WHAT’S STOPPING DOCTORS REPURPOSING GENERIC MEDICINES? ANSWER—NOT A LOT!
If only they knew this during SARS-CoV-2
[Note: This article appeared in GMP Review AUG/SEPT 2021 when Hedley was helping Dr Tess Lawrie as Director, New Product Development & Supply, EbMCsquared CiC. This is recycled from January 2022]
WHAT’S STOPPING DOCTORS REPURPOSING GENERIC MEDICINES?
For decades, it has been assumed only pharmaceutical companies have the wherewithal to develop or repurpose medicines. This article challenges that assumption based on changing business models in the industry. These changes have created a skills-base of qualified contractors and contract organisations able to offer everything required to bring a medicine to market.
The message to doctors, other health professionals and healthcare systems (referred to as doctors from here on) is that there is just one gap in their armoury—knowledge of the supply-chain that delivers medicines to patients.
COULD DOCTORS REALLY DO IT THEMSELVES?
SARS-CoV-2 has made a case for doctors having access to repurposed generic medicines when they are found to work in medical practice. Ivermectin is a prime example.
However, repurposed medicines have not become available as a licence is required to use the medicine in an indication that is different from the original approval to market. Getting a licence depends on a generics company submitting a licence application but, if there is no worthwhile money to be made, it is unlikely to happen, as has been the case for COVID-1.
So, is it only a generics company that can apply for a licence? Absolutely not —with a little bit of help, doctors could repurpose their own generic medicines.
SURELY THIS CAN’T BE TRUE?
If you think I’m pulling your leg, listen to this.
As the large pharmaceutical companies have grown during the blockbuster era, they have divested the facilities, skills and logistics processes required to develop a medicine. Today, there is a vast array of contractor companies, working to a fee-for-service business model, ready and waiting to help people develop and repurpose medicines.
All anyone who wants to develop a medicine needs to know is where to go to get the help they need.
True, it will require raising and spending some cash, but nothing like the eye-watering amounts spent by pharmaceutical companies.
I’M A DOCTOR WISHING TO REPURPOSE A MEDICINE - WHAT DO I NEED TO KNOW?
Let’s assume you are wishing to repurpose a generic, prescription-only medicine.
1) There are broadly two classes of medicines involved:
● Small-molecule - that means they are made using industrial chemistry (for example, aspirin).
● Biologics (large-molecule) - biologics are essentially made from living things, such as animal and human cells (for example, monoclonal antibodies, vaccines).
It is important to know which class of medicine you wish to repurpose, as the requirements and Regulations are very different – biologics (eg. injections) are far more challenging to develop, manufacture and distribute than small-molecule medicines.
Historically, the large pharmaceutical companies have carried out the research & development activities (R&D) to bring a novel medicine to market, for both small-molecule and biologic products.
The products these companies develop, and market, are known as originator (or innovator) products.
Copies of small-molecule originator products are known as generics. Copies of originator biologics are known as biosimilars.
Assuming you wish to repurpose a generic small-molecule medicine, you will need to know about the Regulatory Authorities.
2) Regulatory Authorities
Regulatory Authorities principally approve drugs for clinical trials and sale, inspect organisations and facilities for suitability to operate, and monitor the safety of medicines.
Regulations are laws so are not to be taken lightly.
Fortunately, most Regulatory Authorities have comprehensive websites and should be your first source of reference for all Regulatory matters.
Additionally, the global organisation The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) has worked with the three major Regulatory Authorities – Food & Drug Administration (US FDA), European Medicines Agency (EU EMA) and the Pharmaceuticals and Medical Device Agency (Japan PMDA) – to harmonise certain key aspects of Regulations globally.
The good news for those repurposing medicines is that the rules have been clearly spelt out.
The less good news is that you must know where to look and how to know what applies to your particular circumstances…but more good news — there are skilled and experienced regulatory affairs, and other experienced experts, out there waiting to help.
3) Licencing a medicine for market
Knowledge of the major Regulatory Authority fundamentals will allow you to understand the support you will need to submit a licence application. Submission of an (electronic) Common Technical Document is mandatory for applications to market a prescription-only product.
There are three modules to be submitted:
● Module 3: Chemistry (Chemistry, Manufacturing & Controls - CMC)
● Module 4: Nonclinical Study reports
● Module 5: Clinical Study Reports.
The decision to approve, or not, is based on the contents of the eCTD, together with answers to Regulatory Authority questions arising from the review.
DOCTORS HAVE A HEAD-START - BUT THERE’S A HANDICAP TO OVERCOME
This is where the news becomes really encouraging for doctors. Modules 4 & 5 will have a mountain of Regulatory and real-world data (RWD) and real-world evidence (RWE) behind them — and RWD/RWE are increasingly being pursued by Regulatory Authorities as a source of information to support decision-making.
Doctors are constantly developing RWD/RWE in their day-to-day work treating patients and SARS-CoV-2 has brought this to the fore. It would be a relatively short step to start collecting and formatting the data for Regulatory Authorities to review, especially if it were for repurposing a long-standing generic medicine.
That’s the head-start. So, what is the handicap?
Module 3 is unchartered territory for doctors (see Figure 1 below). This section of the eCTD filing is where all the details of suppliers, manufacturers, material and product specifications, test procedures and other data specified by the RA must be declared. It is, in effect, the supply-chain, from beginning to end.
The issue is that none of these aspects are covered in schools of learning for those with ambitions to forge a career in medicine or the medicines industry. Without a supply-chain, however, there is no medicine, no matter how much science has gone into the development.
If, as a doctor or prospective drug developer, the above has made you think about repurposing a medicine you found to be effective, please feel free to contact Hedley on h.Rees@pharmaflowltd.com for a no obligation discussion.
Figure 1: Common Technical Document (eCTD)
Author – Hedley Rees
Hedley is also author of Supply Chain Management in the Drug Industry: Delivering Patient Value for Pharmaceuticals and Biologics J Wiley & Sons, NJ 2011 and Managing Director at PharmaFlow Limited, a UK based consultancy specialising in operations and supply chain management within the life sciences sector.
Clients range from large pharmaceutical companies to emerging biotech, and include investors, lawyers, other consultancies, facility design & build specialists and third-party logistics providers (3PLs). Assignments span early-stage clinical trial supply chains up to complex multi-product supply networks covering global territories.
Prior to this, Hedley held senior positions at Bayer UK, British Biotech, Vernalis, Ortho-Clinical Diagnostics and OSI Pharmaceuticals (now Astellas). His early career was spent as an industrial engineer in the automotive, consumer durables and FMCG sectors.
He graduated from the University of Wales as a production engineer (B.Eng. (Tech) Hons, holds a Diploma in Management Studies (DMS) from the University of South Wales and an Executive MBA from Cranfield University School of Management.
Hedley is also a passionate advocate of paradigm-shifting resurgence of the pharmaceutical industry.
Thanks Hedley. Also simpler than actually getting a repurposed drug licensed for a new indication, is that certainly in the UK doctors can prescribe drugs for another indication if they think fit. So long as they explain to the patient that they are prescribing off-licence and get informed consent, I am not aware of a problem, in theory. In practice for Covid the problem arose when colleagues determined to follow an NHS guideline to the letter regardless of the patient’s response or lack of and then made life difficult for colleagues who wanted to try a cheap safe readily available drug.
As a neonatologist, I often had to do this and I could just sign a form for our pharmacy saying that drug X was required and there was no effective licensed alternative.
Appreciate the information on small molecules and biologics as well as the additional information on generics and biosimilars. On that note, are you familiar with Steve Kirsch and VSRF - Vaccine Safety Research. Kirsch is lives in the Bay Area and has a massive following in the US. Many of his guests include MDs but he has not had anyone on his weekly Thursday night show with supply chain experience. I think you would be a great fit for one of his broadcast's!