Imagine a situation where post-approval changes took 18–24 months to be reviewed. Think about the impact on biomanufacturers who would need staggered timelines for implementing changes across different markets and different products. And their need for complex processes that affect inventories, time, money, resources, security, compliance, etc.

This was the picture facing biotherapeutic importers into Colombia because its health agency, INVIMA, took a long time to review post-approval changes that might only take six months elsewhere (or do not require any review). This is because INVIMA has limited resources for post-approval changes and has some extra requirements that are different from other agencies and so it reviewed any change (even with no impact on product quality).

This is why BioPhorum was asked to step in to bring its global harmonization experience to the table and apply its broad industry knowledge and its ability to work directly with regulatory agencies. In Colombia, the situation was even more complex than in other countries, as INVIMA’s ways of working were a direct consequence of a governmental decree. Direct interaction with the Colombian Ministry of Health was therefore also required to get the decree modified.

Significant impact

Why is this a big deal? Well, Colombia is third in LATAM countries in terms of spending on pharmaceuticals and biologics.

This situation is having a significant impact on manufacturers. Until a change is approved, they cannot distribute an amended product in that market and must distribute the old one. As well as holding expensive inventories, there is a compliance risk because manufacturers must be 100% sure they send the right product to the right market.

It also means manufacturers cannot react quickly enough if there is an urgent need for an older product, which might need to be manufactured. This would need more testing and submission work, cause increased costs and supply delays, and increase the risk of mistakes and products being rejected by the regulator.

Industry group collaboration

The AFIDRO and ANDI industry groups had been pushing for a change by demonstrating to INVIMA and the Ministry of Health that harmonization on post-approval submissions would help prevent stock-outs and ensure patient access to drugs. At the end of 2019, the groups asked BioPhorum for help as they hoped a global perspective would add value to the case for change.

Using BioPhorum’s post-approval strategy expertise, we created a team to examine Colombia’s regulatory environment around post-approval changes. We secured a meeting with INVIMA in April 2020, but this was postponed when Covid struck.

However, we used this pause to develop and align our position with AFIDRO and ANDI so that when we eventually spoke to INVIMA, we had one voice representing the global and local industries.

BioPhorum actions

At the end of 2021, AFIDRO arranged another meeting for us with INVIMA. We explained the benefits of harmonizing the requirements for post-approval changes with the WHO guidelines adopted by many other agencies, such as simplifying INVIMA’s review of documents.

We also discussed how using files from other agencies that have approved a change could save INVIMA’s resources and contribute to manufacturing efficiencies. Our successful work with the Brazilian regulator was a significant factor in the Colombian agency listening to us.

The agency agreed with our proposals but, unfortunately, a barrier to progress was that Colombian post-approval changes are governed by a government decree, not just a guideline, which was more difficult to amend.

To overcome this, we needed to talk to the Colombian Ministry of Health, which is responsible for new regulations and amendment issuance in Colombia. AFIDRO arranged this meeting for December 2021, where we explained the differences in the WHO guidelines and why Colombia should have a harmonized regulation for post-approval changes.

Presidential sign-off

The result is that the amended decree was signed off in March 2022. As a result, post-approval changes will now be reviewed by INVIMA according to WHO guidelines and in much shorter timescales than currently.

“There is no doubt that BioPhorum’s expertise has helped us on the path towards regulatory harmonization,” said Diana Chavarro, Regulatory Policy and Intelligence PACA Partner at Bayer. “As one of our industry priorities in Colombia, we will hopefully soon see an improvement in the efficiency in our post-approval change timelines.”

Planning for success, INVIMA is preparing its new post-approval change guideline, which is intended to go live by August 2022. BioPhorum will be supporting this public consultation before the final issuance.

This is a superb example of BioPhorum’s collaborative approach and how its ‘one voice’ strategy is improving harmonization across the global biopharmaceutical industry. Building on its success in Brazil and Colombia, the regulatory team plans to address similar issues in other countries – such as South Korea – to improve the review of post-approval changes.