Guidance for Specials Manufacturers in the UK

Introduction and Purpose

In the United Kingdom, the Medicines and Healthcare products Regulatory Agency (MHRA) publishes guidance to help Manufacturing Specials (MS) licence holders interpret and apply Good Manufacturing Practice (GMP) requirements when manufacturing unlicensed medicinal products, commonly known as ‘specials’. This guidance provides detailed expectations for quality systems, premises, documentation, and production practices for MS holders.
Source: Guidance for 'specials' manufacturers

Scope of the Guidance

The guidance applies specifically to the manufacture of products under an MS licence. It does not cover importation of unlicensed products, though many requirements overlap. It also applies to other unlicensed preparations such as radiopharmaceuticals but excludes Advanced Therapy Medicinal Products regulated separately.
Source: Guidance for 'specials' manufacturers

Quality Management Expectations

Product Quality Reviews

Although not mandatory for all MS manufacturers, performing periodic quality reviews (PQRs) incorporating relevant elements of Chapter 1 of the EU GMP guide is strongly recommended, especially where multiple batches of the same product are produced.
Source: Guidance for 'specials' manufacturers

Data Trending

MS manufacturers are expected to conduct data trending for areas such as environmental monitoring, complaints, and deviations. Trend data should help identify changes in quality indicators over time.
Source: Guidance for 'specials' manufacturers

Capacity Planning

Facilities should implement a capacity plan to ensure adequate resources for production and ancillary tasks, helping to mitigate risk due to overload and bottlenecks in manufacturing processes.
Source: Guidance for 'specials' manufacturers

Premises and Equipment Requirements

Surface Sanitisation

Guidance addresses sanitisation of preparation and processing areas. While manual methods (e.g., spray and wipe) are acceptable, evidence must prove these processes control contamination within defined limits. Advanced technologies like vapourised hydrogen peroxide (VHP) may offer advantages if applied effectively.
Source: Guidance for 'specials' manufacturers

Shared Facilities and Equipment

Specials manufacturers should assess the suitability of shared facilities for different product types, particularly between aseptic ‘specials’ and biological products, to prevent cross-contamination risk.
Source: Guidance for 'specials' manufacturers

Documentation and Records

Site Master File

MS units are expected to maintain a Site Master File (SMF) containing detailed information about the facility, operations, and quality management systems unless justified otherwise due to site simplicity.
Source: Guidance for 'specials' manufacturers

Document Retention

Batch documents and related records must be retained for at least one year after expiry or five years after release, whichever is longer, to comply with regulatory expectations.
Source: Guidance for 'specials' manufacturers

Production and Supplier Controls

Supplier Qualification

MS holders must ensure GMP compliance for active substances and excipients, using audits and evidence such as GMP certificates or independent audit results to confirm quality suitability.
Source: Guidance for 'specials' manufacturers

Starting Material Checks

Manufacturers should conduct appropriate checks of starting materials and components, including ensuring materials are suitable for purpose and pose no undue risk to final product quality. Processes should include risk assessments and documented evidence.
Source: Guidance for 'specials' manufacturers

Aseptic Manufacturing and Contamination Control

For sterile and aseptic production, processes should be designed to minimise aseptic manipulations and maintain contamination control strategies aligned with principles in EU GMP Annex 1, even though the product is unlicensed.
Source: Guidance for 'specials' manufacturers

Labelling and Packaging Requirements

The guidance outlines expectations for effective labelling systems, including readability checks and GMP-aligned documentation, to ensure product safety and traceability.
Source: Guidance for 'specials' manufacturers

Summary

The UK MHRA guidance for ‘specials’ manufacturers provides comprehensive expectations for GMP application, from quality management and premises requirements to documentation, supplier controls, and aseptic processing. Although specific to unlicensed products, these principles align closely with broader pharmaceutical GMP standards.
Source: Guidance for 'specials' manufacturers