# Guidance for 'specials' manufacturers

Source: https://www.keypedia.com/records/uk_mhra_guidance/uk-mhra/7004aab8-093a-4a21-bb70-1a597de3e265
Type: Guidance
Published: January 30, 2015
Updated: February 25, 2021

> The UK Medicines and Healthcare products Regulatory Agency (MHRA) has updated its guidance for Manufacturers Specials (MS) licence holders regarding the 'packing down' and aseptic preparation of unlicensed medicines. This revision, originally published in 2013 and updated based on recent inspection findings, clarifies necessary interpretations of Good Manufacturing Practice (GMP) for products manufactured using closed systems. The primary focus of the document is to enhance sterility assurance through improved operational standards. Key technical areas identified for improvement include cleaning validation, pooling procedures, the use of sporicidal agents for disinfection, eye drop manufacturing protocols, and the identification of microorganisms. To ensure compliance, the MHRA requires most changes to be implemented within a three-month timeframe. However, more significant updates related to sterility assurance—such as cleaning validation and pooling—must be completed within six months of the document's publication. During this transition period, licence holders are explicitly required to perform interim risk-reduction actions to mitigate potential safety risks. This regulatory framework ensures that manufacturers of unlicensed medicines maintain high safety standards while adapting their processes to meet the latest MHRA expectations.

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## Content

Guidance for Manufacturers Specials licence holders on ‘packing down’ medicines during the coronavirus (COVID-19) outbreak The purpose of this document is to provide guidance for manufacturing specials ( MS ) licence holders in the interpretation of good manufacturing practice ( GMP ) requirements that should be applied when manufacturing unlicensed medicines. This includes guidance on the appropriate standards for the manufacture of aseptically prepared products under an MS licence using essentially closed systems. This document was first published in September 2013. It has now been updated based on experience during inspections and stakeholder feedback. Areas where changes have been made are listed in the appendix. Some changes may have an operational impact so there will be a grace period to allow the changes to be implemented. We expect most changes should be implemented within 3 months. However due to the significance of the following changes these should be implemented by 6 months after the publication of this document: 3.3.6 - Cleaning validation 3.5.19 – Pooling (except the requirements for pooling batch records and conduct of media fill studies reflective of the process, which should be implemented within 3 months) 3.5.20 – Disinfection using sporicidal agents 3.5.27 – Eye drop manufacture 3.6.9 – Identification of microorganisms Due to the significant impact of these changes on sterility assurance, licence holders should ensure that, where relevant, interim risk reducing actions are considered during the 3 to 6-month implementation phase.

## Attachments

- [Guidance for 'specials' manufacturers](/government/publications/guidance-for-specials-manufacturers/guidance-for-specials-manufacturers)
- [Guidance for 'specials' manufacturers](https://assets.publishing.service.gov.uk/media/603526f28fa8f54330a8e25f/QA_Version_3_-_Aseptic_manip_updates.pdf)
- [Appendix: updates to the document](https://assets.publishing.service.gov.uk/media/5a7f735d40f0b62305b87387/Appendix_to_updated_specials_guidance.pdf)