Selected issues concerning the transport of medicines and vaccines

GDP/DPD certification and cargo-space mapping according to DIN 91323

The Minister of Health regulation on Good Distribution Practice for medicinal products requires, among other things, that entrepreneurs engaged in wholesale trade of these products map the temperature of the cargo space of vehicles intended for their transport. In our country, however, there are no uniform requirements for qualification and certification of vehicles for medicine transport. Bodies providing such services set their own procedural criteria, which often have no basis in any technical standards or test methods used by competent national institutions (e.g. the Central Refrigeration Centre COCH in Kraków) and foreign ones. Unification of national procedures for production, testing and certification of vehicles for medicine distribution is enabled by the document published by PKN: PKN-DIN SPEC 91323:2019-08 “Commercial vehicles with temperature-controlled cargo space used for distribution of pharmaceutical products (for human or veterinary use) - Guidelines for qualification” in the Polish language version. The document was issued on the initiative and with the participation of the Central Refrigeration Centre COCH in Kraków. As a member of the PKN refrigeration committee and at the same time a scientific body authorised to test and certify both refrigerated vehicles under ATP and vehicles for medicine transport, COCH had already pointed earlier to difficulties in compiling requirements for test conditions and certification of vehicles for transport and distribution of temperature-sensitive products, in particular medicines and vaccines. Only a few months after the document was published, the global epidemic situation changed, which should draw even more attention from our national institutions supervising pharmaceuticals to the still unclear rules on their transport. This article aims to present the content of the document in the most accessible way possible, as a potential solution to this problem.

VEHICLE CLASSIFICATION

The document provides for two basic vehicle categories, on the basis of which test conditions and procedures are selected:

• Category A – vans (delivery vehicles)
• Category B – box trucks, trailers, semi-trailers

Each of these categories covers vehicles whose bodies have:

1. similar shape and cross-sections;
2. a similar length range;
3. the same type and quality of compartment wall insulation;
4. refrigeration and heating equipment of the same type;
5. similar systems and layout of air-flow ducts.

The specification also includes a list of documents that should be submitted as part of qualification.

TEST CONDITIONS

Requirements for temperature measurement systems

For temperature measurement systems used to qualify vehicles according to PKN-DIN SPEC 91323, an error limit of ≤ ± 0.5 K applies; each instrument should be calibrated at least once a year.

Required ambient (external) temperatures

These were defined as applicable for the territory of Germany; however, a reservation was added that where vehicles are used in other regions, local maximum and minimum temperatures should be taken as the basis for determining these temperatures. Information on temperatures in Poland is contained in National Annex NA to PKN-DIN SPEC 91323.

Required temperatures in the cargo space (internal)

The internal temperature ranges are set by medicine manufacturers. PKN-DIN SPEC 91323 presents six such possible ranges, with the reservation that temperature ranges other than those specified in the table below may be used if they result from relevant quality requirements for the goods to be transported according to the client’s recommendations Table 2. Internal temperatures recommended during tests according to PKN-DIN SPEC 91323:2019-08 NOTES:

1. At the minimum external temperature at least the upper limit of the specified transport temperature range should be reached, and at the maximum at least the lower limit.
2. Category A and B commercial vehicles should be tested in at least one of the temperature ranges.
3. For multi-compartment vehicles, selection of temperature ranges, tests and division into temperature zones is carried out in accordance with the guidelines set out in PKN-DIN SPEC 91323.

Placement of temperature measurement points outside the body

Temperature outside the body should be measured by at least four sensors placed at the centre of the four largest external surfaces of the compartments (e.g. roof, floor, side walls) at a distance of 100 mm from their surface. For vans (Category A vehicles) an additional temperature sensor should be placed in the driver’s cab, at mid-height of its rear wall, 100 mm from its surface. Placement of temperature measurement points inside the cargo compartment Placement of measurement points depends on the dimensions of the cargo compartments. Compartments of Category A and B vehicles are treated separately and within each category compartments are divided into two groups depending on cargo-space length. Placement of measurement sensors is shown schematically in Figures 1 to 4.

TEST PROCEDURE

Tests should be performed at specified rotational speeds of the refrigeration or heating unit depending on the type of drive of these units, i.e. for drive independent of the vehicle engine and for drive provided directly or indirectly by the vehicle combustion engine. Idle speeds and mean operating speeds are determined in accordance with DIN EN 16440-1:2015-05. During the tests, inter alia the following parameters are recorded: internal and external temperatures, set temperatures on the controller and cooling time, rotational speed, time to reach set temperature, etc. Tests of the vehicle under summer and winter conditions (checking the refrigeration and heating system) and simulation of disturbances and failures are provided for.

1. Vehicle test under summer conditions – cooling mode

Preparing the vehicle for tests

The vehicle with open cargo-compartment doors and equipped with a complete temperature measurement system is placed in the test chamber and exposed to the external temperature, e.g. +38°C, in order to equalise the temperature of the walls of the tested compartment with that temperature. Temperature equalisation time should be at least 6 h. After temperature equalisation the body doors are closed and the refrigeration unit is started with the appropriate temperature set-point; this is the start of the cooling phase.

I Cooling phase

It ends when the readings of all internal temperature measurement sensors are within the required temperature range.

II Steady state and defrosting

Continuation of the previous phase, lasting at least 2 h within the range controlled by the temperature controller. If the test is performed for transport temperatures in the range 2 to 8 °C or lower, after 2 h of testing a defrost cycle should be carried out, after which the test should be continued for a further 2 h.

III Simulation of disturbances and failures

After completion of phase II, a test of the effect of opening the body doors and a simulation of unit failure are performed.

2. Vehicle test under winter conditions – heating mode

Preparing the vehicle for tests

Analogous to summer conditions, except that the external temperature corresponds to winter conditions (e.g. −20°C). After temperature equalisation the body doors are closed and the heating unit is started with the appropriate temperature set-point; this is the start of the heating phase.

I Heating phase

It ends when the readings of all internal temperature measurement sensors are within the required temperature range.

II Steady state

Continuation of the previous phase, lasting at least 2 h within the range controlled by the temperature controller.

III Simulation of disturbances and failures

Simulations are performed analogously to summer conditions.

CRITERIA FOR ASSESSING TEST RESULTS

- Test in cooling / heating mode The result is positive if, during the final 2 hours of steady state, temperatures at all measurement points remain within the required range. - Simulation of equipment disturbances and failures Results of disturbance simulation tests are considered positive if, after restarting the equipment, the temperatures inside the body achieved during steady state are restored. There are no acceptance criteria for failure simulation test results; however, this information is very helpful and recommended when planning measures to protect the cargo should such a situation occur.

SUMMARY

Use of the document presented in this article helps introduce and apply uniform criteria for testing and certification of means of transport by different testing laboratories and certification bodies. It enables the certification body to recognise tests of a prototype unit when a manufacturer applies for certification of serially produced identical means of transport. The requirements may also be useful in designing specialised means of transport for medicine transport. Meeting the requirements of this Specification will make it easier for manufacturers and users of means of transport for pharmaceutical products to obtain a Good Distribution Practices (GDP) certificate, widely recognised in countries across our continent. Good Distribution Practice (GDP) certification requires that persons dealing with pharmaceutical products meet the World Health Organization (WHO) stringent standards for safety and protection. Although GDP certification is not a global requirement, EU pharmaceutical companies and their logistics partners must comply with GDP rules. The Good Distribution Practices (GDP) certification programme implemented at COCH defines the conditions necessary to obtain the relevant certificate (EU GDP) for means of transport (vehicles) intended for transport and storage of sensitive products (temperature-sensitive products), including medicines, for conformity with the requirements of the normative document – Requirements for Good Distribution Practice with regard to means of transport of sensitive products transported under controlled/regulated temperature. Obtaining a certificate (EU GDP) for a given type/model of means of transport (vehicle) intended for transport and storage of sensitive products is available to every manufacturer/supplier that ensures stable organisational and technical conditions for production/supply of the said means of transport with specified parameters confirmed by relevant tests. A certificate may be issued for a means of transport (vehicle) that holds a valid ATP certificate and meets the requirements of the above document within the scope specified by the manufacturer/supplier in the certification application.

The Central Refrigeration Centre “COCH” in Kraków is the only body in Poland that

• is an accredited product certification body, inter alia for means of transport of sensitive products transported under controlled/regulated temperature (Polish Centre for Accreditation No. AC 036), meeting the requirements of PN-EN ISO/IEC 17065.
• has a laboratory accredited inter alia for testing according to PKN-DIN SPEC 91323:2019-08 (Polish Centre for Accreditation No. AB 308), meeting the requirements of PN-EN ISO/IEC 17025

We perform temperature distribution tests (so-called mapping) of the interior of thermally insulated bodies with an installed refrigeration or refrigeration-heating unit, for single- or multi-compartment means of transport, for winter and summer periods. On the basis of the test, the temperature distribution (temperature map) inside the means of transport is determined (including identification of locations of minimum and maximum temperature) and the average measured temperatures are compared with temperatures read by sensors that are part of the vehicle equipment. Table 3 presents an example test programme. We have test chambers capable of simulating summer and winter conditions over a very wide range, and professional measuring equipment. Chamber dimensions allow testing of all types of bodies (semi-trailers, trailers, trucks, vans, tanks, etc.). Basic technical data of one of the test chambers:

• • Geometric dimensions: length 22 m, height 5 m, width 4 m;
  • Temperature control range: from −30°C to +55°C;
  • Relative humidity control range: from 20% to 100%;
  • Air velocity control range: from 0 m/s to 5 m/s

In agreement with the client, the laboratory also performs other non-standard tests within available testing capabilities. At the client’s request the test programme can be modified, e.g. longer test duration, additional temperature sensors, simulation of additional failures, testing of a loaded body, testing of a body with different partition wall positions, etc. We also perform temperature distribution tests in stationary chambers.

REFERENCES

1. REGULATION OF THE MINISTER OF HEALTH of 13 March 2015 on the requirements of Good Distribution Practice, JOURNAL OF LAWS OF THE REPUBLIC OF POLAND, Warsaw, 19 March 2015, item 381
2. PKN-DIN SPEC 91323:2019-08 PKN Warsaw
3. Warczak W., Szczepański B., Bednarczyk L., Niedojadło D., Kurcz L., Temperature-controlled means of transport intended for distribution of pharmaceutical products – requirements according to PKN-DIN SPEC 91323, Chłodnictwo, No. 1, 2020
4. / accessed 18.02.2021
5. Certification Programme PR-06. Certification of Good Distribution Practices with regard to means of transport of sensitive products transported under controlled/regulated temperature. COCH Kraków, 2016.
6. DIN SPEC 91323: 2016-03 BEUTH VERLAG GmbH, 10772 Berlin

Article prepared by:

MSc Eng. Dorota Niedojadło +48 667 600 635

MSc Eng. Bogdan Szczepański +48 503 021 131

laboratorium@coch.pl certyfikacja@coch.pl