PPORD – GB REACH and EU REACH
Product and process orientated research and development
If wanting to manufacture or import over 1 tonne of a substance for your own trials or customer trials, it is possible to apply for a Production and Process Orientated Research and Development (PPORD) derogation. This can last 5 years and re-application for a further 5 years is possible if it can be justified (for example supplying intermediates to permit clinical trials of a pharmaceutical).
The dossier is prepared using IUCLID and submitted through EU REACH IT or GB Comply with REACH Gateway, and fees will apply. A key part of the submission is a justification.
Denehurst can offer support for justification and training on IUCLID for dossier preparation. It is not difficult.
PPORD Dossier creation for submission
This short guide has been prepared to help with PPORD completion and in the most, applies to both EU, GB or Turkish REACH. Where there is a difference in expectation, then this is highlighted. Of course, if manufacturing in the UK and exporting to the EU or vice-versa, two Inquiries are needed.
For more information on when PPORDs can be used, information can be found on the ECHA and HSE web-sites.
https://echa.europa.eu/regulations/reach/registration/research-and-development
https://www.hse.gov.uk/reach/new-ppord.htm
This guide assumes a working knowledge of IUCLID and the EU REACH IT / GB Comply with REACH systems.
To prepare the IUCLID file, sections 1, 2 and 3 need completing with dossier type (working context) identified as EU REACH PPORD.
Section 1.1
This section starts with identifying the substance, the type of substance and the identity of who is making the Registration and their role in the supply line.
For EU, the legal entity needs to be identified and linked to the Legal Entity file (LEOX) exported from the REACH IT account. You only have to import into IUCLID for the first Registration and once imported, it is retained in the library of linked Legal Entities. This ‘official’ legal entity linked to REACH IT can of course be used for GB REACH, but if GB only, then you can create the legal entity in IUCLID by selecting ‘new’; this should include contact details etc. and will later be linked to ‘Site’ information and ‘Contacts’.
Unless you have found and downloaded the relevant Reference Substance from ECHA (several hundred ‘common’ substances can be downloaded), a new one will need creating. When creating a new reference substance, it needs naming and an EC number selecting if it exists. If not on the pre-installed EC Inventory list, the drop-down option below for ‘no inventory information available’ needs to be used.
Complete as much of the section as possible and either add a structure (picture file) with formula etc, or (for UVCB) add something in the ‘remarks’ box. Describe the substance as well as possible – many dossier fail through poor descriptions.
Having saved the reference substance details, the rest of Section 1.1 will include considering if Mono-consistent, Multi-constituent or UVCB, and select ‘origin’ of substance
See Inquiries Page [link] for further details on substance identity.
For GB REACH, contact details are expected to be added in Section 1.1 (even though already in the Legal Entity details).
Section 1.2
This needs to set the purity and composition for the substance.
The Inquiries page provides detail on this [link]
Section 1.4
The simple rule is that there should be sufficient evidence presented in Section 1.4 to confirm the identity described in 1.1 and 1.2. Therefore, if claiming a certain structure, molecular weight and purity, section 1.4 needs the evidence. This is less critical for a PPORD than with an Inquiry as it is acceptable to claim the substance is under development and precise chemical identity and purity is perhaps part of the process research.
In many cases, this will need a variety of methods and if the substance is still in pilot plant or laboratory stage of development, methods may not have been considered fully and this method development could indeed be part of the justification for the PPORD development work. Evidence may therefore be based on both measured results and on theoretical chemistry based on firm evidence of the identity of starting materials.
There is no simple guidance to follow and will need input from experienced analytical chemists.
The basic requirements are:
NMR spectra
IR spectra
UV-Vis spectra (at pH range of 4 – 9 if water soluble)
Chromatography method
If any of these cannot be provided, there must be a good reason – there are few valid reasons not to perform the spectra and suggesting that the spectra is meaningless is unfortunately not considered a good reason. However, unlike making an Inquiry, the basic analysis is less critical, but the more evidence that can be provided, the better.
Chromatography is often not possible, but if GC or LC methods can be performed, liking them to Mass Spectroscopy may give a sufficient level of evidence for chemical identity. Other methods like Gel Permeation Chromatography (GPC) may be used for high molecular weight materials and a good chemist may be able to suggest other methods. Inorganic substances, for example, lead to a range of analytical issues and element analysis may be decided as the best options.
Optical analysis is identified in IUCLID as a requirement – obviously, this only need to be considered if different isomers exist.
It is worth spending the time on this as rejections of the PPORD (and any subsequent Inqiry) will be time consuming itself and the level of analysis developed for the PPORD will in turn be required later if a full registration is sought.
Other important notes for submitting analysis details:
• Try to get all the spectra into one report to attach to the IUCLID file; it is possible to create repeat blocks to add separate files, but a single spectra report is the best way.
• The chromatography and other analysis should again be condensed to a single report and attached to the IUCLID section prompting these details.
• For all analysis work, try to use the same sample, recording a batch number or laboratory code with dates, identity of the facility where analysis took place, details of equipment, sample preparation, methods etc
• GLP is not required, but it is recommended that work is performed to Good Laboratory Practice standards with maintenance of records, signatures of responsible people, and internal checking.
See the Inquiries page for more information [link]
Section 1.8 Recipients
For GB REACH, it is expected that recipients of material to use in trials is added. Of course, if importing for your own use, this is not applicable, but you may want to clarify in this section.
Section 1.9 Justification
This section is only visible in the index is in the PPORD Working Context
This field is repeatable and allows more than one process research application to be described if necessary. It also prompts the question of whether it is a medicinal product or is just not placed on the market. Note that to be valid for a PPORD, the substance should not be placed on the open market, but should only be supplied for restricted uses to specified recipients; it should never be supplied to non-skilled users or the general public.
The section allows the option to add a document and it is recommended to use the pre-REACH PORD application form as a guide. An example of a completed version is attached to this guide.
The justifications for a PPORD must meet the restrictions laid down in the legal text and in associated guidance and include indications of tonnage, use patterns, levels of exposure etc.
Experience is that GB PPORDs are more carefully scrutinised than for EU. It is important to get this right and the more detail that can be added to justify use, the better
Section 2.1 GHS Classification
Although there are no formal data requirements for testing substances for a PPORD, it must be remembered that UK and European supply legislation and International Transport rules apply to all chemicals and the supplier must have sufficient knowledge about the substance to allow recommendations to be made for labelling and safe handling. A Safety Data Sheet is required.
The phrase ‘Caution: not yet fully tested’ is recommended for the SDS and label.
Section 2 can be completed using GHS / CLP end-points, but there needs to be some justification if claims are made that the substance is non-hazardous.
Section 3.2 Sites
Section 1.8 indicates the sites of recipients (customers), but 3.2 relates to the site of manufacture in the UK / EU or your site as an importer/user.
Section 11 – Guidance on safe use
This section is effectively the details expected on the SDS including transport classification.
Section 13 – Other reports
This is where the SDS is attached, and of course must be consistent with Section 11 and also with the classification entered in Section 2.1.
Creating the dossier
Once complete and the pdf attachments included, you need to create the dossier for submission. Validation happens automatically, but of course it is worth using the Validation tool; all ‘submission’ errors must be fixed and it is recommended to fix as many quality errors as you can; some are not possible to fix (especially relating to composition if using > or < to describe relative percentages.
Exporting the dossier
The Dossier file can now be exported as ‘.i6z’ file and you can save to your own directories. This is the file that is uploaded in EU REACH IT or in GB Comply with REACH
What next ?
Within a few hours (working days) you will get a message with reference numbers and either get a rejection or acceptance comment – this first part is to check the administration and completeness.
If accepted, an invoice will be received and it is advised to pay as promptly as possible to ensure that the review period can start.
Note of warning for companies with complex vendor ‘supplier systems’. Setting up account systems with ECHA for the EU is not easy and it must be done in Euros and by electronic transfer (not cheque).
Annex – Completed generic PPORD justification
This template is based on the pre-REACH PORD requirements and still covers the justification for a REACH PPORD (the old PORD was a national submission and the PPORD is across Europe). A ‘Word’ version can be provided on request.
Research & Development details
What is the envisaged use of the substance?
Substance x is required for the synthesis of a pharmaceutical intermediate. Previous trials have been quite successful and further scale-up is required, to remove or reduce impurities formed in these previous. At this time, without scale-up, the manufacturer does not know if the impurity targets can be achieved. Therefore, an R & D plan, including pilot plant production, is necessary to test the reproducibility of lab trial into production scale.
What R&D work has already been carried out either by yourself or, if appropriate, by the customers involved in the R&D programme (e.g. internally or under the <100kg p.a. scientific R&D derogation)?
Kilo quantities have already been synthesised, but scale up is required to ensure commercial production can produce the high specification material required.
What is your justification for wanting to use this derogation (including an assurance that you do not currently know whether you can achieve the desired effect)?
Scale-up of production processes
What additional information will be gained through the proposed R&D program?
Confirmation of methods and systems to be used to meet high standards of purity required
Please give a summary of the R&D plan, included the process to be investigated, the timetable and a proposed start date.
Plan is to ……
What is the justification for the quantity involved in the proposed R&D program (including the justification for the number of batches and the quantity per batch, etc.)?
It is considered four batches will be sufficient to complete the trials
Please confirm that the substance, or any preparation containing it, will only be handled by the customers staff under controlled conditions and will not be made available to the general public.
The substance will not be supplied to the general public or to any organisation other than the customer [details]
If supply is greater than 1 t.p.a., please supply sufficient information about the process, disposal procedures, etc. to demonstrate that the potential for environmental exposure will be kept to a minimum. Details of the process should include batch sizes, identification of any potential losses (e.g. process emissions to waste water, reactor washings and residual material left in containers) and information regarding any treatment of wastes and waste disposal practices for all potential waste streams.
The substance will be consumed in trials by the customer in [ ]. Any waste, including residue from packaging, will be disposed of as chemical waste with the warning that the substance has not yet been fully tested. There will be no loss of washings to waste water and all waste will be collected for chemical waste disposal. The substance is produced and used at dedicated chemical plants with high levels of control for worker protection and environmental loss.
Do you intend to use the substance to produce articles and, if so, would these be made available to the general public?
No