GN14 Explained: What Pharma Wholesale Distributors Need To Know

Unlicensed Medicines: Key Guidance Note 14 (GN14) requirements for wholesale distributors

When a pharmaceutical wholesaler becomes involved in the sale and supply of unlicensed medicines, often referred to as “Specials”, the scope of their Wholesale Distributors Authorisation (WDA) must include unlicensed medicines. Where unlicensed medicines are imported, this must also be reflected in their WDA.

Once confirmed that the WDA covers all activities relating to the purchasing, holding and supplying of unlicensed medicines, Guidance Note 14 must be adhered to. In this blog we run through the requirements of GN14 and what they mean for you as a WDA holder.

Traceability, record-keeping and documentation

One of the key elements of GN14 is traceability.

Wholesale distributors of unlicensed medicines must maintain:

• Complete records of where the unlicensed medicines came from (supplier), the product name, form, pack size, quantity and date of delivery.
• Records of to whom the products were supplied to including batch numbers, dates and quantities.
• Details of the prescriber and evidence of the patient’s special clinical need justification for the order. Please note: Cost, convenience or operational needs of the business are NOT considered to be acceptable as a special clinical need for an unlicensed medicine.
• Records of any suspected adverse events or reactions linked to unlicensed medicines.
• Details of any over-labelling or translated patient information leaflets or packaging. Wholesale distributors must ensure that any patient information is legible and written in English.
• Records relating to the importation (where relevant and in conjunction with an MS (Manufacturer Specials) licence), sale and supply of unlicensed medicines must be retained for at least 5 years.

Quality Management, Risk Assessment and Control

Given the elevated risk profile of unlicensed medicines, wholesale distributors must integrate GN14 and MHRA  expectations into the Pharmaceutical Quality Management System (PQMS) and Standard Operating Procedures (SOPs).

Key expectations include:

• Qualification and Risk assessment of Suppliers:
  Wholesale distributors must assess the regulatory status, quality standards, reliability and GDP compliance levels of suppliers of unlicensed medicines PRIOR to approving them as a supplier and AGAIN at periodic intervals. Supplier qualification evidence must be retained.

• Quality Technical Agreement:
  There must be a written agreement in place between the supplier and the wholesale distributor which clearly sets out the roles and responsibilities of both parties, and is reflective of the activites being outsourced.
  N.B Unless something is outsourced, you do NOT need to sign a technical agreement with any supplier or customer. We frequently see people requesting signature of TAs that hold no value. Signing agreements that serve no purpose can evidence to inspectors that you DO NOT KNOW WHAT YOU ARE DOING.

• Audits and Supplier Oversight:
  An audit or assessment of unlicensed medicines suppliers should be performed as part of the supplier onboarding process and again at periodic intervals, based on risk. The Quality Technical Agreement between both parties should allow for audits.

• Quarantine and Release Controls:
  A written procedure should document the goods in controls for unlicensed medicines, including the requirement to quarantine the product until acceptance checks of the products identity, including falsification checks, approved supplier confirmation and verification of documentation have been completed.

• Personnel Training and Competence:
  All personnel who handle unlicensed medicines in any capacity, e.g. taking orders, picking and packing, handling deviations and CAPAs, handling complaints etc. must be trained. Training should not only be in GDP, but also in the specific challenges and regulatory expectations of unlicensed medicine supply, storage and distribution.

• Deviations and CAPAs: As with any other GDP deviation or customer complaint relating to GDP activities, any deficiencies or complaints relating to unlicensed medicines must be documented and managed via approved written procedures.
  

• Management Review and Self-Inspections:
  Include unlicensed medicine aspects within self-inspections and management reviews to check GN14 compliance levels and highlight any deficiencies within the system.

• Importation into the UK:
  If looking to import an unlicensed medicine into the UK the applicant should hold a WDA(H) and an MS licence, and inform the licensing authority 28 days ahead of the import. If the 28 days pass without contact, or the import is approved, you may proceed.
  

If you are purchasing unlicensed medicines from a third party wholesaler you should be aware of how they sourced that product, and by what means. There have been IAG cases where wholesalers have procured ULMs from a site with no MS and who obtained those medicines illegally. 

Regulatory interaction and Inspection Readiness

Wholesale distributors of unlicensed medicines should:

• Be ready for MHRA GDP inspections at any time:
  Inspectors may review unlicensed medicines supply routes, audit trails, import notifications (where relevant), and records of prescriber origin orders, including patient prescriptions (personal details redacted) during their inspections. Even if the unlicensed medicines are not reviewed as part of the inspection, the activities should always be fully compliant and audit ready.

• Maintain open communications with the MHRA:
  This is particularly for import notifications, variation of licence scope and for urgent out-of-hours requests. See MHRA Inspectorate blog for more information on urgent import of unlicensed medicines.

• Deficiencies and CAPAs:
  Have corrective action plans in place for any inspection findings, with a clear root cause analysis, CAPA and evidence of implementation.

Why GN14 is non-negotiable

Unlicensed medicines are high-risk medicinal products therefore regulatory scrutiny is strong.
MHRA inspectors expect to see a thorough understanding of GN14, rigorous control, documentation and oversight.

Unlicensed medicines often lack full stability, validated manufacturing oversight or full clinical use history; they may also have special storage conditions. This elevates the risk of defects, improper formulation, degradation, labelling errors and adverse events. It is imperative that wholesale distributors perform full supplier due diligence and qualification exercises before purchasing unlicensed medicines and again at periodic intervals.

You must be able to trace unlicensed medicines from the prescriber to manufacturer to distributor to the dispensing party.
Any gaps in the chain can lead to regulatory enforcement, reputational damage or worse, risk to patient safety.

There should be a clinical need and there is an expectation that there is a link between prescriber, patient and supplier. 

Licence conditions relating to unlicensed medicines are strict. The MHRA expects that unlicensed medicines are handled as high-risk products and as such are risk assessed, documented and handled in accordance with written procedures that are fully trained to personnel who are then assessed for competency in the activities relating to unlicensed medicines.

From licensing and import notification, to rigorous documentation, storage control, supplier oversight, clinical need confirmation, training and audit readiness, GN14 requires that unlicensed medicines be handled in line with all regulatory guidelines and National law requirements.

Common unlicensed medicine deficiencies in MHRA GDP Inspections

 During GDP inspections, inspectors often flag recurring deficiencies specifically tied to unlicensed medicine supply.

Based on our consultant’s industry experience, some common deficiencies noted by inspectors include:

• Inadequate documentation of the special clinical need for an unlicensed medicine:
  Inspectors often find that distributors or suppliers cannot demonstrate that a licensed alternative was not suitable for the patient, or that the clinical justification was missing or against GN14 guidelines e.g. liquid required as it is easier for peg tube administration. This is a key expectation of GN14.

• Poor labelling implementation:
  Imported Specials sometimes carry non-English labelling. Inspectors find over labels that obscure original critical data, labels peeling off etc. Labelling should be checked as part of your goods in review process.

• Insufficient import notification/excessive import:
  Wholesalers sometimes import without giving the required 28 days’ notice or bring in more units that notified. In some more serious cases, the importation notification has not be submitted to the MHRA for approval.

• Weak supplier oversight:
  Some distributors fail to adequately qualify, audit or re-assess their unlicensed medicines suppliers, or accept deliveries with incomplete documentation.

• Traceability gaps:
  Missing or incomplete batch numbers, inconsistent records across all stages of operations, missing end used documentation e.g. missing prescriber information.

• Temperature excursions and missing root cause analysis:
  Lack of comprehensive handling of temperature excursions, failure to record as deviations, lack of or inadequate root cause analysis and CAPAs.

• Lack of personnel training or awareness:
  Staff not knowing the additional risks or regulatory expectations relating to the sale, supply and marketing of unlicensed medicines. Failure to follow GN14 guidelines.
  

• Absence of internal audits/management oversight of unlicensed medicines:
  Some distributors treat unlicensed medicines as ‘special orders’ meaning that they are handled outside of the Pharmaceutical Quality Management System, this does not go down well with the inspector and will likely result in a major or critical deficiency.

Being aware of these typical findings can help you ensure that you proactively review your unlicensed medicine operations and investigate and remediate any deficiencies… before an MHRA inspector finds them.

Help and Support

Paradigm Shift Consulting have a number of GDP consultants who specialise in unlicensed medicines and are available to support you every step of the way in your unlicensed medicines journey. Including:

• WDA licence applications and variations
• Controlled drug licence applications and variations
• Medicinal cannabis/CBPM import and supply 
• SOP review and updates
• Performing gap assessments of your operations
• Assisting with supplier or internal audits
• And much, much more.

Please contact us today for further information.

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