Comply with good manufacturing practice (GMP) and good distribution practice (GDP), and prepare for an inspection.
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
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, MHRA may carry out an inspection of both areas on behalf of the Veterinary Medicines Directorate.
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 2015.
- Green Guide: Rules and Guidance for Pharmaceutical Distributors 2015.
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. You will be told 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 can’t 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 be given 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.
Product-related GMP inspections
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).
EMA uses inspectors from EU member states to ensure compliance with GMP principles.
MHRA may inspect you if we’re informed about possible GMP or GDP breaches by:
- a whistle blower
- 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 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.
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
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.
A non-critical deficiency which:
- has or may produce a product that doesn’t 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
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.
If you’re being inspected for GMP you should complete an interim assessment if there are changes to your site following your first inspection.
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 their case referral but the company 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
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.
Fees for inspection
For further information on the planning of inspections, email firstname.lastname@example.org.