What do multinational medical cannabis cultivators have in common? They’ve achieved the gold standard for international quality compliance: Good Manufacturing Practice certification.
GMP, as it is commonly known, is a codified set of rules and regulations that ensure the quality, safety and efficacy of a drug. It covers all aspects of the production process and is audited and certified by regulatory agencies.
Canadian multinational cannabis firms eager to plant their flags in burgeoning international medical markets are racing to have their facilities GMP certified.
Put simply, GMP certification is generally a prerequisite to the export of medical cannabis. But it’s a long, costly process and not for everyone.
So, why undertake this procedure if it is so expensive and time consuming? Three reasons:
- To ensure your products are compliant with the highest quality standard.
- To give your product a reputational advantage.
- To allow your company to conduct business across borders.
Delaware-based Noramco, a specialty active pharmaceutical ingredient (API) company, has CGMP certification (the U.S. version of GMP).
“By complying with GMP, the business benefit would be international opportunities and getting you to a quality standard that makes sure you don’t have business risk later on, because of the high level of rigor applied to your manufacturing process, testing, packaging, stability of the product and distribution,” said Bill Grubb, vice president of global business development at Noramco, which produces synthetic cannabinoids.
The first step in becoming GMP-certified is called a gap assessment. It involves assessing what your quality-management system currently involves and what else is necessary, depending on which GMP certification you’re seeking.
“You’re looking at what is missing to bridge the gap between (Good Production Practices, or GPP) and GMP, which is the typical scenario in Canada,” Lahnakoski said.
The gap assessment then allows you to prepare an implementation timeline, and that can vary from company to company.
This also is the step where you will determine if it will take you six months to reach GMP certification, or perhaps a year or more.
Determine Your Goal
Grubb says the first step is establishing your objective.
“Why do you want GMP? Is it to sell to Europe? Is it to supply the drug companies and be an API supplier? Is it only for marketing purposes?” he said.
After establishing an objective, it is more apparent which GMP certification your company should pursue.
Karina Lahnakoski, vice president of quality and regulatory at the Ontario, Canada, consulting firm Cannabis Compliance, said most Canadian companies are pursuing EU-GMP, which applies to medical products in the European Union.
“Many of the countries coming onboard (with medical cannabis laws) are in the EU and therefore accepting the EU-GMP standard. It is also likely that meeting the EU-GMP standard means you will conform to GMP production practices put in place by other countries coming online, as the EU standard is very high,” she said.
Other GMP certifications include CGMP in the United States and Canada’s Guide-104 GMP and ICH-GMP. The latter, which stands for International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use, is not commonly used in the medical cannabis industry.
CGMP in the United States, EU-GMP in Europe and Guide-104 GMP in Canada are effectively the same thing. But agencies in respective jurisdictions administer certification, and they’re generally applicable for businesses only for the jurisdictions where they are certified.
So, if you want to manufacture drugs or active pharmaceutical ingredients in Canada, you need Guide-104 GMP. If you want to want to sell medicine in the European Union, your facility needs EU-GMP certification.
Following are some of the key steps to GMP certification, according to Lahnakoski.
Gap Assessment
The first step in becoming GMP-certified is called a gap assessment. It involves assessing what your quality-management system currently involves and what else is necessary, depending on which GMP certification you’re seeking.
“You’re looking at what is missing to bridge the gap between (Good Production Practices, or GPP) and GMP, which is the typical scenario in Canada,” Lahnakoski said.
The gap assessment then allows you to prepare an implementation timeline, and that can vary from company to company.
This also is the step where you will determine if it will take you six months to reach GMP certification, or perhaps a year or more.
Update Documentation
High-level documentation needs to be created.
Most companies don’t have a master validation plan, a quality manual or a site master file. Those are high-level documents that describe the entire company and how it runs, and they’re required to be submitted to the competent authority—whether that’s the Federal Institute for Drugs and Medical Devices in Germany, Health Canada or the U.S. Food and Drug Administration.
Update SOPs
Keep in mind your company may need to update dozens or perhaps hundreds of standard operating procedures (SOPs).
Typical producers can have between a few dozen and 200-plus SOPs. Generally, they all need to be updated for GMP compliance, even if that means updating the regulatory references within the SOPs.
Add Missing Programs
In the case of licensed Canadian companies, which must follow Good Production Practices (GPP) standards, programs for GMP that are not in GPP need to be implemented. Key programs include validation and stability.
A stability program for your products establishes an expiration date. That’s not a requirement for GPP—considered a lower level of quality assurance—and it can be a time-consuming, data-driven process.
“If you’re doing a stability program and you want a one-year expiry, you need to test the products for a year. Put it in the chamber and take it out every few months and test it,” Lahnakoski said. “It’s not something you can implement overnight. You need to generate data before the inspector comes in.”
The length of the stability program usually depends on what your importer wants for an expiry date.
“If you’re working with an importer who says they don’t want short-dated product and wants a six-month date on the product, you’re going to have to generate that much data,” Lahnakoski said.
Is it possible to extrapolate data for stability programs to get an expiry date? Yes, see the ICH guideline for that.
Prove It
After implementing GMP, and all your new programs and updated SOPs, it’s time to run with those systems for a number of months to demonstrate that you’re functioning as a GMP-compliant company.
Mock Inspection
Lahnakoski recommends staging a mock inspection.
“You don’t want all these people coming over from Europe to inspect you unless you are confident you’re going to pass. It’s a lot of money invested, and reputational damage can be done if you’re not ready,” she said.
Importer’s Audit
After implementing GMP in your facility, accumulating sufficient data and demonstrating you can function as a GMP company, it is time to bring in the importer’s Qualified Person (QP) for an audit. A third-party auditor also can handle this key stage.
“You’re meeting the requirements of the regulator, but you’re also in a relationship with an importer on the other side. And that importer has a Qualified Person who is responsible for releasing your product when it comes to their market. The QP will audit you and may also have their own requirements they may impose,” Lahnakoski said. “So you need to know who you’re working with, and what they need from you.”
For example, some QPs won’t accept irradiated medical cannabis products, so the licensed producer has to put into place a specification for products just for that customer to ensure no irradiated products get shipped to that country.
Regulator’s Inspection
After the QP—or third-party auditor—is done with you, that person will call in the respective government body (called “competent authority”) for the GMP inspection.
Passing the inspection is not guaranteed. The approval rate for Canadian licensed producers is less than 100%.
There will always be observations to address after the inspection, and communication with the authority to close those observations in an acceptable manner.
Other Considerations
Go it alone or hire a consultant?
Having the insight of consultants who have experienced multiple Good Manufacturing Practice (GMP) programs and inspections can be helpful to ensure best practices from across the industry are taken into consideration.
There’s no question that this route gives the site a better chance to pass the inspection.
But it’s not cheap.
Does your competitor have GMP Certification?
Want to know if your competitor has EU-GMP certification, or a different GMP certification that could be used mostly for marketing purposes? It’s no secret.
Check out the EU-GMP certification database at: eudragmdp.ema.europa.eu/inspections/gmpc/searchGMPCompliance.do
The Canadian database is at: healthycanadians.gc.ca/apps/gmp-bpf/searchResult-en.html
Brush up on Mutual Recognition Agreements
Jurisdictions have mutual recognition agreements (MRA) among them that recognize their respective GMP certifications.
The caveat is those agreements don’t always cover medical cannabis, which is why Canadian multinationals are racing to
get EU-GMP certification.
However, mutual recognition agreements between some European countries and Australia do cover medical cannabis,
if it is regulated as a medicine in the other country.
That means a medical cannabis company in Australia that has GMP certification from the Australian Therapeutic Goods Administration can export medical marijuana to Europe without seeking a separate EU-GMP certification.
“Applicants would be required to provide the relevant evidence to demonstrate that the medicinal cannabis product has been manufactured in accordance with the Code of GMP (or equivalent manufacturing standard) as would be applied to domestic manufacturers,” an Australian Department of Health spokesperson told Marijuana Business Magazine.
