Good Agricultural and Collection Practices VS Good Manufacturing Practices (GACP vs GMP)
If you were at the Australian Medicinal Cannabis Conference 2019, you would’ve heard two key phrases being thrown around: Good Agricultural and Collection Practices and Good Manufacturing Practices (a.k.a. GACP vs GMP). In this blog, I’ll break down these two terms in the context of how they apply to the Medicinal Cannabis industry.
The two “holy bibles” for GACP vs GMP are, respectively:
- WHO guidelines on good agricultural and collection practices (GACP) for medicinal plants and
- PIC/S guide to GMP for medicinal products, specifically Part 1 (Basic Requirements for Medicinal Products) and Annex 7 (Manufacture of Herbal Medicinal Products).
I’ll start from the top…
1. GACP applications in the Cultivation and Production of Medicinal Cannabis
Let’s not forget, cannabis is being grown as a medicinal plant to be used as stock to generate a concentrated active component. To achieve consistency in your product, there are some 5 key areas that you need to consider:
- Identify your site – good site selection minimises the number of pollutants in the surrounding environment (i.e. in the soil, or from neighbours), and should ideally be in a location that has a compatible climate for your desired strains. However, this isn’t always the case, and if you’re working with some troubling elements, it is important to identify them beforehand, so you can design-in some risk-mitigating elements (and they don’t come back to affect your product quality later on). As we have covered extensively before, unique attributes of the site should be factored into your facility design (and also influence your choice of grow method, e.g. indoor, greenhouse, outdoor, etc.).
- Control your source materials and services – this doesn’t just apply to strain selection (which should include knowledge of the identity, quality and performance of seeds, as well as vetting the vendor to ensure legal purchase, e.g. from hemp farmers). Control over source materials also applies to vendors who provide you with growing mediums, fertilizers, nutrient mixes, etc. There are also security issues to consider if relying on third party vendors to perform particular tasks, e.g. transport products, or pick up waste for destruction.
- Standardise your processes and methods – here is where your Standard Operating Procedures can come into play. Consistency is key and in order to generate a harvest that has reliable levels of active ingredients, all aspects of cultivation should be considered, e.g. frequency of feed, light intensity, cleaning regimes, humidity control, pest management systems, monitoring environmental conditions, harvest methods, plant material quality checks, drying conditions, etc. Record keeping requirements should also be established and internal audits performed to verify the quantities of critical materials on site.
- Manage personnel and visitors – the number one source of contamination in multiple industries is, and will always be, personnel. Considerations should be made for standardising your gowning and hygiene requirements to minimise the chances of microbiological outbreaks which are time consuming and costly to get back under control.
- Ensure equipment is fit for use – as with personnel, poorly maintained equipment can also be a big source of contamination, especially if not regularly maintained, cleaned or stored in pest-free locations.
2. The Transition between GACP vs GMP
PIC/S Annex 7 details the transition from GACP vs GMP as the table below:
* Manufacturers should ensure that these steps are carried out in accordance with the marketing authorisation/registration. For those initial steps that take place in the field, as justified in the marketing authorisation/registration, the standards of Good Agricultural and Collection Practice for starting materials of herbal origin (GACP) is applicable. GMP is applicable to further cutting and drying steps.
** Regarding the expression from plants and distillation, if it is necessary for these activities to be an integral part of harvesting to maintain the quality of the product within the approved specifications, it is acceptable that they are performed in the field, provided that the cultivation is in compliance with GACP. These circumstances should be regarded as exceptional and justified in the relevant marketing authorisation/ registration documentation. For activities carried out in the field, appropriate documentation, control, and validation according to the GMP principles should be assured. Regulatory authorities may carry out GMP inspections of these activities in order to assess compliance.
More jargon and caveats! What does this all mean?
Basically, after you generate raw material (i.e. dried plant matter for further processing, or initial crude extracts of resin), any processing after that is considered within the jurisdiction of GMP and crosses over into the Pharmaceutical realm. At this point, the WHO’s “recommendations” turn in to full-fledged GMP responsibilities – just look at the list below from EudraLex:
3. The Similarities and Differences between GACP vs GMP
Now, eyeballing the previous list you might think, “Ah, it looks like there may be some space for overlap between the two,” and you would be correct. However, like with all regulations, the devil is in the detail: the GACP “shoulds” often turn into GMP “musts.”
|Item||GMP requirements (simplified)||GACP minimum|
|Pharmaceutical Quality System||All pertinent policies, standard operating procedures and supporting forms, logbooks, registers, etc. have to be issued and controlled (usually by the Quality Assurance Department). Documents must reflect the actual processes that are performed and may not be used unless they are approved and active.||Recommendation for documented procedures and policies. No requirement for documents to be controlled, however it is generally good practice to limit the ability of staff to edit master records just from a business security point of view.
If you need help, PharmOut has a |
set of templates that can be purchased and customised to your processes.
|Personnel||Strict personnel control as well as training requirements specific to each job role. Personnel must be adequately trained (and each training instance documented) on critical activities prior to being allowed to perform them unsupervised. This can include but is not limited to: gowning, cleaning, waste disposal, and other technical activities.||Recommendation to ensure all personnel should receive adequate |
botanical and agricultural training prior to commencing work. Personnel should also be made aware of security and hygiene requirements.
|Premises and Equipment||Extensive requirements for construction and maintenance – all critical items of equipment will require validation activities prior to being used in routine production.||Recommendation to choose, maintain and clean equipment and work spaces carefully so that plants are not accidentally contaminated during processing.|
|Documentation||As detailed in the PQS section, all documentation must be controlled and approved prior to being used as “active” references for the site. Any records generated must be reviewed and reconciled appropriately.||Records should be kept of cultivation processes, including any application of pesticides (if applicable). ODC requirement to track the quantities of Scheduled material on site all the way through to their final fate.|
|Production||Standardised processes must be in place. Batch records and forms must be used to document production processes. Only validated equipment should be used. Production processes may also require validation to verify that they are able to consistently generate products of the required quality.||Recommendation to control and standardise critical production activities, e.g. harvest, drying and trimming, so that a consistent quality of product is achievable.|
|Quality Control||Control over the sampling, testing and release of materials (both raw materials and finished products) is required. This may also include the verification that cleanrooms are at the appropriate environmental microbial levels for production activities.||Starting plant material should be characterised prior to use and release, this includes:
|Outsourced activities||Vendor Assurance is a critical component of all GMP facilities. Materials may not be sourced until the vendor has gone through the Quality approval process.||Recommendation to identify approved vendors to source critical materials from. Technical agreements recommended to outline relationships and responsibilities in place for the supplier and receiver.|
|Complaints and Product Recalls||Critical chain of control and investigation – all customer complaints are required to be evaluated and product recall initiated if deemed necessary.||No comment in GACP manual however this aspect can be touched on in technical agreements – in the case where plant material is identified to be faulty the supplier may be expected to conduct their own investigation into their starting materials to determine the source of contamination (if any).|
|Self-Inspection||Internal Audits are required and compliance is tracked on internal quality metrices. Corrective and Presentative Actions often implemented as a part of continuous improvement initiatives.||Recommendation for internal audits – ODC security requirement to audit stock quantities of scheduled material on site to verify that records are accurate.|
3.1. A Final Complication with GACP vs GMP
Because there are always complications: these regulations have been interpreted specifically for the Australian level of PIC/S and the Australian distinction between GACP vs GMP.
However, in other parts of the world such as Europe (or specifically, Germany), they do not make any distinction between GACP vs GMP and will expect that the cultivation activities in place for receipted medicinal plant material are performed under GMP standards.
So what? Well, this is important because if you’ve been using unvalidated seed to sale software to track your cultivation processes, then Germany will be unhappy with your product and you may have to design in extra documentation steps to become compliant (which will then make your operators unhappy).
With this in mind, it’s important to consider your target market so that you incorporate the appropriate level of GACP vs GMP required. Given the variety in the size and capacities of the cultivation operations in Australia, there is no point in introducing a system that you don’t actually need when your intent is to just supply local manufacturers.
In an industry where reducing costs is going to be an important factor, identifying what you do and don’t need to invest in for your business can turn into a critical factor.
If you want to have a chat, or find out more information on the differences between GACP vs GMP, please feel free to get in touch here.
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