Table of Contents

By Tony Dunford
Editor

• The Professor, AI, and superbugs
  By the Editor

• VACCINE MANUFACTURE IN AFRICA – PROGRESS & CHALLENGES
  By Richard van Duyse

• THE PROJECT MANAGERS NOTEBOOK part 8
  By “Aubonne”

• CHANGE CONTROL
  The second in a new series of articles on complex areas of QA, tools & techniques.
  By the Editor

• BLOWBACK & IGNORANCE, USA STYLE
  By the Editor

The Professor, AI, and superbugs

By the Editor

A dramatic interview with the BBC by Professor Penades of Imperial College, shows how artificial intelligence can radically help research.

His team had been working on why some superbugs are immune to antibiotics. By asking Google to help with a problem that the team had been investigating for over 10 years, via a short prompt, he was shocked to find that it came up with four useful hypotheses in 2 days. Given that his research had not been published, these could not have been found by the AI system in the public domain.

To be clear the 10 years’ work included time to research the one of the hypotheses. But years of work could have been saved had the four possible hypotheses AI put forward been available at the start. (The team had never envisaged one of the hypotheses but are now working on it).

The researchers had been trying to find out how some superbugs - dangerous germs that are resistant to antibiotics - get created. Their working hypothesis is that the superbugs can form a “tail” from different viruses which allows them to spread between species. Professor Penades likened it to the superbugs having keys which enable them to move from home to home or host species to host species. Critically, this hypothesis was unique to the research team and had not been published anywhere else nor had anybody in the team had shared their findings.

In the 4 AI hypotheses, was it’s top answer, which was that some superbugs may make tails, in exactly the way the researchers had envisaged.

The Editor

VACCINE MANUFACTURE IN AFRICA – PROGRESS & CHALLENGES

By Richard van Duyse

Experienced international vaccine industry consultant. Specialized in project & operational management, facility design, start-ups, & technology transfers. Bachelor of Applied Science (B.Sc).

INTRODUCTION Historically, Africa has depended heavily on foreign suppliers of vaccines, but this is changing as nations there aim to strengthen health systems and reduce external reliance. In this article I’d like to illustrate how many countries on the continent are seeking to build self-sufficiency in vaccine production, and I’ll resume some key developments and players:

1 African Vaccine Manufacturing Initiative (AVMI):

Launched in 2009, AVMI has been pivotal in pushing for local vaccine production & capacity across the continent. It hopes to enable the countries there to respond more quickly to public health challenges.

2 The African Medicines Agency (AMA):

The AMA was establishment in 2019 as a specialised agency of the African Union (AU). As of January 2024, 27 nations had ratified its treaty. This aims to provide regulatory support, streamline approval processes for local production, and standardize safety & quality of local vaccines to achieve ML 3 recognition from WHO. It will get support from the EMA.

3 The AU and Africa CDC’s Agenda have emphasized the need to boost local production of essential medicines, including vaccines. The broader agenda is to reduce Africa's dependence on these imports, reflected in the “Partnership for African Vaccine Manufacturing (PAVM)”.

4 Here are some of the countries & companies involved in current & planned facilities:

• Kenya: The Kenya BioVax Institute plans to manufacture vaccines for human and animal diseases vaccines locally.

• South Africa: Companies like Aspen Pharmacare and Biovac have already been involved in vaccine production.

• Egypt: Gennvax Egypt has ambitious plans for local vaccine manufacture & is already working with specialists. VACSERA has been involved in producing vaccines for hepatitis B, & COVID-19.

• Ghana: The Government is successfully implementing their roadmap for local vaccine production by 2031 and supporting local companies long term.

• Senegal: Institute Pasteur, Dakar is involved in the manufacturing of Yellow Fever vaccine which is pre-qualified by WHO.

• Rwanda: In Kigali a modular factory will be completed soon for vaccine production and end-to-end delivery, and will have the capacity to produce mRNA vaccines, via Technology Transfer.

Ethiopia recently announced the establishment of a vaccine manufacturing plant.

5 The mRNA Technology Transfer Hub:

The WHO and MPP have partnered with Afrigen and others in South Africa to set up a technology transfer hub for mRNA vaccines, to prime local production like those for COVID-19, & malaria. The following African companies are participating in the project:

• Biovac in Cape Town, South Africa
• Pasteur Institute of Tunis in Tunisia
• Pasteur Institute de Dakar in Senegal
• Biovaccines Nigeria Limited in Logos, Nigeria
• BioGeneric Pharma S.A.E. in Cairo, Egypt
• BioVax in Nairobi, Kenya

6 The global COVAX initiative provided vaccines to African countries during the pandemic, but the continent faced supply shortages and delays. This spurred increased efforts from African governments, private companies, and international partners to invest in the continent’s vaccine capability.

7 There are significant Challenges to the scaling up vaccine production in Africa however:

• The production of vaccines requires advanced technology, skilled labour, and high-quality manufacturing facilities. Vaccines manufacture is capital-intensive, and many African countries may not have the financial resources to build and maintain these facilities.

• The Regulatory Frameworks need strengthening hence the AMA needs to be effective in ensuring local vaccine safety and efficacy.

• Political and Economic Stability: Wars, terrorism, and national rivalry, cause economic uncertainty. Poor accessibility can hinder projects in general.

8 Collaboration and Support commitment from International partners, including the GAVI Advance Market Commitment, the Gates Foundation, CEPI, & WHO, have been secured.

Conclusion:

Manufacturing vaccines in Africa is a crucial step toward strengthening health security and independence. Although challenges remain, the growing momentum and collaboration are promising signs that the continent’s vaccine manufacturing capabilities will continue to expand in the coming years.

(The Galenisys team of Arabic, English, & French members have already worked on more than a dozen pharma projects for WHO, Government, or private companies in Africa. The Editor)

CHANGE CONTROL

by Steve Biddulph

Fellow of Royal Society of Biology. Board level pharma experience. QSM and Aseptic Manufacturing & Control Expertise. Galenisys Managing Director.

The 2nd article in the series which deal with tricky areas within a fully functioning GMP compliant Quality Assurance System.

One of the most difficult areas, for any company in the Life Sciences, is to manage change. Change control ensures that planned modifications to the activities that impact Product Quality, Regulatory filings and/or cGMP compliance. Examples are: the design of facilities, utilities or equipment, manufacturing processes, testing programmes and methods, warehousing and distribution of a product, the undertakings in regulatory dossiers and many other support activities will have no adverse or unforeseen affects neither on product quality nor on regulatory compliance. It provides a mechanism for continually improving the performance of manufacturing processes, equipment, facilities, testing regimes, etc. in order to enhance efficiency or implement corrective actions without negatively impacting the clinical and safety profiles of products.

Products are a function of the manufacturing process and of the starting materials and equipment used in their manufacture. Any changes to these could affect product quality and even the product safety and clinical profiles.

Change control requires the impact of proposed modifications to be evaluated both technically and by the Regulatory department and to be approved on the basis of documented evidence, including validation studies where appropriate, and requires all necessary regulatory approvals to be in place prior to implementation.

There are many difficult areas in industrial operations for change control. One of these is maintenance. If a component in a piece of equipment is replaced, should this be managed through change control ? Many people in our industry use a “like for like” approach but if the equipment is a critical step in manufacture or control, then the replacement will require validation. An example of this would be replacing a vacuum pump on an autoclave.

One company changed a starting material from a new supplier using the same specification as the replaced material. Unfortunately, the new material caused many adverse drug events in the market place and this could have been avoided by careful validation of the biological properties of the material from the new supplier. This could have been managed through change control but the process was by-passed.

There are many pitfalls awaiting the unsuspecting company where change control is concerned. At Galenisys we have a robust change control process to share with any companies who are encountering difficulties.

Just contact us

THE PROJECT MANAGERS NOTEBOOK part 8

CHECK THE DELIVERABLES & GET OFF YOUR BUTT !
By “Aubonne”

OK, now the project is well advanced. You’re into the really busy phase when multiple contractors are jostling on site, and progress is tangible. But complications are arising. How should your “smooth project management system” be working?

Hopefully your package contracts will have included “payment milestones” and the clear related deliverables that would justify the interim payments. These formal requests for payments should be made to the General Contractor or the Client as per the Project Responsibility Structure (See part 4 of this series), together with sign off by those in the Responsibility Matrix (see part 7) including eg the design engineers who scoped the package.

A typical payment milestone would be delivery to site of a piece of equipment, not yet operational. For suppliers or contractors, prompt payment is very important. And if the system works smoothly, it engenders their confidence.

It’s rare for a project to have no claims or changes of scope. We talked about this in part 7. These must be treated promptly in order to avoid costly delays, lengthy arguments, disputes, or even later arbitration. It's not uncommon that truculent contractors will deliberately slow down activity to put pressure on the client over unresolved issues.

The client should ensure that for each stage payment the supplier or contractor formally confirms that he has identified & advised the client of any Changes or Claims resulting from situations known before the date of the invoice, otherwise any future claims relating to these matters will be invalid.

At this stage, equipment and facility Qualification will have been planned, and may well have started. Multiple interdependencies will have become obvious. Eg are the personnel, steam, power, and instrument air etc for the autoclave Operational Qualification now available.

There should be regular weekly progress meetings with all the contractors concerned. In these, actions items from the previous meeting should be ticked off, new physical /program clashes dealt with, and revised priorities established. The Minutes should be issued the same day to all concerned.

Get off your butt !

As we've said, there's a lot going on out there on site and the only way to find out the real progress on the project is to be out there as well. One of the curses of the modern project is the computer screen, & the project software which constantly demands updating. This encourages reported “progress” being based on subcontractor say-so & promises!

Besides, it's cold out there in winter. What better than to sit in a warm office looking at the screen; with the ability to chat with colleagues and have a coffee when bored?

I well recall one large project where progress was slowing. To remedy this the general contractor replaced the majority of his local team because they had become “office bound” & out of touch!

“Aubonne”

BLOWBACK & IGNORANCE, USA STYLE

By the Editor

The effects on Health, Research, & the Pharmaceutical Industry.

I fondly remember my father-in-law who qualified at Kew Gardens and became a lecturer in horticulture. When in retirement he spent lots of time in his garden, tending a wide range of flowers, shrubs and vegetables. In old age he couldn't maintain these. And one day an enthusiastic neighbour volunteered to clear up the garden.

My father-in-law watched helplessly in horror as the man cut down to ground level everything in the front garden, including shrubs he’d taken years to nurture, & killing some by such treatment out of season.

Ignorance!

On a much larger scale, Elon Musk’s Doge unelected zealots have descended on the US Agency of International Development (USAID) firing many staff, with the intention of “feeding it into the woodchipper”; and gained access to the US payment system aimed at cutting off funding.

The resulting damage is worldwide eg:

• In South Africa, one of the biggest HIV clinics has had to lay off staff funded by the USAID.

• In Malawi USAID stopped. It funded anti-retroviral drugs - one of the major reasons why life expectancy there had risen from 45 in 2000 to 63 in 2022.

• Many local and international charities face imminent insolvency.

• DOGE stopped $750m - $1bn of funds owed to contractors for work already completed.

But it's not just that American nationals working for the agency now have no jobs. There's also lost income for farmers in Iowa, and other US agricultural States who are paid by USAID for the cereals which go to refugees in war-torn areas in Africa, Gaza and elsewhere.

Cuts to the infrastructure of American Science

There’s “blowback” elsewhere too. The National Scientific Federation (NSF) and the National Oceanic and Atmospheric Administration (NOAA) have been told to prepare for hefty reductions to their budgets and staff of up to 50%. Research institutions, many in “Republican States”, getting funding from the National Institutes of Health (NIH), have been warned of restrictions on how they can spend their money. They routinely employ the funds to cover between 50 and 70% of indirect costs including support staff salaries & maintaining laboratory equipment.

The Economist estimates that there will be cuts in the funding for research and studies in 10 major areas of medicine including cancer & cardiovascular diseases, of up to 20%. Deliberately and suddenly downsizing American Science is surely not a way to “Make America Great Again”.

The other expected impact on the Pharmaceutical Industry is the promised and actual increases in tariffs on US imports from China, the EU, & elsewhere, imposed by the new administration. These will surely cause retaliatory tariffs from the USA’s traditional trading partners. But 8 of the top 15 pharmaceutical companies in the world by 2024 sales revenue are American, who will be juicy targets for this retaliation. We remember our physics lessons – “every action has an equal & opposite reaction”

The trend to “onshoring” & sufficiency will surely accelerate, reducing the production economies of scale and causing disruption as supply chains are reconfigured.

Galenisys advice to manufacturing companies is to look at these aspects, & in particular the sources of their key bill of materials items.

The Editor