On October 1st 2018, the HPRA issued an update to its guidance on Batch-Specific Requests (BSRs) for Human Medicines. The update to version 3 of this guidance is available by clicking the link below.
While many of the key elements of the guidance in version 2 remain, e.g. MA holders are strongly discouraged from applying for a BSR when batch(es) are not in line with the product’s finished product specifications, there are some important changes that the reader should assess in advance of pursuing a BSR with the HPRA.
The main changes from version 2 to version 3 are detailed in points A to F below:
- A. Batch-specific requests (BSR) are accepted for critical medicines, with non-critical deviations, to bring a batch of product into compliance with its marketing authorisation to ensure maintenance of supply. The term critical is clarified in the EMA paper ‘Criteria for Classification of Critical Medicinal Products for Human and Veterinary Use’ EMA/24304/2016.
A medicinal product is critical when it is both
- an integral part of the treatment for or prevention of a disease, which is life-threatening or irreversibly progressive, or without which the public and animal health could be severely harmed.
- where appropriate alternatives are not available.
In exceptional instances, a BSR may be accepted for non-critical nationally authorised (including herbal and homeopathic products) products in order to correct a quality defect or to bring a batch into compliance with its registered MA dossier.
- B. BSRs should not be submitted for batches with an unexpected deviation during manufacture or distribution. The QP must deal with deviations as per section 3 in Annex 16 to the ‘European Guidelines for Good Manufacturing Practice for Medicinal Products for Human and Veterinary Use’. It should be noted that section 3 in Annex 16, as referenced, can be applied provided that compliance with the registered specifications for active substances, excipients, packaging materials and medicinal products are met.
- C. BSRs, previously limited in duration to 3 months, are no longer necessarily time bound. The three month restriction still applies where the BSR is requested to assure continued supply, however, if the BSR is intended as part of a corrective action for a quality defect, g. to bring the product back in line with the MA, the BSR has indefinite validity.
- D. The updated guidance clarifies the specific use of BSRs in relation to extensions requested for the implementation of changes to labels/leaflets agreed during renewal, where an approved variation is in place.
- E. A further significant clarification is provided on the use of BSRs for the rubber banding of patient leaflets and Caution-in-Use (CIU) letters, or the insertion of the product into sleeves/bags with leaflets and CIU letters. The rubber banding or insertion operations are not required to be performed by an authorised manufacturer under GMP, provided the packs are not being opened or reassembled. The operation should be supervised and overseen by the Responsible Person (RP) at an authorised wholesaler, and reconciliation should be performed on the leaflets and CIU letters.
- F. BSRs may be categorised as urgent when the product is critical and there is no alternative product on the market. The HPRA have committed to having a rapid turn-around time for urgent BSRs. For non-urgent BSRs, relating to products which are not critical to the Irish market, the HPRA have committed to targeting the commencement of assessing these requests within five working days of receipt.
If you would like further information or wish to discuss how PharmaLex can support you with the preparation and submission of Batch-Specific Requests, please connect with us at +353 1 846 4742 or firstname.lastname@example.org.