Quality and compliance

Türkiye İTS — İlaç Takip Sistemi

Every pack of medicine in the Turkish supply chain carries a GS1 DataMatrix code — the karekod — encoding the GTIN (application identifier 01), the serial number (AI 21), the expiry date (AI 17) and the batch number (AI 10).

İTS differs from the European model in an important respect. The EU Falsified Medicines Directive operates end-to-end verification: the pack is registered at manufacture and verified at dispense. İTS is full track-and-trace: every movement of every pack through the chain is notified to the system. The pack's history, not merely its endpoints, is recorded.

The karekod requirement has been mandatory since 1 January 2010, with the full track-and-trace phase in operation from March 2012.

EU GDP cold chain (2013/C 343/01)

The EU Guidelines on Good Distribution Practice of medicinal products for human use are the standard applied to cold-chain consignments.

• Qualified thermal packaging or temperature-controlled containers appropriate to the product and the route.
• Vehicles and containers temperature-mapped under representative seasonal conditions, so that the mapping reflects the conditions actually encountered.
• Temperature-monitoring devices calibrated at least annually, with calibration certificates available.
• A continuous temperature record for each shipment, including the logger serial number, the sampling interval and the minimum and maximum values recorded.
• Delivery documentation stating the batch number, quantity, consignee and the applicable transport and storage conditions.

Why cold chain matters — the mechanism, not the adjective

Monoclonal antibodies and most biologics are stored at 2–8 °C, protected from light, not frozen and not shaken. Those four conditions are not packaging conventions; each one addresses a specific degradation route.

Heat and freeze–thaw cycling drive protein aggregation and denaturation. The protein's higher-order structure is what carries its activity, and once it unfolds or aggregates the molecule is no longer the molecule that was authorised. Aggregates also raise the immunogenicity risk: the patient may mount an anti-drug antibody response to material that should never have reached them.

The clinically important point is that the vial can look entirely normal. Loss of potency is not visible. There is no inspection at the bedside that detects a product that spent six hours at 30 °C in transit. This is why the temperature record for the specific consignment, and not a general assurance, is what matters.

Freezing is generally not recoverable. A product that has frozen should be treated as compromised, not as a product that has returned to specification because it is now at 5 °C.

Certificate of Analysis — WHO Model Certificate format

WHO Technical Report Series 1010, Annex 4 (2018). A Certificate of Analysis in this format states:

• Name and address of the issuing laboratory.
• Certificate identification number, with page x of y on every page.
• Sample registration number and the date the sample was received.
• Product name, dosage form, strength and pack size.
• Batch number.
• Date of manufacture.
• Expiry date or retest date.
• Name and address of the original manufacturer.
• Reference to the test procedures used and to the specification applied.
• Results obtained, stated against the specification limits.
• Conclusion on whether the sample conforms to the specification.
• Date and signature of the head of the laboratory or of the authorised person.

Suspect product procedure

Applied per the EU GDP guidelines where a product is suspected of being falsified.

• Immediate quarantine of the affected stock.
• Physical segregation from saleable stock, in a clearly identified area.
• Notification of the competent authority and of the marketing authorisation holder.
• The product is not returned to saleable stock under any circumstances.
• Records of the incident and of the action taken are retained.

Verification resources

Related pages for verification of a specific pack or a specific alert.