Regulatory Lifecycle Management

It covers keeping the MA current and valid for as long as the product is on the market: variations, SmPC/PIL and packaging updates, MA transfers, the five-year renewal, sales authorisations and monitoring of suspension risks. Under Article 25 of the Regulation on the Marketing Authorisation of Human Medicinal Products, the MAH must submit the changes needed to reflect scientific and technical progress in manufacturing and control methods for TİTCK’s approval, update the SmPC and PIL, and notify TİTCK of any change to the product.

A Type IA minor variation has minimal or no impact on the quality, safety or efficacy of the product. A Type II major variation may have a significant impact on them. Type IB covers variations that are neither Type IA, Type II nor an extension. An extension (çeşitleme) meets the criteria in Annex 1 of the Regulation and requires a new MA application. A variation whose type cannot be determined is treated as Type IB; it is handled as Type II if the MAH requests it or TİTCK concludes that it has a significant impact.

A Type IA variation may be implemented before the procedure is completed; it is notified within 12 months of implementation, or immediately where immediate notification is required. If rejected, implementation stops at once. For Type IB, the notification is deemed accepted if no negative opinion is received within 30 days of the acknowledgement of a valid notification, and it may be implemented only after that. Type II applications are assessed within 60 days, which may be extended to 90 days for changes to indications and certain groupings; the clock stops when further information is requested. Type II may be implemented only after approval.

As a rule, each variation is submitted separately. Grouping is possible provided a fee is paid for each variation: several Type IA variations for one MA, or the same Type IA variation for several MAs, can be notified together; variations to one MA can be combined where they fall under a case listed in Annex 3; and in other cases the same variations for several MAs can be combined if TİTCK accepts. TİTCK recommends submitting applications on the same subject for different products at the same time.

No. Where a variation leads to a revision of the SmPC, packaging information or PIL, that revision is treated as part of the variation and no separate variation is submitted. No new sales authorisation is needed for changes to the packaging information or the PIL.

Before the product is placed on the market, a new sales authorisation must be obtained after a pack size change, after moving the manufacturing site from abroad to Türkiye or vice versa, after an MA transfer, and for products whose suspension has been lifted. When a variation moving the manufacturing site between Türkiye and abroad is approved, a new MA is issued. For variations that change the barcode, products with the old barcode may, on request, be manufactured and placed on the market for six months after approval.

The transfer requires a contract drawn up before a notary, a record confirming that the full, approved and current product dossier has been handed over to the transferee, documents showing that the transferee can fulfil the MAH’s obligations (including the pharmacovigilance officer and scientific service), the current SmPC, PIL and packaging samples, and a document confirming the GMP compliance of the manufacturing site. TİTCK assesses the transfer within 30 days; if requested documents are not provided within 30 days, the application is cancelled and the file returned. An MA that has not been renewed cannot be transferred.

According to TİTCK, all variations for the product should be concluded before the transfer. Where TİTCK requests updates during the transfer, applications are filed under the MA Transfer (Administrative) Type IA/IB or MA Transfer (Quality) Type II document types. If the parties submit a notarised agreement, products with the old barcode may be manufactured for one year after the new MA is issued and placed on the market only by the transferee.

The main grounds in Article 22 of the Regulation include changes to the formula, strength, packaging or SmPC without TİTCK approval; failure to update the SmPC and PIL; failure to respond to TİTCK instructions on time; no commercial batch placed on the market within 30 months of authorisation; and a previously marketed product being absent from the market for 30 consecutive months. If the grounds for suspension are not refuted within six months, the MA is cancelled. The MAH must notify TİTCK at least 30 days in advance if it cannot supply a marketed product.

Where there is a risk to public health, the MAH implements urgent safety restrictions on its own initiative and informs TİTCK immediately. If TİTCK gives no feedback within 24 hours, the restrictions are deemed accepted, with full responsibility resting with the MAH. The related variation application is submitted within 15 days of the start of the restriction.