“I’m sure a lot of you don’t know what we do in Jordan,” said Jordanian Food and Drug Administration (JFDA)’s head of clinical studies, Rana Malkawi, at the DIA Biosimilars Conference in London last month.
To rectify an apparent lack of understanding regarding biosimilar development in the Middle East, Malkawi offered delegates insight from a regulatory perspective, detailing manufacturing requirements and approval processes for marketing authorisation holders.
Marketing authorisation holder status
As in Europe, the marketing authorisation holder (MAH) in Jordan is responsible for the quality and the safety of the product, Malkawi explained. “They are responsible for the batch release of the final product as well as for the post-market follow up.”
However, unlike the European system, Jordanian regulators insist that MAHs own a manufacturing site, or come from an office owned by a manufacturing site.
“This is what is giving us a headache at JFDA,” according to Malkawi. “A lot of applications come [to Jordan] and they know that [MAH requirements] in Europe is only an office. [The office is] not owned by a manufacturing site and it’s not a manufacturing site.”
According to Malkawi, the JFDA is exploring alternative models whereby drug companies with an office structure only could be eligible for MAH status in Jordan.
Manufacturing site accreditation
Manufacturing facility inspections and accreditation are of particular importance to the JFDA, Malkawi told delegates.
“We have two types of manufacturing sites. One does not need to be accredited by the JFDA – the site responsible for the production of the master cell bank (MCB) and the working cell bank (WCB),” she explained. Approved dossiers, however, provide full characterisations of MCB and WCB, including purity testing, identity, and stability details, as well as copies of good manufacturing practice (GMP) and good laboratory practice (GLP).
All other sites involved in the manufacture of biosimilars require JFDA accreditation. According to Malkawi, these facilities cover any step of the manufacturing process, from active ingredient production and storage of the WCB, to the finished product and batch released sites, she explained.
If MAHs comply with the administrative requirements of the JFDA – meaning that the site has been approved by two of Jordan’s reference agencies – the JFDA does not need to do an on-side inspection, she told delegates. These agencies regulate the US, EU, Australia, Japan and Canada.
“If you fail to give us an inspection for a GMP or a CPP (certificate of pharmaceutical product) from two of our reference countries, we have to go and do an on-site inspection of these sites,” she added.
Reference biological products
Reference biological products used in comparability exercises, must be registered in one of Jordan’s reference countries.
“Our reference countries are chosen so that they have basic foundations or guidelines for biosimilars. The product must be registered by the European Union’s centralised procedure, or registered in the US, Australia, Japan, Canada, and/or Jordan,” she told delegates.
Why does Jordan feature in this list? “Because we have confidence that any product that is registered in Jordan is registered according to the international guidelines, so there is no compromise in any of the safety aspects,” she said.
In Jordan, the biosimilar product has the same definition as in the EMA, she added.
JFDA defines a biosimilar as a biological medicinal product that is similar to the reference biological product (RBP) in terms of quality, safety and efficacy, and contains a version of the active substance that is similar, in molecular and biological terms, to the active substance of the RBP.
Upon submission of a biosimilar application, Malkawi explained the JFDA requests data for six months of immunogenicity. “That should be followed up from one year after the product is on the market.”
“In addition, we mandate all biosimilar manufacturers to have a post-market study for biosimilars in at least 50 patients…so that we can monitor any potential differences in safety between the biosimilar and the reference drug,” she said.