Good distribution practice (GDP): what it requires

Where the rules come from

European Union

the Guidelines of 5 November 2013 on Good Distribution Practice of medicinal products for human use (2013/C 343/01), published in the Official Journal on 23 November 2013 and applied from the day after. They rest on Articles 84 and 85b(3) of Directive 2001/83/EC, and Article 80(g) obliges every holder of a wholesale distribution authorization to comply with them. They replaced the GDP guidelines of 1994 and a March 2013 version.

Active substances

have their own EU guidelines, 2015/C 95/01, which apply to importers and distributors of active substances.

Worldwide

WHO's Good storage and distribution practices for medical products (TRS 1025, Annex 7, 2020) covers storage and distribution in one document and applies to everyone in the chain, naming manufacturers, wholesalers, brokers, logistics providers, transport companies, and forwarding agents.

PIC/S

the inspectorates' cooperation scheme publishes its own GDP guide (PE 011-1, in force since 1 June 2014). It is adapted from the EU text rather than copied: nine chapters, no chapter on brokers, and "designated responsible person(s)" in place of a single Responsible Person. Each member authority decides whether it is binding.

Who has to comply

In the EU, anyone acting as a wholesale distributor has to hold a wholesale distribution authorization and comply with GDP. That includes:

Wholesale distributors

including those operating in free zones and free warehouses.

Manufacturers

that distribute their own products. The guidelines say they must therefore comply with GDP.

Exporters

export counts as wholesale distribution.

Brokers

who arrange sales without handling the product. They register, and chapter 10 sets their obligations.

Contracted warehouses

premises the distributor does not operate itself are covered by a contract and by a separate wholesale distribution authorization.

Carriers and logistics providers

are not required by the guidelines to hold an authorization of their own. They are bound through the distributor's written contract and audited by it, and the distributor keeps the responsibility for what it contracts out.

The EU GDP guidelines, chapter by chapter

The EU guidelines have eleven chapters and a glossary. Ten set requirements; the last says what the guidelines replace and when they apply.

The Responsible Person

Every wholesale distributor has to designate a Responsible Person. The qualifications follow national law, and the guidelines say a degree in pharmacy is desirable. The Responsible Person has to carry out the role personally, be continuously contactable, and may delegate duties but not responsibilities.

The guidelines list twelve responsibilities. Among them: keeping the quality system in place, managing training, coordinating recalls, handling complaints, making sure suppliers and customers are approved, approving subcontracted activities, making sure self-inspections happen, and deciding what happens to returned, rejected, recalled, or falsified product, including whether it can go back to saleable stock.

In the UK the role sits in regulation 45 of the Human Medicines Regulations 2012. A second role, the Responsible Person (import), was added from 31 December 2020 for wholesalers in Great Britain that import from approved countries: they confirm that each imported batch has been certified by a Qualified Person or equivalently.

What GDP says about temperature

Temperature runs through the guidelines, from the warehouse to the truck:

Premises (3.1, 3.2.1)

are kept within acceptable temperature limits. A storage area is temperature-mapped before use, monitors go where the mapping found the extremes, and it is mapped again when a risk assessment or a significant change calls for it.

Equipment (3.3)

used to monitor and control temperature is calibrated at defined intervals based on risk, traceably to a national or international standard, with alarms that are set appropriately and regularly tested.

Returns (6.3)

a temperature-sensitive product goes back to saleable stock only with documented evidence that it was kept in its authorized storage conditions the whole time.

Transport (9.1 to 9.4)

the supplying distributor keeps products within their limits in transit and must be able to show that they were. Delivery routes are risk-assessed to decide where temperature control is needed, and the equipment that monitors temperature in vehicles and containers is calibrated at least once a year. An excursion is reported to the distributor and the recipient and investigated. Temperature-controlled vehicles are mapped under representative conditions, taking seasonal variation into account, and customers can ask for evidence that the product stayed within its storage conditions.

Two things the guidelines do not say, though they are often attributed to them. They do not set a recording interval or require real-time monitoring: they require that conditions be monitored, recorded, and demonstrable. When real-time monitoring is worth having anyway is the subject of why real-time temperature monitoring. And they do not require annual mapping of storage areas: mapping is done before use and then as risk dictates. The once-a-year rule is for calibrating transport monitoring equipment.

What happens after a breach is covered in our guide to temperature excursions, chapter 9 in more depth in our guide to pharmaceutical transport, and the kinds of equipment used to monitor temperature in our guide to cold chain monitoring devices.

Inspections and GDP certificates

Wholesale distributors are subject to repeated inspections by the national authority that granted their authorization, and inspections may be unannounced. Within 90 days of an inspection that finds the distributor compliant, the authority issues a GDP certificate. Certificates, and statements of non-compliance, go into EudraGMDP, the EU database run by the European Medicines Agency, which is publicly accessible. EU GDP asks distributors to use it to check that their suppliers are authorized.

EU law does not set a fixed inspection interval; each national authority sets its own, on a risk basis. In the UK, the MHRA said in 2023 that it intends inspection periods of around three to four years. A "GDP certificate" offered by a private certification body is a different thing: in the EU, the regulatory certificate comes only from a national authority after an inspection.

What inspectors find

The UK's MHRA published its last analysis of GDP inspection findings for inspections carried out in 2016. In a sample of 148 inspections, these were the areas where inspectors most often recorded a major deficiency:

Source: MHRA GDP Inspection Deficiency Data 2016 (published November 2017), the most recent GDP analysis the MHRA has published. Only major deficiencies were analyzed.

GDP in the UK after Brexit

Great Britain still applies the EU guidelines as they stood at the end of 2020: the Human Medicines Regulations 2012 keep them in force until the MHRA publishes guidelines of its own, and none has replaced them. Northern Ireland follows the EU guidelines directly. The MHRA's "Green Guide", Rules and Guidance for Pharmaceutical Distributors, collects the UK requirements in one volume.

GDP in the United States

There is no single US regulation called good distribution practice. The same ground is covered by several texts:

21 CFR Part 205

the federal minimum standards for state licensing of wholesale distributors. Section 205.50 requires storage at the temperatures the labeling or USP sets, temperature and humidity recording to document proper storage, inspection of incoming shipments, and quarantine of damaged or doubtful product.

21 CFR 211.142 and 211.150

the current good manufacturing practice (CGMP) rules for manufacturers' warehousing and distribution procedures.

The Drug Supply Chain Security Act

covers product tracing, not temperature. Its enhanced, electronic package-level tracing took effect on 27 November 2023, and FDA's exemption for small dispensers runs to 27 November 2027. FDA proposed national licensing standards for wholesale distributors and third-party logistics providers in 2022; the rule is still a proposal.

USP <1079.2>

the United States Pharmacopeia (USP) chapter that sets out how mean kinetic temperature is used to evaluate temperature excursions in storage and transport. It belongs to the <1079> family of chapters on storing and transporting drug products.

NABP Drug Distributor Accreditation

formerly VAWD, a voluntary accreditation of distributors that store, handle, and ship prescription drugs.

GDP, GMP, and GxP

Good manufacturing practice (GMP) governs how products are made and controlled. Good distribution practice keeps that quality intact through storage, trade, and transport, and protects the chain against falsified, stolen, and substandard products. GxP is the umbrella for all the good practice guides, from laboratory and clinical practice through manufacturing to distribution. The two meet at the manufacturer that ships its own products, which needs both, and at every excursion, where the distributor's record is judged against the manufacturer's stability data, often with the help of mean kinetic temperature.

Where monitoring fits

Much of GDP comes down to being able to show what happened to a product: in a storage area, on a truck, on a return. Controlant's devices record temperature and location for every shipment and send it while the shipment moves, so the evidence a customer can ask for under 9.4, and that 9.1 expects the distributor to be able to show, exists by the time the product arrives. Zero-Touch Release can then release product automatically when it stayed within its stability budget, based on rules the customer's quality team sets.