Information on new arrangements for inspections during the coronavirus (COVID-19) outbreak. Exceptional good distribution practice (GDP) flexibilities for medicines during the coronavirus (COVID-19) outbreak

Overview

Good manufacturing practice (GMP) is the minimum standard that a medicines manufacturer must meet in their production processes. Products must:

be of consistent high quality
be appropriate to their intended use
meet the requirements of the marketing authorisation (MA) or product specification

Good distribution practice (GDP) requires that medicines are obtained from the licensed supply chain and are consistently stored, transported and handled under suitable conditions, as required by the MA or product specification.

Organisations that may have to comply with good manufacturing practice (GMP) and/or good distribution practice (GDP) include:

manufacturer licence holders
wholesale dealer licence holders
blood establishment authorisation holders
non-UK sites employed by UK MA holders

The Medicines and Healthcare products Regulatory Agency (MHRA) carries out inspections to check if manufacturing and distribution sites comply with GMP or GDP. You will be inspected when you apply for a manufacturer or wholesaler dealer licence and then periodically based on risk assessments. Overseas manufacturing sites are also inspected.

If an organisation manufactures or distributes both human and veterinary medicines, the MHRA may carry out an inspection of both areas on behalf of the Veterinary Medicines Directorate.

The MHRA and the European Medicines Agency (EMA) have published guidance on GMP and GDP:

Volume 4 of the rules governing medicinal products in the EU
EU GDP guidelines
Orange guide: rules and guidance for pharmaceutical manufacturers and distributors 2022
Green guide: rules and guidance for pharmaceutical distributors 2022
Guidance for UK manufacturer’s licence and manufacturer’s authorisation holders (for investigational medicinal products) – on the use of stand alone contract laboratories (PDF, 185 KB, 3 pages) - on the use of standalone contract laboratories

Types of inspection

Inspections under the risk-based compliance programme

Every manufacturer and wholesaler has a risk rating or score and we prioritise inspections for those with the highest ratings or scores. We will tell you about these inspections in advance, although under the short-notice inspection programme we may send little or no notification. At the inspection, GMP and/or GDP inspectors examine the systems used to manufacture and/or distribute medicines.

Your GMP rating is based on:

your compliance report
internal information about previous inspection history
organisational changes

You cannot appeal against your rating.

An increase in risk will be peer reviewed by a GMP operations manager, a member of the compliance management team (CMT) or a GMP expert inspector before being finalised.

You will receive a full copy of the reasons for your risk rating once the inspection has closed.

For GDP inspections your risk score is based on what activities take place on site and the number and type of deficiencies observed. This indicates the likely date of your next inspection and this information is included on the inspection report.

Inspections may sometimes be carried out with other MHRA inspections, such as with good clinical practice or good pharmacovigilance practice.

The MHRA conducts product-related GMP inspections when assessing an application for a UK marketing authorisation. This inspection checks if the manufacturer complies with GMP. We tell you about this inspection in advance.

Product-related inspections can also be requested by the European Medicines Agency (EMA):

Committee for Human Medicinal products (CHMp) during the pre-application of a centralised marketing authorisation application
Co-ordination group for Mutual Recognition and Decentralised Procedures – human (CMDh)

The EMA uses inspectors from EU member states to ensure compliance with GMP principles.

Triggered inspections

The MHRA may inspect you if we’re informed about possible GMP or GDP breaches by:

a whistleblower
other MHRA departments
another regulatory authority

We may send little or no notification of these inspections in advance.

Complete a compliance report

You will have to complete either a GDP or GMP compliance report before an inspection unless it is a triggered inspection which are only notified at short notice.

You should send completed compliance reports to the email address given by the inspector. Hard copies of compliance reports will not be accepted.

GDP compliance report (MS Word Document, 251 KB)
GMP pre-inspection compliance report (MS Word Document, 404 KB)
GMP interim compliance report (MS Word Document, 342 KB)
GMP compliance report and interim update guidance (PDF, 104 KB, 7 pages)
GMP Quality Control Laboratory Pre-Inspection Compliance Report (MS Word Document, 56.2 KB)
GMP QC compliance report and interim update guidance (PDF, 156 KB, 6 pages)

The inspection

During an inspection the inspection team will:

interview relevant personnel
review documents
conduct site visits

Site visits may include any facility or process involved in producing, purchasing and distributing medicines, including:

manufacturing areas
quality control (QC) laboratories
stock and stock management
storage areas
temperature monitoring
returns areas
purchasing and sales functions
transportation arrangements

The inspection team may ask for additional documentation and samples for testing during the inspection. They may also change the focus of the inspection if they suspect serious non-compliance.

At the closing meeting the inspector will provide feedback and discuss any deficiencies with you and agree timelines for corrective actions.

Grading of inspection findings

Deficiencies found during inspections are graded at 3 levels. The definitions below are summaries. For the full definition see page 47 of the EMA compilation of community procedures on inspections and exchange of information

Critical deficiency

A deficiency which has produced or significantly risks producing a product which is harmful to humans or veterinary patients or which could result in a harmful residue in a food-producing animal.

Any departure from good distribution practice that results in a significant risk to patients. This includes an activity which increases the risk of counterfeit medicines reaching patients.

Major deficiency

A non-critical deficiency which:

has or may produce a product that does not comply with its marketing authorisation
indicates a major deviation from GMP or GDP or from the terms of the manufacturer licence or wholesale licence
indicates a failure to carry out satisfactory batch release procedures or (within EU) a failure of the qualified person or responsible person to fulfil their legal duties
a combination of several ‘other’ deficiencies which on their own may not be major but together may represent a major deficiency and should be explained and reported as such

Other

A deficiency which cannot be classified as either critical or major, or there is not enough information to classify it as critical or major, but which indicates a departure from good manufacturing and distribution practice.

Actions after the inspection

After the inspection closing meeting, you will receive a post inspection letter confirming any deficiencies found.

You must respond to the inspector by email to confirm the proposed corrective actions and dates for when these actions will be completed. The inspector will review your response. If they accept it, you will receive a GMP or GDP certificate with your inspection report. An unacceptable response may lead to compliance escalation if further requests for information are unsatisfactory.

If you’re being inspected for GMP you should complete an interim assessment if there are changes to your site following your first inspection.

See our guidance on responding to a post-inspection letter.

Compliance escalation process

If your compliance is found to be poor but has not hit the threshold for regulatory action, you may go through the compliance escalation process. The aim of this process is to support companies to achieve compliance before regulatory action becomes necessary.

Once the process has been completed you will be returned to the routine risk-based inspection programme. However, you could still be referred for regulatory action if you do not make the necessary improvements.

The process may also be used if the Inspection Action Group has closed its case referral but the company needs to be monitored until remedial action plans have been completed.

The process may include:

making recommendations on close monitoring of compliance improvement work through inspection
meetings and correspondence with company senior management clearly outlining the consequences of continued non-compliance

Information sheets

Re-inspection of site under Compliance Management (PDF, 29.3 KB, 1 page)

Compliance Management - Specials Manufacturers (PDF, 36.1 KB, 1 page)

Compliance Management - MIA MIA(IMP) and third country manufacture (PDF, 37.4 KB, 2 pages)

Compliance Management - Contract Laboratory (PDF, 29.4 KB, 1 page)

Compliance Management - Active Substance (PDF, 29.6 KB, 1 page)

Regulatory action – UK Wholesaler (PDF, 83.7 KB, 2 pages)

Common deficiencies found in GMP inspections

To help you understand the areas where GMP inspectors have found compliance problems during GMP inspections in the UK and overseas, the GMP inspectorate produces a report of common deficiencies from previous GMP inspections.

The GMP Inspectorate has compiled an anonymised raw data set, so that stakeholders can do their own tailored analysis of our findings specific to their supply chain.

Suspension of your licence

If the inspector finds critical deficiencies, or that agreed action plans from previous inspection deficiencies have not been resolved, they will contact the Inspection Action Group (IAG). The IAG can refuse or suspend your licence, increase inspection visits or request a meeting with the licence holder.

Information Sheets

Re-inspection of site under Regulatory Action (PDF, 32.4 KB, 1 page)

Regulatory Action - Specials manufacturers (PDF, 37.9 KB, 2 pages)

Regulatory Action - MIA MIA(IMP) and Third Country manufacture (PDF, 39.5 KB, 2 pages)

Regulatory Action Contract Laboratory (PDF, 33.6 KB, 2 pages)

Regulatory Action - Active Substance (PDF, 34.1 KB, 2 pages)

Deficiency data (2018) (MS Excel Spreadsheet, 456 KB)

Fees for inspection

The daily rate inspection fee includes preparation for, reporting and close-out of the inspection.

Inspections with critical findings or other significant non-compliance requiring referral to the GMDP Compliance Management Team and/or Inspection Action Group may require the inspector(s) to spend additional time beyond that covered by the daily rate overseeing the adequacy of the company’s corrective and preventative actions (CAPA) and the company’s return to compliance. For such inspections, an office-based inspection fee may be charged for this additional time spent by the inspector(s) on such activities (for example, reviewing CAPA plans, impact assessments and periodic CAPA status updates).

See Fees for GMP and GDP inspections.

Contact

For further information on good manufacturing practices, complete the GMP contact form (MS Word Document, 16.3 KB) and email it to gmpinspectorate@mhra.gov.uk.

If your email relates to a good distribution practice, email gdp.inspectorate@mhra.gov.uk.

For further information on the planning of GMP inspections, email inspectionplanning@mhra.gov.uk and for GDP inspections gdpplanning@mhra.gov.uk

GxP inspections from 1 January 2021

From 1 January 2021, the MHRA’s GxP risk-based inspection programmes will remain unchanged.

GMP inspection outcomes from EEA regulatory authorities will continue to be recognised under a new mutual recognition agreement.

Inspections performed by existing mutual recognition partners will also continue to be accepted, if they are within the scope of the mutual recognition agreement in place before 1 January 2021.

Medicines: good manufacturing practice and good distribution practice