Without urgent regulatory change improving quality is a fool’s game, says CPhI expert


Girish Malhotra believes the pharma industry should be allowed to commercialise process improvements without regulatory re-approval

CPhI expert Girish Malhotra is calling for a radical solution to improve pharma manufacturing processes in Part 1 of CPhI's annual report, published by UBM EMEA ahead of next month's CPhI Worldwide 2015.

In his article, Malhotra argues that for far too long the pharma industry has allowed the status quo to continue, and that for true continual improvement it needs to make it easier for companies to make vital alterations to manufacturing processes, without being hindered by a full re-approval process.

Under his guidelines, the pharma industry will be allowed to commercialise process improvements (yield, process/operating conditions, operating parameters, cycle time) in the manufacture of approved APIs and their formulations. Guarantees on quality will then be provided from the manufacturing company, and they must ensure that the product efficacy and performance will not lessen, and the product will be equal to or better than the approved product produced by the company.

If for any reason these standards are not met, Malhotra suggests a stipulation that the company proposing improvements will be barred from making the product using the alternative process for the next two or three years. And, if they do decide to use the alternate process, they will have to go through the full re-approval process.

After the fact process change is extremely difficult

Girish also states that minor changes that do not alter the current filed processing methods will be excluded, and this will apply to over-the-counter (OTC), branded and generic products.

The US Food and Drug Administration (FDA) established 21CFR314.7[1] and it assures that there is no 'by manufacturer’s choice' deviation from the manufacturing methods and practices that have been filed for the components involved in the manufacture of any saleable drug – the active pharmaceutical ingredient (API) and their formulation – and labelling, packaging, etc. But, as every change has to be reported, drastic process changes, even when there are clear benefits for the finished drug and patient, are discouraged.

'21 CFR314.70 encourages ‘continuous improvements’ in the processes that will create the best product for clinical trials and that’s the way it should be,' said Malhotra.

'However, in my estimation under the current rules all of this has to be done prior to going to clinical trials. QbD (Quality by Design) becomes a natural part of the process development before a process is commercialised. But after the fact process change is extremely difficult.'

Malhotra believes that the benefits of a new regulatory regime far outweigh the risks, as cost reduction, improved profits and a larger customer base due to improved manufacturing technologies and efficiencies, will be a huge step forward.

In spite of a commitment to continuous improvement, anything 'after the fact' under the current regulatory environment simply will not happen due to the financial and time constraints of re-approval. Thus, although the current regulations and QbD are well intentioned, they do not yet breed a culture of continuous improvement.

Malhotra added: 'I admit that my proposal is quite audacious, but unless such bold steps are considered, very little will change in the current pharma’s manufacturing methodologies, or anywhere, for that matter. If incorporated in a pharmaceutical manufacturing landscape, continuous improvements and innovation could become a routine and it could be extended to the whole healthcare industry. It has an opportunity to add as much as 20% of the global population (~1.4 billion) to its customer base, an unprecedented opportunity for any industry on the planet. Profits will improve and healthcare costs can come down. It would be a win-win.'

Sign up for your free email newsletter

The full article will be featured within the CPhI annual report, which is to be released at CPhI Worldwide 2015 in Madrid, 13–15 October.