 · Evidence: Change control procedure

Contract sterilizer identified (name, address); ISO 13485 certificate valid and covering sterilization

Annex IX §2.2; ISO 13485 §4.1.5 · Evidence: Certificate copy

Quality / technical agreement with sterilizer defines responsibilities (validation, release, deviations, notification of changes)

ISO 13485 §7.4 · Evidence: Signed agreement

Sterilizer listed as critical supplier and subject to NB unannounced audit provisions

Annex IX §3.4 · Evidence: Supplier list entry

Non-conforming cycle handling and deviations procedure in place; history of deviations reviewed

ISO 13485 §8.3 · Evidence: Deviation log summary

Label indicates sterile state and sterilization method (ISO 15223-1 symbol, e.g. STERILE EO / STERILE R)

Annex I §23.2(n); ISO 15223-1 · Evidence: Label artwork

Sterile packaging bears: sterile identification, declaration of sterile condition, method, manufacturer, device description, manufacturing date, use-by date

Annex I §23.3(a)–(h) · Evidence: Sterile pack artwork

Instruction to check IFU for what to do if sterile packaging is damaged or unintentionally opened before use

Annex I §23.3(i) · Evidence: Label / IFU text

'Do not use if package is damaged' symbol and single-use / do-not-resterilize symbols where applicable

ISO 15223-1; Annex I §23.2(i) · Evidence: Artwork

Use-by date matches validated shelf life (H12)

Annex I §23.2(j) · Evidence: Cross-check

IFU storage and handling conditions match those used in shelf-life and transport studies

Annex I §23.4(f) · Evidence: IFU vs study conditions

Single-use devices: IFU states known risks of reuse/resterilization

Annex I §23.4(p) · Evidence: IFU text

Reusable devices: validated reprocessing instructions and cycle limit in IFU (link to F5/F6)

Annex I §23.4(n) · Evidence: IFU text

Risk file covers sterility-related hazards: non-sterility, pyrogens, residuals, packaging breach, shelf-life expiry, material degradation

EN ISO 14971; Annex I §3 · Evidence: Risk analysis rows + controls traced to validation reports

Biological evaluation performed on final, sterilized (and aged where relevant) device

EN ISO 10993-1 · Evidence: BEP/BER statement on test article

Sterilant residuals and endotoxin conclusions referenced in the BER

ISO 10993-1, -7, -11 · Evidence: BER cross-reference

CER / literature on infection-related complications considered; sterility claims consistent with clinical data

Annex XIV; MDCG 2020-6 · Evidence: CER section reference

PMS plan / PSUR trend non-sterility complaints, infections, packaging failures

Art. 83–86 · Evidence: PMS plan, complaint trend

PMCF addresses long-term implant infection where relevant

Annex XIV Part B · Evidence: PMCF plan

Permanent-contact EO residual limits applied (not limited/prolonged)

ISO 10993-7 · Evidence: Residuals report category

Endotoxin tested per batch or on justified sampling plan for implants

ANSI/AAMI ST72 · Evidence: Release records

Absorbable / polymer implants: radiation or EO effect on degradation profile and mechanical properties verified over shelf life

Annex I §10.1 · Evidence: Post-sterilization + aged mechanical / degradation data

Implant cleanliness (particulates, residual processing aids) demonstrated before sterilization

ISO 19227 · Evidence: Cleanliness report

Implant card / patient information does not contradict sterile-state information

Art. 18 · Evidence: Implant card review

Overall quality of editing (language, formatting, consistency, no leftover template text)

General QC · Evidence: Full TD read-through

Manufacturer name and address are captured correctly throughout

Annex II §1.1; Art. 10 · Evidence: TD, labels, IFU, DoC and reports cross-check

Procedures / protocols are correctly identified and numbered

General QC · Evidence: Document list vs references in TD

Records are correctly captured, identified and numbered

General QC · Evidence: Record IDs vs references in TD

Latest and prevailing harmonised and non-harmonised standards used throughout

Art. 8; Annex II §4 · Evidence: Standards list vs OJEU / current editions