Good manufacturing practices (GMP): Manufacture of investigational medicinal products (IMPs)

Under the new directive, all IMPs need to be manufactured to GMP1 to ensure that they are fit for consumption by patients and volunteers.

Richmond Pharmacology has a Good Manufacturing Practice License.

Exemption for hospitals and health centres

A brief outline of the principles and guidelines governing Good Manufacturing Practice for Medicinal Products:

Quality management

  • To achieve quality manufacture of IMPs, Quality Assurance (QA) systems need to incorporate GMP guidelines and Quality Control (QC).
  • Full control and traceability of the changes made to product specifications and manufacturing instructions during development.

Personnel

  • Appropriate training of all personnel involved with IMPs
  • The Qualified Person, with relevant knowledge, should be responsible for ensuring that there are systems in place for meeting the Annex requirements

Premises and equipment

  • All risks of cross-contamination should be minimised, to be reflected in the design of equipment and premises, inspection/test methods and acceptance limits used after cleaning.

Documentation

  • Specifications and instructions

    • Should be as comprehensive as possible and periodically assessed during development with updates where necessary. Each new version should be thorough and traceable to the previous document.
    • Rationales for and consequences of changes should be recorded.
  • Order

    • Should be precise, presented in writing, and formally authorised. It should refer to the Product Specification File and the relevant clinical trial protocol as appropriate.
  • Product specification file

    • 'Should be continually updated as development of the product proceeds, ensuring traceability to the previous versions'. It should include, or refer to, a number of specific documents (see Annex 13 for a full listing).
  • Manufacturing formulae and processing instructions

    • Clear and adequate written instructions and records are to be produced for every manufacturing operation or supply.
  • Packaging Instructions

    • IMPs are normally packed in an individual way for each subject included in the clinical trial. The number of units to be packaged should be specified prior to the start of the packaging operations, including quality control and retention sample units. A sufficient reconciliation process must be established.
  • Processing, testing and packaging batch records

    • Concerns the detailing of batch records to accurately determine the sequence of operations.
    • Relates to the time that batch manufacturing records should be retained.

Production

This section addresses:

  • Packaging Materials
  • Manufacturing operations
  • Principles applicable to comparator product
  • Blinding operations
  • Randomised code
  • Packaging
  • Labelling

Quality control

  • Includes the parameters for performing quality control and information on the retention of samples of IMPs.

Release of batches

  • A listing of the Qualified Person's duties of the with regard to IMPs in different circumstances.

Shipping

  • An outline of the shipping regulations for IMPs, including decoding arrangements and inventory information.

Complaints

  • Complaints procedure and the parties involved.

Recalls and returns

  • Procedures for retrieving and returning IMPs should be agreed by the sponsor. This section also covers the storage and inventory records of returned IMPs.

Destruction

  • The sponsor is responsible for the destruction of unused and/or returned IMPs. Therefore written authorisation must be obtained from the Sponsor before IMPs can be destroyed.
  • A dated certificate or receipt of destruction must be provided to the sponsor when IMPs are destroyed. This section outlines the information to be included in the documentation.

References

  1. European Commission Enterprise Directorate-General – Volume 4: Good manufacturing practices, Annex 13: Manufacture of investigational medicinal products, July 2003
  2. http://www.legislation.hmso.gov.uk/si/si2004/20041031.htm
  • Next: Non-NHS Research Ethics Committees (RECs)
  • Previous: Obtaining authorisation to conduct a clinical trial
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