{"id":242,"date":"2026-03-18T05:56:50","date_gmt":"2026-03-18T05:56:50","guid":{"rendered":"https:\/\/isbm-technology.com\/?p=242"},"modified":"2026-03-18T05:56:50","modified_gmt":"2026-03-18T05:56:50","slug":"pharmaceutical-packaging-bottle-one-step-isbm","status":"publish","type":"post","link":"https:\/\/isbm-technology.com\/fr\/application\/pharmaceutical-packaging-bottle-one-step-isbm\/","title":{"rendered":"Flacon d'emballage pharmaceutique en une \u00e9tape ISBM"},"content":{"rendered":"
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Pharmaceutical Packaging \u00b7 GMP Compliance \u00b7 TGA Requirements \u00b7 Australia Ever-Power<\/p>\n

Process Parameter Settings & Complete Quality Control Guide<\/h2>\n

When a pharmaceutical container fails \u2014 dimensionally, mechanically or in barrier performance \u2014 the consequence is not a production reject or a customer complaint. It is a patient safety event. This guide details every process parameter, every quality test and every TGA regulatory documentation requirement for producing pharmaceutical primary packaging on a machine de moulage par injection-soufflage en une \u00e9tape<\/strong> that meets Australian GMP expectations without compromise.<\/p>\n

\ud83d\udc8a Pharmaceutical Primary Packaging<\/span>
\n\ud83d\udd2c GMP Quality Control<\/span>
\n\ud83d\udccb TGA Compliance \u00b7 Australia<\/span><\/div>\n<\/div>\n

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1. Why Pharmaceutical Containers Demand a Fundamentally Different Approach to ISBM<\/h2>\n

Pharmaceutical primary packaging \u2014 containers in direct contact with a drug product \u2014 operates under an entirely different regulatory and technical framework from food, beverage or cosmetic packaging. In Australia, the Therapeutic Goods Administration (TGA) requires that primary packaging materials comply with the relevant sections of the Australian Register of Therapeutic Goods (ARTG) registration, that extractables and leachables from container materials are characterised within ICH Q3E guideline limits for the drug product’s route of administration, and that the manufacturing process for primary packaging components is operated under a documented quality management system consistent with PIC\/S GMP Guide PE 009. For ISBM container manufacturers, this means the machine, tooling, resin and every process parameter are elements of a validated manufacturing process<\/em> \u2014 not simply inputs to a production operation.<\/p>\n

Le machine de moulage par soufflage automatique<\/strong> architecture of one-step ISBM offers a structural hygiene advantage over two-step alternatives that is architecturally significant for pharmaceutical applications: the closed-loop process \u2014 resin melted, formed into a preform, conditioned, stretched, blown and ejected in a single integrated machine with no intermediate atmospheric exposure \u2014 eliminates the preform handling, storage and transfer steps where microbial and particulate contamination can enter the container interior. This is not an incremental process improvement. It is an architectural difference that simplifies the contamination control programme, reduces the environmental monitoring burden and aligns directly with the GMP preference for process designs that minimise human intervention and open container exposure.<\/p>\n

This guide addresses pharmaceutical ISBM across five angles: resin and material qualification; machine and tooling qualification under the IQ\/OQ\/PQ framework; validated process parameter settings and their engineering rationale; container quality testing programme; and regulatory documentation package. Each section identifies what distinguishes pharmaceutical ISBM from beverage or cosmetic production and explains the technical basis for every additional requirement.<\/p>\n<\/section>\n

\"One-step<\/p>\n

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2. Resin Qualification: Pharmacopoeial Compliance and Acetaldehyde Control<\/h2>\n

2.1 Pharmacopoeial Compliance Requirements<\/h3>\n

PET resin for pharmaceutical primary packaging must comply with the requirements of multiple pharmacopoeial plastic container specifications referenced in the TGA’s regulatory framework. For Australian pharmaceutical manufacturers, the primary reference documents are the United States Pharmacopeia USP <661> Plastic Packaging Systems and Their Materials of Construction, European Pharmacopoeia Ph. Eur. 3.1.15 for PET containers, and ICH Q3E Guidelines for Extractables and Leachables. These references collectively require: biological reactivity tests (cytotoxicity testing per USP <87> or <88> appropriate to the intended route of administration), physicochemical tests (light absorption, non-volatile residue, heavy metals), and extractables characterisation covering volatile organic compounds, semi-volatile compounds and inorganic extractables under conditions that simulate drug product contact. The resin must be supplied with a Certificate of Compliance referencing the specific pharmacopoeial standards met, and this certificate forms part of the container material dossier submitted to the TGA with the drug product registration application.<\/p>\n

2.2 Acetaldehyde Control: The Primary Process-Related Impurity<\/h3>\n

Acetaldehyde (AA) is generated as a natural by-product of PET thermal processing and migrates from the container wall into the drug product. While AA is a regulatory concern in food packaging primarily through beverage taste threshold effects, in pharmaceutical applications the ICH Q3E threshold for AA as a process-related impurity in oral drug products is 22 ppm in the finished drug \u2014 but the migration rate from the container must be characterised and demonstrated to remain below this limit across the full intended shelf life, not merely at the time of manufacture. Every 10 \u00b0C reduction in melt processing temperature reduces AA generation by approximately 30\u201340%. Australia Ever-Power’s fully servo machine de soufflage de bouteilles PET<\/strong> EV series maintains barrel melt temperature within \u00b12 \u00b0C across all zones through closed-loop servo-controlled heating and active barrel cooling \u2014 the thermal management precision that pharmaceutical AA specifications demand and that conventional temperature controllers cannot reliably deliver across a full production shift.<\/p>\n<\/section>\n

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3. Machine and Tooling Qualification: The IQ\/OQ\/PQ Framework<\/h2>\n

GMP pharmaceutical manufacturing requires that all equipment used in or adjacent to the manufacturing process is qualified under a three-phase validation protocol before it is used in production. For a one-step ISBM machine producing pharmaceutical primary packaging components, this protocol covers the machine, the mould tooling and all in-process inspection equipment.<\/p>\n

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IQ \u2014 Installation<\/p>\n

Verifies machine installed correctly, all utilities meet spec, all instrument calibration certificates current and NATA-traceable. Documents serial number, as-built configuration and electrical protection testing.<\/p>\n<\/div>\n

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OQ \u2014 Operational<\/p>\n

Demonstrates machine operates within validated parameter ranges. Establishes upper and lower limits for all critical process parameters with documented engineering rationale for each limit.<\/p>\n<\/div>\n

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PQ \u2014 Performance<\/p>\n

Three consecutive production batches of \u22651,000 containers each, all meeting quality specification. Cpk \u2265 1.33 for weight and wall thickness. AA content within validated limit throughout.<\/p>\n<\/div>\n<\/div>\n

3.1 OQ Validated Process Parameter Ranges<\/h3>\n

The table below defines representative OQ validated process parameter ranges for a standard 100 mL PET oral liquid bottle produced on an Australia Ever-Power four-station full servo machine. Parameters for other container formats \u2014 ophthalmic solutions, oral solid dispensing bottles, parenteral supplement containers \u2014 are established individually during the OQ protocol for each product-machine-tooling combination.<\/p>\n

\n\n\n\n\n\n\n\n\n\n\n
Process Parameter<\/th>\nNominal Set Point<\/th>\nValidated Range<\/th>\nMonitoring Frequency<\/th>\nQuality Impact if Out of Range<\/th>\n<\/tr>\n<\/thead>\n
Barrel melt temp \u2014 zones 1\u20134<\/td>\n275 \u00b0C<\/td>\n270\u2013280 \u00b0C<\/td>\nContinuous<\/td>\n\u2191 AA generation; thermal degradation<\/td>\n<\/tr>\n
Preform conditioning temp<\/td>\n100 \u00b0C<\/td>\n97\u2013103 \u00b0C<\/td>\nContinuous<\/td>\nWall thickness non-uniformity; haze<\/td>\n<\/tr>\n
Blow pressure \u2014 main<\/td>\n3.0 MPa<\/td>\n2.9\u20133.1 MPa<\/td>\nContinuous<\/td>\nVolume deviation; base deformation<\/td>\n<\/tr>\n
Machine cycle time<\/td>\n18 s<\/td>\n17\u201319 s<\/td>\nPer cycle<\/td>\nInsufficient cooling; dimensional drift<\/td>\n<\/tr>\n
Cooling water temperature<\/td>\n12 \u00b0C<\/td>\n10\u201314 \u00b0C<\/td>\nEvery 30 min<\/td>\nShrinkage; neck finish deviation<\/td>\n<\/tr>\n
Injection shot weight<\/td>\n12.0 g<\/td>\n11.8\u201312.2 g<\/td>\n100% inline<\/td>\nWall thickness Cpk failure<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<\/div>\n<\/section>\n

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4. In-Process Quality Control: Three-Level Programme<\/h2>\n

Pharmaceutical container production requires a more structured and fully documented in-process quality control programme than any other ISBM application. The three-level programme below is the minimum required framework under PIC\/S GMP; individual drug product registrations may impose additional or more stringent requirements depending on the product’s route of administration and the risk classification assigned to the container in the ARTG submission.<\/p>\n

Level 1 \u2014 Automated 100% Inline Inspection<\/h3>\n
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Inline weight check<\/span> \u2014 Reject-on-deviation from set point \u00b10.3 g, with automatic diversion to a dedicated reject chute. Every reject event is batch-recorded with timestamp and deviation value for GMP traceability.<\/div>\n
Vision inspection<\/span> \u2014 Camera-based detection of visible defects: gate marks exceeding 0.5 mm, streaks, bubbles, incomplete base push-up and neck finish chip or crack. Reject rate logged per production hour.<\/div>\n
Neck finish OD measurement<\/span> \u2014 Confocal laser sensor measuring neck outside diameter at 100% rate. Containers outside \u00b10.1 mm of nominal neck OD are automatically rejected before they reach the closure application station.<\/div>\n<\/div>\n

Level 2 \u2014 Periodic Operator Sampling Inspection<\/h3>\n
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Wall thickness mapping<\/span> \u2014 Ultrasonic gauge, one container per 500, minimum 12-point measurement map (six axial positions \u00d7 two angular positions). Cpk calculated against the validated wall thickness specification and recorded in the batch record.<\/div>\n
Top-load compression test<\/span> \u2014 One container per 500 at minimum 120 N for a 100 mL oral liquid bottle. Ensures filled container can withstand stacking loads during storage and distribution without permanent deformation.<\/div>\n
Closure leak integrity test<\/span> \u2014 Five containers per batch, closure applied at specified torque, tested at 50 kPa internal pressure for 60 seconds. Zero leakage is the acceptance criterion for all pharmaceutical oral liquid applications.<\/div>\n<\/div>\n

Level 3 \u2014 Batch Release Laboratory Testing<\/h3>\n

Batch release testing by the quality laboratory covers the full pharmacopoeial container specification: biological reactivity per USP <87>, physicochemical tests (non-volatile residue, heavy metals, light transmission), and AA content measurement. This batch release programme mirrors the qualification testing that established the validated parameter ranges, ensuring ongoing comparability between each production batch and the qualification baseline required for TGA audit traceability over the product’s registered shelf life.<\/p>\n<\/section>\n

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5. Pharmaceutical Container Formats and Format-Specific Parameter Considerations<\/h2>\n

Pharmaceutical containers produced on Australia Ever-Power one-step ISBM equipment span four primary formats, each with distinct preform design, stretch ratio and quality control requirements that must be individually documented in the validated process for that format.<\/p>\n

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Oral Liquid Bottles \u2014 50 to 500 mL<\/p>\n

Syrups, suspensions and elixirs. PCO neck finish for tamper-evident closure compatibility. AA target below 10 \u00b5g\/L for oral route. Amber tint option for light-sensitive formulations including most antibiotic suspensions.<\/p>\n<\/div>\n

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Oral Solid Dispensing Bottles \u2014 60 to 1,000 mL<\/p>\n

Tablets, capsules and vitamin supplements. Wide-mouth neck finish for automated packaging line compatibility and child-resistant closure systems. Desiccant canister integration compatibility for hygroscopic formulations.<\/p>\n<\/div>\n

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Ophthalmic Solution Bottles \u2014 5 to 30 mL<\/p>\n

Eye drops with integral dropper tip. Requires ISO Class 7 cleanroom production environment. Tightest contamination control specification across all pharmaceutical packaging categories \u2014 microbial bioburden limit below 10 CFU per container.<\/p>\n<\/div>\n

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Parenteral Supplement Bottles \u2014 100 to 500 mL<\/p>\n

Nutritional preparations for parenteral administration. Highest extractables and leachables characterisation requirements. ICH Q3E toxicological risk assessment mandatory for all identified extractables above reporting threshold.<\/p>\n<\/div>\n<\/div>\n<\/section>\n

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6. Cleanroom Integration and Environmental Control Requirements<\/h2>\n

Pharmaceutical ISBM container production increasingly requires environmental control consistent with ISO 14644-1 cleanroom standards \u2014 particularly for parenteral supplement containers and ophthalmic solutions where contamination specifications are most stringent. Australia Ever-Power’s pharmaceutical-configured machines are designed for installation in ISO Class 7 or ISO Class 8 cleanroom environments with the following standard features: all external machine surfaces are smooth, crevice-free stainless steel or equivalent hygienic grade materials with no horizontal ledge surfaces where particulate can accumulate; the full servo motor drive system eliminates hydraulic oil entirely from the production environment \u2014 removing both a potential particulate contamination source and a microbial growth substrate; and the control cabinet is sealed to IP54 rating with a filtered positive-pressure air purge to prevent particulate ingress from the room environment even during door-open maintenance events.<\/p>\n

Le machine de moulage par soufflage automatique<\/strong> EV series includes an optional ionised air knife at the container ejection station that neutralises static charge accumulated during the blowing process and removes loose particulate from container surfaces immediately before transfer to the downstream inspection and secondary packaging systems. Static charge accumulation on PET containers is the primary mechanism by which airborne particulate adheres to container inner surfaces after ejection \u2014 the ionised air knife addresses this at the point where it matters most, before containers reach any open-air environment.<\/p>\n

Blow air quality for pharmaceutical applications must meet ISO 8573-1 Class 1.2.1 minimum: particulate Class 1 (\u22640.1 \u00b5m particles \u226420,000\/m\u00b3; \u22640.5 \u00b5m \u2264400\/m\u00b3), humidity Class 2 (pressure dew point \u2264\u221240 \u00b0C), and oil Class 1 (\u22640.01 mg\/m\u00b3). The blow air quality certificate forms part of the IQ documentation package and is re-verified at each annual machine qualification review.<\/p>\n

\"Injection<\/p>\n<\/section>\n

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7. Regulatory Documentation Package and TGA Audit Support<\/h2>\n

The regulatory documentation package for pharmaceutical ISBM containers is substantially more extensive than for food or cosmetic packaging, and must be in place before the first commercial production batch is released. Australia Ever-Power provides the following documentation with every pharmaceutical machine installation, structured to directly support the customer’s TGA Drug Master File or ARTG registration submission.<\/p>\n

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\ud83d\udcc4<\/span><\/p>\n

IQ\/OQ Protocol Templates<\/span> \u2014 Populated with machine-specific instrument calibration data and installation verification records. Formatted to PIC\/S GMP PE 009 documentation requirements. Includes calibration schedule and requalification trigger criteria.<\/div>\n<\/div>\n
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\ud83e\uddea<\/span><\/p>\n

Resin Certificate of Analysis and Compliance<\/span> \u2014 For the specific resin grade used in the qualification batches, referencing USP <661>, Ph. Eur. 3.1.15 and ICH Q3E compliance. Retained as a permanent GMP record for the life of the product registration.<\/div>\n<\/div>\n
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\ud83d\udd2c<\/span><\/p>\n

Extractables and Leachables Test Report<\/span> \u2014 Conducted under ICH Q3E relevant extraction conditions (simulant solvent, temperature, duration) appropriate to the drug product contact scenario. Issued by an accredited testing laboratory with NATA certification.<\/div>\n<\/div>\n
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\ud83d\udcbb<\/span><\/p>\n

21 CFR Part 11-Compatible Electronic Batch Record System<\/span> \u2014 Cycle-by-cycle parameter logging with audit trail, user access controls, electronic signature capability and automated alarm log. Satisfies data integrity requirements for TGA facility registration and FDA\/MHRA export market inspections.<\/div>\n<\/div>\n
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\ud83d\udccb<\/span><\/p>\n

Validation Master Plan Template<\/span> \u2014 Pre-formatted for the customer’s quality team to complete with the product-specific PQ data, container specification, validated parameter ranges and acceptance criteria. Australia Ever-Power’s quality team participates in TGA facility inspection preparation at the customer’s request.<\/div>\n<\/div>\n<\/div>\n<\/section>\n

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8. Common Non-Conformances, Root Cause Analysis and CAPA Requirements<\/h2>\n

Pharmaceutical container non-conformances require corrective and preventive action (CAPA) documentation and a formal root cause investigation under GMP \u2014 they cannot be resolved by simply adjusting machine parameters and restarting production without a documented assessment. The three most frequently encountered non-conformances in pharmaceutical ISBM production, their validated root causes and their documented corrective actions are as follows.<\/p>\n

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\u26a0\ufe0f Non-Conformance 1: Acetaldehyde Content Exceedance<\/p>\n<\/div>\n

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Root cause:<\/strong> Barrel temperature zone excursion above the validated upper limit, or introduction of regrind material above the qualified regrind percentage limit \u2014 regrind PET typically has higher intrinsic viscosity degradation and elevated AA precursor concentration versus virgin resin.<\/p>\n

Corrective action:<\/strong> Verify thermocouple calibration against NATA-traceable reference standard; audit regrind usage records for the affected batch; re-qualify the process if regrind percentage has changed from the qualified value. All affected batches placed on hold pending CAPA completion.<\/p>\n<\/div>\n<\/div>\n

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\u26a0\ufe0f Non-Conformance 2: Closure Leak Test Failure<\/p>\n<\/div>\n

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Root cause:<\/strong> Neck finish outside diameter deviation from neck ring tool wear. The PET neck finish OD reduces over time as the neck ring tool wears, reducing the interference fit with the closure thread and compromising the seal.<\/p>\n

Corrective action:<\/strong> Dimensional inspection of neck ring tooling with thread ring gauge; replace neck ring if outside the \u00b10.05 mm wear tolerance limit. Review neck OD trending data from the inline laser measurement system to establish predictive replacement interval.<\/p>\n<\/div>\n<\/div>\n

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\u26a0\ufe0f Non-Conformance 3: Wall Thickness Cpk Below 1.33<\/p>\n<\/div>\n

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Root cause:<\/strong> Conditioning temperature non-uniformity across heater zones \u2014 typically caused by heater element degradation in one or more zones \u2014 or injection unit shot weight variability from screw seal wear.<\/p>\n

Corrective action:<\/strong> Map conditioning zone temperatures with calibrated thermocouple at 10-point grid; replace failed heater elements; verify injection unit shot weight repeatability with ten consecutive cycles on calibrated inline balance. Re-run PQ acceptance testing after corrections are implemented and documented.<\/p>\n<\/div>\n<\/div>\n<\/div>\n<\/section>\n

<\/p>\n

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Australia Ever-Power \u00b7 Condell Park NSW 2200<\/p>\n

Need GMP-Ready Pharmaceutical ISBM Equipment
\nwith Full TGA Documentation Support?<\/h3>\n

Australia Ever-Power supports pharmaceutical packaging producers from initial machine specification through IQ\/OQ\/PQ qualification, with complete GMP documentation packages, cleanroom-configured machines, 21 CFR Part 11 data logging and TGA audit preparation support. Speak to our pharmaceutical packaging specialist today.<\/p>\n

\ud83d\udce9 Request a Pharma Machine Consultation<\/a>
\n\ud83d\udd0d View GMP Machine Specifications<\/a><\/div>\n

\ud83d\udccd 27 Harley Crescent, Condell Park NSW 2200 \u00b7 \ud83d\udcde +61 2 9708 3322 \u00b7 \u2709\ufe0f sales@isbm-technology.com<\/p>\n<\/div>\n<\/article>","protected":false},"excerpt":{"rendered":"

Pharmaceutical Packaging \u00b7 GMP Compliance \u00b7 TGA Requirements \u00b7 Australia Ever-Power Process Parameter Settings & Complete Quality Control Guide When a pharmaceutical container fails \u2014 dimensionally, mechanically or in barrier performance \u2014 the consequence is not a production reject or a customer complaint. It is a patient safety event. This guide details every process parameter, […]<\/p>","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_et_pb_use_builder":"","_et_pb_old_content":"","_et_gb_content_width":"","footnotes":""},"categories":[1],"tags":[],"class_list":["post-242","post","type-post","status-publish","format-standard","hentry","category-uncategorized"],"_links":{"self":[{"href":"https:\/\/isbm-technology.com\/fr\/wp-json\/wp\/v2\/posts\/242","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/isbm-technology.com\/fr\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/isbm-technology.com\/fr\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/isbm-technology.com\/fr\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/isbm-technology.com\/fr\/wp-json\/wp\/v2\/comments?post=242"}],"version-history":[{"count":2,"href":"https:\/\/isbm-technology.com\/fr\/wp-json\/wp\/v2\/posts\/242\/revisions"}],"predecessor-version":[{"id":244,"href":"https:\/\/isbm-technology.com\/fr\/wp-json\/wp\/v2\/posts\/242\/revisions\/244"}],"wp:attachment":[{"href":"https:\/\/isbm-technology.com\/fr\/wp-json\/wp\/v2\/media?parent=242"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/isbm-technology.com\/fr\/wp-json\/wp\/v2\/categories?post=242"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/isbm-technology.com\/fr\/wp-json\/wp\/v2\/tags?post=242"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}