This week, Parul Oza is back on SpeakPharma to take us through the
changes the global pharmaceutical supply chain is experiencing as a result of
the Covid-19 pandemic. This time, the managing director of the Ahmedabad
(India) headquartered complete outsourcing solutions provider talks about the
strengths of the Indian pharmaceutical industry and how it can capitalize on
the opportunities emerging in the post-Covid world. Excerpts:
Welcome back Parul. Covid-19 has turned the focus on the global pharmaceutical supply chain. In your view, why has this happened?
It’s great to be back on SpeakPharma. The past few months have
certainly revealed the fragility of the global pharmaceutical supply chain,
including how dependent it is on China.
Of late, both the US and Europe have said they
want to reduce reliance on imports. Japan too
is talking about shifting production home.
We saw India restrict export of 58 APIs when the crisis broke out. India has also been working on improving its bulk drug manufacturing capacity in order to reduce its dependence on China.
The Indian government has approved two schemes to promote the manufacturing of APIs.
The first scheme — Promotion of Bulk Drug Parks — seeks to develop three mega
bulk drug parks in India in partnership with states; while the second scheme — Production Linked Incentive (PLI) Scheme — seeks to promote domestic manufacturing of critical key starting materials (KSMs) or drug intermediates and APIs in India.
What are some of the KSMs/APIs that need to be
de-risked out of China?
While there is a wide range of products that need alternative sources, the list of products shared by India provides a good sense of where the dependencies (on China) lie. There is dependence on China for antibiotics, vitamins, hormones and even for commonly used medicines like aspirin and paracetamol.
Under the two new schemes in India, financial incentives will be given to
manufacturers of 53 critical bulk drugs on their incremental sales over the base year (2019-20) for a period of
six years.
Do you see Indian companies capitalizing on this opportunity?
India can certainly become the pharmacy of the world. This policy will
also help the government with its aim to attain self-reliance and drug
security, while also boosting manufacturing.
India is already the leading country when it comes to filing DMFs with
the US Food and Drug Administration and it also has an established
inspection track record with most regulatory agencies in the world.
Before China became a global leader, India had a strong track record of
manufacturing APIs and KSMs. Even today, India has a large number of underutilized facilities which are either approved
or approvable. India also boasts of abundant skilled manpower and a deep understanding of process chemistry to
develop novel routes of synthesis. The country has all the necessary supporting
infrastructure available to not only manufacture but also to assure the quality
of a pharmaceutical drug.
This is an opportunity for not just India but the global pharma industry
to capitalize on reducing their dependence on China.
Is there an opportunity to produce APIs and KSMs, which are beyond these
53 critical bulk drugs?
Most certainly. As the pricing pressure continues to increase, companies with APIs that are under patent should consider
Indian units for production of their KSMs.
Finding a KSM manufacturer involves stricter due diligence,
manufacturing set-up and infrastructure evaluation for a given process. It
is akin to developing a KSM manufacturer.
What will be the role of China in view of these announcements?
Shifting supply chains out of China will be a
complex exercise. For more than a decade now, China has overtaken other
countries to become the largest producer of APIs and KSMs. They have developed scale, cost efficiencies, compliance standards and skilled manpower.
When we last spoke, we shared our sartan price trends dashboard, which provided insights into how the prices of
commonly used APIs such such as valsartan, olmesartan and losartan and those of their KSMs had changed since cancer-causing impurities were found in these commonly used blood pressure
drugs.
Interestingly, since the outbreak of
Covid-19, the prices of sartans and their intermediates are witnessing a
marginal decline rather than a surge. This clearly shows that Chinese factories
are active and will continue to remain competitive in the near future.
What recommendations do you have for organizations that want to set up new manufacturing facilities?
Post the sartan, ranitidine and metformin recalls, the global drug industry requires to focus a lot more attention on detail. Chemical manufacturing operations now undergo a completely new level of
scrutiny. Regulatory agencies, such as the European Medicines Agency (EMA) and SwissMedic now mandate that all products manufactured
through chemical synthesis undergo risk evaluation for genotoxic impurities.
While the manufacturing process is one element which introduces the risk
of mutagenic impurities, there are external factors that significantly increase
cross-contamination risk as well.
As most facilities will support the
manufacturing of generic drugs and their intermediates, the pressure on pricing
will continuously exist while regulatory compliance expectations will only
increase.
In view of this, it’s important that companies make intelligent
product selection decisions where they can compete at scale, have the skilled
manpower along with the supporting infrastructure available to assist the
project and ensure there is a laser focus on quality and environmental compliance.
It also helps to engage the services of a project outsourcing specialist
with deep domain knowledge of the industry, its players and the issues
involved. This way, projects are supported by a wider network of professionals
and more information and expertise is made available on a continuous basis in
this rapidly changing environment.
How can a company like CRMO Pharmmatecch assist during these times?
With over 30 years of industry experience, CRMO has developed an expertise in project outsourcing. We can assist with
selecting the right strategic partners and having the right oversight to ensure that project costs and timelines are maintained without compromising on
any quality or regulatory standards.
At CRMO we also assist vendor QA functions with the required level of
expertise to ensure consistent compliance and timely responsiveness to
regulatory queries.
We also provide the necessary risk assessment services to ensure GMP and
non-GMP starting materials are well selected. This way, we can keep projects on
track through accurate forecasting and monitoring, and ensure timely delivery
of products.
It is also imperative to facilitate clear and open communication channels which are
key to a successful transfer or development of any product.
We prize our focus on confidentiality so that technology transfers occur
seamlessly. And over time, we continue to remain a trusted outsourcing partner
for the industry.
For those interested in connecting directly with Parul, she can be contacted at paarul@crmopharmmatecch.com
Impressions: 5774
Last year, we had interviewed Paarul Oza
to understand the challenges being faced by the API (active pharmaceutical
ingredient) industry. Oza is the Managing Director of CRMO Pharmmatecch, an
Indian company (headquartered in Ahmedabad) that provides complete outsourcing
solutions to the pharmaceutical industry. This week, Oza is back on
SpeakPharma. She tells us how the API and intermediate manufacturing industry
is undergoing a complete revamp after the sartan and ranitidine recalls.
Excerpts:
Thanks
for speaking to SpeakPharma. Tell us how the API and chemical manufacturing
industry has evolved over the last few decades. And the impact the recent
sartan and ranitidine recalls have had on the industry.
The
industry has come a long way since the late 1980s. Back in those days, finding
manufacturers who could supply the desired product and meet the quality
specifications was a big challenge.
In
the late 1990s and early 2000s, as API and chemical manufacturing developed in
India and China, supply concerns eased significantly and price became the
primary driver of decision making. However, things began to change drastically
once the Ranbaxy story exploded and the current good manufacturing practices
(cGMP) compliance concerns started taking centerstage.
View Sartan Price Trends Dashboard by CRMO Pharmmatecch
The
recent developments have created an even more drastic shift. Today, it requires out-of-the box thinking to address the issue of long-term sustainable supply of APIs. This, in turn, involves keeping one’s ear to the ground and having deep technical insights that are supported by data analytics.
In order to obtain long-term sustainable supplies at
competitive prices, there is often a need to develop a new supplier rather than
work with existing suppliers who have an established history of problems.
Our sartan price trends dashboard provides insights into how the prices of commonly used APIs such as valsartan, olmesartan and losartan and those of their key
starting materials (KSMs) have changed.
What’s different now on the quality approach?
The
sartan and ranitidine recalls have placed chemical
manufacturing operations under a completely new level of scrutiny, unlike
anything that had been experienced by the industry. Regulatory agencies, such
as the European Medicines Agency (EMA) and SwissMedic, now mandate that all products
manufactured through chemical synthesis undergo risk evaluation for genotoxic
impurities.
While
the manufacturing process is one element which introduces the risk of mutagenic
impurities, there are external factors that significantly increase
cross-contamination risk as well.
View Sartan Price Trends Dashboard by CRMO Pharmmatecch
In a recent warning letter issued by the US Food and Drug
Administration (FDA) to Mylan, an investigation determined that nitrosamine
contamination was recovered from solvents. And the contamination was 40 times
the limit set by Mylan.
The warning letter also highlighted that the problems were not contained within Mylan’s operation as Mylan was supplied solvents (that were contaminated with nitrosamines) from multiple contract
manufacturers.
Even after Mylan suspended the use of recovered solvents from
contract manufacturers and began relying on in-house solvent recovery, the
solvents were still found to contain nitrosamine impurities.
In
August, Lantech Pharmaceuticals Limited, a firm that undertakes contract
solvent recovery facility for valsartan API manufacturing operations, was
issued a warning letter by the FDA after
being placed on an import alert in June. Samples collected from Lantech’s equipment were found to contain mutagenic impurities.
View Sartan Price Trends Dashboard by CRMO Pharmmatecch
As companies often fail to identify the root cause of
genotoxic and other impurities in their APIs, the implementation of audit trail controls
leads to the identification of more problems. As a result, inadequate handling
of manufacturing deviations and out of specification (OOS) results is almost a constant in all warning
letters which are being issued to companies around the world.
Today,
FDA inspectors are evaluating analytical methods and cleaning procedures
followed at sites in a lot more detail than ever before.
What
kind of changes are you witnessing on the supply side?
Environmental
concerns have led to a significant reduction in factories available to produce
KSMs and APIs. Factories in China are closing down due to government controls
and environmental norms. In India, there is a slowdown in permissions being
granted to companies to expand their manufacturing capacities. The net result
is that it is becoming extremely difficult to find manufacturers who are
willing to take on projects.
In
addition, the costs in India and China are increasing. Therefore, finding
reliable manufacturers who can sustain long-term supplies at competitive prices
has become critical.
View Sartan Price Trends Dashboard by CRMO Pharmmatecch
Supply chain professionals who were earlier spoilt for choice with multiple supply options now need ‘out of the box’ thinking to ensure long-term sustainability of supplies.
We
are also observing changes in KSM manufacturing, which used to be done in India
before it moved to China. We find that KSM manufacturing is returning to India
as the government controls in China continue to tighten.
What
role can CRMO Pharmmatecch play in the given scenario? How do you help
manufacturers?
We
have over 30 years of industry experience, and have developed project outsourcing
expertise.
We
undertake detailed market assessment reports. These, coupled with our years of
experience, help us identify suitable outsourcing partners.
View Sartan Price Trends Dashboard by CRMO Pharmmatecch
In addition, we facilitate cGMP compliance inspections to evaluate the capability of companies to meet the expectations of regulators. Our technical capabilities allow us to look at the manufacturing process in detail to ensure traceability, process robustness and cross contamination risk potential.
For those interested in connecting directly with Paarul, she can be contacted at paarul@crmopharmmatecch.com
Impressions: 4868